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

INTRODUCTION: 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. METHODS: We performed an observational cohort study of patients over 18 y of age who were treated with polymyxin B combination therapy. RESULTS: 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). CONCLUSION: CRGNB infections are associated with previous antibiotic and health care exposure. Mortality is related to age and the severity of chronic and acute illness.

Systemic absorption of oral vancomycin in patients with Clostridium difficile infection.

Oral vancomycin is utilized in the treatment of severe Clostridium difficile infection (CDI). We prospectively measured serum vancomycin concentrations (SVC) in patients treated with oral vancomycin. The SVC was measured by immunoassay prior to, and at least 3 days after, the administration of oral vancomycin 125 mg every 6 h. Patients treated with intravenous vancomycin were excluded. Fifty-seven patients with a mean age of 74 y (± 18) were enrolled. There was no detectable SVC in 56 patients (98%); 1 patient had a transient SVC of 6.7 µg/ml that was not detectable on subsequent testing. The severity of the CDI and/or renal failure did not have an effect on SVC. Orally administered vancomycin at 125 mg 4 times daily was not absorbed from the gastrointestinal tract.