Epidemiology and outcome of infections with carbapenem-resistant Gram-negative bacteria treated with polymyxin B-based combination therapy

Abstract

Infections with carbapenem-resistant Gram-negative bacteria (CRGNB) are increasing and are associated with a high mortality. Synergistic effects of combination therapy with a polymyxin, carbapenem, and rifampin have been observed in in vitro studies. Clinical data are limited to retrospective studies. We performed an observational cohort study of patients over 18 y of age who were treated with polymyxin B combination therapy. One hundred and four patients were studied. The mean age was 77 y; 73% had recently received antibiotics, 67% had recently been hospitalized, and 47% lived in a nursing facility. The most common infections were pneumonia and urinary tract infection due to Acinetobacter baumannii (33%), Klebsiella pneumoniae (24%), and Pseudomonas aeruginosa (11%). Treatment regimens included polymyxin B with a carbapenem in 48%, with additional rifampin in 23%. Clinical success was achieved in 50% and reinfection occurred in 25%. Treatment-related acute renal failure occurred in 14.4%. No treatment-related hemodialysis was needed. All-cause hospital mortality was 47% and mortality after 6 months was 77%. No significant difference was found between treatment regimens. Age (odds ratio (OR) 10.4 per 10 y, p = 0.04), severity of acute illness (OR 2.2 per point, p < 0.001), and Charlson score (OR 1.12 per point, p = 0.04) were associated with hospital mortality. K. pneumoniae was associated with increased hospital survival compared to other CRGNB (p = 0.03). CRGNB infections are associated with previous antibiotic and health care exposure. Mortality is related to age and the severity of chronic and acute illness.