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Background: Prophylaxis with fluoroquinolones (FQ) is commonly used in patients with acute leukemia (AL) during neutropenia. This practice is supported by an older meta-analysis reporting reduced mortality using FQ prophylaxis. Later meta-analyses have failed to reproduce this finding, presumably due to higher background FQ resistance rates limiting their effectiveness. Summary: This article reviews the pros and cons of FQ prophylaxis mainly in patients with AL. Most current guidelines do not support universal prophylaxis but rather recommend a selective approach, weighing the benefits against the risks. This recommendation is based on the lack of mortality benefit reported in more recent meta-analyses. FQ prophylaxis was demonstrated to reduce bacteremia and febrile neutropenia episodes, although mostly in trials performed in low-resistance settings (<20%), whereas current FQ resistance rates may reach 30–60%. Other disadvantages of FQ include potential adverse events, antibiotic resistance development, cost, increase in Gram-positive infections and resistant Gram-negative infections following prophylaxis, Clostridioides difficile infection, and an effect on gut microbiota. Key Messages: Taking the above into consideration, alternative approaches other than universal FQ prophylaxis should be considered. Centers with high FQ resistance rates may consider either withholding prophylaxis or providing selective prophylaxis for high-risk patients screened negative for FQ-resistant bacteria. [ABSTRACT FROM AUTHOR]

Background Central nervous system (CNS) infections caused by Klebsiella pneumoniae carbapenemase (KPC)–producing Enterobacterales and difficult-to-treat resistant (DTR) Pseudomonas aeruginosa represent a formidable clinical challenge. Antimicrobial regimens that efficiently penetrate the cerebrospinal fluid (CSF) and achieve sufficient concentrations associated with microbiologic and clinical cure are limited. We evaluated therapy with ceftazidime-avibactam (CAZ-AVI) in order to guide precise dosing in the treatment of CNS infections. Methods Therapeutic drug monitoring (TDM) was performed in 3 patients with health care–associated ventriculitis and meningitis (HAVM) using CAZ-AVI 2.5 g infused intravenously every 8 hours as standard and extended infusion. Simultaneous CSF and plasma samples were obtained throughout the dosing interval in each patient. Concentrations of CAZ and AVI were determined by liquid chromatography/mass spectrometry. Results Bacterial identification revealed KPC-producing Klebsiella pneumoniae (KPC- Kp), DTR Pseudomonas aeruginosa, and KPC-producing Enterobacter cloacae (KPC- Ent.c). All isolates were resistant to carbapenems. The minimum inhibitory concentrations (MICs) of CAZ-AVI were 0.25/4, 4/4, and 0.25/4 μg/mL, respectively. CAZ and AVI concentrations were determined in CSF samples ranging from 29.0 to 15.0 µg/mL (CAZ component) and 4.20 to 0.92 µg/mL (AVI component), respectively. AVI achieved concentrations ≥1 µg/mL in 11 out of 12 CSF samples collected throughout the dosing interval. Clinical and microbiologic cure were attained in all patients. Conclusions Postinfusion concentrations of CAZ-AVI were measured in plasma and CSF samples obtained from 3 patients with complicated CNS infections caused by antimicrobial-resistant isolates. The measured concentrations revealed that standard CAZ and AVI exposures sufficiently attained values correlating to 50% f T > MIC, which are associated with efficient bacterial killing. [ABSTRACT FROM AUTHOR]

Background The Combination Antibiotic Therapy for Methicillin-Resistant Staphylococcus aureus (CAMERA2) trial ceased recruitment in July 2018, noting that a higher proportion of patients in the intervention arm (combination therapy) developed acute kidney injury (AKI) compared to the standard therapy (monotherapy) arm. We analyzed the long-term outcomes of participants in CAMERA2 to understand the impact of combination antibiotic therapy and AKI. Methods Trial sites obtained additional follow-up data. The primary outcome was all-cause mortality, censored at death or the date of last known follow-up. Secondary outcomes included kidney failure or a reduction in kidney function (a 40% reduction in estimated glomerular filtration rate to <60 mL/minute/1.73 m2). To determine independent predictors of mortality in this cohort, adjusted hazard ratios were calculated using a Cox proportional hazards regression model. Results This post hoc analysis included extended follow-up data for 260 patients. Overall, 123 of 260 (47%) of participants died, with a median population survival estimate of 3.4 years (235 deaths per 1000 person-years). Fifty-five patients died within 90 days after CAMERA2 trial randomization; another 68 deaths occurred after day 90. Using univariable Cox proportional hazards regression, mortality was not associated with either the assigned treatment arm in CAMERA2 (hazard ratio [HR], 0.84 [95% confidence interval [CI],.59–1.19]; P =.33) or experiencing an AKI (HR at 1 year, 1.04 [95% CI,.64–1.68]; P =.88). Conclusions In this cohort of patients hospitalized with methicillin-resistant S aureus bacteremia, we found no association between either treatment arm of the CAMERA2 trial or AKI (using CAMERA2 trial definition) and longer-term mortality. [ABSTRACT FROM AUTHOR]

Background: Previous studies demonstrated a 'weekend effect' and a 'night effect' of increased mortality among patients admitted during weekends or night shifts, presumably due to understaffing. Aims: To examine whether death during hospitalisation follows a similar effect regardless of admission time. Methods: A retrospective cohort study among deceased patients hospitalised in the internal medicine wing of a tertiary medical centre in Israel, between 2019 and 2020. Demographic and medical data were retrieved from electronic medical charts. Causes of death were specifically categorised. We applied statistical models to test for differences in mortality using incidence rate ratio (IRR) according to the day, time and cause of death. Results: One thousand, two hundred and seventy‐eight deceased patients were included. All‐cause mortality was similar between weekends and weekdays. When sepsis was the cause of death, higher IRR were demonstrated on Fridays in comparison with weekdays (IRR 1.4; 95% confidence interval (CI) 1.1–1.9; P < 0.05). Other causes of death were not consistent with a 'weekend effect'. Mortality during night shifts was higher in comparison with the afternoon (IRR 1.5; 95% CI 1.3–4.7) and similar to the morning (IRR 1; 95% CI 0.9–1.2). Conclusion: Our study did not find a pattern of 'weekend effect' or 'night effect' on all‐cause mortality among hospitalised patients in internal medicine wards. Our findings suggest that perhaps specifically death from sepsis, and not all‐cause mortality, can be used as a surrogate for the measurement of understaffing or quality of care in the internal ward. [ABSTRACT FROM AUTHOR]