Elsevier

Journal of Infection

Volume 56, Issue 6, June 2008, Pages 432-436
Journal of Infection

Efficacy and safety of high-dose ampicillin/sulbactam vs. colistin as monotherapy for the treatment of multidrug resistant Acinetobacter baumannii ventilator-associated pneumonia

https://doi.org/10.1016/j.jinf.2008.04.002Get rights and content

Summary

Objective

To compare the safety and efficacy of ampicillin/sulbactam (Amp/Sulb) and colistin (COL) in the treatment of multidrug resistant Acinetobacter baumannii ventilator-associated pneumonia (VAP).

Methods

A prospective cohort study in adult critically ill patients with VAP. Patients were randomly assigned to receive Amp/Sulb (9 g every 8 h) or COL (3 MIU every 8 h) intravenously. Dosage was adjusted according to creatinine clearance.

Results

A total of 28 patients were enrolled (15 COL, 13 Amp/Sulb). Resolution of symptoms and signs occurred in 60% (9/15) of the COL group and 61.5% (9/13) of the Amp/Sulb group, improvement in 13.3% (2/15) vs. 15.3% (1/13) and failure in 26.6% (4/15) vs. 23% (3/13), respectively. The difference was not statistically significant. Bacteriologic success was achieved in 66.6% (10/15) vs. 61.5% (8/13) in the COL and Amp/Sulb groups, respectively (p < 0.2). Mortality rates (14 days and 28 days) were 15.3% and 30% for the Amp/Sulb and 20% and 33% for the COL group, respectively. Adverse events were 39.6% (including 33% nephrotoxicity) for the COL group and 30.7% (15.3% nephrotoxicity) for the Amp/Sulb group (p = NS).

Conclusion

Colistin and high-dose ampicillin/sulbactam were comparably safe and effective treatments for critically ill patients with MDR A. baumannii VAP.

Introduction

Ventilator-associated pneumonia due to Acinetobacter baumannii carries significant morbidity and mortality in the intensive care unit (ICU) setting.1 It commonly occurs more than 5–7 days of mechanical ventilation (late-onset VAP) and is associated with antibiotic prescribing practices in the initial ICU stay.2A. baumannii, a nonfermenting gram-negative pathogen, is characterized by the rapid development of resistance to all the major antibiotic classes, including the antipseudomonal penicillins, monobactams, carbapenems, quinolones, and aminoglycosides.3 The emerging therapeutic gap has been partially counterbalanced by the revival of older drugs such as polymyxin E (colistin) and sulbactam, although ongoing studies for newer drugs like glycylcyclines yields promising results.4, 5, 6

Polymyxins are the only antibiotic drug class with relatively unharmed in vitro activity against infection from multidrug resistant (MDR) A. baumannii strains.7 Sulbactam is a β-lactamase inhibitor that has antimicrobial activity against A. baumannii strains.5 In a previous report, we showed that high-dose regimen of this compound (provided in the form of ampicillin/sulbactam, Amp/Sulb) may be an alternative treatment option for late-onset VAP from MDR A. baumannii strains.8 In this study we aimed to compare the clinical efficacy and safety of high-dose ampicillin/sulbactam vs. colistin as monotherapy for the treatment of Acinetobacter VAP.

Section snippets

Methods

This study was performed at a 7-bed and a 12-bed polyvalent intensive care units of the Hippokration General Hospital (Athens, Greece) and the Evgenidion University Hospital (Athens, Greece). The study was approved by the ethical committee and conducted in accordance to its guidelines. Informed consent was requested by the patients' next of kin. Patients were enrolled during a one-year period.

Results

During the study period 30 critically ill patients with MDR A. baumannii VAP were identified. Two patients were excluded from the study because combined antibiotic treatment was provided. Two patients received combination antibiotic therapy and were excluded. Data on the remaining 28 patients are presented in Table 1. The mean (±SD) duration of therapy was 9.2 ± 1.5 days and 9.9 ± 2.6 days for the 2 groups, respectively. The mean (±SD) duration of mechanical ventilation prior to VAP was 10 ± 4 in the

Discussion

The main finding of this study is that high-dose regimen of ampicillin/sulbactam therapy is at least as effective as conventional colistin monotherapy in the treatment for VAP due to MDR A. baumannii strains. Ampicillin/sulbactam in a dose of 9 g intravenously every 8 h was found to induce a clinical success rate equivalent to that of colistin. Additionally, no significant differences in the mortality rates and in the adverse effects were noted.

Data concerning the comparative effectiveness and

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