Nirmatrelvir/ritonavir Use With Tacrolimus in Lung Transplant Recipients: A Single-center Case Series.

BACKGROUND: Limited data and guidelines exist for using nirmatrelvir/ritonavir in solid organ transplant recipients stabilized on tacrolimus for the treatment of mild-to-moderate coronavirus disease. Concern exists regarding the impact of utilizing a 5-d course of nirmatrelvir/ritonavir with calcineurin inhibitors because of significant drug-drug interactions between ritonavir, a potent cytochrome P450 3A inhibitor, and other cytochrome P450 3A substrates, such as tacrolimus. METHODS: We report the successful use of nirmatrelvir/ritonavir in 12 outpatient lung transplant recipients with confirmed severe acute respiratory syndrome coronavirus 2 infection stabilized on tacrolimus immunosuppression. All patients stopped tacrolimus and started nirmatrelvir/ritonavir 10 to 14 h after the last dose of tacrolimus. Tacrolimus was withheld and then reinitiated at a modified dose 48 h following the completion of nirmatrelvir/ritonavir therapy. Tacrolimus trough levels were checked during nirmatrelvir/ritonavir therapy and tacrolimus reinitiation. RESULTS: Ten (10/12) patients were able to resume their original tacrolimus dose within 4 d of completing nirmatrelvir/ritonavir therapy and maintain therapeutic levels of tacrolimus. No patients experienced tacrolimus toxicity or acute rejection during the 30-d postcompletion of nirmatrelvir/ritonavir therapy. CONCLUSIONS: In this cohort of lung transplant recipients on tacrolimus, we demonstrated that nirmatrelvir/ritonavir can be safely used with close monitoring of tacrolimus levels and appropriate dose adjustments of tacrolimus. Further confirmatory studies are needed to determine the appropriate use of therapeutic drug monitoring and tacrolimus dose following completion of nirmatrelvir/ritonavir in the solid organ transplant population.

The Effect of IL-6 Inhibitors on Mortality Among Hospitalized COVID-19 Patients: A Multicenter Study.

BACKGROUND: The effectiveness of interleukin-6 inhibitors (IL-6i) in ameliorating coronavirus disease 2019 (COVID-19) remains uncertain. METHODS: We analyzed data for patients aged ≥18 years admitted with a positive severe acute respiratory syndrome coronavirus 2 polymerase chain reaction test at 4 safety-net hospital systems with diverse populations and high rates of medical comorbidities in 3 US regions. We used inverse probability of treatment weighting via machine learning for confounding adjustment by demographics, comorbidities, and disease severity markers. We estimated the average treatment effect, the odds of IL-6i effect on in-hospital mortality from COVID-19, using a logistic marginal structural model. RESULTS: Of 516 patients, 104 (20.1%) received IL-6i. Estimate of the average treatment effect adjusted for confounders suggested a 37% reduction in odds of in-hospital mortality in those who received IL-6i compared with those who did not, although the confidence interval included the null value of 1 (odds ratio = 0.63; 95% confidence interval, .29-1.38). A sensitivity analysis suggested that potential unmeasured confounding would require a minimum odds ratio of 2.55 to nullify our estimated IL-6i effect size. CONCLUSIONS: Despite low precision, our findings suggested a relatively large effect size of IL-6i in reducing the odds of COVID-19-related in-hospital mortality.

Identification of Factors Impacting Recurrent Clostridium difficile Infection and Development of a Risk Evaluation Tool.

PURPOSE: Recurrent Clostridium difficile infection (RCDI) is a growing concern, yet limited data exists to clarify which patients are at highest risk.  Identification of these patients may better inform decisions of those who may benefit from prophylactic intervention. The purpose of this study was to determine which factors are associated with the recurrence of Clostridium difficile infection (CDI) and to develop a risk stratification tool.  Methods. Patients readmitted within 10 weeks of positive C. difficile polymerase chain reaction (PCR) with symptoms were included in this retrospective case control study.  The primary outcome was analyzed via univariate regression analyses of the independent factors including age, gender, number of CDI episodes, administration of acid blocking agents, antibiotics or chemotherapy, Charlson Comorbidity Index, gastrointestinal conditions, and exposure to healthcare facilities.  Results. Recurrent CDI was identified in 44 of 220 included patients.  In the univariate analysis, factors associated with development of RCDI included antibiotic exposure (OR 2.51, 95% CI 1.14-5.54; p 0.02) and inflammatory bowel disease (OR 5.77, 95% CI 1.24-26.79; p 0.03).  An evaluation tool was created from a well-fit model.  Additional factors included in the tool were chosen based on evaluation of findings from existing literature.  Conclusions. Antibiotic therapy and inflammatory bowel disease were found to be associated with RCDI.  Although a statistically significant association with RCDI was not found for other factors, this is likely related to small sample size.  The creation of an evaluation tool using specific patient factors can help determine the risk of RCDI, while future studies may validate this tool. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.