This study describes lysostaphin's effect against methicillin-sensitive Staphylococcus aureus in suckling rats. Standard techniques determined minimal inhibitory and bactericidal concentrations, pharmacokinetics, and efficacy. The numbers of surviving rats after vancomycin, oxacillin, and lysostaphin treatment were comparable and were different from that of controls (P < 0.00001). Lysostaphin appears effective in the treatment of neonatal S. aureus infection.Additional antibacterial agents for staphylococcal infection are needed (3,9,10,12,13,21,27). Lysostaphin, first identified in 1944 (20), is an endopeptidase which specifically cleaves the cell wall cross-linking pentaglycine bridges of Staphylococcus aureus (25) and is active against nondividing organisms (17,19). We describe the effect of lysostaphin against S. aureus in a neonatal animal model.A clinical methicillin-sensitive S. aureus (MSSA) serotype 5 strain (Hernandez) was stored in tryptic soy broth at Ϫ80°C and grown before each experiment. An MSSA strain allowed comparison of lysostaphin to oxacillin and vancomycin. Minimum bactericidal concentrations (MBCs) and MICs of vancomycin, oxacillin, and lysostaphin were determined (7, 18).Fourteen-day timed-pregnancy Wistar rats (Charles River Laboratories) received antibiotic-free water and food ad libitum and delivered at 21 to 22 days of gestation. Pups remained with their dams throughout the experiment. The Baylor College of Medicine Institutional Animal Use Committee approved the research.Three-day-old pups received 1 mg/kg of body weight/dose of lysostaphin at 1, 6, 24, and 30 h. Blood was obtained by cardiac puncture at 1,2,3,7,8,23,25,26,27, 31, 32, 72, and 96 h after the first dose. Three pups' blood was pooled for each data point, and each time point had two data points. Lysostaphin serum concentration was determined by enzyme-linked immunosorbent assay (26).Plates were coated with 100 l (1 g/ml) of rabbit antilysostaphin for 2 h at room temperature and washed with phosphate-buffered saline plus 0.01% Tween 20, and 100 l of standard or sera was added. After 60 min, plates were washed and incubated with biotinylated rabbit antilysostaphin and ExtrAvidin (catalog no. 81K4875; Sigma) for 30 min separately. Substrate tetramethylbenzidine (catalog no. TMBW0100-01; BioFx) was added. Absorbances were measured and converted to concentrations.Three-day-old pups received 0.2 ml subcutaneously (1 ϫ 10 7 CFU/ml) of S. aureus cephalad to the tail. The bacterial concentration was determined by optical density and confirmed by quantitative culture. In the first experiment, littermate pups were randomly assigned to either earlier treatment at 0.5, 6.5, 24, and 30 h after infection or later treatment at 6, 24, 30, and 48 h after infection. Each pup received 0.2 ml intraperitoneally of lysostaphin (1 mg/kg) or an equal volume of normal saline.In the second experiment, littermate pups randomly received 0.2 ml intraperitoneally of lysostaphin (1 mg/kg), vancomycin (15 mg/kg), oxacillin (50 mg/kg), or normal saline ...

BPD severity was not dependent on site of birth. The NICHD BPD outcome estimator provides fair prediction for extreme outcomes.

Respiratory distress syndrome (RDS) causes significant hypoxia in extremely low birth weight (ELBW) infants. We report an ELBW infant with RDS and pulmonary hypertension whose hypoxia did not respond to inhaled nitric oxide but improved with inhaled prostacyclin. We propose that inhaled prostacyclin alleviated the hypoxia by stimulating surfactant secretion. (2007) 27, 724-726; doi:10.1038/sj.jp.7211811 Journal of PerinatologyKeywords: persistent pulmonary hypertension; hypoxia; respiratory distress syndrome; prostacyclin; surfactant; extremely-low-birth-weight infant Background Hypoxemia is a feature of respiratory distress syndrome. Patent ductus arteriosus (PDA) and persistent pulmonary hypertension of the newborn (PPHN) can exacerbate hypoxemia. Inhaled nitric oxide (iNO) is effective for treatment of PPHN in full-term infants by decreasing pulmonary vascular resistance, thereby decreasing right-to-left shunting and alleviating hypoxemia. Several case reports have similarly shown that inhaled prostacyclin (iPGI 2 ) is effective through pulmonary vasodilation in full-term and preterm infants with PPHN. 1-5 Hypoxemia in our patient was refractory to iNO but improved with iPGI 2 . We propose that this response may be due to a physiological mechanism different from pulmonary vasodilatation.