Meningitis due to Cryptococcus neoformans may be associated with elevated intracranial pressure (ICP), but management of this complication is often overlooked. We retrospectively analyzed 39 consecutive patients with cases of culture-proven, community-acquired meningitis and ascertained adherence to Infectious Diseases Society of America (IDSA) practice guidelines for management of cryptococcal meningitis. Of these 39 patients, 26 (67%) had infection due to C. neoformans. Cerebrospinal fluid opening pressure had been measured for 13 (50%) of these 26 patients, and major deviations from the guidelines with respect to ICP management were observed in the care of 14 (54%). Seven (50%) of these 14 patients developed neuropathies during therapy, compared with 1 of the 5 patients whose care had minor or no deviations from the guidelines (P=.024). Major departures from the IDSA guidelines for management of ICP due to C. neoformans meningitis are common and can be associated with neurological injury during therapy.

Background The impact of remdesivir (RDV) on COVID-19 mortality is controversial, and the mortality effect in sub-groups of baseline disease severity has been incompletely explored. The purpose of this study was to assess the association of RDV with mortality in patients with COVID-19. Methods In this retrospective cohort study we compared persons receiving RDV to persons receiving best supportive care (BSC). Patients hospitalized between 2/28/20 – 5/28/20 with laboratory confirmed SARS-CoV-2 infection were included when they developed COVID-19 pneumonia on chest radiography, and hypoxia requiring supplemental oxygen or SpO2 ≤ 94% on room air. The primary outcome was overall survival assessed with time-dependent Cox proportional-hazards regression and multivariable adjustment, including calendar time, baseline patient characteristics, corticosteroid use and effects for hospital. Results 1,138 patients were enrolled including 286 who received RDV, and 852 treated with BSC, 400 of whom received hydroxychloroquine. Corticosteroids were used in 20.4% of the cohort (12.6% in RDV and 23% in BSC). In persons receiving RDV compared to those receiving BSC the HR (95%CI) for death was 0.46 (0.31 – 0.69) in the univariate model, p<0.001 and 0.60 (0.40 – 0.90) in the risk-adjusted model, p=0.014. In the sub-group of persons with baseline use of low-flow oxygen, the HR (95%CI) for death in RDV compared to BSC was 0.63 (0.39 – 1.00), p=0.049. Conclusion Treatment with RDV was associated with lower mortality compared to BSC. These findings remain the same in the subgroup with baseline use of low-flow oxygen.

Background Antimicrobial susceptibility testing is often needed prior to antimicrobial optimization for patients with Gram-negative bloodstream infections (GN-BSI). Rapid AST (rAST) in combination with antimicrobial stewardship (AS) may decrease time to administration of narrower antibiotics. Methods This was a prospective, non-blinded, randomized trial evaluating the impact of a phenotypic rAST method versus conventional AST (cAST) in hospitalized patients with GN-BSI and source control. The primary outcome was time to narrowest effective therapy. Results 274 patients were randomized and 205 underwent analysis (97 cAST, 108 rAST). Time to susceptibility results was 23  hours shorter in rAST group (cAST: 62 [59, 67] vs rAST: 39 [35, 46] hours; P < .001). The median (IQR) time to narrowest effective therapy was similar between groups (cAST: 73 [44, 138] vs rAST: 64 [42, 92] hours; P = .10). Time to narrowest effective therapy was significantly shorter in a pre-specified subgroup of patients not initially on narrowest therapy and during AS working hours (cAST: 93 [56, 154] vs rAST: 62 [43, 164] hours; P = 0.004). Significant decreases were observed in time (hours) to oral therapy (cAST: 126 [76, 209] vs rAST: 91 [66, 154]; P = 0.02) and median length (days) of hospital stay (LOS) (cAST: 7 [4, 13] vs rAST: 5 [4, 8] days; P = 0.04). Conclusion In patients with GN-BSI, rAST did not significantly decrease time to narrowest effective therapy but did decrease time to oral antibiotics and LOS. Rapid AST using existing microbiology platforms has potential to optimize patient outcomes.