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In vitro interaction of imipenem, sulbactam, colistin and rifampin on 18 imipenem-resistant Acinetobacter baumannii isolates

Abstract number: 1734_60

Antonopoulou H., Kavatha D., Galani I., Chryssouli Z., Lelekis M., Giamarellou H.

Objective: Imipenem-resistant strains of Acinetobacter baumannii (Ab) are increasingly recognized worldwide, leaving colistin and, sometimes, sulbactam, as the only alternative treatment. However, the use of colistin, is limited, due to its adverse effects and poor pharmacokinetics so that other therapeutic options are needed. The aim of this study was to investigate, the in vitro activity of the interaction between imipenem (IMP), colistin (CL), sulbactam (SUL) and rifampin (RIF), on IMP-resistant isolates of Ab.

Methods: Eighteen clinical multidrug-resistant isolates from 12 hospitals of Athens were selected. MICs were determined by broth microdilution and E-tests, according to CLSI guidelines. All isolates were sensitive only to colistin. Genetic analysis was performed by pulse-field gel electrophoresis (PFGE). Time-kill assays were performed for each antibiotic and for the following combinations: CL+SUL, CL+RIF, IMP+SUL, CL+SUL+RIF and CL+SUL+RIF. The concentrations of antibiotics were selected according to their mean serum levels in clinical practice; IMP: 0.02 mg/L, SUL: 0. 03 mg/L, RIF: 0. 0075 mg/L and for CL: 1×MIC. Bacterial growth was determined at 0, 1, 3, 5 and 24 hours of incubation in shaking water bath at 37°C. Synergy between tested antibiotics was defined as any more than 2 log10 decrease of viable cells, compared to log10 decrease achieved by the most active single agent.

Results: Seven strains belonged to one major clone. Other seven strains were possibly related to it. Two other different clones were detected with three and one representatives respectively. Synergy between tested antibiotics, in any time of growth, is shown in table 1. In all, except one isolate, no regrowth was detected after synergy was appeared.

Table 1. Synergy between the tested antibiotics at 1, 3, 5 and 24 h of incubation on the total of 18 isolates

CombinationIncubation timeIndifferent result
1 h3 h5 h24 h 
CL+IMP9 (50%)2 (11.1%)6 (33.3%)1
CL+SUL4 (22.2%)7 (38.8%)5 (27.7%)2
CL+RIF10 (55.5%)6 (33.3%)2 (11.1%)
IMP+SUL1 (5.5%)15 (83.3%)2
CL+SUL+RIF9 (50%)4 (22.2%)4 (22.2%)1 (5.5%)
CL+SUL+IMP8 (44.4%)6 (33.3%)3 (16.6%)1

Conclusions: All tested combinations showed synergistic effect although combinations with RIF seamed to express a faster synergistic effect than those without RIF. All combinations were bactericidal. The triple combinations tested, were not more effective than the double ones. Further, other studies are required to determine the interaction of the tested antibiotics in vivo.

Session Details

Date: 31/03/2007
Time: 00:00-00:00
Session name: European Society of Clinical Microbiology and Infectious Diseases
Subject:
Location: ICC, Munich, Germany
Presentation type:
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