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Objective: To summarize and critically appraise the evidence regarding oral vancomycin prophylaxis (OVP) to prevent recurrent Clostridium difficile infections (RCDIs), identify potential consequences of this emerging practice, and highlight future directions of study. Data Sources: A MEDLINE literature search of English-language publications from 1947 through September 2018 was performed using the search terms vancomycin and C difficile and prophylaxis. Clinical trials were identified on the National Library of Medicine clinical trials registry. Study Selection and Data Extraction: All clinical studies (n = 3) assessing oral vancomycin for secondary prophylaxis of C difficile infection (CDI) were evaluated by all authors. Other search results and references in selected publications were used for background and discussion. Data Synthesis: OVP reduced the risk of RCDI in high-risk patients taking systemic antibiotics. Variable dosing regimens and lack of safety data are limitations. OVP may have an adverse impact on the gastrointestinal microbiome, but this was not examined in the clinical studies. Relevance to Patient Care and Clinical Practice: Although current studies are limited by methodological concerns, clinicians can consider vancomycin 125 mg orally once or twice daily in high-risk patients receiving broad-spectrum antibacterial agents. Results of ongoing trials will define the most appropriate regimen and its impact on outcomes, including collateral damage. Conclusions: OVP reduces the risk of RCDIs and should be considered on a case-by-case basis. Caution is warranted before routine use is implemented because the impact on long-term outcomes has not been assessed and the optimal regimen has not been defined.

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Antidepressants are very widely used and associated with traumatic injury, yet little is known about their potential for harmful drug interactions. We aimed to identify potential drug interaction signals by assessing concomitant medications (precipitant drugs) taken with individual antidepressants (object drugs) that were associated with unintentional traumatic injury. We conducted pharmacoepidemiologic screening of 2000-2015 Optum Clinformatics data, identifying drug interaction signals by performing self-controlled case series studies for antidepressant + precipitant pairs and injury. We included persons aged 16-90 years codispensed an antidepressant and ≥ 1 precipitant drug(s), with an injury during antidepressant therapy. We classified antidepressant persondays as either precipitant-exposed or precipitant-unexposed. The outcome was an emergency department or inpatient discharge diagnosis for unintentional traumatic injury. We used conditional Poisson regression to calculate confounder adjusted rate ratios (RRs) and accounted for multiple estimation via semi-Bayes shrinkage. We identified 330,884 new users of antidepressants who experienced an injury. Among such persons, we studied concomitant use of 7,953 antidepressant + precipitant pairs. Two hundred fifty-six (3.2%) pairs were positively associated with injury and deemed potential drug interaction signals; 22 of these signals had adjusted RRs > 2.00. Adjusted RRs ranged from 1.06 (95% confidence interval: 1.00-1.12, P = 0.04) for citalopram + gabapentin to 3.06 (1.42-6.60) for nefazodone + levonorgestrel. Sixty-five (25.4%) signals are currently reported in a seminal drug interaction knowledgebase. We identified numerous new population-based signals of antidepressant drug interactions associated with unintentional traumatic injury. Future studies, intended to test hypotheses, should confirm or refute these potential interactions.

Background: Vancomycin and piperacillin-tazobactam (VPT) is a common antibiotic combination used in hospitals, and there has been increasing data indicating that the combination is associated with increased rates of acute kidney injury (AKI). It is unclear if the dosing method of vancomycin would mitigate the risk of AKI seen with VPT. Objective: To observe and compare incidence of AKI in patients on VPT when using the trough-based dosing method versus the area-under-the-curve (AUC)-based dosing method. Methods: This was a multi-center, retrospective, observational study at 3 community hospitals. Adults receiving at least 48 hours of VPT were included. Patients with severe renal dysfunction, pregnant patients, prisoners, and patients with central nervous system infections, or malignancy were excluded. The primary outcome was incidence of AKI as defined by the Infectious Disease Society of America (IDSA) criteria. Results: A total of 300 patients were included in the study; 150 patients in both the trough and AUC groups. A total of 23 patients (15%) in the trough group and 17 patients (11%) in the AUC group met the primary outcome (odds ratio [OR]: 0.7058, 95% confidence interval [CI]: [0.3603, 1.3826], P = .3098). Conclusion and Relevance: The incidence of AKI was lower in the AUC group compared with the trough group; however, this was not significant. The results of our study suggest that there is no difference between incidence of AKI when using trough- or AUC-based dosing in those receiving VPT. Because of the small sample size and retrospective nature of the study, more data are needed.