Efficacy and safety of high-dose ampicillin/sulbactam vs. colistin as monotherapy for the treatment of multidrug resistant Acinetobacter baumannii ventilator-associated pneumonia
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
References (25)
- et al.
Colistin as a salvage therapy for nosocomial infections caused by multidrug-resistant bacteria in the ICU
Int J Antimicrob Agents
(2006) - et al.
Evaluation of colistin as an agent against multi-resistant Gram-negative bacteria
Int J Antimicrob Agents
(2005) Multiresistant Acinetobacter infections: a role for sulbactam combinations in overcoming an emerging worldwide problem
Clin Microbiol Infect
(2002)- et al.
Nephrotoxicity of intravenous colistin: a prospective evaluation
Int J Antimicrob Agents
(2005) Ventilator-associated pneumonia
Curr Opin Pulm Med
(2005)- et al.
Risk factors for Acinetobacter baumannii nosocomial bacteremia in critically ill patients: a cohort study
Clin Infect Dis
(2001) - et al.
Multidrug-resistant Acinetobacter infections: an emerging challenge to clinicians
Ann Pharmacother
(2004) - et al.
Colistin: the revival of polymyxins for the management of multidrug-resistant gram-negative bacterial infections
Clin Infect Dis
(2005) - et al.
Efficacy of sulbactam alone and in combination with ampicillin in nosocomial infections caused by multiresistant Acinetobacter baumannii
J Antimicrob Chemother
(1998) Treatment options for multidrug-resistant bacteria
Expert Rev Anti Infect Ther
(2006)
High-dose ampicillin–sulbactam as an alternative treatment of late onset VAP from multidrug-resistant Acinetobacter baumannii
Scand J Infect Dis
Conference summary: ventilator-associated pneumonia
Respir Care
Cited by (187)
Prospective role of cefiderocol in the management of carbapenem-resistant Acinetobacter baumannii infections: Review of the evidence
2023, International Journal of Antimicrobial AgentsGuidelines for the diagnosis, treatment, prevention and control of infections caused by carbapenem-resistant gram-negative bacilli
2023, Journal of Microbiology, Immunology and InfectionSystematic review on estimated rates of nephrotoxicity and neurotoxicity in patients treated with polymyxins
2021, Clinical Microbiology and InfectionCurrent treatment options for pneumonia caused by carbapenem-resistant Acinetobacter baumannii
2024, Current Opinion in Infectious Diseases