Imipenem-Cilastatin or Ampicillin-Sulbactam
Study Objective: To evaluate epidemiology, resistance, and treatment outcomes of Acinetobacter baumannii bacteremia treated with imipenem-cilastatin or ampicillin-sulbactam for 72 hours or longer.
Design: Retrospective analysis.
Setting: University teaching hospital.
Patients: Forty-eight patients with A. baumannii bacteremia.
Intervention: Evaluation of susceptibility and clinical data from 48 patients treated with either ampicillin-sulbactam or imipenem-cilastatin from 1987-1999.
Measurements and Main Results: Comparing ampicillin-sulbactam and imipenem-cilastatin, there were no differences between days of bacteremia (4 vs 2 days, p=0.05), days to resolution of temperature or white blood cell count, success or failure during or at end of treatment, or intensive care unit total or antibiotic-related length of stay (13 vs 10 days, p=0.05). Patients treated with ampicillin-sulbactam had significantly decreased antibiotic treatment costs ($1500 vs $500, p=0.004).
Conclusion: Ampicillin-sulbactam is at least as effective as imipenem-cilastatin based on clinical response at days 2, 7, and end of treatment and is a cost-effective alternative for treatment of A. baumannii infections.

Acinetobacter baumannii is ubiquitous and is becoming a common nosocomial pathogen. The organism is prevalent in intensive care units and has been described frequently in burn patients. Disorders associated with Acinetobacter sp are respiratory tract infections, bacteremia, and secondary meningitis, with major portals of entry being the respiratory tract and vascular devices. Nosocomial pneumonia caused by A. baumannii is significant in ventilator-dependent patients, with mortality ranging from 30-75%.

The pathogen is often multidrug resistant, thus limiting therapeutic options. Antimicrobial susceptibilities of Acinetobacter sp have been studied extensively. Strains with varied susceptibilities range from sensitivity to ß-lactams and quinolones to resistance to nearly all antimicrobials tested. Generally, imipenem-cilastatin is the most active agent against this organism. With amikacin, imipenem-cilastatin often is considered the therapy of choice. Recently, ampicillin-sulbactam has been considered a potential treatment alternative. The sulbactam component has activity against Acinetobacter sp by acting directly on penicillin-binding proteins, resulting in a bactericidal effect. Although still rare, imipenem-cilastatin-resistant organisms have been isolated and frequently are treated with ampicillin-sulbactam.

In the early 1990s our institution experienced an increase in colonization and infection due to A. baumannii. The response was increased administration of imipenem-cilastatin. This was controlled by therapeutic restriction criteria, and the outbreak was contained with stringent infection-control policies. The experience led many practitioners to reevaluate A. baumannii infections, imipenem-cilastatin therapy, and effects of treatment on intensive care unit (ICU) flora. Although generally stable to ß-lactamase inactivation, imipenem-cilastatin is a strong ß-lactamase inducer, and its potential to induce resistance in other organisms is worrisome. This effect was particularly evident as our institution observed a correlation between the increase in imipenem-cilastatin and amikacin therapy for A. baumannii infections and 19% and 8% reductions, respectively, in Pseudomonas aeruginosa susceptibility to those agents. At present, practitioners are prescribing more ampicillin-sulbactam, even for patients with Acinetobacter sp sensitive to imipenem-cilastatin, in an effort to control resistance. However, due to limited clinical data regarding treatment outcomes with ampicillin-sulbactam, we evaluated clinical outcomes in adults with A. baumannii bacteremia who were treated with either combination. We also investigated the epidemiology, susceptibility patterns, and costs of Acinetobacter sp at our institution over the last 11 years.