Factors affecting the effectiveness and safety of polymyxin B in the treatment of Gram-negative bacterial infections: A meta-analysis of 96 articles.

ABSTRACT

PURPOSE: Polymyxin B, with its unique structure and mechanism of action, has emerged as a key therapeutic agent against Gram-negative bacteria. The study aims to explore potential factors to influence its effectiveness and safety. METHODS: A model-based meta-analysis of 96 articles was conducted, focusing on factors like dosage, bacterial species, and combined antibiotic therapy. The analysis evaluated mortality rates and incidence rate of renal dysfunction, also employing parametric survival models to assess 30-d survival rates. RESULTS: In the study involving 96 articles and 9716 patients, polymyxin B's daily dose showed minimal effect on overall mortality, with high-dose group mortality at 33.57% (95% confidence intervals [CI] 29.15-38.00) compared to the low-dose group at 35.44% (95% CI 28.99-41.88), P = 0.64. Mortality significantly varied by bacterial species, with Pseudomonas aeruginosa infections at 58.50% (95% CI 55.42-63.58). Monotherapy exhibited the highest mortality at 40.25% (95% CI 34.75-45.76), P < 0.01. Renal dysfunction was more common in high-dose patients at 29.75% (95% CI 28.52-30.98), with no significant difference across antibiotic regimens, P = 0.54. The 30-d overall survival rate for monotherapy therapy was 63.6% (95% CI 59.3-67.5) and 70.2% (95% CI 64.4-76.2) for association therapy with ß-lactam drugs. CONCLUSIONS: The dosage of polymyxin B does not significantly change death rates, but its effectiveness varies based on the bacterial infection. Certain bacteria like P. aeruginosa are associated with higher mortality. Combining polymyxin B with other antibiotics, especially ß-lactam drugs, improves survival rates. Side effects depend on the dose, with lower doses being safer. These findings emphasize the importance of customizing treatment to balance effectiveness and safety.