Once-daily Dosing of Ceftriaxone against Streptococcus pneumoniae Isolates in an In Vitro Pharmacodynamic Infection Model supplemented with Albumin

ABSTRACT

BACKGROUND: During the era of increasing penicillin resistant Streptococcus pneumoniae, it is important to have knowledge about adequate dosage and dosing interval of ceftriaxone (CTR). We examined efficacies of once-daily CTR and compared results in an in vitro pharmacodynamic infection model (IVPDIM) supplemented with albumin and those without albumin. METHODS: Using three clinically isolated S. pneumoniae that were susceptible (SM24), intermediate (SM47) and resistant (SM60) against CTR, we utilized a two-compartment IVPDIM. CTR 2 g was administered intravenously every 24 h. Human albumin was added with concentration of 4 g/dL. Samples were removed at multiple time points over a 48-h period to determine the colony counts. RESULTS: In SM24 and SM60, bactericidal effects were observed within 6 hours in groups without albumin. The number of colonies during 1st 6 hours were more decreased in albumin-free groups than in albumin-supplemented groups (P<0.05). In SM47, similar results were found during 1st 6 hours (P=0.03). But, regrowth was observed in albumin supplemented group at 30 h. Irrespective of results of minimal inhibitory concentrations and albumin supplementation, bactericidal effects were shown at 24 h in all 3 strains. All groups were decreased below the detection limit at 48 h. Development of resistance was not detected throughout the entire study period in either strain. CONCLUSIONS: Although extents of killing in albumin supplemented broth of once-daily CTR dosing were delayed in all 3 strains compared with those of albumin free broth, final efficacies were not different between the two groups.