Effect of Clindamycin on Aminoglycoside Activity in a Murine Model of Invasive Escherichia coli Infection

Abstract

Previous studies have demonstrated that the early in vitro bactericidal activity of gentamicin and amikacin is inhibited by clindamycin. To investigate the possible clinical implications of these findings, the effect of clindamycin in combination with gentamicin or amikacin was compared with that of the aminoglycoside alone in the treatment of normal and neutropenic mice with Escherichia coli peritonitis and bacteremia. Mice treated with saline or clindamycin alone experienced rapid multiplication of bacteria in the peritoneal cavity, bacteremia, and subsequent death. Gentamicin or amikacin given 2 h after E. coli inoculation significantly reduced the mortality and peritoneal bacterial counts in normal and neutropenic mice in comparison with untreated controls. Prior or simultaneous administration of clindamycin with either aminoglycoside did not inhibit survival or bacterial clearance from the peritoneum. The only clindamycin effect was slight enhancement of survival of neutropenic mice treated with multiple doses of amikacin and clindamycin in comparison to those treated with amikacin alone.