TEICOPLANIN ALONE OR COMBINED WITH RIFAMPIN COMPARED WITH VANCOMYCIN FOR PROPHYLAXIS AND TREATMENT OF EXPERIMENTAL FOREIGN-BODY INFECTION BY METHICILLIN-RESISTANT STAPHYLOCOCCUS-AUREUS

The prophylactic and therapeutic activities of teicoplanin were evalua ted in two different experimental models of foreign body infections ca used by methicillin-resistant Staphylococcus aureus (MRSA). In a guine a pig model of prophylaxis, subcutaneously implanted tissue cages were infected at a >90% rate by 10(2) CFU of MRSA in control animals. A si ngle dose of 30 mg of teicoplanin per kg of body weight administered i ntraperitoneally 6 h before bacterial challenge was as effective as va ncomycin in preventing experimental infection in tissue cages injected with either 10(2), 10(3), or 10(4) CFU of MRSA. In a rat model evalua ting the therapy of chronic tissue cage infection caused by MRSA, the efficacy of a 7-day high-dose (30 mg/kg once daily) regimen of teicopl anin was compared with that of vancomycin (50 mg/kg twice daily), Wher eas high level of teicoplanin were found in tissue cage fluid, continu ously exceeding its MBC for MRSA by 8- to 16-fold, no significant redu ction in the viable counts of MRSA occurred during therapy. In contras t, either vancomycin alone or a combined regimen of high-dose teicopla nin plus rifampin (25 mg/kg twice daily) could significantly decrease the viable counts in tissue cage fluids. Whereas the bacteria recovere d from tissue cage fluids during therapy showed no evidence of teicopl anin resistance, they failed to be killed even by high levels of this antimicrobial agent. The altered susceptibility of in vivo growing bac teria to teicoplanin killing might in part explain the defective activ ity of this antimicrobial agent when used as monotherapy against chron ic S. aureus infections. These data may indicate the need for a combin ed regimen of teicoplanin with other agents such as rifampin to optimi ze the therapy of severe staphylococcal infections.