title: Do We Bury Antibacterials When Launching? Cefaclor Example.
abstract: This study aimed to compare existing dosing regimens of cefaclor with recommended pharmacokinetic/pharmacodynamic (PK/PD) parameters and to see if the proposed dosing regimen could have been the reason for development of bacterial resistance. PKs of cefaclor were determined after administrating the highest therapeutic dose of 750 mg in standard release (SF) and modified release form (MRF) in 12 volunteers. The study was performed on clinical isolates of the most frequent causative agents in urinary and respiratory infections. Minimum inhibitory concentration (MIC), postantibiotic effect, and PK/PD efficacy indices were determined. Peak plasma concentrations of 23.142 ± 5.67 (SF) and 8.7 ± 2.09 μg/mL (MRF) were observed after 40-60 min and 3.04 ± 0.75 h, respectively. MIC for investigated bacterial strains ranged from 1 to 4 mg/L. Postantibiotic effect lasted from 2.10-2.18 ± 0.2 h for Gram-positive to 0.58-0.90 ± 0.05 h for Gram-negative bacteria. PK/PD indices (t > MIC) ranged from 27.08 ± 5.93% to 43.23 ± 6.54% of 8-h dosing interval (SF) and 22.57 ± 8.93% to 49.65 ± 1.95% of 12-h dosing interval (MRF). Plasma levels were below MIC for more than 50% of the dosing interval even for the most sensitive pathogens (MIC = 1 mg/L). During both dosing intervals the total "antibacterial activity" was not longer than 6 h for Gram-positive and 5 h for Gram-negative bacteria for SF and 9 h for Gram-positive and 5 h for Gram-negative bacteria for MRF.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Medicine Novi Sad, University of Novi Sad, 21000 Novi Sad, Serbia.
authors.forename: Zdenko
authors.initials: Z
authors.lastname: Tomić
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Medicine Novi Sad, University of Novi Sad, 21000 Novi Sad, Serbia. Electronic address: aanaa_tomas@yahoo.com.
authors.forename: Ana
authors.initials: A
authors.lastname: Tomas
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Medicine Novi Sad, University of Novi Sad, 21000 Novi Sad, Serbia.
authors.forename: Saša
authors.initials: S
authors.lastname: Vukmirović
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Medicine Novi Sad, University of Novi Sad, 21000 Novi Sad, Serbia.
authors.forename: Momir
authors.initials: M
authors.lastname: Mikov
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Medicine Novi Sad, University of Novi Sad, 21000 Novi Sad, Serbia.
authors.forename: Olga
authors.initials: O
authors.lastname: Horvat
authors.affiliation: Institute of Emergency Medicine, Clinical Center of Vojvodina, 21000 Novi Sad, Serbia.
authors.forename: Nataša
authors.initials: N
authors.lastname: Tomić
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Medicine Novi Sad, University of Novi Sad, 21000 Novi Sad, Serbia.
authors.forename: Ana
authors.initials: A
authors.lastname: Sabo
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D001424:Bacterial Infections / Q000188:drug therapy*; D002433:Cefaclor / Q000008:administration & dosage*; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D005260:Female; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests / Q000379:methods; D008875:Middle Aged; D012141:Respiratory Tract Infections / Q000188:drug therapy; D014552:Urinary Tract Infections / Q000188:drug therapy; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D002433:Cefaclor
keywords: drug design; formulation; pharmacodynamics; pharmacokinetics; pharmacokinetics/pharmacodynamics