PMID- 17307984 OWN - NLM STAT- MEDLINE DCOM- 20070706 LR - 20181113 IS - 0066-4804 (Print) IS - 1098-6596 (Electronic) IS - 0066-4804 (Linking) VI - 51 IP - 5 DP - 2007 May TI - Rapid bactericidal activity of daptomycin against methicillin-resistant and methicillin-susceptible Staphylococcus aureus peritonitis in mice as measured with bioluminescent bacteria. PG - 1787-94 AB - The rising rates of antibiotic resistance accentuate the critical need for new antibiotics. Daptomycin is a new antibiotic with a unique mode of action and a rapid in vitro bactericidal effect against gram-positive organisms. This study examined the kinetics of daptomycin's bactericidal action against peritonitis caused by methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) in healthy and neutropenic mice and compared this activity with those of other commonly used antibiotics. CD-1 mice were inoculated intraperitoneally with lethal doses of MSSA (Xen-29) or MRSA (Xen-1), laboratory strains transformed with a plasmid containing the lux operon, which confers bioluminescence. One hour later, the animals were given a single dose of daptomycin at 50 mg/kg of body weight subcutaneously (s.c.), nafcillin at 100 mg/kg s.c., vancomycin at 100 mg/kg s.c., linezolid at 100 mg/kg via gavage (orally), or saline (10 ml/kg s.c.). The mice were anesthetized hourly, and photon emissions from living bioluminescent bacteria were imaged and quantified. The luminescence in saline-treated control mice either increased (neutropenic mice) or remained relatively unchanged (healthy mice). In contrast, by 2 to 3 h postdosing, daptomycin effected a 90% reduction of luminescence of MSSA or MRSA in both healthy and neutropenic mice. The activity of daptomycin against both MSSA and MRSA strains was superior to those of nafcillin, vancomycin, and linezolid. Against MSSA peritonitis, daptomycin showed greater and more rapid bactericidal activity than nafcillin or linezolid. Against MRSA peritonitis, daptomycin showed greater and more rapid bactericidal activity than vancomycin or linezolid. The rapid decrease in the luminescent signal in the daptomycin-treated neutropenic mice underscores the potency of this antibiotic against S. aureus in the immune-suppressed host. FAU - Mortin, Lawrence I AU - Mortin LI AD - Cubist Pharmaceuticals Inc, Lexington, MA 02421, USA. Lawrence.Mortin@cubist.com FAU - Li, Tongchuan AU - Li T FAU - Van Praagh, Andrew D G AU - Van Praagh AD FAU - Zhang, Shuxin AU - Zhang S FAU - Zhang, Xi-Xian AU - Zhang XX FAU - Alder, Jeff D AU - Alder JD LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20070216 PL - United States TA - Antimicrob Agents Chemother JT - Antimicrobial agents and chemotherapy JID - 0315061 RN - 0 (Acetamides) RN - 0 (Anti-Bacterial Agents) RN - 0 (Oxazolidinones) RN - ISQ9I6J12J (Linezolid) RN - NWQ5N31VKK (Daptomycin) SB - IM MH - Acetamides/pharmacology MH - Animals MH - Anti-Bacterial Agents/*pharmacology MH - Colony Count, Microbial MH - Daptomycin/*pharmacology/therapeutic use MH - Female MH - Linezolid MH - Luminescent Measurements MH - *Methicillin Resistance MH - Mice MH - Microbial Sensitivity Tests MH - Neutropenia/drug therapy MH - Oxazolidinones/pharmacology MH - Peritonitis/*drug therapy MH - Staphylococcus aureus/*drug effects PMC - PMC1855546 EDAT- 2007/02/20 09:00 MHDA- 2007/07/07 09:00 PMCR- 2007/09/01 CRDT- 2007/02/20 09:00 PHST- 2007/02/20 09:00 [pubmed] PHST- 2007/07/07 09:00 [medline] PHST- 2007/02/20 09:00 [entrez] PHST- 2007/09/01 00:00 [pmc-release] AID - AAC.00738-06 [pii] AID - 0738-06 [pii] AID - 10.1128/AAC.00738-06 [doi] PST - ppublish SO - Antimicrob Agents Chemother. 2007 May;51(5):1787-94. doi: 10.1128/AAC.00738-06. Epub 2007 Feb 16.