Influence of cytostatic treatment on the efficacy of erythromycin and roxithromycin in a staphylococcal infection in mice.
Mice made monocytopenic with etoposide or both granulocytopenic and monocytopenic with cyclophosphamide were infected in a thigh muscle with 3 x 10(6) CFU of Staphylococcus aureus; 1 h later erythromycin or roxithromycin was administered, and 4 h after that the number of CFU per thigh was determined. In vitro as well as in vivo, the maximal effect of both antibiotics was only bacteriostatic. Monocytopenia did not diminish the efficacy of either erythromycin or roxithromycin in vivo, whereas the combination of granulocytopenia and monocytopenia markedly decreased the efficacy of both drugs: a 4-fold dose increase was necessary to obtain the same final number of CFU at the site of infection as in the controls. It is concluded that granulocytes contributed substantially to antibiotic efficacy against S. aureus in this short-term infection model.
Calame
W
W
Department of Infectious Diseases, University Hospital, Leiden, The Netherlands.
Guiot
H F
HF
Mattie
H
H
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D003520:Cyclophosphamide / Q000494:pharmacology; D004917:Erythromycin / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005047:Etoposide / Q000494:pharmacology; D007958:Leukocyte Count; D007970:Leukopenia / Q000139:chemically induced; D008297:Male; D051379:Mice; D015575:Roxithromycin / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013047:Specific Pathogen-Free Organisms; D013203:Staphylococcal Infections / Q000188:drug therapy*; D013211:Staphylococcus aureus / Q000254:growth & development
D000970:Antineoplastic Agents; D015575:Roxithromycin; D004917:Erythromycin; D005047:Etoposide; D003520:Cyclophosphamide