title: Pharmacodynamics of ceftriaxone and cefixime against community-acquired respiratory tract pathogens.
abstract: Over the last decade or so there has been a growing interest in routes of antimicrobial administration other than by the conventional intravenous route for institutionalized patients and for some outpatients. Both oral (PO) and intramuscular (IM) routes of administration are less costly than giving antimicrobial agents by vein (IV). In addition, fewer complications such as catheter-related sepsis and phlebitis are associated with non-IV routes of administration. Furthermore, a reduced-dosage, reduced-volume IM administration of ceftriaxone may provide a tolerable route of administration and equivalent bactericidal activities compared with higher dose IV ceftriaxone. The purpose of this study was to determine the time that the drug concentration remained in excess of the minimum inhibitory concentration (MIC) (T > MIC) and the duration of bactericidal activities of ceftriaxone one gram administered IV, ceftriaxone 250 mg given IM and cefixime 400 mg given orally against clinical isolates of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis in adult volunteers. Single doses of each agent were administered and serum concentrations were collected over the standard dosing period of 24 h for all study regimens. Ceftriaxone, regardless of route of administration and dose, resulted in bactericidal activities and T > MIC for 100% of the dosing period for S. pneumoniae, H. influenzae, and M. catarrhalis. Cefixime maintained at least 50% T > MIC and bactericidal activity against both isolates each of H. influenzae and M. catarrhalis. Against both isolates of S. pneumoniae, cefixime achieved T > MIC for at least 50% of the dosing period, but did not maintain bactericidal activity. Reduced dose ceftriaxone given IM seems to be a viable alternative to ceftriaxone IV if the pathogen, susceptibility and infection site are known. Based on T > MIC exceeding 50% of the dosing interval, cefixime would be considered an effective alternative to IV therapy against common respiratory tract pathogens. Clinical studies need to be conducted to confirm these findings.
authors.affiliation: Departments of Infectious Diseases and Clinical Pharmacy Services, Maine Medical Center, 22 Bramhall Street, Portland, ME 04102, USA. owensr@mail.mmc.org
authors.forename: R C
authors.initials: RC
authors.lastname: Owens
authors.forename: P
authors.initials: P
authors.lastname: Tessier
authors.forename: C H
authors.initials: CH
authors.lastname: Nightingale
authors.forename: P G
authors.initials: PG
authors.lastname: Ambrose
authors.forename: R
authors.initials: R
authors.lastname: Quintiliani
authors.forename: D P
authors.initials: DP
authors.lastname: Nicolau
mesh_terms: D000284:Administration, Oral; D000328:Adult; D001770:Blood Bactericidal Activity; D020682:Cefixime / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D002443:Ceftriaxone / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D002511:Cephalosporins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D017714:Community-Acquired Infections / Q000188:drug therapy* / Q000378:metabolism; D018592:Cross-Over Studies; D005260:Female; D006192:Haemophilus Infections / Q000188:drug therapy / Q000378:metabolism; D006193:Haemophilus influenzae / Q000187:drug effects / Q000302:isolation & purification; D006801:Humans; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D008297:Male; D001936:Moraxella catarrhalis / Q000187:drug effects / Q000302:isolation & purification; D016870:Neisseriaceae Infections / Q000188:drug therapy / Q000378:metabolism; D011008:Pneumococcal Infections / Q000188:drug therapy / Q000378:metabolism; D012141:Respiratory Tract Infections / Q000188:drug therapy* / Q000378:metabolism; D013296:Streptococcus pneumoniae / Q000187:drug effects / Q000302:isolation & purification
chemical_list: D002511:Cephalosporins; D002443:Ceftriaxone; D020682:Cefixime