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Streptozocin | [C@@H]1([C@H](O)C(CO)OC(O)[C@@H]1NC(=O)N(N=O)C)O | Classic European guidelines for the management of advanced low-grade pNET recommend [C@@H]1([C@H](O)C(CO)OC(O)[C@@H]1NC(=O)N(N=O)C)O plus 5-fluorouracil/doxorubicin or, currently, temozolomide, with or without capecitabine, as chemotherapy, and everolimus or sunitinib as targeted agents. Although treatment with chemotherapy results in response rates of ~35%, it is associated with severe toxicity [2,[4][5][6][7]. Once patients experience treatment failure, therapeutic options are limited. | 9448188 |
Temozolomide | n1cn2c(n(C)nnc2c1C(N)=O)=O | Classic European guidelines for the management of advanced low-grade pNET recommend streptozocin plus 5-fluorouracil/doxorubicin or, currently, n1cn2c(n(C)nnc2c1C(N)=O)=O, with or without capecitabine, as chemotherapy, and everolimus or sunitinib as targeted agents. Although treatment with chemotherapy results in response rates of ~35%, it is associated with severe toxicity [2,[4][5][6][7]. Once patients experience treatment failure, therapeutic options are limited. | 9448188 |
Everolimus | C[C@@H]1/C=C/C=C/C=C(/[C@H](C[C@H]2O[C@@]([C@H](C)CC2)(O)C(=O)C(=O)N2CCCC[C@H]2C(O[C@H]([C@H](C)C[C@@H]2CC[C@H]([C@@H](C2)OC)OCCO)CC([C@H](C)/C=C(/[C@@H](O)[C@H](C([C@@H](C1)C)=O)OC)C)=O)=O)OC)C | Classic European guidelines for the management of advanced low-grade pNET recommend streptozocin plus 5-fluorouracil/doxorubicin or, currently, temozolomide, with or without capecitabine, as chemotherapy, and C[C@@H]1/C=C/C=C/C=C(/[C@H](C[C@H]2O[C@@]([C@H](C)CC2)(O)C(=O)C(=O)N2CCCC[C@H]2C(O[C@H]([C@H](C)C[C@@H]2CC[C@H]([C@@H](C2)OC)OCCO)CC([C@H](C)/C=C(/[C@@H](O)[C@H](C([C@@H](C1)C)=O)OC)C)=O)=O)OC)C or sunitinib as targeted agents. Although treatment with chemotherapy results in response rates of ~35%, it is associated with severe toxicity [2,[4][5][6][7]. Once patients experience treatment failure, therapeutic options are limited. | 9448188 |
Sunitinib | c1(C(NCCN(CC)CC)=O)c([nH]c(/C=C2/c3c(ccc(F)c3)NC2=O)c1C)C | Classic European guidelines for the management of advanced low-grade pNET recommend streptozocin plus 5-fluorouracil/doxorubicin or, currently, temozolomide, with or without capecitabine, as chemotherapy, and everolimus or c1(C(NCCN(CC)CC)=O)c([nH]c(/C=C2/c3c(ccc(F)c3)NC2=O)c1C)C as targeted agents. Although treatment with chemotherapy results in response rates of ~35%, it is associated with severe toxicity [2,[4][5][6][7]. Once patients experience treatment failure, therapeutic options are limited. | 9448188 |
Etoposide | [C@@H]1([C@H](O)[C@H]([C@H]2[C@@H](CO[C@H](O2)C)O1)O)O[C@@H]1C2C(=CC3OCOC=3C=2)[C@@H](C2C=C(OC)C(=C(OC)C=2)O)[C@@H]2[C@@H]1COC2=O | As in patients with low-grade NET, recommendations for first-line therapy in patients with high-grade tumors include chemotherapy that is based on the pattern of small cell lung cancer with [C@@H]1([C@H](O)[C@H]([C@H]2[C@@H](CO[C@H](O2)C)O1)O)O[C@@H]1C2C(=CC3OCOC=3C=2)[C@@H](C2C=C(OC)C(=C(OC)C=2)O)[C@@H]2[C@@H]1COC2=O and platinum [8]. Although patients with high-grade advanced tumors have the highest response rates, the duration of response is often short, and there is little evidence of benefit beyond 4 treatment cycles [8]. Retreatment with chemotherapy after relapse occurring 3-6 months following the first treatment may be considered but has not been investigated in trials [8]. | 9448188 |
Everolimus | O[C@@H]1/C(=C/[C@H](C(C[C@H](OC([C@@H]2CCCCN2C(=O)C(=O)[C@]2(O)O[C@@H](CC[C@H]2C)C[C@@H](/C(C)=C/C=C/C=C/[C@H](C[C@H](C(=O)[C@@H]1OC)C)C)OC)=O)[C@H](C)C[C@@H]1CC[C@@H](OCCO)[C@H](OC)C1)=O)C)C | O[C@@H]1/C(=C/[C@H](C(C[C@H](OC([C@@H]2CCCCN2C(=O)C(=O)[C@]2(O)O[C@@H](CC[C@H]2C)C[C@@H](/C(C)=C/C=C/C=C/[C@H](C[C@H](C(=O)[C@@H]1OC)C)C)OC)=O)[C@H](C)C[C@@H]1CC[C@@H](OCCO)[C@H](OC)C1)=O)C)C, an orally administered mammalian target of rapamycin (mTOR) inhibitor, has demonstrated both clinical efficacy and acceptable toxicity in patients with low-or intermediate-grade advanced pNET [9]. Positive results from 2 phase II studies subsequently prompted further investigation in this patient group with the prospective, randomized, phase III RADIANT-3 trial [10]. RADIANT-3 was conducted to assess the efficacy and safety of O[C@@H]1/C(=C/[C@H](C(C[C@H](OC([C@@H]2CCCCN2C(=O)C(=O)[C@]2(O)O[C@@H](CC[C@H]2C)C[C@@H](/C(C)=C/C=C/C=C/[C@H](C[C@H](C(=O)[C@@H]1OC)C)C)OC)=O)[C@H](C)C[C@@H]1CC[C@@H](OCCO)[C@H](OC)C1)=O)C)C (10 mg) compared with placebo among patients with low-or intermediategrade advanced pNET and radiologic documentation of disease progression [10]. Results showed median PFS to be significantly longer among patients receiving O[C@@H]1/C(=C/[C@H](C(C[C@H](OC([C@@H]2CCCCN2C(=O)C(=O)[C@]2(O)O[C@@H](CC[C@H]2C)C[C@@H](/C(C)=C/C=C/C=C/[C@H](C[C@H](C(=O)[C@@H]1OC)C)C)OC)=O)[C@H](C)C[C@@H]1CC[C@@H](OCCO)[C@H](OC)C1)=O)C)C than among those receiving placebo [11.0 vs. 4.6 months; hazard ratio, 0.35; 95% confidence interval (CI), 0.27-0.45; p < 0.001). The objective response rate by Response Evaluation Criteria In Solid Tumors version 1.0 (RECIST v1.0) was also higher with O[C@@H]1/C(=C/[C@H](C(C[C@H](OC([C@@H]2CCCCN2C(=O)C(=O)[C@]2(O)O[C@@H](CC[C@H]2C)C[C@@H](/C(C)=C/C=C/C=C/[C@H](C[C@H](C(=O)[C@@H]1OC)C)C)OC)=O)[C@H](C)C[C@@H]1CC[C@@H](OCCO)[C@H](OC)C1)=O)C)C than with placebo (all partial responses: 5 vs. 2%, respectively). Stable disease was observed in 73% of O[C@@H]1/C(=C/[C@H](C(C[C@H](OC([C@@H]2CCCCN2C(=O)C(=O)[C@]2(O)O[C@@H](CC[C@H]2C)C[C@@H](/C(C)=C/C=C/C=C/[C@H](C[C@H](C(=O)[C@@H]1OC)C)C)OC)=O)[C@H](C)C[C@@H]1CC[C@@H](OCCO)[C@H](OC)C1)=O)C)C-treated patients compared with 51% of those receiving placebo, and tumor shrinkage was also greater in the O[C@@H]1/C(=C/[C@H](C(C[C@H](OC([C@@H]2CCCCN2C(=O)C(=O)[C@]2(O)O[C@@H](CC[C@H]2C)C[C@@H](/C(C)=C/C=C/C=C/[C@H](C[C@H](C(=O)[C@@H]1OC)C)C)OC)=O)[C@H](C)C[C@@H]1CC[C@@H](OCCO)[C@H](OC)C1)=O)C)C arm (64%) compared with the placebo arm (21%). O[C@@H]1/C(=C/[C@H](C(C[C@H](OC([C@@H]2CCCCN2C(=O)C(=O)[C@]2(O)O[C@@H](CC[C@H]2C)C[C@@H](/C(C)=C/C=C/C=C/[C@H](C[C@H](C(=O)[C@@H]1OC)C)C)OC)=O)[C@H](C)C[C@@H]1CC[C@@H](OCCO)[C@H](OC)C1)=O)C)C was generally well tolerated; adverse events were primarily grade 1/2 in severity, consistent with known mTOR side effects, and generally reversible. | 9448188 |
Rapamycin | O=C1O[C@H]([C@H](C)C[C@H]2C[C@@H](OC)[C@@H](CC2)O)CC(=O)[C@@H](/C=C(/[C@@H](O)[C@@H](OC)C([C@@H](C[C@@H](/C=C/C=C/C=C(\C)[C@H](C[C@H]2O[C@@]([C@@H](CC2)C)(O)C(=O)C(N2[C@H]1CCCC2)=O)OC)C)C)=O)C)C | Everolimus, an orally administered mammalian target of O=C1O[C@H]([C@H](C)C[C@H]2C[C@@H](OC)[C@@H](CC2)O)CC(=O)[C@@H](/C=C(/[C@@H](O)[C@@H](OC)C([C@@H](C[C@@H](/C=C/C=C/C=C(\C)[C@H](C[C@H]2O[C@@]([C@@H](CC2)C)(O)C(=O)C(N2[C@H]1CCCC2)=O)OC)C)C)=O)C)C (mTOR) inhibitor, has demonstrated both clinical efficacy and acceptable toxicity in patients with low-or intermediate-grade advanced pNET [9]. Positive results from 2 phase II studies subsequently prompted further investigation in this patient group with the prospective, randomized, phase III RADIANT-3 trial [10]. RADIANT-3 was conducted to assess the efficacy and safety of everolimus (10 mg) compared with placebo among patients with low-or intermediategrade advanced pNET and radiologic documentation of disease progression [10]. Results showed median PFS to be significantly longer among patients receiving everolimus than among those receiving placebo [11.0 vs. 4.6 months; hazard ratio, 0.35; 95% confidence interval (CI), 0.27-0.45; p < 0.001). The objective response rate by Response Evaluation Criteria In Solid Tumors version 1.0 (RECIST v1.0) was also higher with everolimus than with placebo (all partial responses: 5 vs. 2%, respectively). Stable disease was observed in 73% of everolimus-treated patients compared with 51% of those receiving placebo, and tumor shrinkage was also greater in the everolimus arm (64%) compared with the placebo arm (21%). Everolimus was generally well tolerated; adverse events were primarily grade 1/2 in severity, consistent with known mTOR side effects, and generally reversible. | 9448188 |
Everolimus | [C@H]([C@@H]1CC([C@@H](/C=C(/[C@@H](O)[C@H](C(=O)[C@H](C)C[C@@H](/C=C/C=C/C=C(\C)[C@@H](OC)C[C@H]2O[C@@](O)(C(=O)C(=O)N3[C@H](C(=O)O1)CCCC3)[C@H](C)CC2)C)OC)C)C)=O)(C[C@@H]1CC[C@H]([C@@H](C1)OC)OCCO)C | Thus, although clinical trials have investigated novel treatments for NET patients experiencing treatment failure and disease progression, data are limited on second and successive lines of treatment and are even sparser for high-grade pNET, which is usually excluded from clinical trials. The RADIANT-3 trial enrolled patients who had previously received antineoplastic therapy; 49 and 50% of the [C@H]([C@@H]1CC([C@@H](/C=C(/[C@@H](O)[C@H](C(=O)[C@H](C)C[C@@H](/C=C/C=C/C=C(\C)[C@@H](OC)C[C@H]2O[C@@](O)(C(=O)C(=O)N3[C@H](C(=O)O1)CCCC3)[C@H](C)CC2)C)OC)C)C)=O)(C[C@@H]1CC[C@H]([C@@H](C1)OC)OCCO)C-treated population received previous somatostatin analogue therapy and chemotherapy, respectively [10]. Here, we describe prolonged clinical response to [C@H]([C@@H]1CC([C@@H](/C=C(/[C@@H](O)[C@H](C(=O)[C@H](C)C[C@@H](/C=C/C=C/C=C(\C)[C@@H](OC)C[C@H]2O[C@@](O)(C(=O)C(=O)N3[C@H](C(=O)O1)CCCC3)[C@H](C)CC2)C)OC)C)C)=O)(C[C@@H]1CC[C@H]([C@@H](C1)OC)OCCO)C plus octreotide long-acting repeatable (LAR) as treatment in a patient with high-grade advanced pNET in the late-line therapy setting. | 9448188 |
Octreotide | N1C([C@H](CC2=CNC3=CC=CC=C32)NC(=O)[C@@H](NC(=O)[C@H](NC([C@@H](N)CC2C=CC=CC=2)=O)CSSC[C@@H](NC([C@@H](NC([C@@H]1CCCCN)=O)[C@@H](C)O)=O)C(=O)N[C@@H]([C@H](O)C)CO)CC1=CC=CC=C1)=O | Thus, although clinical trials have investigated novel treatments for NET patients experiencing treatment failure and disease progression, data are limited on second and successive lines of treatment and are even sparser for high-grade pNET, which is usually excluded from clinical trials. The RADIANT-3 trial enrolled patients who had previously received antineoplastic therapy; 49 and 50% of the everolimus-treated population received previous somatostatin analogue therapy and chemotherapy, respectively [10]. Here, we describe prolonged clinical response to everolimus plus N1C([C@H](CC2=CNC3=CC=CC=C32)NC(=O)[C@@H](NC(=O)[C@H](NC([C@@H](N)CC2C=CC=CC=2)=O)CSSC[C@@H](NC([C@@H](NC([C@@H]1CCCCN)=O)[C@@H](C)O)=O)C(=O)N[C@@H]([C@H](O)C)CO)CC1=CC=CC=C1)=O long-acting repeatable (LAR) as treatment in a patient with high-grade advanced pNET in the late-line therapy setting. | 9448188 |
Octreotide | C1C=CC=CC=1C[C@@H](C(N[C@H]1C(=O)N[C@@H](CC2C=CC=CC=2)C(N[C@@H](CC2=CNC3=CC=CC=C32)C(=O)N[C@@H](CCCCN)C(N[C@@H]([C@@H](C)O)C(=O)N[C@H](CSSC1)C(=O)N[C@H](CO)[C@H](O)C)=O)=O)=O)N | In June 2008, a 34-year-old woman presented with a 2-month history of epigastric and periumbilical pain, fatigue, anorexia, nausea, and emesis. Physical assessment showed mild abdominal distention with painful hepatomegaly extending to the left hypochondrium, no adenopathy, and normal findings on echocardiogram (left ventricular ejection fraction, 72%). Computed tomography (CT) revealed hepatomegaly with multiple lesions (the largest lesion measured approximately 11.5 cm in diameter), a 5 × 7-cm mass in the tail of the pancreas, and a collection of subcapsular hepatic, perihepatic, and perivascular fluid. An analysis of tumoral tissue obtained by liver biopsy showed electron-dense granules containing synaptophysin and chromogranin A (CgA), high mitotic count (30/10 high-power fields), and high expression of Ki-67 (found in 30-40% of tumor cells) ( fig. 1). C1C=CC=CC=1C[C@@H](C(N[C@H]1C(=O)N[C@@H](CC2C=CC=CC=2)C(N[C@@H](CC2=CNC3=CC=CC=C32)C(=O)N[C@@H](CCCCN)C(N[C@@H]([C@@H](C)O)C(=O)N[C@H](CSSC1)C(=O)N[C@H](CO)[C@H](O)C)=O)=O)=O)N scintigraphy confirmed somatostatin receptor expression in the pancreatic tumor and in liver and peritoneal metastases. At the time of diagnosis, the patient's Karnofsky performance status (KPS) was 70%. | 9448188 |
Streptozocin | O=C(N(C)N=O)N[C@H]1C(OC([C@@H](O)[C@@H]1O)CO)O | Chemotherapy was initiated with O=C(N(C)N=O)N[C@H]1C(OC([C@@H](O)[C@@H]1O)CO)O and 5-fluorouracil in July 2008; the patient received 3 cycles of this first-line chemotherapy. In September 2008, clinical and biomarker evaluation demonstrated progressive disease, and treatment was switched to second-line cisplatin and etoposide for 4 cycles. After disease progression, the patient began treatment with O=C(N(C)N=O)N[C@H]1C(OC([C@@H](O)[C@@H]1O)CO)O and doxorubicin. After the completion of 3 cycles, however, the disease continued to progress rapidly, as assessed by radiologic imaging and changes in biomarker levels (CgA value, 4,381 ng/ml) (table 1). | 9448188 |
Cisplatin | N.N.Cl[Pt]Cl | Chemotherapy was initiated with streptozocin and 5-fluorouracil in July 2008; the patient received 3 cycles of this first-line chemotherapy. In September 2008, clinical and biomarker evaluation demonstrated progressive disease, and treatment was switched to second-line N.N.Cl[Pt]Cl and etoposide for 4 cycles. After disease progression, the patient began treatment with streptozocin and doxorubicin. After the completion of 3 cycles, however, the disease continued to progress rapidly, as assessed by radiologic imaging and changes in biomarker levels (CgA value, 4,381 ng/ml) (table 1). | 9448188 |
Etoposide | O(C)c1cc(cc(OC)c1O)[C@@H]1c2c(cc3OCOc3c2)[C@@H](O[C@H]2[C@@H]([C@@H](O)[C@@H]3O[C@H](C)OC[C@H]3O2)O)[C@H]2COC(=O)[C@H]12 | Chemotherapy was initiated with streptozocin and 5-fluorouracil in July 2008; the patient received 3 cycles of this first-line chemotherapy. In September 2008, clinical and biomarker evaluation demonstrated progressive disease, and treatment was switched to second-line cisplatin and O(C)c1cc(cc(OC)c1O)[C@@H]1c2c(cc3OCOc3c2)[C@@H](O[C@H]2[C@@H]([C@@H](O)[C@@H]3O[C@H](C)OC[C@H]3O2)O)[C@H]2COC(=O)[C@H]12 for 4 cycles. After disease progression, the patient began treatment with streptozocin and doxorubicin. After the completion of 3 cycles, however, the disease continued to progress rapidly, as assessed by radiologic imaging and changes in biomarker levels (CgA value, 4,381 ng/ml) (table 1). | 9448188 |
Doxorubicin | O(c1c2C(=O)c3c(c4c(c(O)c3C(c2ccc1)=O)C[C@@](O)(C(=O)CO)C[C@@H]4O[C@H]1C[C@@H]([C@H](O)[C@@H](O1)C)N)O)C | Chemotherapy was initiated with streptozocin and 5-fluorouracil in July 2008; the patient received 3 cycles of this first-line chemotherapy. In September 2008, clinical and biomarker evaluation demonstrated progressive disease, and treatment was switched to second-line cisplatin and etoposide for 4 cycles. After disease progression, the patient began treatment with streptozocin and O(c1c2C(=O)c3c(c4c(c(O)c3C(c2ccc1)=O)C[C@@](O)(C(=O)CO)C[C@@H]4O[C@H]1C[C@@H]([C@H](O)[C@@H](O1)C)N)O)C. After the completion of 3 cycles, however, the disease continued to progress rapidly, as assessed by radiologic imaging and changes in biomarker levels (CgA value, 4,381 ng/ml) (table 1). | 9448188 |
Opioids | C(N1CCC(N(C2C=CC=CC=2)C(CC)=O)CC1)CC1=CC=CC=C1.C1=CC=C(C=C1)C1(C(=O)OCC)CCN(CC1)C.C1=CC2C[C@@H]3[C@]4([C@@]5(CCN3C)C=2C(=C1OC)O[C@H]5C(=O)CC4)O | After 9 months of chemotherapy and 3 lines of therapy, the patient had a KPS of 60%, peritoneal metastases, and palpable hepatomegaly. She required high-dose C(N1CCC(N(C2C=CC=CC=2)C(CC)=O)CC1)CC1=CC=CC=C1.C1=CC=C(C=C1)C1(C(=O)OCC)CCN(CC1)C.C1=CC2C[C@@H]3[C@]4([C@@]5(CCN3C)C=2C(=C1OC)O[C@H]5C(=O)CC4)O to achieve analgesia. Fourth-line treatment with temozolomide (150 mg/m 2 on days 9-14) and capecitabine (1,000 mg/m 2 for 14 days every 3 weeks) was subsequently initiated and led to the achievement of partial radiologic response at 12 weeks (4 cycles); however, the patient experienced disease progression after 6 cycles of therapy. | 9448188 |
Temozolomide | C1=NC(C(=O)N)=C2N1C(N(C)N=N2)=O | After 9 months of chemotherapy and 3 lines of therapy, the patient had a KPS of 60%, peritoneal metastases, and palpable hepatomegaly. She required high-dose opioids to achieve analgesia. Fourth-line treatment with C1=NC(C(=O)N)=C2N1C(N(C)N=N2)=O (150 mg/m 2 on days 9-14) and capecitabine (1,000 mg/m 2 for 14 days every 3 weeks) was subsequently initiated and led to the achievement of partial radiologic response at 12 weeks (4 cycles); however, the patient experienced disease progression after 6 cycles of therapy. | 9448188 |
Paclitaxel | C1=CC([C@@H]([C@@H](O)C(=O)O[C@@H]2C(C)=C3C(C)([C@@](C2)([C@@H](OC(=O)C2C=CC=CC=2)[C@H]2[C@](C)(C(=O)[C@@H]3OC(C)=O)[C@@H](O)C[C@@H]3[C@@]2(OC(=O)C)CO3)O)C)NC(C2=CC=CC=C2)=O)=CC=C1 | In September 2009, after receiving 1 dose of fifth-line weekly C1=CC([C@@H]([C@@H](O)C(=O)O[C@@H]2C(C)=C3C(C)([C@@](C2)([C@@H](OC(=O)C2C=CC=CC=2)[C@H]2[C@](C)(C(=O)[C@@H]3OC(C)=O)[C@@H](O)C[C@@H]3[C@@]2(OC(=O)C)CO3)O)C)NC(C2=CC=CC=C2)=O)=CC=C1, the patient was hospitalized because of toxicity and general deterioration in health. She had uncontrolled pain, esophagitis, and small bowel partial obstruction caused by peritoneal disease progression that prevented her from eating without severe nausea. CgA concentration increased to 4,600 ng/ml, KPS decreased to 50%, and CT demonstrated massive hepatic and peritoneal tumor infiltration ( fig. 2a). Therefore, the patient was given intravenous fluids, morphine, scopolamine butyl bromide, dexamethasone, and subcutaneous octreotide as palliative and conservative therapy. After 1 week, she was able to tolerate oral fluids and drugs and experienced some improvement in general state. Taking into account initial data findings from the recent RADIANT-2 study [11], the patient's age, and her request to receive further lines of treatment, everolimus 10 mg/day plus octreotide LAR 30 mg every 4 weeks were initiated upon patient informed consent and compassionate use guidelines. Octreotide LAR had not previously been administered because of the patient's high baseline Ki-67 index (30-40%). | 9448188 |
Morphine | C1[C@@H]2[C@]34C5=C(C=CC(O)=C5O[C@H]4[C@H](C=1)O)C[C@H]2N(CC3)C | In September 2009, after receiving 1 dose of fifth-line weekly paclitaxel, the patient was hospitalized because of toxicity and general deterioration in health. She had uncontrolled pain, esophagitis, and small bowel partial obstruction caused by peritoneal disease progression that prevented her from eating without severe nausea. CgA concentration increased to 4,600 ng/ml, KPS decreased to 50%, and CT demonstrated massive hepatic and peritoneal tumor infiltration ( fig. 2a). Therefore, the patient was given intravenous fluids, C1[C@@H]2[C@]34C5=C(C=CC(O)=C5O[C@H]4[C@H](C=1)O)C[C@H]2N(CC3)C, scopolamine butyl bromide, dexamethasone, and subcutaneous octreotide as palliative and conservative therapy. After 1 week, she was able to tolerate oral fluids and drugs and experienced some improvement in general state. Taking into account initial data findings from the recent RADIANT-2 study [11], the patient's age, and her request to receive further lines of treatment, everolimus 10 mg/day plus octreotide LAR 30 mg every 4 weeks were initiated upon patient informed consent and compassionate use guidelines. Octreotide LAR had not previously been administered because of the patient's high baseline Ki-67 index (30-40%). | 9448188 |
Scopolamine | C12N(C)C(CC(OC([C@H](c3ccccc3)CO)=O)C1)[C@H]1[C@@H]2O1 | In September 2009, after receiving 1 dose of fifth-line weekly paclitaxel, the patient was hospitalized because of toxicity and general deterioration in health. She had uncontrolled pain, esophagitis, and small bowel partial obstruction caused by peritoneal disease progression that prevented her from eating without severe nausea. CgA concentration increased to 4,600 ng/ml, KPS decreased to 50%, and CT demonstrated massive hepatic and peritoneal tumor infiltration ( fig. 2a). Therefore, the patient was given intravenous fluids, morphine, C12N(C)C(CC(OC([C@H](c3ccccc3)CO)=O)C1)[C@H]1[C@@H]2O1 butyl bromide, dexamethasone, and subcutaneous octreotide as palliative and conservative therapy. After 1 week, she was able to tolerate oral fluids and drugs and experienced some improvement in general state. Taking into account initial data findings from the recent RADIANT-2 study [11], the patient's age, and her request to receive further lines of treatment, everolimus 10 mg/day plus octreotide LAR 30 mg every 4 weeks were initiated upon patient informed consent and compassionate use guidelines. Octreotide LAR had not previously been administered because of the patient's high baseline Ki-67 index (30-40%). | 9448188 |
Butyl bromide | BrCCCC | In September 2009, after receiving 1 dose of fifth-line weekly paclitaxel, the patient was hospitalized because of toxicity and general deterioration in health. She had uncontrolled pain, esophagitis, and small bowel partial obstruction caused by peritoneal disease progression that prevented her from eating without severe nausea. CgA concentration increased to 4,600 ng/ml, KPS decreased to 50%, and CT demonstrated massive hepatic and peritoneal tumor infiltration ( fig. 2a). Therefore, the patient was given intravenous fluids, morphine, scopolamine BrCCCC, dexamethasone, and subcutaneous octreotide as palliative and conservative therapy. After 1 week, she was able to tolerate oral fluids and drugs and experienced some improvement in general state. Taking into account initial data findings from the recent RADIANT-2 study [11], the patient's age, and her request to receive further lines of treatment, everolimus 10 mg/day plus octreotide LAR 30 mg every 4 weeks were initiated upon patient informed consent and compassionate use guidelines. Octreotide LAR had not previously been administered because of the patient's high baseline Ki-67 index (30-40%). | 9448188 |
Bromide | [Br-] | In September 2009, after receiving 1 dose of fifth-line weekly paclitaxel, the patient was hospitalized because of toxicity and general deterioration in health. She had uncontrolled pain, esophagitis, and small bowel partial obstruction caused by peritoneal disease progression that prevented her from eating without severe nausea. CgA concentration increased to 4,600 ng/ml, KPS decreased to 50%, and CT demonstrated massive hepatic and peritoneal tumor infiltration ( fig. 2a). Therefore, the patient was given intravenous fluids, morphine, scopolamine butyl [Br-], dexamethasone, and subcutaneous octreotide as palliative and conservative therapy. After 1 week, she was able to tolerate oral fluids and drugs and experienced some improvement in general state. Taking into account initial data findings from the recent RADIANT-2 study [11], the patient's age, and her request to receive further lines of treatment, everolimus 10 mg/day plus octreotide LAR 30 mg every 4 weeks were initiated upon patient informed consent and compassionate use guidelines. Octreotide LAR had not previously been administered because of the patient's high baseline Ki-67 index (30-40%). | 9448188 |
Dexamethasone | C12CC[C@H]3[C@H]4[C@@](C[C@H](O)[C@@]3([C@@]2(C)C=CC(C=1)=O)F)(C)[C@@](C(CO)=O)([C@@H](C4)C)O | In September 2009, after receiving 1 dose of fifth-line weekly paclitaxel, the patient was hospitalized because of toxicity and general deterioration in health. She had uncontrolled pain, esophagitis, and small bowel partial obstruction caused by peritoneal disease progression that prevented her from eating without severe nausea. CgA concentration increased to 4,600 ng/ml, KPS decreased to 50%, and CT demonstrated massive hepatic and peritoneal tumor infiltration ( fig. 2a). Therefore, the patient was given intravenous fluids, morphine, scopolamine butyl bromide, C12CC[C@H]3[C@H]4[C@@](C[C@H](O)[C@@]3([C@@]2(C)C=CC(C=1)=O)F)(C)[C@@](C(CO)=O)([C@@H](C4)C)O, and subcutaneous octreotide as palliative and conservative therapy. After 1 week, she was able to tolerate oral fluids and drugs and experienced some improvement in general state. Taking into account initial data findings from the recent RADIANT-2 study [11], the patient's age, and her request to receive further lines of treatment, everolimus 10 mg/day plus octreotide LAR 30 mg every 4 weeks were initiated upon patient informed consent and compassionate use guidelines. Octreotide LAR had not previously been administered because of the patient's high baseline Ki-67 index (30-40%). | 9448188 |
Octreotide | [nH]1cc(c2c1cccc2)C[C@@H]1NC(=O)[C@@H](NC(=O)[C@H](NC([C@@H](N)Cc2ccccc2)=O)CSSC[C@@H](NC(=O)[C@@H](NC([C@@H](NC1=O)CCCCN)=O)[C@H](O)C)C(=O)N[C@H](CO)[C@@H](C)O)Cc1ccccc1 | In September 2009, after receiving 1 dose of fifth-line weekly paclitaxel, the patient was hospitalized because of toxicity and general deterioration in health. She had uncontrolled pain, esophagitis, and small bowel partial obstruction caused by peritoneal disease progression that prevented her from eating without severe nausea. CgA concentration increased to 4,600 ng/ml, KPS decreased to 50%, and CT demonstrated massive hepatic and peritoneal tumor infiltration ( fig. 2a). Therefore, the patient was given intravenous fluids, morphine, scopolamine butyl bromide, dexamethasone, and subcutaneous [nH]1cc(c2c1cccc2)C[C@@H]1NC(=O)[C@@H](NC(=O)[C@H](NC([C@@H](N)Cc2ccccc2)=O)CSSC[C@@H](NC(=O)[C@@H](NC([C@@H](NC1=O)CCCCN)=O)[C@H](O)C)C(=O)N[C@H](CO)[C@@H](C)O)Cc1ccccc1 as palliative and conservative therapy. After 1 week, she was able to tolerate oral fluids and drugs and experienced some improvement in general state. Taking into account initial data findings from the recent RADIANT-2 study [11], the patient's age, and her request to receive further lines of treatment, everolimus 10 mg/day plus [nH]1cc(c2c1cccc2)C[C@@H]1NC(=O)[C@@H](NC(=O)[C@H](NC([C@@H](N)Cc2ccccc2)=O)CSSC[C@@H](NC(=O)[C@@H](NC([C@@H](NC1=O)CCCCN)=O)[C@H](O)C)C(=O)N[C@H](CO)[C@@H](C)O)Cc1ccccc1 LAR 30 mg every 4 weeks were initiated upon patient informed consent and compassionate use guidelines. [nH]1cc(c2c1cccc2)C[C@@H]1NC(=O)[C@@H](NC(=O)[C@H](NC([C@@H](N)Cc2ccccc2)=O)CSSC[C@@H](NC(=O)[C@@H](NC([C@@H](NC1=O)CCCCN)=O)[C@H](O)C)C(=O)N[C@H](CO)[C@@H](C)O)Cc1ccccc1 LAR had not previously been administered because of the patient's high baseline Ki-67 index (30-40%). | 9448188 |
Everolimus | C1=C/[C@H](C[C@@H](C)C(=O)[C@@H]([C@@H](/C(=C/[C@@H](C)C(=O)C[C@@H]([C@@H](C[C@H]2C[C@H]([C@H](OCCO)CC2)OC)C)OC([C@@H]2CCCCN2C(=O)C([C@@]2(O)[C@H](C)CC[C@@H](C[C@@H](/C(=C/C=C/1)C)OC)O2)=O)=O)C)O)OC)C | In September 2009, after receiving 1 dose of fifth-line weekly paclitaxel, the patient was hospitalized because of toxicity and general deterioration in health. She had uncontrolled pain, esophagitis, and small bowel partial obstruction caused by peritoneal disease progression that prevented her from eating without severe nausea. CgA concentration increased to 4,600 ng/ml, KPS decreased to 50%, and CT demonstrated massive hepatic and peritoneal tumor infiltration ( fig. 2a). Therefore, the patient was given intravenous fluids, morphine, scopolamine butyl bromide, dexamethasone, and subcutaneous octreotide as palliative and conservative therapy. After 1 week, she was able to tolerate oral fluids and drugs and experienced some improvement in general state. Taking into account initial data findings from the recent RADIANT-2 study [11], the patient's age, and her request to receive further lines of treatment, C1=C/[C@H](C[C@@H](C)C(=O)[C@@H]([C@@H](/C(=C/[C@@H](C)C(=O)C[C@@H]([C@@H](C[C@H]2C[C@H]([C@H](OCCO)CC2)OC)C)OC([C@@H]2CCCCN2C(=O)C([C@@]2(O)[C@H](C)CC[C@@H](C[C@@H](/C(=C/C=C/1)C)OC)O2)=O)=O)C)O)OC)C 10 mg/day plus octreotide LAR 30 mg every 4 weeks were initiated upon patient informed consent and compassionate use guidelines. Octreotide LAR had not previously been administered because of the patient's high baseline Ki-67 index (30-40%). | 9448188 |
Everolimus | [C@]12(O[C@@H](CC[C@H]1C)C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C([C@@H]([C@H](O)/C(C)=C/[C@H](C(C[C@H](OC(=O)[C@@H]1CCCCN1C(C2=O)=O)[C@@H](C[C@@H]1CC[C@@H](OCCO)[C@@H](C1)OC)C)=O)C)OC)=O)O | Fifteen days after the initiation of sixth-line therapy with [C@]12(O[C@@H](CC[C@H]1C)C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C([C@@H]([C@H](O)/C(C)=C/[C@H](C(C[C@H](OC(=O)[C@@H]1CCCCN1C(C2=O)=O)[C@@H](C[C@@H]1CC[C@@H](OCCO)[C@@H](C1)OC)C)=O)C)OC)=O)O plus octreotide LAR, the CgA concentration decreased to 1,388 ng/ml. The patient achieved partial radiologic response (>50% decrease in tumor size) after 2 months of treatment ( fig. 2b). By January 2010, her general health status had markedly improved, corresponding to a KPS of 90%, with pain and oral restrictions alleviated. Clinically important partial response (decrease in tumor size >80%) was confirmed by CT (as per RECIST v1.0; fig. 2c) and by reduced CgA levels after 8 months of therapy with [C@]12(O[C@@H](CC[C@H]1C)C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C([C@@H]([C@H](O)/C(C)=C/[C@H](C(C[C@H](OC(=O)[C@@H]1CCCCN1C(C2=O)=O)[C@@H](C[C@@H]1CC[C@@H](OCCO)[C@@H](C1)OC)C)=O)C)OC)=O)O ( fig. 3). The lowest CgA value, 137 ng/ml, was achieved in August 2010 after approximately 1 year of treatment. | 9448188 |
Octreotide | [C@@H]1([C@@H](C)O)NC([C@@H](NC([C@H](Cc2c3ccccc3[nH]c2)NC([C@H](Cc2ccccc2)NC([C@@H](CSSC[C@@H](NC1=O)C(N[C@H](CO)[C@@H](C)O)=O)NC(=O)[C@@H](N)Cc1ccccc1)=O)=O)=O)CCCCN)=O | Fifteen days after the initiation of sixth-line therapy with everolimus plus [C@@H]1([C@@H](C)O)NC([C@@H](NC([C@H](Cc2c3ccccc3[nH]c2)NC([C@H](Cc2ccccc2)NC([C@@H](CSSC[C@@H](NC1=O)C(N[C@H](CO)[C@@H](C)O)=O)NC(=O)[C@@H](N)Cc1ccccc1)=O)=O)=O)CCCCN)=O LAR, the CgA concentration decreased to 1,388 ng/ml. The patient achieved partial radiologic response (>50% decrease in tumor size) after 2 months of treatment ( fig. 2b). By January 2010, her general health status had markedly improved, corresponding to a KPS of 90%, with pain and oral restrictions alleviated. Clinically important partial response (decrease in tumor size >80%) was confirmed by CT (as per RECIST v1.0; fig. 2c) and by reduced CgA levels after 8 months of therapy with everolimus ( fig. 3). The lowest CgA value, 137 ng/ml, was achieved in August 2010 after approximately 1 year of treatment. | 9448188 |
Everolimus | O[C@@]12C(C(=O)N3CCCC[C@H]3C(O[C@H]([C@H](C)C[C@@H]3CC[C@H]([C@@H](C3)OC)OCCO)CC([C@H](C)/C=C(\C)[C@H]([C@@H](OC)C([C@H](C)C[C@H](C)/C=C/C=C/C=C(/[C@H](C[C@@H](O1)CC[C@H]2C)OC)C)=O)O)=O)=O)=O | Throughout the course of O[C@@]12C(C(=O)N3CCCC[C@H]3C(O[C@H]([C@H](C)C[C@@H]3CC[C@H]([C@@H](C3)OC)OCCO)CC([C@H](C)/C=C(\C)[C@H]([C@@H](OC)C([C@H](C)C[C@H](C)/C=C/C=C/C=C(/[C@H](C[C@@H](O1)CC[C@H]2C)OC)C)=O)O)=O)=O)=O plus octreotide LAR treatment, the patient experienced grade 1 hyperglycemia and grade 2 anemia, which were treated with an antidiabetic diet and erythropoietin plus intravenous iron therapy, respectively. Grade 1 stomatitis was also documented but did not require pharmacologic intervention. After 1 year of treatment, the patient reported sporadic grade 1 emesis, grade 1 diarrhea, and grade 1 hand-foot syndrome. | 9448188 |
Octreotide | C1=C2C(C[C@H]3C(N[C@@H](CCCCN)C(N[C@@H]([C@H](O)C)C(N[C@@H](C(N[C@@H]([C@H](O)C)CO)=O)CSSC[C@@H](NC([C@@H](N)CC4=CC=CC=C4)=O)C(=O)N[C@@H](CC4C=CC=CC=4)C(N3)=O)=O)=O)=O)=CNC2=CC=C1 | Throughout the course of everolimus plus C1=C2C(C[C@H]3C(N[C@@H](CCCCN)C(N[C@@H]([C@H](O)C)C(N[C@@H](C(N[C@@H]([C@H](O)C)CO)=O)CSSC[C@@H](NC([C@@H](N)CC4=CC=CC=C4)=O)C(=O)N[C@@H](CC4C=CC=CC=4)C(N3)=O)=O)=O)=O)=CNC2=CC=C1 LAR treatment, the patient experienced grade 1 hyperglycemia and grade 2 anemia, which were treated with an antidiabetic diet and erythropoietin plus intravenous iron therapy, respectively. Grade 1 stomatitis was also documented but did not require pharmacologic intervention. After 1 year of treatment, the patient reported sporadic grade 1 emesis, grade 1 diarrhea, and grade 1 hand-foot syndrome. | 9448188 |
Everolimus | [C@H](C[C@H]1C[C@H]([C@H](OCCO)CC1)OC)(C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C([C@@]2(O)[C@@H](CC[C@@H](C[C@H](OC)/C(=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@@H]([C@@H](/C(=C/[C@@H](C)C(=O)C1)C)O)OC)C)O2)C)=O | In December 2010, after 15 months of [C@H](C[C@H]1C[C@H]([C@H](OCCO)CC1)OC)(C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C([C@@]2(O)[C@@H](CC[C@@H](C[C@H](OC)/C(=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@@H]([C@@H](/C(=C/[C@@H](C)C(=O)C1)C)O)OC)C)O2)C)=O and octreotide LAR as sixth-line therapy, the patient continued to be asymptomatic and had a KPS of 90%. Assessment by CT demonstrated an increase in the size of a peritoneal node (from 17 mm in early scans to 25 mm). To prevent disease progression, [C@H](C[C@H]1C[C@H]([C@H](OCCO)CC1)OC)(C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C([C@@]2(O)[C@@H](CC[C@@H](C[C@H](OC)/C(=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@@H]([C@@H](/C(=C/[C@@H](C)C(=O)C1)C)O)OC)C)O2)C)=O was administered at a higher dose (15 mg/day), and 1 month later the node had decreased in size (to 21 mm). | 9448188 |
Octreotide | [C@H]([C@@H](C)O)(CO)NC([C@H]1CSSC[C@H](C(N[C@@H](CC2=CC=CC=C2)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H]([C@H](O)C)C(=O)N1)CCCCN)CC1=CNC2C1=CC=CC=2)=O)NC(=O)[C@H](CC1=CC=CC=C1)N)=O | In December 2010, after 15 months of everolimus and [C@H]([C@@H](C)O)(CO)NC([C@H]1CSSC[C@H](C(N[C@@H](CC2=CC=CC=C2)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H]([C@H](O)C)C(=O)N1)CCCCN)CC1=CNC2C1=CC=CC=2)=O)NC(=O)[C@H](CC1=CC=CC=C1)N)=O LAR as sixth-line therapy, the patient continued to be asymptomatic and had a KPS of 90%. Assessment by CT demonstrated an increase in the size of a peritoneal node (from 17 mm in early scans to 25 mm). To prevent disease progression, everolimus was administered at a higher dose (15 mg/day), and 1 month later the node had decreased in size (to 21 mm). | 9448188 |
Everolimus | O(C)[C@@H]1C[C@@H](CC[C@H]1OCCO)C[C@H]([C@H]1OC([C@H]2N(CCCC2)C(=O)C(=O)[C@@]2(O[C@@H](CC[C@H]2C)C[C@@H](/C(=C/C=C/C=C/[C@H](C[C@H](C([C@@H]([C@H](O)/C(=C/[C@H](C(C1)=O)C)C)OC)=O)C)C)C)OC)O)=O)C | After more than 1 year of treatment benefit with O(C)[C@@H]1C[C@@H](CC[C@H]1OCCO)C[C@H]([C@H]1OC([C@H]2N(CCCC2)C(=O)C(=O)[C@@]2(O[C@@H](CC[C@H]2C)C[C@@H](/C(=C/C=C/C=C/[C@H](C[C@H](C([C@@H]([C@H](O)/C(=C/[C@H](C(C1)=O)C)C)OC)=O)C)C)C)OC)O)=O)C, during CT evaluation in March 2011, the patient's liver metastases were shown to have progressed. A diagnostic biopsy was repeated. However, it was possible only to confirm the high Ki-67 index and electron-dense granules containing synaptophysin and CgA. Most of the cells were necrotic, and it was not possible to check for tissue expression of potential O(C)[C@@H]1C[C@@H](CC[C@H]1OCCO)C[C@H]([C@H]1OC([C@H]2N(CCCC2)C(=O)C(=O)[C@@]2(O[C@@H](CC[C@H]2C)C[C@@H](/C(=C/C=C/C=C/[C@H](C[C@H](C([C@@H]([C@H](O)/C(=C/[C@H](C(C1)=O)C)C)OC)=O)C)C)C)OC)O)=O)C response predictors such as mTOR and 4EB1. One week later clinical progression was reported, and 2 weeks later the patient was hospitalized with liver failure, fever, jaundice, painful hepatomegaly, extrinsic compression of the stomach, anorexia, and asthenia. After progressive deterioration in her general health, the patient died on April 4, 2011, 33 months after the initial diagnosis and 19 months after the initiation of treatment with O(C)[C@@H]1C[C@@H](CC[C@H]1OCCO)C[C@H]([C@H]1OC([C@H]2N(CCCC2)C(=O)C(=O)[C@@]2(O[C@@H](CC[C@H]2C)C[C@@H](/C(=C/C=C/C=C/[C@H](C[C@H](C([C@@H]([C@H](O)/C(=C/[C@H](C(C1)=O)C)C)OC)=O)C)C)C)OC)O)=O)C plus octreotide LAR. | 9448188 |
Octreotide | O=C1[C@@H](NC(=O)[C@@H](NC([C@@H](NC(=O)[C@H](NC([C@@H](N)Cc2ccccc2)=O)CSSC[C@@H](NC(=O)[C@H]([C@H](O)C)N1)C(=O)N[C@@H]([C@H](O)C)CO)Cc1ccccc1)=O)Cc1c[nH]c2c1cccc2)CCCCN | After more than 1 year of treatment benefit with everolimus, during CT evaluation in March 2011, the patient's liver metastases were shown to have progressed. A diagnostic biopsy was repeated. However, it was possible only to confirm the high Ki-67 index and electron-dense granules containing synaptophysin and CgA. Most of the cells were necrotic, and it was not possible to check for tissue expression of potential everolimus response predictors such as mTOR and 4EB1. One week later clinical progression was reported, and 2 weeks later the patient was hospitalized with liver failure, fever, jaundice, painful hepatomegaly, extrinsic compression of the stomach, anorexia, and asthenia. After progressive deterioration in her general health, the patient died on April 4, 2011, 33 months after the initial diagnosis and 19 months after the initiation of treatment with everolimus plus O=C1[C@@H](NC(=O)[C@@H](NC([C@@H](NC(=O)[C@H](NC([C@@H](N)Cc2ccccc2)=O)CSSC[C@@H](NC(=O)[C@H]([C@H](O)C)N1)C(=O)N[C@@H]([C@H](O)C)CO)Cc1ccccc1)=O)Cc1c[nH]c2c1cccc2)CCCCN LAR. | 9448188 |
Everolimus | C1CCC[C@H]2C(=O)O[C@@H](CC([C@H](C)/C=C(\C)[C@H]([C@H](C([C@H](C)C[C@H](C)/C=C/C=C/C=C(\C)[C@H](C[C@@H]3CC[C@@H](C)[C@](C(=O)C(N21)=O)(O3)O)OC)=O)OC)O)=O)[C@H](C)C[C@@H]1CC[C@H]([C@H](OC)C1)OCCO | In the case presented here, a patient with high-grade pNET and 5 failed chemotherapy regimens was treated with C1CCC[C@H]2C(=O)O[C@@H](CC([C@H](C)/C=C(\C)[C@H]([C@H](C([C@H](C)C[C@H](C)/C=C/C=C/C=C(\C)[C@H](C[C@@H]3CC[C@@H](C)[C@](C(=O)C(N21)=O)(O3)O)OC)=O)OC)O)=O)[C@H](C)C[C@@H]1CC[C@H]([C@H](OC)C1)OCCO plus octreotide LAR and achieved prolonged objective clinical and radiologic response, including improvement in hepatic and peritoneal metastatic sites, reduction in disease progressive biomarkers, and resolution of constitutional symptoms with improved KPS. The radiologic response persisted for more than 15 months, and CT assessment revealed the important partial radiologic response of >80% decrease in tumor size after 4 months of initiation of C1CCC[C@H]2C(=O)O[C@@H](CC([C@H](C)/C=C(\C)[C@H]([C@H](C([C@H](C)C[C@H](C)/C=C/C=C/C=C(\C)[C@H](C[C@@H]3CC[C@@H](C)[C@](C(=O)C(N21)=O)(O3)O)OC)=O)OC)O)=O)[C@H](C)C[C@@H]1CC[C@H]([C@H](OC)C1)OCCO plus octreotide LAR therapy. The regimen was well tolerated by the patient, and adverse events (hyperglycemia, sporadic emesis, diarrhea, and hand-foot syndrome) were generally manageable and grade 1 in severity. | 9448188 |
Octreotide | C[C@H]([C@@H]1NC([C@@H](NC([C@@H](NC([C@@H](NC(=O)[C@H](NC([C@H](Cc2ccccc2)N)=O)CSSC[C@H](C(=O)N[C@@H]([C@H](O)C)CO)NC1=O)Cc1ccccc1)=O)Cc1c[nH]c2c1cccc2)=O)CCCCN)=O)O | In the case presented here, a patient with high-grade pNET and 5 failed chemotherapy regimens was treated with everolimus plus C[C@H]([C@@H]1NC([C@@H](NC([C@@H](NC([C@@H](NC(=O)[C@H](NC([C@H](Cc2ccccc2)N)=O)CSSC[C@H](C(=O)N[C@@H]([C@H](O)C)CO)NC1=O)Cc1ccccc1)=O)Cc1c[nH]c2c1cccc2)=O)CCCCN)=O)O LAR and achieved prolonged objective clinical and radiologic response, including improvement in hepatic and peritoneal metastatic sites, reduction in disease progressive biomarkers, and resolution of constitutional symptoms with improved KPS. The radiologic response persisted for more than 15 months, and CT assessment revealed the important partial radiologic response of >80% decrease in tumor size after 4 months of initiation of everolimus plus C[C@H]([C@@H]1NC([C@@H](NC([C@@H](NC([C@@H](NC(=O)[C@H](NC([C@H](Cc2ccccc2)N)=O)CSSC[C@H](C(=O)N[C@@H]([C@H](O)C)CO)NC1=O)Cc1ccccc1)=O)Cc1c[nH]c2c1cccc2)=O)CCCCN)=O)O LAR therapy. The regimen was well tolerated by the patient, and adverse events (hyperglycemia, sporadic emesis, diarrhea, and hand-foot syndrome) were generally manageable and grade 1 in severity. | 9448188 |
Everolimus | [C@H]1(/C(=C/[C@@H](C)C(C[C@H](OC(=O)[C@H]2N(CCCC2)C(C([C@@]2(O[C@@H](CC[C@H]2C)C[C@H](OC)/C(C)=C/C=C/C=C/[C@H](C[C@H](C(=O)[C@@H]1OC)C)C)O)=O)=O)[C@@H](C[C@@H]1CC[C@H]([C@H](OC)C1)OCCO)C)=O)C)O | The combination of [C@H]1(/C(=C/[C@@H](C)C(C[C@H](OC(=O)[C@H]2N(CCCC2)C(C([C@@]2(O[C@@H](CC[C@H]2C)C[C@H](OC)/C(C)=C/C=C/C=C/[C@H](C[C@H](C(=O)[C@@H]1OC)C)C)O)=O)=O)[C@@H](C[C@@H]1CC[C@H]([C@H](OC)C1)OCCO)C)=O)C)O plus octreotide LAR demonstrated markedly improved clinical benefit compared with previous first-to fifth-line treatment regimens administered to the patient (table 1). Partial radiologic response was achieved only at 12 weeks with fourth-line temozolomide and capecitabine, but rapid disease progression was observed in <6 months with this regimen and in <3 months with other therapy lines. One explanation for the efficacy of temozolomide and capecitabine is the decreased expression of the DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) in pNET. Future studies should investigate whether low MGMT expression in metastatic pNET is a predictive factor that correlates with response to capecitabine and temozolomide [12]. Treatment with [C@H]1(/C(=C/[C@@H](C)C(C[C@H](OC(=O)[C@H]2N(CCCC2)C(C([C@@]2(O[C@@H](CC[C@H]2C)C[C@H](OC)/C(C)=C/C=C/C=C/[C@H](C[C@H](C(=O)[C@@H]1OC)C)C)O)=O)=O)[C@@H](C[C@@H]1CC[C@H]([C@H](OC)C1)OCCO)C)=O)C)O plus octreotide LAR, on the other hand, resulted in dramatic clinical and CT imaging responses and PFS of 19 months. | 9448188 |
Octreotide | N([C@H]1C(N[C@H](C(=O)N[C@H](C(N[C@H](C(=O)N[C@H](C(=O)N[C@H](CSSC1)C(=O)N[C@@H]([C@@H](C)O)CO)[C@@H](C)O)CCCCN)=O)CC1=CNC2C1=CC=CC=2)CC1C=CC=CC=1)=O)C(=O)[C@@H](N)CC1C=CC=CC=1 | The combination of everolimus plus N([C@H]1C(N[C@H](C(=O)N[C@H](C(N[C@H](C(=O)N[C@H](C(=O)N[C@H](CSSC1)C(=O)N[C@@H]([C@@H](C)O)CO)[C@@H](C)O)CCCCN)=O)CC1=CNC2C1=CC=CC=2)CC1C=CC=CC=1)=O)C(=O)[C@@H](N)CC1C=CC=CC=1 LAR demonstrated markedly improved clinical benefit compared with previous first-to fifth-line treatment regimens administered to the patient (table 1). Partial radiologic response was achieved only at 12 weeks with fourth-line temozolomide and capecitabine, but rapid disease progression was observed in <6 months with this regimen and in <3 months with other therapy lines. One explanation for the efficacy of temozolomide and capecitabine is the decreased expression of the DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) in pNET. Future studies should investigate whether low MGMT expression in metastatic pNET is a predictive factor that correlates with response to capecitabine and temozolomide [12]. Treatment with everolimus plus N([C@H]1C(N[C@H](C(=O)N[C@H](C(N[C@H](C(=O)N[C@H](C(=O)N[C@H](CSSC1)C(=O)N[C@@H]([C@@H](C)O)CO)[C@@H](C)O)CCCCN)=O)CC1=CNC2C1=CC=CC=2)CC1C=CC=CC=1)=O)C(=O)[C@@H](N)CC1C=CC=CC=1 LAR, on the other hand, resulted in dramatic clinical and CT imaging responses and PFS of 19 months. | 9448188 |
Temozolomide | n1(nnc2n(cnc2C(=O)N)c1=O)C | The combination of everolimus plus octreotide LAR demonstrated markedly improved clinical benefit compared with previous first-to fifth-line treatment regimens administered to the patient (table 1). Partial radiologic response was achieved only at 12 weeks with fourth-line n1(nnc2n(cnc2C(=O)N)c1=O)C and capecitabine, but rapid disease progression was observed in <6 months with this regimen and in <3 months with other therapy lines. One explanation for the efficacy of n1(nnc2n(cnc2C(=O)N)c1=O)C and capecitabine is the decreased expression of the DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) in pNET. Future studies should investigate whether low MGMT expression in metastatic pNET is a predictive factor that correlates with response to capecitabine and n1(nnc2n(cnc2C(=O)N)c1=O)C [12]. Treatment with everolimus plus octreotide LAR, on the other hand, resulted in dramatic clinical and CT imaging responses and PFS of 19 months. | 9448188 |
Everolimus | C1(=C/[C@@H](C)C(=O)C[C@@H]([C@@H](C[C@H]2C[C@H]([C@H](OCCO)CC2)OC)C)OC([C@H]2N(CCCC2)C(C(=O)[C@]2([C@H](C)CC[C@@H](C[C@@H](/C(=C/C=C/C=C/[C@@H](C)C[C@H](C(=O)[C@@H]([C@@H]/1O)OC)C)C)OC)O2)O)=O)=O)C | The patient in this study derived a clinical benefit with C1(=C/[C@@H](C)C(=O)C[C@@H]([C@@H](C[C@H]2C[C@H]([C@H](OCCO)CC2)OC)C)OC([C@H]2N(CCCC2)C(C(=O)[C@]2([C@H](C)CC[C@@H](C[C@@H](/C(=C/C=C/C=C/[C@@H](C)C[C@H](C(=O)[C@@H]([C@@H]/1O)OC)C)C)OC)O2)O)=O)=O)C-based therapy similar to the median values reported in the RADIANT trials, which enrolled patients with lowgrade NET [10]. In the phase III RADIANT-3 trial, patients with pNET receiving 10 mg C1(=C/[C@@H](C)C(=O)C[C@@H]([C@@H](C[C@H]2C[C@H]([C@H](OCCO)CC2)OC)C)OC([C@H]2N(CCCC2)C(C(=O)[C@]2([C@H](C)CC[C@@H](C[C@@H](/C(=C/C=C/C=C/[C@@H](C)C[C@H](C(=O)[C@@H]([C@@H]/1O)OC)C)C)OC)O2)O)=O)=O)C achieved a median PFS of 11 months, and 34% of patients were progression free at 18 months [10]. Treatment with the same dose of C1(=C/[C@@H](C)C(=O)C[C@@H]([C@@H](C[C@H]2C[C@H]([C@H](OCCO)CC2)OC)C)OC([C@H]2N(CCCC2)C(C(=O)[C@]2([C@H](C)CC[C@@H](C[C@@H](/C(=C/C=C/C=C/[C@@H](C)C[C@H](C(=O)[C@@H]([C@@H]/1O)OC)C)C)OC)O2)O)=O)=O)C plus octreotide LAR in this case study prolonged PFS to approximately 15-19 months, which is similar to the results reported in RADIANT-2 [11]. Only 4.8% of patients experienced partial response and 64% minor tumor shrinkage (not meeting RECIST v1.0 criteria) in RADIANT-3 [10], whereas our patient achieved major tumor shrinkage with C1(=C/[C@@H](C)C(=O)C[C@@H]([C@@H](C[C@H]2C[C@H]([C@H](OCCO)CC2)OC)C)OC([C@H]2N(CCCC2)C(C(=O)[C@]2([C@H](C)CC[C@@H](C[C@@H](/C(=C/C=C/C=C/[C@@H](C)C[C@H](C(=O)[C@@H]([C@@H]/1O)OC)C)C)OC)O2)O)=O)=O)C plus octreotide LAR. The clinical and radiologic benefits were surprising considering that a poorer clinical outcome might have been expected given the disease stage, high-grade tumor, 5 failed chemotherapies, and poor KPS. | 9448188 |
Octreotide | C1(=O)N[C@H](C(N[C@@H](CC2=CNC3C2=CC=CC=3)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](C(=O)N[C@@H]([C@H](O)C)CO)CSSC[C@H]1NC([C@@H](N)CC1=CC=CC=C1)=O)=O)[C@H](O)C)CCCCN)=O)CC1C=CC=CC=1 | The patient in this study derived a clinical benefit with everolimus-based therapy similar to the median values reported in the RADIANT trials, which enrolled patients with lowgrade NET [10]. In the phase III RADIANT-3 trial, patients with pNET receiving 10 mg everolimus achieved a median PFS of 11 months, and 34% of patients were progression free at 18 months [10]. Treatment with the same dose of everolimus plus C1(=O)N[C@H](C(N[C@@H](CC2=CNC3C2=CC=CC=3)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](C(=O)N[C@@H]([C@H](O)C)CO)CSSC[C@H]1NC([C@@H](N)CC1=CC=CC=C1)=O)=O)[C@H](O)C)CCCCN)=O)CC1C=CC=CC=1 LAR in this case study prolonged PFS to approximately 15-19 months, which is similar to the results reported in RADIANT-2 [11]. Only 4.8% of patients experienced partial response and 64% minor tumor shrinkage (not meeting RECIST v1.0 criteria) in RADIANT-3 [10], whereas our patient achieved major tumor shrinkage with everolimus plus C1(=O)N[C@H](C(N[C@@H](CC2=CNC3C2=CC=CC=3)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](C(=O)N[C@@H]([C@H](O)C)CO)CSSC[C@H]1NC([C@@H](N)CC1=CC=CC=C1)=O)=O)[C@H](O)C)CCCCN)=O)CC1C=CC=CC=1 LAR. The clinical and radiologic benefits were surprising considering that a poorer clinical outcome might have been expected given the disease stage, high-grade tumor, 5 failed chemotherapies, and poor KPS. | 9448188 |
Octreotide | C12NC=C(C1=CC=CC=2)C[C@@H]1NC([C@H](CC2C=CC=CC=2)NC([C@H](NC([C@@H](N)CC2=CC=CC=C2)=O)CSSC[C@H](C(=O)N[C@H](CO)[C@H](O)C)NC([C@@H](NC(=O)[C@H](CCCCN)NC1=O)[C@@H](C)O)=O)=O)=O | Neither RADIANT-3 nor RADIANT-2 included objective tumor response as a secondary endpoint, whereas the PROMID study was a phase III trial investigating the antitumor effects of C12NC=C(C1=CC=CC=2)C[C@@H]1NC([C@H](CC2C=CC=CC=2)NC([C@H](NC([C@@H](N)CC2=CC=CC=C2)=O)CSSC[C@H](C(=O)N[C@H](CO)[C@H](O)C)NC([C@@H](NC(=O)[C@H](CCCCN)NC1=O)[C@@H](C)O)=O)=O)=O LAR in patients with metastatic neuroendocrine midgut tumors [13]. Median time to tumor progression was 14.3 months (95% CI, 11.0-28.8 months) and 6.0 months (95% CI, 3.7-9.4 months) in patients who received C12NC=C(C1=CC=CC=2)C[C@@H]1NC([C@H](CC2C=CC=CC=2)NC([C@H](NC([C@@H](N)CC2=CC=CC=C2)=O)CSSC[C@H](C(=O)N[C@H](CO)[C@H](O)C)NC([C@@H](NC(=O)[C@H](CCCCN)NC1=O)[C@@H](C)O)=O)=O)=O LAR and placebo, respectively [12]. The PROMID patient population was drug naive and excluded those with a prolonged (>4 weeks) history of previous therapies. The PROMID and RADIANT-2 studies included patients with well-differentiated midgut tumors, which are indolent [11,13]. The estimated time to tumor progression for our patient was similar to that reported for patients in PROMID, but the tumor regression seen in our patient was better than that reported for those patients [12]. | 9448188 |
Everolimus | C1=C/C=C/[C@H](C[C@@H](C)C(=O)[C@@H]([C@H](O)/C(C)=C/[C@H](C(C[C@@H]([C@@H](C[C@H]2C[C@H]([C@H](OCCO)CC2)OC)C)OC([C@@H]2CCCCN2C(=O)C(=O)[C@]2([C@@H](CC[C@H](O2)C[C@H](OC)/C(C)=C/1)C)O)=O)=O)C)OC)C | Our patient tolerated C1=C/C=C/[C@H](C[C@@H](C)C(=O)[C@@H]([C@H](O)/C(C)=C/[C@H](C(C[C@@H]([C@@H](C[C@H]2C[C@H]([C@H](OCCO)CC2)OC)C)OC([C@@H]2CCCCN2C(=O)C(=O)[C@]2([C@@H](CC[C@H](O2)C[C@H](OC)/C(C)=C/1)C)O)=O)=O)C)OC)C plus octreotide LAR as a sixth-line regimen for the management of high-grade pNET with minimal toxicity, similar to what has been reported in the RADIANT-3, RADIANT-2, and PROMID trials [11,13]. Treatment strategies associated with reduced toxicity, as demonstrated with C1=C/C=C/[C@H](C[C@@H](C)C(=O)[C@@H]([C@H](O)/C(C)=C/[C@H](C(C[C@@H]([C@@H](C[C@H]2C[C@H]([C@H](OCCO)CC2)OC)C)OC([C@@H]2CCCCN2C(=O)C(=O)[C@]2([C@@H](CC[C@H](O2)C[C@H](OC)/C(C)=C/1)C)O)=O)=O)C)OC)C-based therapy, become particularly important in the late-line setting because health-related quality of life often outweighs clinical benefit in patients with reduced lifespans. | 9448188 |
Octreotide | C1(N[C@H](C(=O)N[C@H](CSSC[C@@H](NC([C@H](Cc2ccccc2)N)=O)C(=O)N[C@@H](Cc2ccccc2)C(N[C@H](C(N[C@H]1CCCCN)=O)Cc1c[nH]c2c1cccc2)=O)C(=O)N[C@H](CO)[C@H](O)C)[C@@H](C)O)=O | Our patient tolerated everolimus plus C1(N[C@H](C(=O)N[C@H](CSSC[C@@H](NC([C@H](Cc2ccccc2)N)=O)C(=O)N[C@@H](Cc2ccccc2)C(N[C@H](C(N[C@H]1CCCCN)=O)Cc1c[nH]c2c1cccc2)=O)C(=O)N[C@H](CO)[C@H](O)C)[C@@H](C)O)=O LAR as a sixth-line regimen for the management of high-grade pNET with minimal toxicity, similar to what has been reported in the RADIANT-3, RADIANT-2, and PROMID trials [11,13]. Treatment strategies associated with reduced toxicity, as demonstrated with everolimus-based therapy, become particularly important in the late-line setting because health-related quality of life often outweighs clinical benefit in patients with reduced lifespans. | 9448188 |
Everolimus | C[C@@H]1/C=C(\C)[C@H]([C@H](C(=O)[C@@H](C[C@@H](/C=C/C=C/C=C(/[C@@H](OC)C[C@@H]2CC[C@@H](C)[C@@](C(C(=O)N3CCCC[C@H]3C(=O)O[C@H]([C@@H](C[C@@H]3CC[C@@H](OCCO)[C@@H](C3)OC)C)CC1=O)=O)(O)O2)C)C)C)OC)O | The effect of C[C@@H]1/C=C(\C)[C@H]([C@H](C(=O)[C@@H](C[C@@H](/C=C/C=C/C=C(/[C@@H](OC)C[C@@H]2CC[C@@H](C)[C@@](C(C(=O)N3CCCC[C@H]3C(=O)O[C@H]([C@@H](C[C@@H]3CC[C@@H](OCCO)[C@@H](C3)OC)C)CC1=O)=O)(O)O2)C)C)C)OC)O in poorly differentiated tumors is unknown; these tumors are usually excluded from clinical trials because of their aggressiveness. However, these tumors have a better response rate to chemotherapy and may express more mTOR than welldifferentiated tumors, and mTOR elevation appears to be consistent across the primary tumor site [14,15]. Although there are no published studies that confirm it, C[C@@H]1/C=C(\C)[C@H]([C@H](C(=O)[C@@H](C[C@@H](/C=C/C=C/C=C(/[C@@H](OC)C[C@@H]2CC[C@@H](C)[C@@](C(C(=O)N3CCCC[C@H]3C(=O)O[C@H]([C@@H](C[C@@H]3CC[C@@H](OCCO)[C@@H](C3)OC)C)CC1=O)=O)(O)O2)C)C)C)OC)O may be a valuable treatment option in patients with poorly differentiated NET, either before the initiation of chemotherapy to sensitive tumor cells or after chemotherapy to help maintain response over time. It should be noted that the only chemotherapy regimen with confirmed activity in this setting is cisplatin and etoposide. | 9448188 |
Cisplatin | N.N.Cl[Pt]Cl | The effect of everolimus in poorly differentiated tumors is unknown; these tumors are usually excluded from clinical trials because of their aggressiveness. However, these tumors have a better response rate to chemotherapy and may express more mTOR than welldifferentiated tumors, and mTOR elevation appears to be consistent across the primary tumor site [14,15]. Although there are no published studies that confirm it, everolimus may be a valuable treatment option in patients with poorly differentiated NET, either before the initiation of chemotherapy to sensitive tumor cells or after chemotherapy to help maintain response over time. It should be noted that the only chemotherapy regimen with confirmed activity in this setting is N.N.Cl[Pt]Cl and etoposide. | 9448188 |
Etoposide | c1c2c(cc3[C@H]([C@@H]4[C@@H]([C@@H](c13)c1cc(c(O)c(c1)OC)OC)C(OC4)=O)O[C@@H]1O[C@@H]3CO[C@H](O[C@H]3[C@H](O)[C@H]1O)C)OCO2 | The effect of everolimus in poorly differentiated tumors is unknown; these tumors are usually excluded from clinical trials because of their aggressiveness. However, these tumors have a better response rate to chemotherapy and may express more mTOR than welldifferentiated tumors, and mTOR elevation appears to be consistent across the primary tumor site [14,15]. Although there are no published studies that confirm it, everolimus may be a valuable treatment option in patients with poorly differentiated NET, either before the initiation of chemotherapy to sensitive tumor cells or after chemotherapy to help maintain response over time. It should be noted that the only chemotherapy regimen with confirmed activity in this setting is cisplatin and c1c2c(cc3[C@H]([C@@H]4[C@@H]([C@@H](c13)c1cc(c(O)c(c1)OC)OC)C(OC4)=O)O[C@@H]1O[C@@H]3CO[C@H](O[C@H]3[C@H](O)[C@H]1O)C)OCO2. | 9448188 |
Everolimus | [C@H](C)([C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@@]2(O)[C@@H](CC[C@H](O2)C[C@@H](/C(=C/C=C/C=C/[C@@H](C)C[C@H](C([C@H](OC)[C@@H](/C(=C/[C@H](C(C1)=O)C)C)O)=O)C)C)OC)C)C[C@H]1C[C@H]([C@H](OCCO)CC1)OC | Treatment with [C@H](C)([C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@@]2(O)[C@@H](CC[C@H](O2)C[C@@H](/C(=C/C=C/C=C/[C@@H](C)C[C@H](C([C@H](OC)[C@@H](/C(=C/[C@H](C(C1)=O)C)C)O)=O)C)C)OC)C)C[C@H]1C[C@H]([C@H](OCCO)CC1)OC plus octreotide LAR demonstrated definitive clinical response and prolonged PFS of more than 15 months in this heavily pretreated patient with high-grade pNET. Despite this regimen having been a sixth-line therapy, it improved clinical benefit with minimal toxicity compared with the 5 other previous lines of treatment the patient had received. In summary, this case study suggests the combination of [C@H](C)([C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@@]2(O)[C@@H](CC[C@H](O2)C[C@@H](/C(=C/C=C/C=C/[C@@H](C)C[C@H](C([C@H](OC)[C@@H](/C(=C/[C@H](C(C1)=O)C)C)O)=O)C)C)OC)C)C[C@H]1C[C@H]([C@H](OCCO)CC1)OC plus octreotide LAR may offer a valuable treatment strategy for patients with heavily pretreated, advanced, high-grade pNET. | 9448188 |
Octreotide | N1[C@H](C(=O)N[C@H](CSSC[C@@H](NC(=O)[C@H](Cc2ccccc2)N)C(N[C@H](C(N[C@H](C(N[C@@H](CCCCN)C1=O)=O)Cc1c[nH]c2c1cccc2)=O)Cc1ccccc1)=O)C(=O)N[C@H](CO)[C@H](O)C)[C@@H](C)O | Treatment with everolimus plus N1[C@H](C(=O)N[C@H](CSSC[C@@H](NC(=O)[C@H](Cc2ccccc2)N)C(N[C@H](C(N[C@H](C(N[C@@H](CCCCN)C1=O)=O)Cc1c[nH]c2c1cccc2)=O)Cc1ccccc1)=O)C(=O)N[C@H](CO)[C@H](O)C)[C@@H](C)O LAR demonstrated definitive clinical response and prolonged PFS of more than 15 months in this heavily pretreated patient with high-grade pNET. Despite this regimen having been a sixth-line therapy, it improved clinical benefit with minimal toxicity compared with the 5 other previous lines of treatment the patient had received. In summary, this case study suggests the combination of everolimus plus N1[C@H](C(=O)N[C@H](CSSC[C@@H](NC(=O)[C@H](Cc2ccccc2)N)C(N[C@H](C(N[C@H](C(N[C@@H](CCCCN)C1=O)=O)Cc1c[nH]c2c1cccc2)=O)Cc1ccccc1)=O)C(=O)N[C@H](CO)[C@H](O)C)[C@@H](C)O LAR may offer a valuable treatment strategy for patients with heavily pretreated, advanced, high-grade pNET. | 9448188 |
Serina | OC([C@@H](N)CO)=O | However, in some applications, the objective is not individual level predictions, but rather to learn about population-level distributions of a given outcome.Examples include sentiment analysis for Twitter users (Giachanou and Crestani, 2016), estimating the prevalence of chronic fatigue syndrome (Valdez et al., 2018), and cause of death distribution estimation from verbal autopsies (King et al., 2008;McCormick et al., 2016;OC([C@@H](N)CO)=O et al., 2015;Byass et al., 2012;Miasnikof et al., 2015). | 210718461 |
Mimic | C1C(C)=CC(=CC=1C)C(=O)N(C(C)(C)C)NC(C1=CC=C(CC)C=C1)=O | To C1C(C)=CC(=CC=1C)C(=O)N(C(C)(C)C)NC(C1=CC=C(CC)C=C1)=O the motivating verbal autopsy application, we used N = 1000, n = 300, C = 5, p L = E L (y r ) = | 210718461 |
Serina | OC[C@@H](C(O)=O)N | We now apply GBQL to the PHMRC dataset introduced in Section 1.The number of observations within India, Mexico, Philippines, and Tanzania are 2973, 1586, 1259, and 2023, respectively.To address countryspecific dataset shift, for each country, we used the three remaining countries as training data for four methods commonly used for cause of death predictions: InterVA (Byass et al., 2012), InSilicoVA (McCormick et al., 2016), NBC (Miasnikof et al., 2015), and Tariff (OC[C@@H](C(O)=O)N et al., 2015).The first three methods are probabilistic, while Tariff produces a score for each cause that needed to be normalized to be in [0, 1].Model training was done using the openVA package version 1.0.8(Li et al., 2019).We considered both compositional predictions (for Tariff, this was the normalized score) and classifications (single-class categorical predictions based on the most likely cause of death for an individual per each algorithm).For GBQL in the test country, we then sampled labeled data L of varying sizes (n=25, 100, 200, 400) to investigate the effect of increasing the number of known labels.Sampling was performed such that p L = ( 1 5 , . . ., 1 5 ), as in Section 4. For comparisons, we obtained estimates using the Probabilistic Average (PA, Bella et al., 2010) method for compositional predictions, which should align with the GBQL estimate for n = 0 (Section 3.6) for our choice of priors, as well as estimates using the Adjusted PA method.We repeated this 500 times for each size of n. Results for the average CCNAA when using compositional predictions are shown in Figure 5a. | 210718461 |
Thiotepa | N1(P(=S)(N2CC2)N2CC2)CC1 | Several surgical techniques are available for treating pterygium, such as bare sclera, simple conjunctival closure, sliding conjunctival flaps, and conjunctival autografts. Adjunctive therapies, such as pos toperative beta radiation or N1(P(=S)(N2CC2)N2CC2)CC1 drops and intraoperative mitomycin C, can be used to prevent the recurrence of pterygium (1) . | 21338758 |
Mitomycin | C1(C)=C(C(C2[C@H]([C@@]3(OC)[C@@H]4[C@@H](N4)CN3C=2C1=O)COC(=O)N)=O)N | Several surgical techniques are available for treating pterygium, such as bare sclera, simple conjunctival closure, sliding conjunctival flaps, and conjunctival autografts. Adjunctive therapies, such as pos toperative beta radiation or thiotepa drops and intraoperative C1(C)=C(C(C2[C@H]([C@@]3(OC)[C@@H]4[C@@H](N4)CN3C=2C1=O)COC(=O)N)=O)N C, can be used to prevent the recurrence of pterygium (1) . | 21338758 |
Mitomycin | O=C1C(=C(C(C2=C1N1[C@]([C@@H]2COC(N)=O)(OC)[C@@H]2[C@H](C1)N2)=O)N)C | Severe scleral dellen (SD) is a rare complication during the early postoperative period following pterygium surgery. The few reports describing this condition are all related to the bare sclera technique without adjunctive therapy (2,3) or with intraoperative O=C1C(=C(C(C2=C1N1[C@]([C@@H]2COC(N)=O)(OC)[C@@H]2[C@H](C1)N2)=O)N)C C (4,5) or beta radiation (6) . However, we are unaware of any report of SD associated with pterygium excision followed by minimal cauterization of episcleral vessels and simple conjunctival closure. | 21338758 |
Lidocaine | N(C(=O)CN(CC)CC)c1c(cccc1C)C | A 45-year-old bricklayer with a primary pterygium on the nasal side of his right eye underwent surgical excision with minimal cauterization of episcleral vessels and simple conjunctival closure with two stitches (7/0 silk). The procedure was carried out under topical and subconjunctival anesthesia (N(C(=O)CN(CC)CC)c1c(cccc1C)C 2% and epinephrine 1/200.000). No adjunctive therapy was used intraoperatively. Dexamethasone (0.5 mg/g) and chloramphenicol (10 mg/g) ointment were applied and the eye was patched. His medical and ocular histories were unremarkable. The day following surgery, the outcome looked favorable; there was a nasal corneal epithelial defect and the edges of the conjunctival incision were in close apposition with no signs of infection or excessive inflammation. Topical steroids, antibiotics, and artificial tears were prescribed. | 21338758 |
Epinephrine | C1(C=CC([C@H](CNC)O)=CC=1O)O | A 45-year-old bricklayer with a primary pterygium on the nasal side of his right eye underwent surgical excision with minimal cauterization of episcleral vessels and simple conjunctival closure with two stitches (7/0 silk). The procedure was carried out under topical and subconjunctival anesthesia (lidocaine 2% and C1(C=CC([C@H](CNC)O)=CC=1O)O 1/200.000). No adjunctive therapy was used intraoperatively. Dexamethasone (0.5 mg/g) and chloramphenicol (10 mg/g) ointment were applied and the eye was patched. His medical and ocular histories were unremarkable. The day following surgery, the outcome looked favorable; there was a nasal corneal epithelial defect and the edges of the conjunctival incision were in close apposition with no signs of infection or excessive inflammation. Topical steroids, antibiotics, and artificial tears were prescribed. | 21338758 |
Dexamethasone | C[C@@]12C=CC(C=C2CC[C@H]2[C@@H]3C[C@H]([C@](C(CO)=O)([C@]3(C[C@@H]([C@@]21F)O)C)O)C)=O | A 45-year-old bricklayer with a primary pterygium on the nasal side of his right eye underwent surgical excision with minimal cauterization of episcleral vessels and simple conjunctival closure with two stitches (7/0 silk). The procedure was carried out under topical and subconjunctival anesthesia (lidocaine 2% and epinephrine 1/200.000). No adjunctive therapy was used intraoperatively. C[C@@]12C=CC(C=C2CC[C@H]2[C@@H]3C[C@H]([C@](C(CO)=O)([C@]3(C[C@@H]([C@@]21F)O)C)O)C)=O (0.5 mg/g) and chloramphenicol (10 mg/g) ointment were applied and the eye was patched. His medical and ocular histories were unremarkable. The day following surgery, the outcome looked favorable; there was a nasal corneal epithelial defect and the edges of the conjunctival incision were in close apposition with no signs of infection or excessive inflammation. Topical steroids, antibiotics, and artificial tears were prescribed. | 21338758 |
Chloramphenicol | C(N[C@H](CO)[C@H](O)c1ccc(cc1)[N+](=O)[O-])(=O)C(Cl)Cl | A 45-year-old bricklayer with a primary pterygium on the nasal side of his right eye underwent surgical excision with minimal cauterization of episcleral vessels and simple conjunctival closure with two stitches (7/0 silk). The procedure was carried out under topical and subconjunctival anesthesia (lidocaine 2% and epinephrine 1/200.000). No adjunctive therapy was used intraoperatively. Dexamethasone (0.5 mg/g) and C(N[C@H](CO)[C@H](O)c1ccc(cc1)[N+](=O)[O-])(=O)C(Cl)Cl (10 mg/g) ointment were applied and the eye was patched. His medical and ocular histories were unremarkable. The day following surgery, the outcome looked favorable; there was a nasal corneal epithelial defect and the edges of the conjunctival incision were in close apposition with no signs of infection or excessive inflammation. Topical steroids, antibiotics, and artificial tears were prescribed. | 21338758 |
Gentamicin | NC1CC(N)C(OC2OC(C(NC)C)CCC2N)C(C1OC1OC[C@](C(C1O)NC)(C)O)O | One week later, the patient arrived at the emergency department complaining of moderate pain and a black dot in his right eye. His best corrected visual acuity was 10/10 and intraocular pressure was 15 mmHg. Slit lamp examination revealed severe scleral thinning reaching the choroid (Figure 1). The conjunctival sutures were no longer in place. The anterior chamber was deep with no Tyndall effect, whereas the pupils were isocoric and normoreactive. The fundus showed transparent media with no other abnormal findings. The patient refused improper eye handling, therapeutic failure, or going back to work in a dusty environment. Reconstructive surgery through a conjunctival flap was offered, but the patient refused; therefore, a conservative medical treatment was prescribed that included NC1CC(N)C(OC2OC(C(NC)C)CCC2N)C(C1OC1OC[C@](C(C1O)NC)(C)O)O antibiotic ointment (3 mg/g), patching for 7 days, and daily outpatient monitoring, which was followed by intensive ocular lubrication (carmellose 10 mg/mL every hour) for 6 weeks. Within a few weeks, the conjunctival defect was replaced by granulation tissue, and later with a flap of adjacent conjunctiva. The photographic series illustrates the patient's evolution (Figures 2 and 3). | 21338758 |
Carmellose | C(O)(C)=O.OC(C=O)C(O)C(C(O)CO)O | One week later, the patient arrived at the emergency department complaining of moderate pain and a black dot in his right eye. His best corrected visual acuity was 10/10 and intraocular pressure was 15 mmHg. Slit lamp examination revealed severe scleral thinning reaching the choroid (Figure 1). The conjunctival sutures were no longer in place. The anterior chamber was deep with no Tyndall effect, whereas the pupils were isocoric and normoreactive. The fundus showed transparent media with no other abnormal findings. The patient refused improper eye handling, therapeutic failure, or going back to work in a dusty environment. Reconstructive surgery through a conjunctival flap was offered, but the patient refused; therefore, a conservative medical treatment was prescribed that included gentamicin antibiotic ointment (3 mg/g), patching for 7 days, and daily outpatient monitoring, which was followed by intensive ocular lubrication (C(O)(C)=O.OC(C=O)C(O)C(C(O)CO)O 10 mg/mL every hour) for 6 weeks. Within a few weeks, the conjunctival defect was replaced by granulation tissue, and later with a flap of adjacent conjunctiva. The photographic series illustrates the patient's evolution (Figures 2 and 3). | 21338758 |
Vasoconstrictor | C1C(=C(O)C=CC=1[C@H](CNC)O)O | Whereas the growth of blood vessels in the wound bed is considered to contribute to pterygium recurrence, some authors have recommended cauterization of episcleral vessels, especially at the limbus. However, it appears that coagulation of the episcleral vessels, which do not bleed, neither avoids recurrences nor contributes to accomplishing better esthetic results during pterygium surgery (personal communication of Lawrence W. Hirst). The cauterization applied to our patient was performed carefully and only with the purpose of avoiding bleeding during surgery. Nonetheless, this factor has to be considered in the etiology of scleral perforation as it may cause local ischemia. In the cases reported in the literature, whether episcleral vessel cauterization was used or its duration is unclear. (2)(3)(4)(5)(6) Subconjunctival anesthesia containing a C1C(=C(O)C=CC=1[C@H](CNC)O)O agent (epinephrine) also may have been a contributory factor for local ischemia in the present case. Topical corticosteroids enhance collagenases and inhibit collagen synthesis, which may have also contributed to SD formation, as proposed by Mitra et al. (3) . Therefore, they should be removed immediately. | 21338758 |
Epinephrine | C1C([C@H](CNC)O)=CC(O)=C(O)C=1 | Whereas the growth of blood vessels in the wound bed is considered to contribute to pterygium recurrence, some authors have recommended cauterization of episcleral vessels, especially at the limbus. However, it appears that coagulation of the episcleral vessels, which do not bleed, neither avoids recurrences nor contributes to accomplishing better esthetic results during pterygium surgery (personal communication of Lawrence W. Hirst). The cauterization applied to our patient was performed carefully and only with the purpose of avoiding bleeding during surgery. Nonetheless, this factor has to be considered in the etiology of scleral perforation as it may cause local ischemia. In the cases reported in the literature, whether episcleral vessel cauterization was used or its duration is unclear. (2)(3)(4)(5)(6) Subconjunctival anesthesia containing a vasoconstrictor agent (C1C([C@H](CNC)O)=CC(O)=C(O)C=1) also may have been a contributory factor for local ischemia in the present case. Topical corticosteroids enhance collagenases and inhibit collagen synthesis, which may have also contributed to SD formation, as proposed by Mitra et al. (3) . Therefore, they should be removed immediately. | 21338758 |
Ceftriaxone | C1(N=C(N(NC1=O)C)SCC1=C(N2C([C@@H](NC(=O)/C(=N/OC)C3=CSC(=N3)N)C2SC1)=O)C(O)=O)=O | Culture results were collected, and susceptibility results were analyzed.Organisms in this study could have been isolated from any source including skin swabs, tissue cultures following surgical excision, bronchoalveolar lavage, sputum, tracheal aspirate, urine, bone, or blood.Due to the retrospective nature of the study and resource limitations, specific genetic data for resistance mechanisms are not routine at the study center and were not available for classification.Organisms were considered to be DTp if they fell into one or more of the following categories: MDR (non-susceptibility to at least one agent in three or more antimicrobial categories), XDR (non-susceptibility to at least one agent in all but two or fewer antimicrobial categories), vancomycin-resistant, confirmed or presumed ESBL-production [C1(N=C(N(NC1=O)C)SCC1=C(N2C([C@@H](NC(=O)/C(=N/OC)C3=CSC(=N3)N)C2SC1)=O)C(O)=O)=O minimum inhibitory concentration (MIC) ≥ 2 µg/mL], confirmed or presumed AmpC-production (resistance to C1(N=C(N(NC1=O)C)SCC1=C(N2C([C@@H](NC(=O)/C(=N/OC)C3=CSC(=N3)N)C2SC1)=O)C(O)=O)=O, cefotaxime, and ceftazidime), carbapenemresistant (confirmed carbapenemase producers or resistant to at least one carbapenem), or methicillin-resistant Staphylococcus aureus (MRSA), CRAB, Stenotrophomonas spp., or DTR-Pseudomonas (not susceptible to at least one antibiotic in at least three antibiotic classes for which P. aeruginosa susceptibility is generally expected: penicillins, cephalosporins, fluoroquinolones, aminoglycosides, and carbapenems).Susceptible pathogens were defined as strains whose MIC were interpreted to be susceptible to a given antibiotic.Non-susceptible pathogens were defined as strains whose MICs were interpreted to be resistant or intermediate to a given antibiotic.An organism's intrinsic resistance was taken into consideration and the organism was not classified as resistant if intrinsically resistant (e.g., Enterococcus casseliflavus was not considered to be vancomycin-resistant).Organisms not meeting any of the above criteria were classified as non-DTp.Information on culture sources and length of stay prior to culture obtainment were also collected. | 271556193 |
Cefotaxime | [C@@H]1(NC(=O)C(=NOC)C2=CSC(N)=N2)C(N2[C@H]1SCC(COC(=O)C)=C2C(O)=O)=O | Culture results were collected, and susceptibility results were analyzed.Organisms in this study could have been isolated from any source including skin swabs, tissue cultures following surgical excision, bronchoalveolar lavage, sputum, tracheal aspirate, urine, bone, or blood.Due to the retrospective nature of the study and resource limitations, specific genetic data for resistance mechanisms are not routine at the study center and were not available for classification.Organisms were considered to be DTp if they fell into one or more of the following categories: MDR (non-susceptibility to at least one agent in three or more antimicrobial categories), XDR (non-susceptibility to at least one agent in all but two or fewer antimicrobial categories), vancomycin-resistant, confirmed or presumed ESBL-production [ceftriaxone minimum inhibitory concentration (MIC) ≥ 2 µg/mL], confirmed or presumed AmpC-production (resistance to ceftriaxone, [C@@H]1(NC(=O)C(=NOC)C2=CSC(N)=N2)C(N2[C@H]1SCC(COC(=O)C)=C2C(O)=O)=O, and ceftazidime), carbapenemresistant (confirmed carbapenemase producers or resistant to at least one carbapenem), or methicillin-resistant Staphylococcus aureus (MRSA), CRAB, Stenotrophomonas spp., or DTR-Pseudomonas (not susceptible to at least one antibiotic in at least three antibiotic classes for which P. aeruginosa susceptibility is generally expected: penicillins, cephalosporins, fluoroquinolones, aminoglycosides, and carbapenems).Susceptible pathogens were defined as strains whose MIC were interpreted to be susceptible to a given antibiotic.Non-susceptible pathogens were defined as strains whose MICs were interpreted to be resistant or intermediate to a given antibiotic.An organism's intrinsic resistance was taken into consideration and the organism was not classified as resistant if intrinsically resistant (e.g., Enterococcus casseliflavus was not considered to be vancomycin-resistant).Organisms not meeting any of the above criteria were classified as non-DTp.Information on culture sources and length of stay prior to culture obtainment were also collected. | 271556193 |
Ceftazidime | C1(C[N+]2=CC=CC=C2)CS[C@H]2[C@@H](NC(/C(=N\OC(C(O)=O)(C)C)C3N=C(N)SC=3)=O)C(N2C=1C(=O)[O-])=O | Culture results were collected, and susceptibility results were analyzed.Organisms in this study could have been isolated from any source including skin swabs, tissue cultures following surgical excision, bronchoalveolar lavage, sputum, tracheal aspirate, urine, bone, or blood.Due to the retrospective nature of the study and resource limitations, specific genetic data for resistance mechanisms are not routine at the study center and were not available for classification.Organisms were considered to be DTp if they fell into one or more of the following categories: MDR (non-susceptibility to at least one agent in three or more antimicrobial categories), XDR (non-susceptibility to at least one agent in all but two or fewer antimicrobial categories), vancomycin-resistant, confirmed or presumed ESBL-production [ceftriaxone minimum inhibitory concentration (MIC) ≥ 2 µg/mL], confirmed or presumed AmpC-production (resistance to ceftriaxone, cefotaxime, and C1(C[N+]2=CC=CC=C2)CS[C@H]2[C@@H](NC(/C(=N\OC(C(O)=O)(C)C)C3N=C(N)SC=3)=O)C(N2C=1C(=O)[O-])=O), carbapenemresistant (confirmed carbapenemase producers or resistant to at least one carbapenem), or methicillin-resistant Staphylococcus aureus (MRSA), CRAB, Stenotrophomonas spp., or DTR-Pseudomonas (not susceptible to at least one antibiotic in at least three antibiotic classes for which P. aeruginosa susceptibility is generally expected: penicillins, cephalosporins, fluoroquinolones, aminoglycosides, and carbapenems).Susceptible pathogens were defined as strains whose MIC were interpreted to be susceptible to a given antibiotic.Non-susceptible pathogens were defined as strains whose MICs were interpreted to be resistant or intermediate to a given antibiotic.An organism's intrinsic resistance was taken into consideration and the organism was not classified as resistant if intrinsically resistant (e.g., Enterococcus casseliflavus was not considered to be vancomycin-resistant).Organisms not meeting any of the above criteria were classified as non-DTp.Information on culture sources and length of stay prior to culture obtainment were also collected. | 271556193 |
Carbapenem | C1N2[C@H](CC=1)CC2=O | Culture results were collected, and susceptibility results were analyzed.Organisms in this study could have been isolated from any source including skin swabs, tissue cultures following surgical excision, bronchoalveolar lavage, sputum, tracheal aspirate, urine, bone, or blood.Due to the retrospective nature of the study and resource limitations, specific genetic data for resistance mechanisms are not routine at the study center and were not available for classification.Organisms were considered to be DTp if they fell into one or more of the following categories: MDR (non-susceptibility to at least one agent in three or more antimicrobial categories), XDR (non-susceptibility to at least one agent in all but two or fewer antimicrobial categories), vancomycin-resistant, confirmed or presumed ESBL-production [ceftriaxone minimum inhibitory concentration (MIC) ≥ 2 µg/mL], confirmed or presumed AmpC-production (resistance to ceftriaxone, cefotaxime, and ceftazidime), C1N2[C@H](CC=1)CC2=Oresistant (confirmed C1N2[C@H](CC=1)CC2=Oase producers or resistant to at least one C1N2[C@H](CC=1)CC2=O), or methicillin-resistant Staphylococcus aureus (MRSA), CRAB, Stenotrophomonas spp., or DTR-Pseudomonas (not susceptible to at least one antibiotic in at least three antibiotic classes for which P. aeruginosa susceptibility is generally expected: penicillins, cephalosporins, fluoroquinolones, aminoglycosides, and C1N2[C@H](CC=1)CC2=Os).Susceptible pathogens were defined as strains whose MIC were interpreted to be susceptible to a given antibiotic.Non-susceptible pathogens were defined as strains whose MICs were interpreted to be resistant or intermediate to a given antibiotic.An organism's intrinsic resistance was taken into consideration and the organism was not classified as resistant if intrinsically resistant (e.g., Enterococcus casseliflavus was not considered to be vancomycin-resistant).Organisms not meeting any of the above criteria were classified as non-DTp.Information on culture sources and length of stay prior to culture obtainment were also collected. | 271556193 |
Penicillins | CC1(C)[C@@H](N2[C@H](S1)[C@H](NC(Cc1ccccc1)=O)C2)C(=O)O | Culture results were collected, and susceptibility results were analyzed.Organisms in this study could have been isolated from any source including skin swabs, tissue cultures following surgical excision, bronchoalveolar lavage, sputum, tracheal aspirate, urine, bone, or blood.Due to the retrospective nature of the study and resource limitations, specific genetic data for resistance mechanisms are not routine at the study center and were not available for classification.Organisms were considered to be DTp if they fell into one or more of the following categories: MDR (non-susceptibility to at least one agent in three or more antimicrobial categories), XDR (non-susceptibility to at least one agent in all but two or fewer antimicrobial categories), vancomycin-resistant, confirmed or presumed ESBL-production [ceftriaxone minimum inhibitory concentration (MIC) ≥ 2 µg/mL], confirmed or presumed AmpC-production (resistance to ceftriaxone, cefotaxime, and ceftazidime), carbapenemresistant (confirmed carbapenemase producers or resistant to at least one carbapenem), or methicillin-resistant Staphylococcus aureus (MRSA), CRAB, Stenotrophomonas spp., or DTR-Pseudomonas (not susceptible to at least one antibiotic in at least three antibiotic classes for which P. aeruginosa susceptibility is generally expected: CC1(C)[C@@H](N2[C@H](S1)[C@H](NC(Cc1ccccc1)=O)C2)C(=O)O, cephalosporins, fluoroquinolones, aminoglycosides, and carbapenems).Susceptible pathogens were defined as strains whose MIC were interpreted to be susceptible to a given antibiotic.Non-susceptible pathogens were defined as strains whose MICs were interpreted to be resistant or intermediate to a given antibiotic.An organism's intrinsic resistance was taken into consideration and the organism was not classified as resistant if intrinsically resistant (e.g., Enterococcus casseliflavus was not considered to be vancomycin-resistant).Organisms not meeting any of the above criteria were classified as non-DTp.Information on culture sources and length of stay prior to culture obtainment were also collected. | 271556193 |
Cephalosporins | C(=O)(O)C1N2C([C@@H](NC(=O)CCC[C@H](C(=O)O)N)[C@H]2SCC=1COC(=O)C)=O | Culture results were collected, and susceptibility results were analyzed.Organisms in this study could have been isolated from any source including skin swabs, tissue cultures following surgical excision, bronchoalveolar lavage, sputum, tracheal aspirate, urine, bone, or blood.Due to the retrospective nature of the study and resource limitations, specific genetic data for resistance mechanisms are not routine at the study center and were not available for classification.Organisms were considered to be DTp if they fell into one or more of the following categories: MDR (non-susceptibility to at least one agent in three or more antimicrobial categories), XDR (non-susceptibility to at least one agent in all but two or fewer antimicrobial categories), vancomycin-resistant, confirmed or presumed ESBL-production [ceftriaxone minimum inhibitory concentration (MIC) ≥ 2 µg/mL], confirmed or presumed AmpC-production (resistance to ceftriaxone, cefotaxime, and ceftazidime), carbapenemresistant (confirmed carbapenemase producers or resistant to at least one carbapenem), or methicillin-resistant Staphylococcus aureus (MRSA), CRAB, Stenotrophomonas spp., or DTR-Pseudomonas (not susceptible to at least one antibiotic in at least three antibiotic classes for which P. aeruginosa susceptibility is generally expected: penicillins, C(=O)(O)C1N2C([C@@H](NC(=O)CCC[C@H](C(=O)O)N)[C@H]2SCC=1COC(=O)C)=O, fluoroquinolones, aminoglycosides, and carbapenems).Susceptible pathogens were defined as strains whose MIC were interpreted to be susceptible to a given antibiotic.Non-susceptible pathogens were defined as strains whose MICs were interpreted to be resistant or intermediate to a given antibiotic.An organism's intrinsic resistance was taken into consideration and the organism was not classified as resistant if intrinsically resistant (e.g., Enterococcus casseliflavus was not considered to be vancomycin-resistant).Organisms not meeting any of the above criteria were classified as non-DTp.Information on culture sources and length of stay prior to culture obtainment were also collected. | 271556193 |
Carbapenems | N12C(C(=O)O)=CCC1CC2=O | Culture results were collected, and susceptibility results were analyzed.Organisms in this study could have been isolated from any source including skin swabs, tissue cultures following surgical excision, bronchoalveolar lavage, sputum, tracheal aspirate, urine, bone, or blood.Due to the retrospective nature of the study and resource limitations, specific genetic data for resistance mechanisms are not routine at the study center and were not available for classification.Organisms were considered to be DTp if they fell into one or more of the following categories: MDR (non-susceptibility to at least one agent in three or more antimicrobial categories), XDR (non-susceptibility to at least one agent in all but two or fewer antimicrobial categories), vancomycin-resistant, confirmed or presumed ESBL-production [ceftriaxone minimum inhibitory concentration (MIC) ≥ 2 µg/mL], confirmed or presumed AmpC-production (resistance to ceftriaxone, cefotaxime, and ceftazidime), carbapenemresistant (confirmed carbapenemase producers or resistant to at least one carbapenem), or methicillin-resistant Staphylococcus aureus (MRSA), CRAB, Stenotrophomonas spp., or DTR-Pseudomonas (not susceptible to at least one antibiotic in at least three antibiotic classes for which P. aeruginosa susceptibility is generally expected: penicillins, cephalosporins, fluoroquinolones, aminoglycosides, and N12C(C(=O)O)=CCC1CC2=O).Susceptible pathogens were defined as strains whose MIC were interpreted to be susceptible to a given antibiotic.Non-susceptible pathogens were defined as strains whose MICs were interpreted to be resistant or intermediate to a given antibiotic.An organism's intrinsic resistance was taken into consideration and the organism was not classified as resistant if intrinsically resistant (e.g., Enterococcus casseliflavus was not considered to be vancomycin-resistant).Organisms not meeting any of the above criteria were classified as non-DTp.Information on culture sources and length of stay prior to culture obtainment were also collected. | 271556193 |
Mafenide | c1(CN)ccc(S(N)(=O)=O)cc1 | Hierarchical data were collected according to patient, pathogen, and date of infection.Exposures of topical and systemic antimicrobials were tracked over time.Exposure was recorded at the pathogen level and was defined as exposure to any patient site (i.e., exposure at the patient level) prior to each culture obtainment.For example, a single patient could have had an infection present early in the hospital stay that may have had different (likely less) exposures than pathogens that were treated a month later in the same stay.Topical agents analyzed in this study included: c1(CN)ccc(S(N)(=O)=O)cc1, bacitracin, silver sulfadiazine, mupirocin, Dakin's, silver nitrate solution, hypochlorous acid, other topicals, solid silver dressings, as well as chlorohexidine gluconate (CHG) and nasal decolonization.Exposures to systemic antimicrobial classes were also collected, including: non-pseudomonal beta-lactams (i.e., cefazolin, ceftriaxone, ampicillin, or ampicillin-sulbactam), anti-pseudomonal betalactams (i.e., piperacillin-tazobactam, cefepime), carbapenems (i.e., meropenem, ertapenem, or imipenem-cilastain), fluoroquinolones (i.e., ciprofloxacin or levofloxacin), anti-MRSA agents (i.e., vancomycin, daptomycin, or linezolid), aminoglycosides (i.e., amikacin, gentamicin, or tobramycin), extended-spectrum beta-lactam beta-lactamase inhibitors (i.e., ceftazidime-avibactam, meropenem-vaborbactam, or ceftolozane-tazobactam), metronidazole, tetracyclines (i.e., doxycycline or minocycline), sulfamethoxazole-trimethoprim, and antifungals (i.e., fluconazole, micafungin, or isavuconazole). | 271556193 |
Silver sulfadiazine | c1cnc([N-]S(c2ccc(cc2)N)(=O)=O)nc1.[Ag+] | Hierarchical data were collected according to patient, pathogen, and date of infection.Exposures of topical and systemic antimicrobials were tracked over time.Exposure was recorded at the pathogen level and was defined as exposure to any patient site (i.e., exposure at the patient level) prior to each culture obtainment.For example, a single patient could have had an infection present early in the hospital stay that may have had different (likely less) exposures than pathogens that were treated a month later in the same stay.Topical agents analyzed in this study included: mafenide, bacitracin, c1cnc([N-]S(c2ccc(cc2)N)(=O)=O)nc1.[Ag+], mupirocin, Dakin's, silver nitrate solution, hypochlorous acid, other topicals, solid silver dressings, as well as chlorohexidine gluconate (CHG) and nasal decolonization.Exposures to systemic antimicrobial classes were also collected, including: non-pseudomonal beta-lactams (i.e., cefazolin, ceftriaxone, ampicillin, or ampicillin-sulbactam), anti-pseudomonal betalactams (i.e., piperacillin-tazobactam, cefepime), carbapenems (i.e., meropenem, ertapenem, or imipenem-cilastain), fluoroquinolones (i.e., ciprofloxacin or levofloxacin), anti-MRSA agents (i.e., vancomycin, daptomycin, or linezolid), aminoglycosides (i.e., amikacin, gentamicin, or tobramycin), extended-spectrum beta-lactam beta-lactamase inhibitors (i.e., ceftazidime-avibactam, meropenem-vaborbactam, or ceftolozane-tazobactam), metronidazole, tetracyclines (i.e., doxycycline or minocycline), sulfamethoxazole-trimethoprim, and antifungals (i.e., fluconazole, micafungin, or isavuconazole). | 271556193 |
Sulfadiazine | c1cc(N)ccc1S(Nc1ncccn1)(=O)=O | Hierarchical data were collected according to patient, pathogen, and date of infection.Exposures of topical and systemic antimicrobials were tracked over time.Exposure was recorded at the pathogen level and was defined as exposure to any patient site (i.e., exposure at the patient level) prior to each culture obtainment.For example, a single patient could have had an infection present early in the hospital stay that may have had different (likely less) exposures than pathogens that were treated a month later in the same stay.Topical agents analyzed in this study included: mafenide, bacitracin, silver c1cc(N)ccc1S(Nc1ncccn1)(=O)=O, mupirocin, Dakin's, silver nitrate solution, hypochlorous acid, other topicals, solid silver dressings, as well as chlorohexidine gluconate (CHG) and nasal decolonization.Exposures to systemic antimicrobial classes were also collected, including: non-pseudomonal beta-lactams (i.e., cefazolin, ceftriaxone, ampicillin, or ampicillin-sulbactam), anti-pseudomonal betalactams (i.e., piperacillin-tazobactam, cefepime), carbapenems (i.e., meropenem, ertapenem, or imipenem-cilastain), fluoroquinolones (i.e., ciprofloxacin or levofloxacin), anti-MRSA agents (i.e., vancomycin, daptomycin, or linezolid), aminoglycosides (i.e., amikacin, gentamicin, or tobramycin), extended-spectrum beta-lactam beta-lactamase inhibitors (i.e., ceftazidime-avibactam, meropenem-vaborbactam, or ceftolozane-tazobactam), metronidazole, tetracyclines (i.e., doxycycline or minocycline), sulfamethoxazole-trimethoprim, and antifungals (i.e., fluconazole, micafungin, or isavuconazole). | 271556193 |
Mupirocin | O[C@@H](C)[C@H](C)[C@H]1[C@@H](O1)C[C@H]1CO[C@H]([C@H](O)[C@@H]1O)C/C(=C/C(OCCCCCCCCC(O)=O)=O)C | Hierarchical data were collected according to patient, pathogen, and date of infection.Exposures of topical and systemic antimicrobials were tracked over time.Exposure was recorded at the pathogen level and was defined as exposure to any patient site (i.e., exposure at the patient level) prior to each culture obtainment.For example, a single patient could have had an infection present early in the hospital stay that may have had different (likely less) exposures than pathogens that were treated a month later in the same stay.Topical agents analyzed in this study included: mafenide, bacitracin, silver sulfadiazine, O[C@@H](C)[C@H](C)[C@H]1[C@@H](O1)C[C@H]1CO[C@H]([C@H](O)[C@@H]1O)C/C(=C/C(OCCCCCCCCC(O)=O)=O)C, Dakin's, silver nitrate solution, hypochlorous acid, other topicals, solid silver dressings, as well as chlorohexidine gluconate (CHG) and nasal decolonization.Exposures to systemic antimicrobial classes were also collected, including: non-pseudomonal beta-lactams (i.e., cefazolin, ceftriaxone, ampicillin, or ampicillin-sulbactam), anti-pseudomonal betalactams (i.e., piperacillin-tazobactam, cefepime), carbapenems (i.e., meropenem, ertapenem, or imipenem-cilastain), fluoroquinolones (i.e., ciprofloxacin or levofloxacin), anti-MRSA agents (i.e., vancomycin, daptomycin, or linezolid), aminoglycosides (i.e., amikacin, gentamicin, or tobramycin), extended-spectrum beta-lactam beta-lactamase inhibitors (i.e., ceftazidime-avibactam, meropenem-vaborbactam, or ceftolozane-tazobactam), metronidazole, tetracyclines (i.e., doxycycline or minocycline), sulfamethoxazole-trimethoprim, and antifungals (i.e., fluconazole, micafungin, or isavuconazole). | 271556193 |
Chlorohexidine | Clc1ccc(N/C(=N/C(=NCCCCCCN=C(/N=C(\N)Nc2ccc(Cl)cc2)N)N)N)cc1 | Hierarchical data were collected according to patient, pathogen, and date of infection.Exposures of topical and systemic antimicrobials were tracked over time.Exposure was recorded at the pathogen level and was defined as exposure to any patient site (i.e., exposure at the patient level) prior to each culture obtainment.For example, a single patient could have had an infection present early in the hospital stay that may have had different (likely less) exposures than pathogens that were treated a month later in the same stay.Topical agents analyzed in this study included: mafenide, bacitracin, silver sulfadiazine, mupirocin, Dakin's, silver nitrate solution, hypochlorous acid, other topicals, solid silver dressings, as well as Clc1ccc(N/C(=N/C(=NCCCCCCN=C(/N=C(\N)Nc2ccc(Cl)cc2)N)N)N)cc1 gluconate (CHG) and nasal decolonization.Exposures to systemic antimicrobial classes were also collected, including: non-pseudomonal beta-lactams (i.e., cefazolin, ceftriaxone, ampicillin, or ampicillin-sulbactam), anti-pseudomonal betalactams (i.e., piperacillin-tazobactam, cefepime), carbapenems (i.e., meropenem, ertapenem, or imipenem-cilastain), fluoroquinolones (i.e., ciprofloxacin or levofloxacin), anti-MRSA agents (i.e., vancomycin, daptomycin, or linezolid), aminoglycosides (i.e., amikacin, gentamicin, or tobramycin), extended-spectrum beta-lactam beta-lactamase inhibitors (i.e., ceftazidime-avibactam, meropenem-vaborbactam, or ceftolozane-tazobactam), metronidazole, tetracyclines (i.e., doxycycline or minocycline), sulfamethoxazole-trimethoprim, and antifungals (i.e., fluconazole, micafungin, or isavuconazole). | 271556193 |
Gluconate | O[C@H]([C@H](C(=O)[O-])O)[C@H](O)[C@H](O)CO | Hierarchical data were collected according to patient, pathogen, and date of infection.Exposures of topical and systemic antimicrobials were tracked over time.Exposure was recorded at the pathogen level and was defined as exposure to any patient site (i.e., exposure at the patient level) prior to each culture obtainment.For example, a single patient could have had an infection present early in the hospital stay that may have had different (likely less) exposures than pathogens that were treated a month later in the same stay.Topical agents analyzed in this study included: mafenide, bacitracin, silver sulfadiazine, mupirocin, Dakin's, silver nitrate solution, hypochlorous acid, other topicals, solid silver dressings, as well as chlorohexidine O[C@H]([C@H](C(=O)[O-])O)[C@H](O)[C@H](O)CO (CHG) and nasal decolonization.Exposures to systemic antimicrobial classes were also collected, including: non-pseudomonal beta-lactams (i.e., cefazolin, ceftriaxone, ampicillin, or ampicillin-sulbactam), anti-pseudomonal betalactams (i.e., piperacillin-tazobactam, cefepime), carbapenems (i.e., meropenem, ertapenem, or imipenem-cilastain), fluoroquinolones (i.e., ciprofloxacin or levofloxacin), anti-MRSA agents (i.e., vancomycin, daptomycin, or linezolid), aminoglycosides (i.e., amikacin, gentamicin, or tobramycin), extended-spectrum beta-lactam beta-lactamase inhibitors (i.e., ceftazidime-avibactam, meropenem-vaborbactam, or ceftolozane-tazobactam), metronidazole, tetracyclines (i.e., doxycycline or minocycline), sulfamethoxazole-trimethoprim, and antifungals (i.e., fluconazole, micafungin, or isavuconazole). | 271556193 |
Cefazolin | c1nnnn1CC(=O)N[C@@H]1C(N2[C@@H]1SCC(=C2C(O)=O)CSc1sc(C)nn1)=O | Hierarchical data were collected according to patient, pathogen, and date of infection.Exposures of topical and systemic antimicrobials were tracked over time.Exposure was recorded at the pathogen level and was defined as exposure to any patient site (i.e., exposure at the patient level) prior to each culture obtainment.For example, a single patient could have had an infection present early in the hospital stay that may have had different (likely less) exposures than pathogens that were treated a month later in the same stay.Topical agents analyzed in this study included: mafenide, bacitracin, silver sulfadiazine, mupirocin, Dakin's, silver nitrate solution, hypochlorous acid, other topicals, solid silver dressings, as well as chlorohexidine gluconate (CHG) and nasal decolonization.Exposures to systemic antimicrobial classes were also collected, including: non-pseudomonal beta-lactams (i.e., c1nnnn1CC(=O)N[C@@H]1C(N2[C@@H]1SCC(=C2C(O)=O)CSc1sc(C)nn1)=O, ceftriaxone, ampicillin, or ampicillin-sulbactam), anti-pseudomonal betalactams (i.e., piperacillin-tazobactam, cefepime), carbapenems (i.e., meropenem, ertapenem, or imipenem-cilastain), fluoroquinolones (i.e., ciprofloxacin or levofloxacin), anti-MRSA agents (i.e., vancomycin, daptomycin, or linezolid), aminoglycosides (i.e., amikacin, gentamicin, or tobramycin), extended-spectrum beta-lactam beta-lactamase inhibitors (i.e., ceftazidime-avibactam, meropenem-vaborbactam, or ceftolozane-tazobactam), metronidazole, tetracyclines (i.e., doxycycline or minocycline), sulfamethoxazole-trimethoprim, and antifungals (i.e., fluconazole, micafungin, or isavuconazole). | 271556193 |
Ceftriaxone | O=c1c(nc(n(C)[nH]1)SCC1CSC2[C@@H](C(N2C=1C(O)=O)=O)NC(/C(=N/OC)c1csc(N)n1)=O)=O | Hierarchical data were collected according to patient, pathogen, and date of infection.Exposures of topical and systemic antimicrobials were tracked over time.Exposure was recorded at the pathogen level and was defined as exposure to any patient site (i.e., exposure at the patient level) prior to each culture obtainment.For example, a single patient could have had an infection present early in the hospital stay that may have had different (likely less) exposures than pathogens that were treated a month later in the same stay.Topical agents analyzed in this study included: mafenide, bacitracin, silver sulfadiazine, mupirocin, Dakin's, silver nitrate solution, hypochlorous acid, other topicals, solid silver dressings, as well as chlorohexidine gluconate (CHG) and nasal decolonization.Exposures to systemic antimicrobial classes were also collected, including: non-pseudomonal beta-lactams (i.e., cefazolin, O=c1c(nc(n(C)[nH]1)SCC1CSC2[C@@H](C(N2C=1C(O)=O)=O)NC(/C(=N/OC)c1csc(N)n1)=O)=O, ampicillin, or ampicillin-sulbactam), anti-pseudomonal betalactams (i.e., piperacillin-tazobactam, cefepime), carbapenems (i.e., meropenem, ertapenem, or imipenem-cilastain), fluoroquinolones (i.e., ciprofloxacin or levofloxacin), anti-MRSA agents (i.e., vancomycin, daptomycin, or linezolid), aminoglycosides (i.e., amikacin, gentamicin, or tobramycin), extended-spectrum beta-lactam beta-lactamase inhibitors (i.e., ceftazidime-avibactam, meropenem-vaborbactam, or ceftolozane-tazobactam), metronidazole, tetracyclines (i.e., doxycycline or minocycline), sulfamethoxazole-trimethoprim, and antifungals (i.e., fluconazole, micafungin, or isavuconazole). | 271556193 |
Ampicillin | C1(C)(C)[C@@H](N2C(=O)[C@@H](NC([C@H](N)C3=CC=CC=C3)=O)[C@H]2S1)C(=O)O | Hierarchical data were collected according to patient, pathogen, and date of infection.Exposures of topical and systemic antimicrobials were tracked over time.Exposure was recorded at the pathogen level and was defined as exposure to any patient site (i.e., exposure at the patient level) prior to each culture obtainment.For example, a single patient could have had an infection present early in the hospital stay that may have had different (likely less) exposures than pathogens that were treated a month later in the same stay.Topical agents analyzed in this study included: mafenide, bacitracin, silver sulfadiazine, mupirocin, Dakin's, silver nitrate solution, hypochlorous acid, other topicals, solid silver dressings, as well as chlorohexidine gluconate (CHG) and nasal decolonization.Exposures to systemic antimicrobial classes were also collected, including: non-pseudomonal beta-lactams (i.e., cefazolin, ceftriaxone, C1(C)(C)[C@@H](N2C(=O)[C@@H](NC([C@H](N)C3=CC=CC=C3)=O)[C@H]2S1)C(=O)O, or C1(C)(C)[C@@H](N2C(=O)[C@@H](NC([C@H](N)C3=CC=CC=C3)=O)[C@H]2S1)C(=O)O-sulbactam), anti-pseudomonal betalactams (i.e., piperacillin-tazobactam, cefepime), carbapenems (i.e., meropenem, ertapenem, or imipenem-cilastain), fluoroquinolones (i.e., ciprofloxacin or levofloxacin), anti-MRSA agents (i.e., vancomycin, daptomycin, or linezolid), aminoglycosides (i.e., amikacin, gentamicin, or tobramycin), extended-spectrum beta-lactam beta-lactamase inhibitors (i.e., ceftazidime-avibactam, meropenem-vaborbactam, or ceftolozane-tazobactam), metronidazole, tetracyclines (i.e., doxycycline or minocycline), sulfamethoxazole-trimethoprim, and antifungals (i.e., fluconazole, micafungin, or isavuconazole). | 271556193 |
Ampicillin-sulbactam | C12C(S(C(C)(C1C(=O)O)C)(=O)=O)CC2=O.O=C(NC1C2SC(C(N2C1=O)C(=O)O)(C)C)C(N)C1=CC=CC=C1 | Hierarchical data were collected according to patient, pathogen, and date of infection.Exposures of topical and systemic antimicrobials were tracked over time.Exposure was recorded at the pathogen level and was defined as exposure to any patient site (i.e., exposure at the patient level) prior to each culture obtainment.For example, a single patient could have had an infection present early in the hospital stay that may have had different (likely less) exposures than pathogens that were treated a month later in the same stay.Topical agents analyzed in this study included: mafenide, bacitracin, silver sulfadiazine, mupirocin, Dakin's, silver nitrate solution, hypochlorous acid, other topicals, solid silver dressings, as well as chlorohexidine gluconate (CHG) and nasal decolonization.Exposures to systemic antimicrobial classes were also collected, including: non-pseudomonal beta-lactams (i.e., cefazolin, ceftriaxone, ampicillin, or C12C(S(C(C)(C1C(=O)O)C)(=O)=O)CC2=O.O=C(NC1C2SC(C(N2C1=O)C(=O)O)(C)C)C(N)C1=CC=CC=C1), anti-pseudomonal betalactams (i.e., piperacillin-tazobactam, cefepime), carbapenems (i.e., meropenem, ertapenem, or imipenem-cilastain), fluoroquinolones (i.e., ciprofloxacin or levofloxacin), anti-MRSA agents (i.e., vancomycin, daptomycin, or linezolid), aminoglycosides (i.e., amikacin, gentamicin, or tobramycin), extended-spectrum beta-lactam beta-lactamase inhibitors (i.e., ceftazidime-avibactam, meropenem-vaborbactam, or ceftolozane-tazobactam), metronidazole, tetracyclines (i.e., doxycycline or minocycline), sulfamethoxazole-trimethoprim, and antifungals (i.e., fluconazole, micafungin, or isavuconazole). | 271556193 |
Piperacillin-tazobactam | O=C1N(CCN(C1=O)CC)C(=O)N[C@H](C(=O)N[C@H]1[C@@H]2N(C1=O)[C@H](C(S2)(C)C)C(=O)[O-])c1ccccc1.[C@@]1(Cn2nncc2)(C)S([C@@H]2CC(=O)N2[C@H]1C(O)=O)(=O)=O.[Na+] | Hierarchical data were collected according to patient, pathogen, and date of infection.Exposures of topical and systemic antimicrobials were tracked over time.Exposure was recorded at the pathogen level and was defined as exposure to any patient site (i.e., exposure at the patient level) prior to each culture obtainment.For example, a single patient could have had an infection present early in the hospital stay that may have had different (likely less) exposures than pathogens that were treated a month later in the same stay.Topical agents analyzed in this study included: mafenide, bacitracin, silver sulfadiazine, mupirocin, Dakin's, silver nitrate solution, hypochlorous acid, other topicals, solid silver dressings, as well as chlorohexidine gluconate (CHG) and nasal decolonization.Exposures to systemic antimicrobial classes were also collected, including: non-pseudomonal beta-lactams (i.e., cefazolin, ceftriaxone, ampicillin, or ampicillin-sulbactam), anti-pseudomonal betalactams (i.e., O=C1N(CCN(C1=O)CC)C(=O)N[C@H](C(=O)N[C@H]1[C@@H]2N(C1=O)[C@H](C(S2)(C)C)C(=O)[O-])c1ccccc1.[C@@]1(Cn2nncc2)(C)S([C@@H]2CC(=O)N2[C@H]1C(O)=O)(=O)=O.[Na+], cefepime), carbapenems (i.e., meropenem, ertapenem, or imipenem-cilastain), fluoroquinolones (i.e., ciprofloxacin or levofloxacin), anti-MRSA agents (i.e., vancomycin, daptomycin, or linezolid), aminoglycosides (i.e., amikacin, gentamicin, or tobramycin), extended-spectrum beta-lactam beta-lactamase inhibitors (i.e., ceftazidime-avibactam, meropenem-vaborbactam, or ceftolozane-tazobactam), metronidazole, tetracyclines (i.e., doxycycline or minocycline), sulfamethoxazole-trimethoprim, and antifungals (i.e., fluconazole, micafungin, or isavuconazole). | 271556193 |
Cefepime | O=C(/C(=N/OC)C1=CSC(=N1)N)N[C@@H]1C(=O)N2C(C(=O)[O-])=C(CSC12)C[N+]1(CCCC1)C | Hierarchical data were collected according to patient, pathogen, and date of infection.Exposures of topical and systemic antimicrobials were tracked over time.Exposure was recorded at the pathogen level and was defined as exposure to any patient site (i.e., exposure at the patient level) prior to each culture obtainment.For example, a single patient could have had an infection present early in the hospital stay that may have had different (likely less) exposures than pathogens that were treated a month later in the same stay.Topical agents analyzed in this study included: mafenide, bacitracin, silver sulfadiazine, mupirocin, Dakin's, silver nitrate solution, hypochlorous acid, other topicals, solid silver dressings, as well as chlorohexidine gluconate (CHG) and nasal decolonization.Exposures to systemic antimicrobial classes were also collected, including: non-pseudomonal beta-lactams (i.e., cefazolin, ceftriaxone, ampicillin, or ampicillin-sulbactam), anti-pseudomonal betalactams (i.e., piperacillin-tazobactam, O=C(/C(=N/OC)C1=CSC(=N1)N)N[C@@H]1C(=O)N2C(C(=O)[O-])=C(CSC12)C[N+]1(CCCC1)C), carbapenems (i.e., meropenem, ertapenem, or imipenem-cilastain), fluoroquinolones (i.e., ciprofloxacin or levofloxacin), anti-MRSA agents (i.e., vancomycin, daptomycin, or linezolid), aminoglycosides (i.e., amikacin, gentamicin, or tobramycin), extended-spectrum beta-lactam beta-lactamase inhibitors (i.e., ceftazidime-avibactam, meropenem-vaborbactam, or ceftolozane-tazobactam), metronidazole, tetracyclines (i.e., doxycycline or minocycline), sulfamethoxazole-trimethoprim, and antifungals (i.e., fluconazole, micafungin, or isavuconazole). | 271556193 |
Carbapenems | O=C(O)C1=CCC2N1C(C2)=O | Hierarchical data were collected according to patient, pathogen, and date of infection.Exposures of topical and systemic antimicrobials were tracked over time.Exposure was recorded at the pathogen level and was defined as exposure to any patient site (i.e., exposure at the patient level) prior to each culture obtainment.For example, a single patient could have had an infection present early in the hospital stay that may have had different (likely less) exposures than pathogens that were treated a month later in the same stay.Topical agents analyzed in this study included: mafenide, bacitracin, silver sulfadiazine, mupirocin, Dakin's, silver nitrate solution, hypochlorous acid, other topicals, solid silver dressings, as well as chlorohexidine gluconate (CHG) and nasal decolonization.Exposures to systemic antimicrobial classes were also collected, including: non-pseudomonal beta-lactams (i.e., cefazolin, ceftriaxone, ampicillin, or ampicillin-sulbactam), anti-pseudomonal betalactams (i.e., piperacillin-tazobactam, cefepime), O=C(O)C1=CCC2N1C(C2)=O (i.e., meropenem, ertapenem, or imipenem-cilastain), fluoroquinolones (i.e., ciprofloxacin or levofloxacin), anti-MRSA agents (i.e., vancomycin, daptomycin, or linezolid), aminoglycosides (i.e., amikacin, gentamicin, or tobramycin), extended-spectrum beta-lactam beta-lactamase inhibitors (i.e., ceftazidime-avibactam, meropenem-vaborbactam, or ceftolozane-tazobactam), metronidazole, tetracyclines (i.e., doxycycline or minocycline), sulfamethoxazole-trimethoprim, and antifungals (i.e., fluconazole, micafungin, or isavuconazole). | 271556193 |
Meropenem | [C@@H]1(NC[C@H](C1)SC1=C(C(O)=O)N2C([C@H]([C@H](O)C)[C@H]2[C@H]1C)=O)C(N(C)C)=O | Hierarchical data were collected according to patient, pathogen, and date of infection.Exposures of topical and systemic antimicrobials were tracked over time.Exposure was recorded at the pathogen level and was defined as exposure to any patient site (i.e., exposure at the patient level) prior to each culture obtainment.For example, a single patient could have had an infection present early in the hospital stay that may have had different (likely less) exposures than pathogens that were treated a month later in the same stay.Topical agents analyzed in this study included: mafenide, bacitracin, silver sulfadiazine, mupirocin, Dakin's, silver nitrate solution, hypochlorous acid, other topicals, solid silver dressings, as well as chlorohexidine gluconate (CHG) and nasal decolonization.Exposures to systemic antimicrobial classes were also collected, including: non-pseudomonal beta-lactams (i.e., cefazolin, ceftriaxone, ampicillin, or ampicillin-sulbactam), anti-pseudomonal betalactams (i.e., piperacillin-tazobactam, cefepime), carbapenems (i.e., [C@@H]1(NC[C@H](C1)SC1=C(C(O)=O)N2C([C@H]([C@H](O)C)[C@H]2[C@H]1C)=O)C(N(C)C)=O, ertapenem, or imipenem-cilastain), fluoroquinolones (i.e., ciprofloxacin or levofloxacin), anti-MRSA agents (i.e., vancomycin, daptomycin, or linezolid), aminoglycosides (i.e., amikacin, gentamicin, or tobramycin), extended-spectrum beta-lactam beta-lactamase inhibitors (i.e., ceftazidime-avibactam, [C@@H]1(NC[C@H](C1)SC1=C(C(O)=O)N2C([C@H]([C@H](O)C)[C@H]2[C@H]1C)=O)C(N(C)C)=O-vaborbactam, or ceftolozane-tazobactam), metronidazole, tetracyclines (i.e., doxycycline or minocycline), sulfamethoxazole-trimethoprim, and antifungals (i.e., fluconazole, micafungin, or isavuconazole). | 271556193 |
Ertapenem | [C@H]([C@H]1C(N2[C@@H]1[C@H](C(=C2C(O)=O)S[C@H]1C[C@H](NC1)C(NC1=CC=CC(C(=O)O)=C1)=O)C)=O)(C)O | Hierarchical data were collected according to patient, pathogen, and date of infection.Exposures of topical and systemic antimicrobials were tracked over time.Exposure was recorded at the pathogen level and was defined as exposure to any patient site (i.e., exposure at the patient level) prior to each culture obtainment.For example, a single patient could have had an infection present early in the hospital stay that may have had different (likely less) exposures than pathogens that were treated a month later in the same stay.Topical agents analyzed in this study included: mafenide, bacitracin, silver sulfadiazine, mupirocin, Dakin's, silver nitrate solution, hypochlorous acid, other topicals, solid silver dressings, as well as chlorohexidine gluconate (CHG) and nasal decolonization.Exposures to systemic antimicrobial classes were also collected, including: non-pseudomonal beta-lactams (i.e., cefazolin, ceftriaxone, ampicillin, or ampicillin-sulbactam), anti-pseudomonal betalactams (i.e., piperacillin-tazobactam, cefepime), carbapenems (i.e., meropenem, [C@H]([C@H]1C(N2[C@@H]1[C@H](C(=C2C(O)=O)S[C@H]1C[C@H](NC1)C(NC1=CC=CC(C(=O)O)=C1)=O)C)=O)(C)O, or imipenem-cilastain), fluoroquinolones (i.e., ciprofloxacin or levofloxacin), anti-MRSA agents (i.e., vancomycin, daptomycin, or linezolid), aminoglycosides (i.e., amikacin, gentamicin, or tobramycin), extended-spectrum beta-lactam beta-lactamase inhibitors (i.e., ceftazidime-avibactam, meropenem-vaborbactam, or ceftolozane-tazobactam), metronidazole, tetracyclines (i.e., doxycycline or minocycline), sulfamethoxazole-trimethoprim, and antifungals (i.e., fluconazole, micafungin, or isavuconazole). | 271556193 |
Ciprofloxacin | C1CN(c2cc3c(cc2F)c(c(cn3C2CC2)C(O)=O)=O)CCN1 | Hierarchical data were collected according to patient, pathogen, and date of infection.Exposures of topical and systemic antimicrobials were tracked over time.Exposure was recorded at the pathogen level and was defined as exposure to any patient site (i.e., exposure at the patient level) prior to each culture obtainment.For example, a single patient could have had an infection present early in the hospital stay that may have had different (likely less) exposures than pathogens that were treated a month later in the same stay.Topical agents analyzed in this study included: mafenide, bacitracin, silver sulfadiazine, mupirocin, Dakin's, silver nitrate solution, hypochlorous acid, other topicals, solid silver dressings, as well as chlorohexidine gluconate (CHG) and nasal decolonization.Exposures to systemic antimicrobial classes were also collected, including: non-pseudomonal beta-lactams (i.e., cefazolin, ceftriaxone, ampicillin, or ampicillin-sulbactam), anti-pseudomonal betalactams (i.e., piperacillin-tazobactam, cefepime), carbapenems (i.e., meropenem, ertapenem, or imipenem-cilastain), fluoroquinolones (i.e., C1CN(c2cc3c(cc2F)c(c(cn3C2CC2)C(O)=O)=O)CCN1 or levofloxacin), anti-MRSA agents (i.e., vancomycin, daptomycin, or linezolid), aminoglycosides (i.e., amikacin, gentamicin, or tobramycin), extended-spectrum beta-lactam beta-lactamase inhibitors (i.e., ceftazidime-avibactam, meropenem-vaborbactam, or ceftolozane-tazobactam), metronidazole, tetracyclines (i.e., doxycycline or minocycline), sulfamethoxazole-trimethoprim, and antifungals (i.e., fluconazole, micafungin, or isavuconazole). | 271556193 |
Linezolid | C1=C(C=CC(=C1F)N1CCOCC1)N1C(O[C@@H](CNC(C)=O)C1)=O | Hierarchical data were collected according to patient, pathogen, and date of infection.Exposures of topical and systemic antimicrobials were tracked over time.Exposure was recorded at the pathogen level and was defined as exposure to any patient site (i.e., exposure at the patient level) prior to each culture obtainment.For example, a single patient could have had an infection present early in the hospital stay that may have had different (likely less) exposures than pathogens that were treated a month later in the same stay.Topical agents analyzed in this study included: mafenide, bacitracin, silver sulfadiazine, mupirocin, Dakin's, silver nitrate solution, hypochlorous acid, other topicals, solid silver dressings, as well as chlorohexidine gluconate (CHG) and nasal decolonization.Exposures to systemic antimicrobial classes were also collected, including: non-pseudomonal beta-lactams (i.e., cefazolin, ceftriaxone, ampicillin, or ampicillin-sulbactam), anti-pseudomonal betalactams (i.e., piperacillin-tazobactam, cefepime), carbapenems (i.e., meropenem, ertapenem, or imipenem-cilastain), fluoroquinolones (i.e., ciprofloxacin or levofloxacin), anti-MRSA agents (i.e., vancomycin, daptomycin, or C1=C(C=CC(=C1F)N1CCOCC1)N1C(O[C@@H](CNC(C)=O)C1)=O), aminoglycosides (i.e., amikacin, gentamicin, or tobramycin), extended-spectrum beta-lactam beta-lactamase inhibitors (i.e., ceftazidime-avibactam, meropenem-vaborbactam, or ceftolozane-tazobactam), metronidazole, tetracyclines (i.e., doxycycline or minocycline), sulfamethoxazole-trimethoprim, and antifungals (i.e., fluconazole, micafungin, or isavuconazole). | 271556193 |
Amikacin | [C@H](C(=O)N[C@H]1[C@H](O[C@@H]2[C@@H]([C@@H](N)[C@@H]([C@H](O2)CO)O)O)[C@H]([C@H](O[C@H]2O[C@H](CN)[C@H]([C@@H]([C@H]2O)O)O)[C@@H](N)C1)O)(O)CCN | Hierarchical data were collected according to patient, pathogen, and date of infection.Exposures of topical and systemic antimicrobials were tracked over time.Exposure was recorded at the pathogen level and was defined as exposure to any patient site (i.e., exposure at the patient level) prior to each culture obtainment.For example, a single patient could have had an infection present early in the hospital stay that may have had different (likely less) exposures than pathogens that were treated a month later in the same stay.Topical agents analyzed in this study included: mafenide, bacitracin, silver sulfadiazine, mupirocin, Dakin's, silver nitrate solution, hypochlorous acid, other topicals, solid silver dressings, as well as chlorohexidine gluconate (CHG) and nasal decolonization.Exposures to systemic antimicrobial classes were also collected, including: non-pseudomonal beta-lactams (i.e., cefazolin, ceftriaxone, ampicillin, or ampicillin-sulbactam), anti-pseudomonal betalactams (i.e., piperacillin-tazobactam, cefepime), carbapenems (i.e., meropenem, ertapenem, or imipenem-cilastain), fluoroquinolones (i.e., ciprofloxacin or levofloxacin), anti-MRSA agents (i.e., vancomycin, daptomycin, or linezolid), aminoglycosides (i.e., [C@H](C(=O)N[C@H]1[C@H](O[C@@H]2[C@@H]([C@@H](N)[C@@H]([C@H](O2)CO)O)O)[C@H]([C@H](O[C@H]2O[C@H](CN)[C@H]([C@@H]([C@H]2O)O)O)[C@@H](N)C1)O)(O)CCN, gentamicin, or tobramycin), extended-spectrum beta-lactam beta-lactamase inhibitors (i.e., ceftazidime-avibactam, meropenem-vaborbactam, or ceftolozane-tazobactam), metronidazole, tetracyclines (i.e., doxycycline or minocycline), sulfamethoxazole-trimethoprim, and antifungals (i.e., fluconazole, micafungin, or isavuconazole). | 271556193 |
Gentamicin | C1(OC2C(O)C(OC3OC[C@](C(C3O)NC)(C)O)C(N)CC2N)C(N)CCC(O1)C(NC)C | Hierarchical data were collected according to patient, pathogen, and date of infection.Exposures of topical and systemic antimicrobials were tracked over time.Exposure was recorded at the pathogen level and was defined as exposure to any patient site (i.e., exposure at the patient level) prior to each culture obtainment.For example, a single patient could have had an infection present early in the hospital stay that may have had different (likely less) exposures than pathogens that were treated a month later in the same stay.Topical agents analyzed in this study included: mafenide, bacitracin, silver sulfadiazine, mupirocin, Dakin's, silver nitrate solution, hypochlorous acid, other topicals, solid silver dressings, as well as chlorohexidine gluconate (CHG) and nasal decolonization.Exposures to systemic antimicrobial classes were also collected, including: non-pseudomonal beta-lactams (i.e., cefazolin, ceftriaxone, ampicillin, or ampicillin-sulbactam), anti-pseudomonal betalactams (i.e., piperacillin-tazobactam, cefepime), carbapenems (i.e., meropenem, ertapenem, or imipenem-cilastain), fluoroquinolones (i.e., ciprofloxacin or levofloxacin), anti-MRSA agents (i.e., vancomycin, daptomycin, or linezolid), aminoglycosides (i.e., amikacin, C1(OC2C(O)C(OC3OC[C@](C(C3O)NC)(C)O)C(N)CC2N)C(N)CCC(O1)C(NC)C, or tobramycin), extended-spectrum beta-lactam beta-lactamase inhibitors (i.e., ceftazidime-avibactam, meropenem-vaborbactam, or ceftolozane-tazobactam), metronidazole, tetracyclines (i.e., doxycycline or minocycline), sulfamethoxazole-trimethoprim, and antifungals (i.e., fluconazole, micafungin, or isavuconazole). | 271556193 |
Tobramycin | C([C@H]1O[C@H](O[C@@H]2[C@@H](N)C[C@@H](N)[C@H](O[C@H]3O[C@@H]([C@H]([C@H](N)[C@H]3O)O)CO)[C@H]2O)[C@@H](C[C@@H]1O)N)N | Hierarchical data were collected according to patient, pathogen, and date of infection.Exposures of topical and systemic antimicrobials were tracked over time.Exposure was recorded at the pathogen level and was defined as exposure to any patient site (i.e., exposure at the patient level) prior to each culture obtainment.For example, a single patient could have had an infection present early in the hospital stay that may have had different (likely less) exposures than pathogens that were treated a month later in the same stay.Topical agents analyzed in this study included: mafenide, bacitracin, silver sulfadiazine, mupirocin, Dakin's, silver nitrate solution, hypochlorous acid, other topicals, solid silver dressings, as well as chlorohexidine gluconate (CHG) and nasal decolonization.Exposures to systemic antimicrobial classes were also collected, including: non-pseudomonal beta-lactams (i.e., cefazolin, ceftriaxone, ampicillin, or ampicillin-sulbactam), anti-pseudomonal betalactams (i.e., piperacillin-tazobactam, cefepime), carbapenems (i.e., meropenem, ertapenem, or imipenem-cilastain), fluoroquinolones (i.e., ciprofloxacin or levofloxacin), anti-MRSA agents (i.e., vancomycin, daptomycin, or linezolid), aminoglycosides (i.e., amikacin, gentamicin, or C([C@H]1O[C@H](O[C@@H]2[C@@H](N)C[C@@H](N)[C@H](O[C@H]3O[C@@H]([C@H]([C@H](N)[C@H]3O)O)CO)[C@H]2O)[C@@H](C[C@@H]1O)N)N), extended-spectrum beta-lactam beta-lactamase inhibitors (i.e., ceftazidime-avibactam, meropenem-vaborbactam, or ceftolozane-tazobactam), metronidazole, tetracyclines (i.e., doxycycline or minocycline), sulfamethoxazole-trimethoprim, and antifungals (i.e., fluconazole, micafungin, or isavuconazole). | 271556193 |
Ceftolozane-tazobactam | S1(=O)(=O)[C@H]2N([C@@H](C(=O)O)[C@]1(C)Cn1ccnn1)C(=O)C2.O=C(C1N2[C@H](SCC=1C[n+]1cc(c(N)n1C)NC(=O)NCCN)[C@@H](C2=O)NC(=O)/C(=N/OC(C)(C(=O)O)C)c1nsc(N)n1)[O-].OS(=O)(O)=O | Hierarchical data were collected according to patient, pathogen, and date of infection.Exposures of topical and systemic antimicrobials were tracked over time.Exposure was recorded at the pathogen level and was defined as exposure to any patient site (i.e., exposure at the patient level) prior to each culture obtainment.For example, a single patient could have had an infection present early in the hospital stay that may have had different (likely less) exposures than pathogens that were treated a month later in the same stay.Topical agents analyzed in this study included: mafenide, bacitracin, silver sulfadiazine, mupirocin, Dakin's, silver nitrate solution, hypochlorous acid, other topicals, solid silver dressings, as well as chlorohexidine gluconate (CHG) and nasal decolonization.Exposures to systemic antimicrobial classes were also collected, including: non-pseudomonal beta-lactams (i.e., cefazolin, ceftriaxone, ampicillin, or ampicillin-sulbactam), anti-pseudomonal betalactams (i.e., piperacillin-tazobactam, cefepime), carbapenems (i.e., meropenem, ertapenem, or imipenem-cilastain), fluoroquinolones (i.e., ciprofloxacin or levofloxacin), anti-MRSA agents (i.e., vancomycin, daptomycin, or linezolid), aminoglycosides (i.e., amikacin, gentamicin, or tobramycin), extended-spectrum beta-lactam beta-lactamase inhibitors (i.e., ceftazidime-avibactam, meropenem-vaborbactam, or S1(=O)(=O)[C@H]2N([C@@H](C(=O)O)[C@]1(C)Cn1ccnn1)C(=O)C2.O=C(C1N2[C@H](SCC=1C[n+]1cc(c(N)n1C)NC(=O)NCCN)[C@@H](C2=O)NC(=O)/C(=N/OC(C)(C(=O)O)C)c1nsc(N)n1)[O-].OS(=O)(O)=O), metronidazole, tetracyclines (i.e., doxycycline or minocycline), sulfamethoxazole-trimethoprim, and antifungals (i.e., fluconazole, micafungin, or isavuconazole). | 271556193 |
Metronidazole | C1=C(N(CCO)C(=N1)C)[N+]([O-])=O | Hierarchical data were collected according to patient, pathogen, and date of infection.Exposures of topical and systemic antimicrobials were tracked over time.Exposure was recorded at the pathogen level and was defined as exposure to any patient site (i.e., exposure at the patient level) prior to each culture obtainment.For example, a single patient could have had an infection present early in the hospital stay that may have had different (likely less) exposures than pathogens that were treated a month later in the same stay.Topical agents analyzed in this study included: mafenide, bacitracin, silver sulfadiazine, mupirocin, Dakin's, silver nitrate solution, hypochlorous acid, other topicals, solid silver dressings, as well as chlorohexidine gluconate (CHG) and nasal decolonization.Exposures to systemic antimicrobial classes were also collected, including: non-pseudomonal beta-lactams (i.e., cefazolin, ceftriaxone, ampicillin, or ampicillin-sulbactam), anti-pseudomonal betalactams (i.e., piperacillin-tazobactam, cefepime), carbapenems (i.e., meropenem, ertapenem, or imipenem-cilastain), fluoroquinolones (i.e., ciprofloxacin or levofloxacin), anti-MRSA agents (i.e., vancomycin, daptomycin, or linezolid), aminoglycosides (i.e., amikacin, gentamicin, or tobramycin), extended-spectrum beta-lactam beta-lactamase inhibitors (i.e., ceftazidime-avibactam, meropenem-vaborbactam, or ceftolozane-tazobactam), C1=C(N(CCO)C(=N1)C)[N+]([O-])=O, tetracyclines (i.e., doxycycline or minocycline), sulfamethoxazole-trimethoprim, and antifungals (i.e., fluconazole, micafungin, or isavuconazole). | 271556193 |
Doxycycline | O=C1C(C(N)=O)=C([C@]2(C(=O)C3[C@@H]([C@@H](C)C4C=CC=C(C=4C=3O)O)[C@H](O)[C@H]2[C@@H]1N(C)C)O)O | Hierarchical data were collected according to patient, pathogen, and date of infection.Exposures of topical and systemic antimicrobials were tracked over time.Exposure was recorded at the pathogen level and was defined as exposure to any patient site (i.e., exposure at the patient level) prior to each culture obtainment.For example, a single patient could have had an infection present early in the hospital stay that may have had different (likely less) exposures than pathogens that were treated a month later in the same stay.Topical agents analyzed in this study included: mafenide, bacitracin, silver sulfadiazine, mupirocin, Dakin's, silver nitrate solution, hypochlorous acid, other topicals, solid silver dressings, as well as chlorohexidine gluconate (CHG) and nasal decolonization.Exposures to systemic antimicrobial classes were also collected, including: non-pseudomonal beta-lactams (i.e., cefazolin, ceftriaxone, ampicillin, or ampicillin-sulbactam), anti-pseudomonal betalactams (i.e., piperacillin-tazobactam, cefepime), carbapenems (i.e., meropenem, ertapenem, or imipenem-cilastain), fluoroquinolones (i.e., ciprofloxacin or levofloxacin), anti-MRSA agents (i.e., vancomycin, daptomycin, or linezolid), aminoglycosides (i.e., amikacin, gentamicin, or tobramycin), extended-spectrum beta-lactam beta-lactamase inhibitors (i.e., ceftazidime-avibactam, meropenem-vaborbactam, or ceftolozane-tazobactam), metronidazole, tetracyclines (i.e., O=C1C(C(N)=O)=C([C@]2(C(=O)C3[C@@H]([C@@H](C)C4C=CC=C(C=4C=3O)O)[C@H](O)[C@H]2[C@@H]1N(C)C)O)O or minocycline), sulfamethoxazole-trimethoprim, and antifungals (i.e., fluconazole, micafungin, or isavuconazole). | 271556193 |
Minocycline | C12=C(C=CC(O)=C1C(O)=C1C(=O)[C@@]3(O)[C@@H](C[C@@H]1C2)[C@@H](C(C(C(N)=O)=C3O)=O)N(C)C)N(C)C | Hierarchical data were collected according to patient, pathogen, and date of infection.Exposures of topical and systemic antimicrobials were tracked over time.Exposure was recorded at the pathogen level and was defined as exposure to any patient site (i.e., exposure at the patient level) prior to each culture obtainment.For example, a single patient could have had an infection present early in the hospital stay that may have had different (likely less) exposures than pathogens that were treated a month later in the same stay.Topical agents analyzed in this study included: mafenide, bacitracin, silver sulfadiazine, mupirocin, Dakin's, silver nitrate solution, hypochlorous acid, other topicals, solid silver dressings, as well as chlorohexidine gluconate (CHG) and nasal decolonization.Exposures to systemic antimicrobial classes were also collected, including: non-pseudomonal beta-lactams (i.e., cefazolin, ceftriaxone, ampicillin, or ampicillin-sulbactam), anti-pseudomonal betalactams (i.e., piperacillin-tazobactam, cefepime), carbapenems (i.e., meropenem, ertapenem, or imipenem-cilastain), fluoroquinolones (i.e., ciprofloxacin or levofloxacin), anti-MRSA agents (i.e., vancomycin, daptomycin, or linezolid), aminoglycosides (i.e., amikacin, gentamicin, or tobramycin), extended-spectrum beta-lactam beta-lactamase inhibitors (i.e., ceftazidime-avibactam, meropenem-vaborbactam, or ceftolozane-tazobactam), metronidazole, tetracyclines (i.e., doxycycline or C12=C(C=CC(O)=C1C(O)=C1C(=O)[C@@]3(O)[C@@H](C[C@@H]1C2)[C@@H](C(C(C(N)=O)=C3O)=O)N(C)C)N(C)C), sulfamethoxazole-trimethoprim, and antifungals (i.e., fluconazole, micafungin, or isavuconazole). | 271556193 |
Sulfamethoxazole-trimethoprim | C1C(NS(=O)(=O)C2=CC=C(N)C=C2)=NOC=1C.C1N=C(N)N=C(C=1CC1=CC(=C(OC)C(=C1)OC)OC)N | Hierarchical data were collected according to patient, pathogen, and date of infection.Exposures of topical and systemic antimicrobials were tracked over time.Exposure was recorded at the pathogen level and was defined as exposure to any patient site (i.e., exposure at the patient level) prior to each culture obtainment.For example, a single patient could have had an infection present early in the hospital stay that may have had different (likely less) exposures than pathogens that were treated a month later in the same stay.Topical agents analyzed in this study included: mafenide, bacitracin, silver sulfadiazine, mupirocin, Dakin's, silver nitrate solution, hypochlorous acid, other topicals, solid silver dressings, as well as chlorohexidine gluconate (CHG) and nasal decolonization.Exposures to systemic antimicrobial classes were also collected, including: non-pseudomonal beta-lactams (i.e., cefazolin, ceftriaxone, ampicillin, or ampicillin-sulbactam), anti-pseudomonal betalactams (i.e., piperacillin-tazobactam, cefepime), carbapenems (i.e., meropenem, ertapenem, or imipenem-cilastain), fluoroquinolones (i.e., ciprofloxacin or levofloxacin), anti-MRSA agents (i.e., vancomycin, daptomycin, or linezolid), aminoglycosides (i.e., amikacin, gentamicin, or tobramycin), extended-spectrum beta-lactam beta-lactamase inhibitors (i.e., ceftazidime-avibactam, meropenem-vaborbactam, or ceftolozane-tazobactam), metronidazole, tetracyclines (i.e., doxycycline or minocycline), C1C(NS(=O)(=O)C2=CC=C(N)C=C2)=NOC=1C.C1N=C(N)N=C(C=1CC1=CC(=C(OC)C(=C1)OC)OC)N, and antifungals (i.e., fluconazole, micafungin, or isavuconazole). | 271556193 |
Fluconazole | C1(F)=CC(F)=C(C=C1)C(O)(CN1N=CN=C1)CN1C=NC=N1 | Hierarchical data were collected according to patient, pathogen, and date of infection.Exposures of topical and systemic antimicrobials were tracked over time.Exposure was recorded at the pathogen level and was defined as exposure to any patient site (i.e., exposure at the patient level) prior to each culture obtainment.For example, a single patient could have had an infection present early in the hospital stay that may have had different (likely less) exposures than pathogens that were treated a month later in the same stay.Topical agents analyzed in this study included: mafenide, bacitracin, silver sulfadiazine, mupirocin, Dakin's, silver nitrate solution, hypochlorous acid, other topicals, solid silver dressings, as well as chlorohexidine gluconate (CHG) and nasal decolonization.Exposures to systemic antimicrobial classes were also collected, including: non-pseudomonal beta-lactams (i.e., cefazolin, ceftriaxone, ampicillin, or ampicillin-sulbactam), anti-pseudomonal betalactams (i.e., piperacillin-tazobactam, cefepime), carbapenems (i.e., meropenem, ertapenem, or imipenem-cilastain), fluoroquinolones (i.e., ciprofloxacin or levofloxacin), anti-MRSA agents (i.e., vancomycin, daptomycin, or linezolid), aminoglycosides (i.e., amikacin, gentamicin, or tobramycin), extended-spectrum beta-lactam beta-lactamase inhibitors (i.e., ceftazidime-avibactam, meropenem-vaborbactam, or ceftolozane-tazobactam), metronidazole, tetracyclines (i.e., doxycycline or minocycline), sulfamethoxazole-trimethoprim, and antifungals (i.e., C1(F)=CC(F)=C(C=C1)C(O)(CN1N=CN=C1)CN1C=NC=N1, micafungin, or isavuconazole). | 271556193 |
Micafungin | N1C([C@H]2N(C(=O)[C@H]([C@H](O)C)NC([C@@H](NC(C3C=CC(C4=NOC(C5C=CC(OCCCCC)=CC=5)=C4)=CC=3)=O)C[C@H]([C@H](NC([C@@H]3[C@H]([C@H](CN3C([C@H]([C@H](O)CC(=O)N)NC([C@@H]1[C@H](O)[C@@H](O)C1=CC(=C(C=C1)O)OS(=O)(=O)O)=O)=O)C)O)=O)O)O)=O)C[C@H](O)C2)=O | Hierarchical data were collected according to patient, pathogen, and date of infection.Exposures of topical and systemic antimicrobials were tracked over time.Exposure was recorded at the pathogen level and was defined as exposure to any patient site (i.e., exposure at the patient level) prior to each culture obtainment.For example, a single patient could have had an infection present early in the hospital stay that may have had different (likely less) exposures than pathogens that were treated a month later in the same stay.Topical agents analyzed in this study included: mafenide, bacitracin, silver sulfadiazine, mupirocin, Dakin's, silver nitrate solution, hypochlorous acid, other topicals, solid silver dressings, as well as chlorohexidine gluconate (CHG) and nasal decolonization.Exposures to systemic antimicrobial classes were also collected, including: non-pseudomonal beta-lactams (i.e., cefazolin, ceftriaxone, ampicillin, or ampicillin-sulbactam), anti-pseudomonal betalactams (i.e., piperacillin-tazobactam, cefepime), carbapenems (i.e., meropenem, ertapenem, or imipenem-cilastain), fluoroquinolones (i.e., ciprofloxacin or levofloxacin), anti-MRSA agents (i.e., vancomycin, daptomycin, or linezolid), aminoglycosides (i.e., amikacin, gentamicin, or tobramycin), extended-spectrum beta-lactam beta-lactamase inhibitors (i.e., ceftazidime-avibactam, meropenem-vaborbactam, or ceftolozane-tazobactam), metronidazole, tetracyclines (i.e., doxycycline or minocycline), sulfamethoxazole-trimethoprim, and antifungals (i.e., fluconazole, N1C([C@H]2N(C(=O)[C@H]([C@H](O)C)NC([C@@H](NC(C3C=CC(C4=NOC(C5C=CC(OCCCCC)=CC=5)=C4)=CC=3)=O)C[C@H]([C@H](NC([C@@H]3[C@H]([C@H](CN3C([C@H]([C@H](O)CC(=O)N)NC([C@@H]1[C@H](O)[C@@H](O)C1=CC(=C(C=C1)O)OS(=O)(=O)O)=O)=O)C)O)=O)O)O)=O)C[C@H](O)C2)=O, or isavuconazole). | 271556193 |
Isavuconazole | c1([C@@](Cn2ncnc2)([C@@H](C)c2nc(-c3ccc(C#N)cc3)cs2)O)c(F)ccc(F)c1 | Hierarchical data were collected according to patient, pathogen, and date of infection.Exposures of topical and systemic antimicrobials were tracked over time.Exposure was recorded at the pathogen level and was defined as exposure to any patient site (i.e., exposure at the patient level) prior to each culture obtainment.For example, a single patient could have had an infection present early in the hospital stay that may have had different (likely less) exposures than pathogens that were treated a month later in the same stay.Topical agents analyzed in this study included: mafenide, bacitracin, silver sulfadiazine, mupirocin, Dakin's, silver nitrate solution, hypochlorous acid, other topicals, solid silver dressings, as well as chlorohexidine gluconate (CHG) and nasal decolonization.Exposures to systemic antimicrobial classes were also collected, including: non-pseudomonal beta-lactams (i.e., cefazolin, ceftriaxone, ampicillin, or ampicillin-sulbactam), anti-pseudomonal betalactams (i.e., piperacillin-tazobactam, cefepime), carbapenems (i.e., meropenem, ertapenem, or imipenem-cilastain), fluoroquinolones (i.e., ciprofloxacin or levofloxacin), anti-MRSA agents (i.e., vancomycin, daptomycin, or linezolid), aminoglycosides (i.e., amikacin, gentamicin, or tobramycin), extended-spectrum beta-lactam beta-lactamase inhibitors (i.e., ceftazidime-avibactam, meropenem-vaborbactam, or ceftolozane-tazobactam), metronidazole, tetracyclines (i.e., doxycycline or minocycline), sulfamethoxazole-trimethoprim, and antifungals (i.e., fluconazole, micafungin, or c1([C@@](Cn2ncnc2)([C@@H](C)c2nc(-c3ccc(C#N)cc3)cs2)O)c(F)ccc(F)c1). | 271556193 |
Cephalosporins | O=C(O)C1N2C([C@@H](NC(=O)CCC[C@H](C(O)=O)N)[C@H]2SCC=1COC(=O)C)=O | During this study period, the institution's microbiology laboratory utilized the Brucker MALDI Biotyper for the identification of bacteria and yeast.This system uses mass spectrometry to determine the proteomic fingerprints of microorganisms and compares these to the research-use-only database for microbial identification.The BD Phoenix™ automated system was used as a backup method for identification, and was the primary system used for antimicrobial susceptibility testing.The identification of microbes was based on the results of 45 chromogenic and fluorogenic substrates.ESBL production identified in isolates of E. coli, K. pneumoniae, and K. oxytoca was based on differential responses to third-generation O=C(O)C1N2C([C@@H](NC(=O)CCC[C@H](C(O)=O)N)[C@H]2SCC=1COC(=O)C)=O in the presence and absence of the beta-lactamase inhibitor clavulanic acid.Carbapenem resistance for other organisms was determined by resistance to either meropenem or ertapenem, which were the representative carbapenems on the antimicrobial susceptibility testing panel.The BD Phoenix system uses a Carbapenemaseproducing Organism Detect Panel.Specific genetic testing for resistance at our institution requires samples to be sent out to consulting laboratories, and must be requested.The rules for antibiotic reporting and interpretation for MIC values from the BD Phoenix™ system were based on United States Food and Drug Administration-cleared interpretations built within the automated system.Additional or reflex-sensitivity testing that may have been reported was done iteratively or collaboratively according to intramural antimicrobial stewardship guidance and adhered to Clinical & Laboratory Standards Institute breakpoints using the Kirby-Bauer disk diffusion method.Disk diffusion was rare and utilized only in cases of ceftazidime-avibactam, meropenem-vaborbactam, or ceftolozane-tazobactam susceptibilities for multidrug-resistant Acinetobacter spp., Enterobacterales spp., or Pseudomonas spp.Quality control for Phoenix identification and MICs followed the package insert for the Phoenix products.Kirby-Bauer interpretation, reporting and quality control followed CLSI recommendations. | 271556193 |
Carbapenem | [C@@H]12N(C(=O)C2)C=CC1 | During this study period, the institution's microbiology laboratory utilized the Brucker MALDI Biotyper for the identification of bacteria and yeast.This system uses mass spectrometry to determine the proteomic fingerprints of microorganisms and compares these to the research-use-only database for microbial identification.The BD Phoenix™ automated system was used as a backup method for identification, and was the primary system used for antimicrobial susceptibility testing.The identification of microbes was based on the results of 45 chromogenic and fluorogenic substrates.ESBL production identified in isolates of E. coli, K. pneumoniae, and K. oxytoca was based on differential responses to third-generation cephalosporins in the presence and absence of the beta-lactamase inhibitor clavulanic acid.[C@@H]12N(C(=O)C2)C=CC1 resistance for other organisms was determined by resistance to either meropenem or ertapenem, which were the representative [C@@H]12N(C(=O)C2)C=CC1s on the antimicrobial susceptibility testing panel.The BD Phoenix system uses a [C@@H]12N(C(=O)C2)C=CC1aseproducing Organism Detect Panel.Specific genetic testing for resistance at our institution requires samples to be sent out to consulting laboratories, and must be requested.The rules for antibiotic reporting and interpretation for MIC values from the BD Phoenix™ system were based on United States Food and Drug Administration-cleared interpretations built within the automated system.Additional or reflex-sensitivity testing that may have been reported was done iteratively or collaboratively according to intramural antimicrobial stewardship guidance and adhered to Clinical & Laboratory Standards Institute breakpoints using the Kirby-Bauer disk diffusion method.Disk diffusion was rare and utilized only in cases of ceftazidime-avibactam, meropenem-vaborbactam, or ceftolozane-tazobactam susceptibilities for multidrug-resistant Acinetobacter spp., Enterobacterales spp., or Pseudomonas spp.Quality control for Phoenix identification and MICs followed the package insert for the Phoenix products.Kirby-Bauer interpretation, reporting and quality control followed CLSI recommendations. | 271556193 |
Meropenem | [C@H](C)(O)[C@H]1C(=O)N2C(C(O)=O)=C([C@H](C)[C@H]12)S[C@H]1C[C@H](NC1)C(=O)N(C)C | During this study period, the institution's microbiology laboratory utilized the Brucker MALDI Biotyper for the identification of bacteria and yeast.This system uses mass spectrometry to determine the proteomic fingerprints of microorganisms and compares these to the research-use-only database for microbial identification.The BD Phoenix™ automated system was used as a backup method for identification, and was the primary system used for antimicrobial susceptibility testing.The identification of microbes was based on the results of 45 chromogenic and fluorogenic substrates.ESBL production identified in isolates of E. coli, K. pneumoniae, and K. oxytoca was based on differential responses to third-generation cephalosporins in the presence and absence of the beta-lactamase inhibitor clavulanic acid.Carbapenem resistance for other organisms was determined by resistance to either [C@H](C)(O)[C@H]1C(=O)N2C(C(O)=O)=C([C@H](C)[C@H]12)S[C@H]1C[C@H](NC1)C(=O)N(C)C or ertapenem, which were the representative carbapenems on the antimicrobial susceptibility testing panel.The BD Phoenix system uses a Carbapenemaseproducing Organism Detect Panel.Specific genetic testing for resistance at our institution requires samples to be sent out to consulting laboratories, and must be requested.The rules for antibiotic reporting and interpretation for MIC values from the BD Phoenix™ system were based on United States Food and Drug Administration-cleared interpretations built within the automated system.Additional or reflex-sensitivity testing that may have been reported was done iteratively or collaboratively according to intramural antimicrobial stewardship guidance and adhered to Clinical & Laboratory Standards Institute breakpoints using the Kirby-Bauer disk diffusion method.Disk diffusion was rare and utilized only in cases of ceftazidime-avibactam, [C@H](C)(O)[C@H]1C(=O)N2C(C(O)=O)=C([C@H](C)[C@H]12)S[C@H]1C[C@H](NC1)C(=O)N(C)C-vaborbactam, or ceftolozane-tazobactam susceptibilities for multidrug-resistant Acinetobacter spp., Enterobacterales spp., or Pseudomonas spp.Quality control for Phoenix identification and MICs followed the package insert for the Phoenix products.Kirby-Bauer interpretation, reporting and quality control followed CLSI recommendations. | 271556193 |
Ertapenem | C[C@@H](O)[C@H]1C(N2C(C(O)=O)=C(S[C@H]3C[C@H](NC3)C(=O)NC3C=C(C=CC=3)C(=O)O)[C@@H]([C@@H]21)C)=O | During this study period, the institution's microbiology laboratory utilized the Brucker MALDI Biotyper for the identification of bacteria and yeast.This system uses mass spectrometry to determine the proteomic fingerprints of microorganisms and compares these to the research-use-only database for microbial identification.The BD Phoenix™ automated system was used as a backup method for identification, and was the primary system used for antimicrobial susceptibility testing.The identification of microbes was based on the results of 45 chromogenic and fluorogenic substrates.ESBL production identified in isolates of E. coli, K. pneumoniae, and K. oxytoca was based on differential responses to third-generation cephalosporins in the presence and absence of the beta-lactamase inhibitor clavulanic acid.Carbapenem resistance for other organisms was determined by resistance to either meropenem or C[C@@H](O)[C@H]1C(N2C(C(O)=O)=C(S[C@H]3C[C@H](NC3)C(=O)NC3C=C(C=CC=3)C(=O)O)[C@@H]([C@@H]21)C)=O, which were the representative carbapenems on the antimicrobial susceptibility testing panel.The BD Phoenix system uses a Carbapenemaseproducing Organism Detect Panel.Specific genetic testing for resistance at our institution requires samples to be sent out to consulting laboratories, and must be requested.The rules for antibiotic reporting and interpretation for MIC values from the BD Phoenix™ system were based on United States Food and Drug Administration-cleared interpretations built within the automated system.Additional or reflex-sensitivity testing that may have been reported was done iteratively or collaboratively according to intramural antimicrobial stewardship guidance and adhered to Clinical & Laboratory Standards Institute breakpoints using the Kirby-Bauer disk diffusion method.Disk diffusion was rare and utilized only in cases of ceftazidime-avibactam, meropenem-vaborbactam, or ceftolozane-tazobactam susceptibilities for multidrug-resistant Acinetobacter spp., Enterobacterales spp., or Pseudomonas spp.Quality control for Phoenix identification and MICs followed the package insert for the Phoenix products.Kirby-Bauer interpretation, reporting and quality control followed CLSI recommendations. | 271556193 |
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