Introduction: Coccidioidal meningitis (CM) is the most lethal form of disseminated coccidioidomycosis. Current guidelines recommend fluconazole as initial therapy but there has been a paucity of data regarding failure of fluconazole and optimal fluconazole dosage in the treatment of CM. We conducted this study to understand risk factors for fluconazole failure. Methods: We conducted a single-center retrospective chart review of patients diagnosed with coccidioidal meningitis between 1 January 1988 and 15 May 2021. Relevant demographic and clinical variables were collected, along with outcomes including treatment failure and death at any point. Univariate tests were conducted using the chi-squared goodness of fit test and analysis of variance. Results: Among 71 patients who began treatment for CM with fluconazole, 22 (31%) developed worsening meningitis at a median time of 206 days. Longer time from symptom onset to diagnosis of CM was a risk factor for fluconazole failure. Although the absolute failure rate of fluconazole starting dose of 400 mg daily was higher than that of 800 mg daily, the differences did not achieve statistical significance (p = 0.39). Conclusion: Fluconazole failure is not uncommon in the treatment of CM. A dose of 800 mg daily was not superior to a dose of 400 mg daily. All patients on fluconazole for CM require close monitoring.

Randomized trials of procalcitonin-guided algorithms to discontinue antibiotics in critically ill patients with sepsis report reduced antibiotic duration and possible mortality benefit. However, open-label trial designs, inconsistent algorithm adherence, and unclear stewardship practices have limited confidence in procalcitonin's benefit. The ADAPT-Sepsis trial addressed several of these gaps through a concealed intervention, robust stewardship, and head-to-head comparison with C-reactive protein (CRP). Procalcitonin-guided care reduced antibiotic use without significantly impacting mortality, although CRP-guided care showed no benefit. However, algorithm adherence was suboptimal, and the absolute reduction in antibiotic duration with procalcitonin was only 1 day. As shorter fixed-duration therapy becomes standard, procalcitonin's utility in the intensive care unit may decline. Embedding procalcitonin and other biomarkers into multifaceted stewardship strategies, and addressing barriers to clinician trust and implementation, is essential. Future research should also evaluate whether biomarker use earlier in the sepsis care pathway, particularly in Emergency Departments, can improve diagnostic accuracy and enhance patient outcomes.

Introduction. The impact of renal allograft rejection treatment on infection development has not been formally defined in the literature. Methods. We conducted a retrospective cohort study of 185 rejection (case) and 185 nonrejection (control) kidney transplant patients treated at our institution from 2014 to 2020 to understand the impact of rejection on infection development. Propensity scoring was used to match cohorts. We collected data for infections within 6 months of rejection for the cases and 18 months posttransplant for controls. Results. In 370 patients, we identified 466 infections, 297 in the controls, and 169 in the cases. Urinary tract infections (38.9%) and cytomegalovirus viremia (13.7%) were most common. Cumulative incidence of infection between the case and controls was 2.17 (CI 1.54–3.05); . There was no difference in overall survival (HR 0.90, CI 0.49–1.66) or graft survival (HR 1.27, CI 0.74–2.20) between the groups. There was a significant difference in overall survival (HR 2.28, CI 1.14–4.55; ) and graft survival (HR 1.98, CI 1.10–3.56; ) when patients with infection were compared to those without. Conclusions. As previously understood, rejection treatment is a risk factor for subsequent infection development. Our data have defined this relationship more clearly. This study is unique, however, in that we found that infections, but not rejection, negatively impacted both overall patient survival and allograft survival, likely due to our institution’s robust post-rejection protocols. Clinicians should monitor patients closely for infections in the post-rejection period and have a low threshold to treat these infections while also restarting appropriate prophylaxis.

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been shown to reduce organ dysfunction in renal and cardiovascular disease. There are limited data on the role of SGLT2i in acute organ dysfunction. We conducted a study to assess the effect of SGLT2i taken prior to intensive care unit (ICU) admission in diabetic patients admitted with septic shock.Methods: This retrospective cohort study used electronic medical records and included diabetic patients admitted to the ICU with septic shock. We compared diabetic patients on SGLT2i to those who were not on SGLT2i prior to admission. The primary outcome was in-hospital mortality, and secondary outcomes included hospital and ICU length of stay, use of renal replacement therapy, and 28- and 90-day mortality. Results: A total of 98 diabetic patients was included in the study, 36 in the SGLT2i group and 62 in the non-SGLT2i group. The Sequential Organ Failure Assessment and Acute Physiology and Chronic Health Evaluation III scores were similar in the groups. Inpatient mortality was significantly lower in the SGLT2i group (5.6% vs. 27.4%, P=0.008). There was no significant difference in secondary outcomes.Conclusion: Our study found that diabetic patients on SGLT2i prior to hospitalization who were admitted to the ICU with septic shock had lower inpatient mortality compared to patients not on SGLT2i.