title: Antibacterial activity and PK/PD of ceftriaxone against penicillin-resistant Streptococcus pneumoniae and beta-lactamase-negative ampicillin-resistant Haemophilus influenzae isolates from patients with community-acquired pneumonia.
abstract: The suitability of ceftriaxone for penicillin-resistant Streptococcus pneumoniae (PRSP) and ampicillin-resistant Haemophilus influenzae (especially beta-lactamase-negative ampicillin-resistant (BLNAR) H. influenzae) and the relationship between in vitro antimicrobial activities and pharmacokinetic parameters were evaluated. The values for percentage of time above the MIC (%T>MIC) for ceftriaxone, cefotiam, flomoxef, sulbactam/cefoperazone, sulbactam/ampicillin, and meropenem, using 400 S. pneumoniae isolates and 430 H. influenzae isolates from patients with community-acquired pneumonia (CAP) from more than 100 geographically diverse medical centers during January to July of 2005, were calculated by measuring the MIC for each isolate and by using patameters of pharmacokinetics. A broth microdilution method was used to determine the MIC, using the guidelines of the Clinical and Laboratory Standards Institute (CLSI). Meropenem showed the lowest MIC against penicillin-susceptible S. pneumoniae, followed by sulbactam/cefoperazone and ceftriaxone. Ceftriaxone had the best activity against penicillin-resistant S. pneumoniae and beta-lactamase-negative and beta-lactamase-producing ampicillin-resistant H. influenzae. Ceftriaxone was unique, showing a long elimination half-life and low MIC values where its serum level duration time was above the MIC for longer than other cephalosporins. Accordingly, the %T>MIC of ceftriaxone for a once-daily administration greatly exceeded the efficacy levels of those for the other antibacterial agents tested. Ceftriaxone has an excellent balance between in vitro antimicrobial activities and pharmacokinetic profiles; and therefore remains effective as a therapeutic agent against PRSP and BLNAR H. influenzae in CAP.
authors.affiliation: Departments of Microbiology and Infectious Disease, Faculty of Medicine, Toho University, 5-21-16 Omorinishi, Ota-ku, Tokyo 143-8540, Japan. akira@med.toho-u.ac.jp
authors.forename: Akira
authors.initials: A
authors.lastname: Ohno
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Ishii
authors.forename: Intetsu
authors.initials: I
authors.lastname: Kobayashi
authors.forename: Keizo
authors.initials: K
authors.lastname: Yamaguchi
mesh_terms: D000668:Ampicillin Resistance; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D002443:Ceftriaxone / Q000493:pharmacokinetics / Q000494:pharmacology*; D017714:Community-Acquired Infections / Q000382:microbiology*; D024881:Drug Resistance, Bacterial; D006192:Haemophilus Infections / Q000188:drug therapy / Q000382:microbiology*; D006193:Haemophilus influenzae / Q000187:drug effects* / Q000201:enzymology / Q000302:isolation & purification; D006801:Humans; D008826:Microbial Sensitivity Tests; D010403:Penicillin Resistance; D018410:Pneumonia, Bacterial / Q000188:drug therapy / Q000382:microbiology*; D011018:Pneumonia, Pneumococcal / Q000188:drug therapy / Q000382:microbiology*; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000302:isolation & purification; D001618:beta-Lactamases / Q000172:deficiency
chemical_list: D000900:Anti-Bacterial Agents; D002443:Ceftriaxone; D001618:beta-Lactamases