Polymyxin B and Doxycycline Use in Patients with Multidrug-Resistant Acinetobacter baumannii Infections in the Intensive Care Unit

Abstract

Background: Multidrug-resistant Acinetobacter baumannii (MDR-Ab) has emerged as an increasingly problematic cause of hospital-acquired infections in the intensive care unit (ICU). MDR-Ab is resistant to most standard antimicrobials but often retains susceptibility to polymyxin B and doxycycline. Objective: To evaluate the efficacy and toxicity of polymyxin B and doxycycline in the treatment of MDR-Ab infections. Methods: A retrospective chart review was conducted between March 2002 and May 2005 in patients who received doxycycline or polymyxin B for treatment of MDR-Ab infections in ICUs within Grady Memorial Hospital, Atlanta, GA. Results: Thirty-seven patients with MDR-Ab infections were treated with polymyxin B or doxycycline. Median age was 41 years and median ICU length of stay was 18 days prior to acquisition of MDR-Ab. Clinical cure was observed in 22 of 29 (76%) evaluable patients treated with polymyxin B and 2 of 4 (50%) patients treated with doxycycline. In patients with follow-up cultures, microbiological cure was observed in 17 of 21 (81%) patients treated with polymyxin B and 2 of 3 (67%) patients treated with doxycycline. Nephrotoxicity developed in 21% (7 of 33) of patients who received polymyxin B. Neurotoxicity was observed in 2 (6%) patients who received polymyxin B. No adverse reactions were observed with doxycycline. Overall, crude mortality was 27% (9 of 33) and 75% (3 of 4) among those who received polymyxin B and doxycycline, respectively. Three (9%) deaths were attributed to polymyxin B treatment failure, and no deaths were attributed to doxycycline treatment failure. Conclusions: Polymyxin B was effectively used to treat a substantial proportion of critically ill patients with MDR-Ab infection and was associated with a similar rate of nephrotoxicity as previously reported. Doxycycline monotherapy was used in a limited number of patients for the treatment of MDR-Ab; further evaluation of its efficacy in larger numbers of patients is warranted.

In Vitro Assessment and Multicenter Cohort Study of Comparative Nephrotoxicity Rates Associated with Colistimethate versus Polymyxin B Therapy

“…Until recently, only a limited number of studies evaluated nephrotoxicity in patients who received polymyxin B. Among these reports, similar discrepancies in nephrotoxicity rates exist, ranging from 4.0% to 60.0% (21)(22)(23).…”

Acinetobacter baumannii : Emergence of a Successful Pathogen

“…Overall, the efficacy of the drug has been highly encouraging in both adult and pediatric populations, with favorable or curative responses ranging from 57% to Ͼ80% (158,185,207,241,283,301,327,357,369,409,451,517). In several recent prospective cohort studies across a range of infection types, the outcomes for patients receiving definitive therapy with colistin for colistin-only-susceptible organisms were similar to those for patients receiving combinations of other antibiotics (predominantly carbapenems with or without other antibiotics) for more susceptible organisms (185,451).…”

Intravenous polymyxins: Revival with puzzle

“…So CMS dosing should be adjusted in renal impaired patients according to estimated glomerular filtration rate or creatinine clearance (31,39), and polymyxin B used to be so (43). However, recent data suggest that polymyxin B does not require adjustment for renal dysfunction (78,85,86).…”