Antagonism between penicillin and erythromycin against Streptococcus pneumoniae: does it exist?

Penicillin and erythromycin are commonly used for the treatment of serious infections caused by Streptococcus pneumoniae and combined as empiric therapy of community-acquired pneumonia. A concern about potential antagonism between these drugs prompted a protocol designed to test the hypothesis in timed kill curve experiments with several interpretive criteria applied. Four clinical isolates of S.pneumoniae from the United States referred to the SENTRY Antimicrobial Surveillance Program and one QC strain (ATCC 49619) were tested. Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) were determined for each isolate using reference dilution methods (NCCLS). Penicillin MBC results matched very closely to the MIC values. Penicillin and erythromycin were tested at clinically relevant concentrations of 10 and 1 microg/ml, respectively, alone and in combination. Interpretations were calculated comparing the penicillin + erythromycin killing effect versus penicillin or erythromycin rates tested alone. There was consistent bactericidal activity against S. pneumoniae by each drug alone and combined over the monitored five-hour period, except for an erythromycin induced-resistant isolate. Drug interactions ranged from synergy to antagonism, depending on the criteria applied. Antagonism risk of macrolide-penicillin combinations appeared to be minimal and method-dependent by in vitro tests.