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.

In vitro and in vivo studies of three antibiotic combinations against gram-negative bacteria and Staphylococcus aureus

“…Animal studies were performed by using a modification of a neutropenic mouse model previously reported from this laboratory (6). BALB/c mice (22 to 24 g) were made neutropenic with two intraperitoneal injections of 200 mg of cyclophosphamide per kg, separated by an interval of 54 to 56 h. This dosage schedule produced maximal granulocytopenia on day 4 after the first injection more consistently than did the single dose used in the earlier study.…”

In Vitro Elution and Antibacterial Activity of Clindamycin, Amikacin, and Vancomycin from R‐gel Polymer

“…Coverage is provided against most aerobic gram‐positive cocci and anaerobic bacteria including Staphylococcus, Bacteroides, Fusobacterium, Actinomyces , and Peptostreptococcus . Previous studies evaluating the combination of amikacin and clindamycin have conflicting results showing antagonism, no significant effect, or even synergism 22,23 . A study evaluating clindamycin and aminoglycosides against 50 strains of S. aureus found synergistic effects at 24 and 48 hours 24 …”

“…Previous studies evaluating the combination of amikacin and clindamycin have conflicting results showing antagonism, no significant effect, or even synergism. 22,23 A study evaluating clindamycin and aminoglycosides against 50 strains of S. aureus found synergistic effects at 24 and 48 hours. 24 An in vivo study in dogs comparing elution of antibiotics from AIPMMA found that pharmacologically, clindamycin was better at maintaining high concentrations in seroma fluid, granulation tissue and bone than cefazolin, ciprofloxacin, ticarcillin, tobramycin, or vancomycin.…”