Oxacillin-susceptible Staphylococci Research Articles

An in vitro evaluation of HRE 664, a novel penem antibiotic

HRE 664 is a novel parenteral penem with a broad antimicrobial spectrum. In this study, HRE 664 inhibited 90% of Enterobacteriaceae at ≤2.0 μg/ml, Haemophilus influenzae and Neisseria gonorrhoeae at ≤0.5 μg/ml, oxacillin-susceptible staphylococci at ≤0.13 μg/ml, oxacillin-resistant staphylococci at ≤8.0 μg/ml, enterococci at ≤8.0 μg/ml, and streptococci at ≤0.13 μg/ml. All strains of Pseudomonas aeruginosa were resistant (MICs were >32 μg/ml). HRE 664 exhibited a minimal inoculum effect and good bactericidal activity with all organisms tested except an oxacillin-resistant Staphylococcus aureus . With the latter, there was a marked inoculum effect and no on-scale bactericidal endpoints. No measurable hydrolysis of HRE 664 occurred with any of the five Gram-negative bacterial β-lactamases tested. When stored at −20°C, HRE 664 showed no significant loss of activity for up to 6 wk, but detectable deterioration occurred thereafter. At −60°C, no loss in HRE 664 potency was observed for up to 12 wk. Proposed HRE 664 MIC quality control parameters are: 0.03–0.13 μg/ml for S. aureus ATCC 29213, 0.25–1.0 μg/ml for Escherichia coli 25922, and 2.0–8.0 μg/ml for Enterococcus faecalis ATCC 29212.

Serum bactericidal activity and postantibiotic effect in serum of patients with urinary tract infection receiving high-dose amikacin.

Ten patients received a 30-min infusion of amikacin (30 mg/kg) on day 1 and 15 mg/kg on day 2. Mean serum creatinine was 1.1 +/- 0.3 (standard deviation) mg/dl before and 1.0 +/- 0.3 mg/dl 3 days after the second infusion. Mean serum amikacin concentrations before, at the end of infusion, and 1, 6, 12, and 24 h after 30 and 15 mg/kg were 0, 157, 79, 31, 16, 5, 5, 85, 51, 19, 12, and 5 mg/liter, respectively. Five strains each of Staphylococcus aureus, Staphylococcus epidermidis susceptible and resistant to oxacillin, Streptococcus (Enterococcus) faecalis, corynebacterium sp. strain JK, Listeria monocytogenes, Mycobacterium fortuitum (three strains), Klebsiella pneumoniae, Serratia marcescens, Acinetobacter calcoaceticus, and Pseudomonas aeruginosa were tested. Serum bactericidal activities (SBAs) were greater than or equal to 1:8 in greater than or equal to 80% of the sera 1 and 6 h after 30 mg/kg and in greater than or equal to 60% of the sera 1 and 6 h after 15 mg/kg against Staphylococcus aureus and Staphylococcus epidermidis susceptible to oxacillin, A. calcoaceticus, and K. pneumoniae. L. monocytogenes, Serratia marcescens, and P. aeruginosa had lower SBAs. Very low or no activity was observed against oxacillin-resistant staphylococci and Streptococcus faecalis. The study of the killing rate in serum confirmed these results. Postantibiotic effect was studied by incubating a strain from each species in serum samples obtained 1 and 6 h after both regimens for 0.5, 1, or 2 h. The duration of postantibiotic effect depended on the duration of contact and the concentration of amikacin for the following organisms: oxacillin-susceptible staphylococci, L. monocytogenes, P. aeruginosa, A. calcoaceticus, K. pneumoniae, and Serratia marcescens. M. fortuitum was killed after 30 min of contact. No postantibiotic effect was observed with Streptococcus faecalis, Corynebacterium sp. strain JK, or oxacillin-resistant staphylococci. Amikacin at 30 mg/kg provided high levels and SBAs against susceptible pathogens. Prolonged postantibiotic effects were observed. No signs of nephrotoxicity occurred.

Viability of staphylococci in various diluents.

Standardized suspensions of 78 staphylococci and micrococci were stored in different diluents and tested periodically for 3 weeks to determine their ability to maintain viability. In 92% of the tests, diluent suspensions yielded viable organisms for at least 21 days. Organism survival was maintained in the following order, from best to worst: skim milk, tap water, 0.9% NaCl, deionized water, Dianeal (peritoneal dialysis) fluid, 0.2% bovine serum albumin and 5% glycerol. In 81% of the instances, oxacillin-susceptible staphylococci survived better than oxacillin-resistant staphylococci.