Interaction between penicillin and erythromycin treatment on Streptococcus pneumoniae in a murine pneumonia model

Abstract number: 1134_04_81

Fischer R.L., Frimodt-Møller N.

Objectives:  

The antimicrobial response after treatment with penicillin (P) and erythromycin (E) in combination was investigated against S. pneumoniae in a murine pneumonia model.

Methods:  

Pneumonia was induced in outbred, immunocompetent mice by inoculation of a S. pneumoniae intranasally. Two strains were used, D39 (serotype 2) and serotype 6A from Iceland, both P and E susceptible. All mice were treated BID in groups of 6 mice at 24 and 30 hours after inoculation. The following five BID dose regimens were tested: P 3 mg/kg, E 3 or 13 mg/kg, P 3 mg/kg in combination with E 3 mg/kg and finally P 3 mg/kg in combination with E 13 mg/kg. In addition, the combination of the two compounds was either dosed simultaneous or P was given a half hour later than the E treatment. Colony counts from lung homogenates were determined at start of treatment and 24 hours after start of treatment. Time-kill curves with P and E alone and in combination against the two strains were performed in addition.

Results:  

In vitro antagonism was shown for the combination of P and E, i.e. same killing effect as for E alone but less so than for P alone. Not only P, but also E had a cidal effect on both strains in vivo when tested individually. The E mean log reduction in colony counts compared to start of treatment was 1.6 for BID 3 mg/kg and 3 for BID 13 mg/kg, similar for both strains. The P and E combination did not increase the effect on the tested pneumococci compared to the effect of P alone (see Fig). The colony counts for strain 6A after P treatment was not significantly different to the treatment with E 3 mg/kg ( P 3 mg/kg, whereas, E had an antagonistic effect on P for the D39 strain (P = 0.04, Mann–Whitney test). No difference in effect was observed between dosing simultaneous and using half hour separation of the two compounds.

Conclusion:  

Combination treatment with a beta-lactam and a macrolide is commonly recommended for empiric treatment of community acquired pneumonia. Testing such a combination in the experimental mouse pneumonia model showed no additive effect on the pneumococci, and a significant antagonistic effect was observed for one strain. We recommend that the combination of P and E should not be administered if a pneumococcal etiology is suspected.