In Vitro Synergistic Antimicrobial Effect of Imipenem and Colistin Against an Isolate of Multidrug-resistant Enterobacter cloacae

Background/Purpose: Enterobacter cloacae is an important nosocomial pathogen responsible for various infections. Little is known about the synergistic effects of imipenem and colistin against multidrug-resistant E. cloacae. Therefore, we investigated the in vitro effects of imipenem and colistin against a clinical isolate of multidrug-resistant E. cloacae. Methods: A strain of E. cloacae, designed Ent 831, was isolated from the sputum of a woman who developed severe pneumonia in a medical intensive care unit. Minimal inhibitory concentrations (MICs) of imipenem and colistin were determined by the agar dilution method. The synergistic effects were investigated using the time-kill method. Results: MICs of imipenem and colistin for E. cloacae strain Ent 831 were 0.5 μg/mL and 1.0 μg/mL, respectively. Using a standard ino culum (5 × 10⁵) CFU/mL), synergism was shown with a concentration of two times the MICs of imipenem and colistin. Furthermore, four times the MIC of imipenem completely inhibited bacterial growth for more than 48 hours, but four times the MICs of colistin resulted in re-growth after 4 hours. There was no synergism between imipenem and colistin at two times the MICs against a high concentration inoculum (6.24 × 10⁶) CFU/mL). Nevertheless, imipenem, with or without colistin, at a concentration of four times MICs could inhibit the growth of bacteria for more than 48 hours. Conclusion: High-dose imipenem, alone or in combination with colistin, is effective against multidrug-resistant E. cloacae. Colistin alone, even at a high dose, is not effective. However, in vitro susceptibility to antimicrobial compounds does not always correlate with clinical success. Thus further testing of these antibiotic combinations in animal models is needed in order to predict their suitability for clinical use.