title: Treatment of methicillin-resistant Staphylococcus aureus in neonatal mice: lysostaphin versus vancomycin.
abstract: S. aureus is a significant cause of late-onset sepsis in neonates. Increasing antibiotic resistance, however, requires additional treatment options. Lysostaphin, an endopeptidase, has that potential. The objective of this study is to compare lysostaphin versus vancomycin against methicillin-resistant Staphylococcus aureus (MRSA) in a neonatal mouse model. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against MRSA strain USA300 were determined using standard methods. To determine pharmacokinetics, neonatal pups received either vancomycin or lysostaphin intraperitoneal and serum samples were obtained. To evaluate efficacy, pups were infected s.c. and littermates randomized to receive either saline, vancomycin, or lysostaphin intraperitoneal. Pups were observed for survival and growth. Quantitative blood cultures were obtained 24 h after infection. The MIC/MBC for vancomycin and lysostaphin were 0.71/1.19 microg/mL and <0.008/0.015 microg/mL, respectively. Mean lysostaphin concentrations ranged from 2.34 to 8.92 microg/mL. Mean vancomycin concentrations ranged from 1.72 to 11.2 microg/mL. Lysostaphin improved survival compared with placebo (p < 0.00001) and vancomycin (p < 0.03). There was no significant difference in growth among the groups. All treatment regimens resulted in less bacteremia compared with placebo (p < 0.0001). Lysostaphin appears to be more effective than vancomycin in treating MRSA in a neonatal model.
authors.affiliation: Department of Pediatrics, Texas Children's Hospital, Houston, Texas 77030, USA.
authors.forename: Frank X
authors.initials: FX
authors.lastname: Placencia
authors.forename: Lingkun
authors.initials: L
authors.lastname: Kong
authors.forename: Leonard E
authors.initials: LE
authors.lastname: Weisman
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D016470:Bacteremia / Q000188:drug therapy / Q000382:microbiology; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D007274:Injections, Intraperitoneal; D008248:Lysostaphin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D016106:Methicillin Resistance; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000472:pathogenicity; D051379:Mice; D008826:Microbial Sensitivity Tests; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D014640:Vancomycin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin; D008248:Lysostaphin