Chemotherapy of systemic murine infection due to beta-lactam antibiotic 'tolerant' and non-'tolerant' Staphylococcus aureus.
Two in vitro beta-lactam antibiotic (oxacillin, cefotaxime) 'tolerant' (MBC:MIC ratios = greater than 32) strains of Staphylococcus aureus served to intraperitoneally infect cyclophosphamide-pretreated (leukopenic) NMRI mice. With larger bacterial inocula (approximately 5 X 10(8) CFU) neither oxacillin nor gentamicin or netilmicin yielded optimal chemotherapeutic results. Only combination chemotherapy, in particular oxacillin combined with netilmicin, consistently reduced mouse mortality significantly (p less than 0.001). In contrast, moderate 'tolerant' staphylococcal inocula (approximately 2 X 10(8) CFU) were amenable to chemotherapy with either oxacillin or netilmicin, but not with cefotaxime or gentamicin. Oxacillin combined with either gentamicin or netilmicin resulted in significantly lowered murine mortality rates (p less than 0.001). Cefotaxime combined with either aminoglycoside antibiotic gave less satisfactory results. Systemic murine infections due to three non-'tolerant' strains of S. aureus were amenable to chemotherapy with oxacillin, cefotaxime or netilmicin alone and to combination chemotherapy. It is recommended that cases of life-threatening S. aureus infection, not complicated by acute endocarditis, initially be treated with oxacillin plus netilmicin until availability of laboratory results (antibiogram, documentation of 'tolerance').
D000818:Animals; D002439:Cefotaxime / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000627:therapeutic use; D004361:Drug Tolerance; D005839:Gentamicins / Q000627:therapeutic use; D051379:Mice; D009428:Netilmicin / Q000627:therapeutic use; D010068:Oxacillin / Q000627:therapeutic use*; D013203:Staphylococcal Infections / Q000188:drug therapy*
D005839:Gentamicins; D009428:Netilmicin; D003520:Cyclophosphamide; D002439:Cefotaxime; D010068:Oxacillin