EFFICACY AND SAFETY OF NEW ANTIBIOTICS AGAINST MULTI-DRUG-RESISTANT BACTERIA

Abstract

Multidrug-resistant (MDR) bacterial infections are a major therapeutic problem because resistance to commonly used antimicrobial agents can significantly limit available options. This study compared the effectiveness and safety of newer antibiotics against MDR bacterial infections, with 96 treatment–comparator comparisons conducted for eight new antibiotics. The primary efficacy endpoints were clinical cure and microbiological eradication. We also evaluated 28-day mortality, overall adverse events, serious adverse events, nephrotoxicity, onset of Clostridioides difficile infection (CDI), and emergence of resistance as safety and clinical endpoints. Paired-samples t-tests or Wilcoxon signed-rank tests were used to evaluate the study-level treatment and comparator event rates depending on the distribution of paired differences, and differences among antibiotics were assessed using one-way or Welch analysis of variance. The mean difference in mean clinical cure was 23.04 percentage points (95% CI 21.59–24.49; P < 0.001) in favour of the newer antibiotics. Microbiological eradication was also significantly better (74.07% vs. 53.27%; difference = 20.80 percentage points; P < 0.001). There were no significant differences in the incidence of C. difficile infection between antibiotic groups, and newer antibiotics were associated with lower incidence of adverse events, serious adverse events, nephrotoxicity, and emergence of resistance. However, 28-day mortality was modestly higher with newer antibiotics (25.05% vs. 22.26%; P < 0.001). Efficacy and safety varied widely among individual antibiotics. Overall, newer antibiotics showed significant benefits in clinical and microbiological outcomes for MDR bacteria, but antibiotic choice should consider efficacy, toxicity, resistance characteristics, and survival outcomes