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Synergy Testing between Sulbactam and Meropenem/ Colistin in MDR Acinetobacter baumannii-calcoaceticus Complex Isolated from Ventilator Associated Pneumonia

Shalini Anandan, Lydia Jennifer, Shalini Anandan, Agila Kumari Pragasam, Baby Abirami Shankar, Balaji Veeraraghavan, John Victor Peter and Shoma V Rao

Background: A. baumannii-calcoaceticus (Abc) complex has surfaced as a major nosocomial pathogen causing blood stream infection and ventilators associated pneumonia (VAP). Carbapenems have come to be the cornerstone of treatment for Abc complex. However, there has been an increased incidence of infections with carbapenem resistant strains. To validate the clinical practice of combination antibiotic therapy, in-vitro combinations of antibiotics have been examined using checkerboard methods, E-tests, and the reference, time-kill assay.

Method: A prospective pilot study was conducted for the duration of one year. Twenty five isolates of carbapenem resistant Abc complex cultured from endotracheal aspirates of patients admitted in medical and surgical intensive care units diagnosed with ventilator associated pneumonia were collected. Isolates were tested for MIC (Minimum inhibitory concentration) by micro-broth dilution method for meropenem, sulbactam and colistin. Synergism between sulbactam plus meropenem and sulbactam plus colistin was tested by micro-broth checkerboard assay and the reference, time kill assay.

Result: Minimum inhibitory concentration ranges (μg/ml) for sulbactam, meropenem, and colistin were 16-512, 16-256, and 0.5-64, respectively. MIC50 for sulbactam, meropenem, and colistin was 128, 128 and 1, correspondingly, and MIC90 for sulbactam, meropenem, and colistin was 256, 256 and 2, respectively. In the checkerboard assay and time-kill assay, a higher percentage of synergy was noted for the combination of sulbactam plus meropenem.

Conclusion: Against multi-drug resistant (MDR) isolates of Abc complex, commendable synergy was seen with time kill assay for sulbactam plus meropenem combination. Therefore, in-vitro combinations of antimicrobial agents are most effective than the single agent against multidrug resistant organism.