Comparison of the investigational drug, LY146032, with vancomycin in experimental pneumonia due to methicillin-resistant Staphylococcus aureus.
The efficacy of LY146032 was compared with that of vancomycin in experimental pneumonia due to methicillin-resistant Staphylococcus aureus (MRSA). Emphysematous hamsters were challenged intratracheally with MRSA and given LY146032 (20 mg/kg 24h), vancomycin (40 mg/kg/24h) or normal saline by subcutaneous injection. Following infection with 2 X 10(9) cfu, survival among antibiotic-treated animals was significantly greater than that of the control group (P less than 0.01 at 96 h); however, no significant difference in survival between the hamsters given LY146032 and vancomycin was seen. To evaluate the influence of the antibiotics on the rate of bacterial killing within the lungs (pulmonary clearance), animals were challenged with a high inoculum (1 X 10(9) cfu) or low inoculum (1 X 10(6) cfu). Animals treated with LY146032 demonstrated a significant advantage in pulmonary clearance versus controls at both inocula; however, animals treated with vancomycin showed a statistically significant increase in pulmonary clearance versus controls only at the lower inoculum. We conclude that in this experimental model, LY146032 was as effective as vancomycin in treating infection with MRSA.
Kephart
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Department of Medicine, Boston Veterans Administration Medical Center.
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D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006224:Cricetinae; D017576:Daptomycin; D007442:Intubation, Intratracheal; D008297:Male; D008647:Mesocricetus; D008712:Methicillin; D008826:Microbial Sensitivity Tests; D010403:Penicillin Resistance; D010455:Peptides / Q000493:pharmacokinetics / Q000627:therapeutic use; D011023:Pneumonia, Staphylococcal / Q000188:drug therapy* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects; D014640:Vancomycin / Q000493:pharmacokinetics / Q000627:therapeutic use*
D000900:Anti-Bacterial Agents; D010455:Peptides; D014640:Vancomycin; D017576:Daptomycin; D008712:Methicillin