Persistence in serum and lungs of guinea pigs of erythromycin, gentamicin, chloramphenicol and rifampicin and their in-vitro activities against Legionella pneumophila.
The penetration and persistence in the serum and lungs of guinea pigs after parenteral administration of erythromycin, gentamicin, chloramphenicol and rifampicin, and their in-vitro activities against Legionella pneumophila were investigated. The most active agent was rifampicin (MIC 0.0625 mg/l, MBC 0.125 mg/l) and effective levels of this drug were present in serum and lungs up to 10 h after injection. Erythromycin accumulated to very high levels in the lungs and had good bacteriostatic activity in vitro. Gentamicin was highly bactericidal in liquid culture but showed poor lung penetration on injection. Chloramphenicol, the least inhibitory of the four antibiotics, had an MIC of 1.0 mg/l. Active chloramphenicol was not detected in guinea pig serum and lungs following ip or im administration. The differences in the penetration and persistence of these drugs in the lungs of guinea pigs may explain the reported poor correlation between in-vitro and in-vivo activity against L. pneumophila. The results are useful for evaluating regimens for therapy of Legionnaires' disease in the aerosol infected guinea pig model.
D000818:Animals; D002701:Chloramphenicol / Q000378:metabolism* / Q000494:pharmacology; D004917:Erythromycin / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D005839:Gentamicins / Q000378:metabolism* / Q000494:pharmacology; D006168:Guinea Pigs; D007875:Legionella / Q000187:drug effects*; D008168:Lung / Q000378:metabolism*; D008826:Microbial Sensitivity Tests; D012293:Rifampin / Q000378:metabolism* / Q000494:pharmacology
D005839:Gentamicins; D004917:Erythromycin; D002701:Chloramphenicol; D012293:Rifampin