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

Hur, Ji An; Chun, Hye Sun; Park, Sun Hee; Choi, Su Mi; Kim, Sihyun; Lee, Dong Gun; Choi, Jung Hyun; Yoo, Jin Hong; Shin, Wan Shik

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.