SAN DIEGO, CA – Carbapenem-resistant gram-negative bacterial (CRGNB) infections are strongly associated with previous antibiotic use and health care exposure, stated Robbert Crusio, from Maimonides Medical Center, Brooklyn, NY, at IDWeek 2012. Synergistic effects of combination therapy consisting of a polymyxin with a carbapenem and a rifampin were observed in in vitro studies.

Dr. Robbert Crusio of Maimonides Medical Center, Brooklyn, NY, and colleagues conducted a prospective observational cohort study of CRGNB infections between November 2009 and November 2010 at a 700-bed community teaching hospital to identify study risk factors, outcomes, and toxicity of combination therapy consisting of polymyxin B and a carbapenems, with or without rifampin.

A total of 104 patients were assigned to polymyxin B 2.5mg/kg/day + carbapenem (n=62), polymyxin B + tigecycline (n=4), polymyxin B + ampicillin/sulbactam (n=8), polymyxin B + carbapenem and rifampin (n=24), polymyxin B + tigecycline and rifampin (n=4), and other (n=2). Patients were followed until 6 months after discharge or expiration. Susceptibility was determined by automated broth microdilution method and Kirby-Bauer. Study outcomes included length of stay, clinical and microbiological success, renal insufficiency, and mortality.

Clinical and microbiological success were achieved in approximately 50% of patients.

Nephrotoxicity was observed in 8.7% of patients, with complete recovery after completion of treatment in 33%. No patients needed treatment-related renal replacement therapy.  Multivariate logistic regression analysis showed that age was significantly associated with clinical success (every 10 years odds ratio [OR] -2.38; P<0.045), all-cause mortality (every 10 years OR 2.9 P<0.018), and all-cause mortality at 6 months (every 10 years OR 3.08 P<0.025). The weighted score for acute illness (defined as one point for each factor present: shock, respiratory failure, acute renal failure, myocardial infarction and encephalopathy) was significantly associated with clinical success (OR -1.78 for each additional point, p≤0.015) and all-cause mortality (OR 2.2 for each additional point p≤0.003).

“No predictors of hospital length of stay were found,” concluded the study investigators.   In addition, no difference in outcomes was observed between the different treatment regimens. Dr. Crusio noted, “Further studies concentrating on the pharmacokinetics, pharmacodynamics, susceptibility breakpoints, and evaluation of different antibiotic combination regimens are needed.