Recent reports have demonstrated that vancomycin (VAN) may lead to an increase in the incidence of acute kidney injury (AKI) when it is combined with antipseudomonal beta-lactams. This study compared the incidence of AKI associated with VAN plus piperacillin-tazobactam (TZP) or cefepime (FEP). This was a retrospective, matched cohort study that was conducted at an academic medical center between September 2010 and September 2014 and that included adult patients without severe chronic or structural kidney disease, dialysis, pregnancy, cystic fibrosis, or a hospital transfer receiving TZP-VAN or FEP-VAN for at least 48 h. The primary outcome was the difference in the AKI incidence between the TZP-VAN and FEP-VAN groups, evaluated using the risk, injury, failure, loss of kidney function, and endstage kidney disease (RIFLE) criteria. Patients in the two groups were matched on the basis of age, sex, severity of illness, baseline creatinine clearance, hypotension, number of nephrotoxicity risk factors, and intravenous contrast exposure. In total, 4,193 patients met all inclusion criteria (3,605 received TZP-VAN and 588 received FEP-VAN). The unadjusted AKI incidence was 21.4% in patients receiving TZP-VAN, whereas it was 12.6% in patients receiving FEP-VAN (P Ͻ 0.001). After the patients were matched, 1,633 patients receiving TZP-VAN and 578 patients receiving FEP-VAN were evaluated. The AKI incidence remained higher in patients receiving TZP-VAN than in those receiving FEP-VAN (21.4% versus 12.5%, P Ͻ 0.0001). This trend remained true for all classifications of the RIFLE criteria. After controlling for remaining confounders, TZP-VAN therapy was associated with 2.18 times the odds of AKI than FEP-VAN therapy (95% confidence interval, 1.64 to 2.94 times) in logistic regression. AKI was significantly more common in patients receiving vancomycin in combination with piperacillin-tazobactam than in those receiving vancomycin in combination with cefepime. This finding reinforces the need for the judicious use of combination empirical antimicrobial therapy.

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37 Background: Immune checkpoint inhibitors (ICI) have provided landmark breakthrough achieving success in prolonging survival in multiple cancer types. As a new class of therapy immune related serious adverse drug reactions (sADRs) have had limited reporting. This includes neurologic based, with reports limited to clinical trials and case-based. Ours is the largest database analysis to date reporting neurological adverse events after ICI therapy. Methods: We analyzed the FDA Adverse Event Reporting System (FAERS) database for pembrolizumab, atezolizumab, nivolumab, and ipilimumab two years prior their FDA approval to September 2017, to include all cases reported with Guillain-Barré syndrome (GBS), Myasthenia gravis, ocular myasthenia, and myasthenic syndrome after the usage of ICI. Results: A total 35,726 cases were reported in FAERS. We identified a total of 263 cases of which 121 (46%) were GBS, 112 (42.6%) myasthenia gravis, 22 myasthenic syndrome (8.4%), and 8 (3%) ocular myasthenia. The mean age in our study was 66 years, with 63% being male. The majority of the cases were reported in the United States (49%), followed by Japan (10%), France (6%), and Australia (5.7%). Over 30% of patients presented more than one significant symptom. Around 20% of these patients were taking more than one immune checkpoint inhibitor, combining ipilimumab with either nivolumab or pembrolizumab. A significantly higher proportion of patients with GBS taking more than one ICI (28.1%, p = 0.013). Nivolumab was the most common ICI in patients with myasthenia gravis, myasthenic syndrome, and ocular myasthenia, while ipilimumab was the most common in patients with GBS. Sixty four percent of these patients required hospitalization, 17% were reported as life threatening events, 7% resulted in disability, and 22% died. Conclusions: Neurological adverse events associated with ICI are relatively uncommon, but can have serious clinical consequences. Recognizing and detailing neurological immune syndromes in relation to ICI therapy are essential in the oncological and neurological practice due to the growing usage of these agents in cancer treatment.