Synergistic effect of erythromycin on polymorphonuclear cell antibacterial activity against erythromycin-resistant phenotypes of Streptococcus pyogenes.

To evaluate the synergistic activity of erythromycin and human polymorphonuclear cells (PMNs) on the binomial erythromycin-resistant (ERY(R)) Streptococcus pyogenes/host, the phagocytic and bactericidal activities of PMNs against ERY(R) streptococcal strains (cMLS(B), M, and iMLS(B) A, B and C phenotypes) were assessed in the presence of the macrolide. The results showed that when erythromycin, PMNs and streptococci [both erythromycin-sensitive (ERY(S)) and ERY(R)] were simultaneously present in the culture medium, PMN phagocytic activity was similar to that of drug-free controls. In contrast, the results emphasised a significant high increase in intracellular killing by PMNs in the presence of erythromycin not only for ERY(S) streptococci but also for ERY(R)S. pyogenes with high (cMLS(B), iMLS(B) A and iMLS(B) B phenotypes) and moderate (M and iMLS(B) C phenotypes) erythromycin resistance compared with controls without drug. From literature data it emerged that, even if intracellularly concentrated, erythromycin is relatively inactive because of its instability. The results indicate that the enhanced intra-PMN streptococcal killing detected is mainly attributable to PMN bactericidal systems that synergise with intracellular erythromycin in eradicating ERY(R)S. pyogenes strains (both with high and moderate resistance). These data confirm that the antibiotic resistance detected in vitro does not always imply a failure of antimicrobial treatment.