Sepsis & Septic Shock

Inhaled Amikacin for the Prevention of VAP

In a multicenter, double-blind, randomized controlled trial involving critically ill adults undergoing mechanical ventilation for over 72 hours, patients were administered either inhaled amikacin (20 mg/kg ideal body weight daily) or a placebo for three days. The study aimed to determine the efficacy of preventive inhaled antibiotics in reducing ventilator-associated pneumonia.

Out of the 847 patients analyzed, 15% in the amikacin group and 22% in the placebo group developed ventilator-associated pneumonia within 28 days. The amikacin group showed a significant reduction in the incidence of pneumonia with a difference in restricted mean survival time of 1.5 days (P=0.004). Furthermore, the amikacin group had fewer infection-related ventilator complications compared to the placebo group. The research concludes that a 3-day course of inhaled amikacin can decrease the occurrence of ventilator-associated pneumonia in patients ventilated for at least three days.

A two-day course of antibiotics for complicated appendicitis Appendicitis

This open-label, non-inferiority trial conducted across 15 Dutch hospitals assessed the efficacy and safety of reducing postoperative intravenous antibiotic duration from 5 days to 2 days in patients aged ≥8 years with complex appendicitis, amidst rising concerns regarding antimicrobial resistance. The primary endpoint was a composite of infectious complications and mortality within a 90-day post-appendicectomy period. The trial showed no significant difference in the primary endpoint between the two groups, suggesting that a shorter antibiotic course is non-inferior to a longer one, with additional benefits of lowered adverse effects, and potentially reduced hospital stay and costs.

Activities of the newer antibiotics against gram-negative resistant organisms.

Ceftobiprole for Treatment of Complicated Staphylococcus aureus Bacteremia

In a phase 3, double-blind, noninferiority trial, ceftobiprole's effectiveness was compared with daptomycin for treating complicated Staphylococcus aureus bacteremia, including the methicillin-resistant strains. The study population comprised 390 patients, 387 of whom had confirmed S. aureus bacteremia. The primary outcome was to determine overall treatment success 70 days post-randomization. Both drugs demonstrated comparable effectiveness, with ceftobiprole proving to be noninferior to daptomycin. Notably, the occurrence of adverse events was similar between the two treatment groups, although gastrointestinal issues, primarily mild nausea, appeared more frequent in the ceftobiprole group.

Conclusions:

Ceftobiprole demonstrates noninferiority when compared to daptomycin in the treatment of patients with complicated S. aureus bacteremia. The overall safety profiles of both drugs were comparable, though a higher incidence of gastrointestinal issues, especially mild nausea, was noted with ceftobiprole.

A Large-Scale Multicenter Retrospective Study on Nephrotoxicity Associated With Empiric Broad-Spectrum Antibiotics in Critically Ill Patients

In this retrospective cohort study, researchers investigated the association between commonly prescribed empiric antibiotics on ICU admission and the risk of acute kidney injury (AKI). The study included 35,654 patients who received either vancomycin and piperacillin-tazobactam, vancomycin and cefepime, or vancomycin and meropenem exclusively. AKI was defined based on the Kidney Disease: Improving Global Outcomes stage 2 or 3 criteria using serum creatinine levels.

The results indicated that vancomycin and piperacillin-tazobactam were associated with a higher risk of AKI and initiation of dialysis compared to both vancomycin and cefepime and vancomycin and meropenem. The odds of AKI were particularly significant in patients without renal insufficiency who received a longer duration of vancomycin and piperacillin-tazobactam therapy compared to vancomycin and meropenem therapy.