Linezolid alone or combined with rifampin against methicillin-resistant Staphylococcus aureus in experimental foreign-body infection.

Abstract

We investigated the activity of linezolid, alone and in combination with rifampin (rifampicin), against a methicillin-resistant Staphylococcus aureus (MRSA) strain in vitro and in a guinea pig model of foreign-body infection. The MIC, minimal bactericidal concentration (MBC) in logarithmic phase, and MBC in stationary growth phase were 2.5, >20, and >20 microg/ml, respectively, for linezolid; 0.01, 0.08, and 2.5 microg/ml, respectively, for rifampin; and 0.16, 0.63, >20 microg/ml, respectively, for levofloxacin. In time-kill studies, bacterial regrowth and the development of rifampin resistance were observed after 24 h with rifampin alone at 1x or 4x the MIC and were prevented by the addition of linezolid. After the administration of single intraperitoneal doses of 25, 50, and 75 mg/kg of body weight, linezolid peak concentrations of 6.8, 12.7, and 18.1 microg/ml, respectively, were achieved in sterile cage fluid at approximately 3 h. The linezolid concentration remained above the MIC of the test organism for 12 h with all doses. Antimicrobial treatments of animals with cage implant infections were given twice daily for 4 days. Linezolid alone at 25, 50, and 75 mg/kg reduced the planktonic bacteria in cage fluid during treatment by 1.2 to 1.7 log(10) CFU/ml; only linezolid at 75 mg/kg prevented bacterial regrowth 5 days after the end of treatment. Linezolid used in combination with rifampin (12.5 mg/kg) was more effective than linezolid used as monotherapy, reducing the planktonic bacteria by >or=3 log(10) CFU (P < 0.05). Efficacy in the eradication of cage-associated infection was achieved only when linezolid was combined with rifampin, with cure rates being between 50% and 60%, whereas the levofloxacin-rifampin combination demonstrated the highest cure rate (91%) against the strain tested. The linezolid-rifampin combination is a treatment option for implant-associated infections caused by quinolone-resistant MRSA.

• Authors: Daniela Baldoni, Manuel Haschke, Zarko Rajacic, Werner Zimmerli, Andrej Trampuz
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 53 Issue 3 Pg. 1142-8 (Mar 2009) ISSN: 1098-6596 [Electronic] United States
• PMID: 19075065 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Acetamides
• Anti-Bacterial Agents
• Oxazolidinones
• Linezolid
• Rifampin

Topics

• Acetamides (administration & dosage, pharmacology, therapeutic use)
• Animals
• Anti-Bacterial Agents (administration & dosage, pharmacology, therapeutic use)
• Colony Count, Microbial
• Dose-Response Relationship, Drug
• Drug Therapy, Combination
• Foreign-Body Reaction (drug therapy, prevention & control)
• Guinea Pigs
• Injections, Intraperitoneal
• Linezolid
• Male
• Methicillin-Resistant Staphylococcus aureus
• Microbial Sensitivity Tests
• Models, Animal
• Oxazolidinones (administration & dosage, pharmacology, therapeutic use)
• Plankton (drug effects)
• Rifampin (administration & dosage, pharmacology, therapeutic use)
• Staphylococcal Infections (drug therapy)
• Staphylococcus aureus (drug effects)
• Time Factors