Abstract
An in vitro pharmacokinetic model was used to determine if aztreonam could enhance the pharmacodynamics of cefepime or ceftazidime against an isogenic panel of Pseudomonas aeruginosa 164, including wild-type (WT), partially derepressed (PD), and fully derepressed (FD) phenotypes. Logarithmic-phase cultures were exposed to peak concentrations achieved in serum with 1- or 2-g intravenous doses, elimination pharmacokinetics were simulated, and viable bacterial counts were measured over three 8-h dosing intervals. In studies with cefepime and cefepime-aztreonam against the PD strain, samples were also filter sterilized, assayed for active cefepime, and assayed for nitrocefin hydrolysis activity before and after overnight dialysis. Against WT strains, the cefepime-aztreonam combination was the most active regimen, but viable counts at 24 h were only 1 log below those in cefepime-treated cultures. Against PD and FD strains, the antibacterial activity of cefepime-aztreonam was significantly enhanced over that of each drug alone, with 3.5 logs of killing by 24 h. Hydrolysis and bioassay studies demonstrated that aztreonam was inhibiting the extracellular cephalosporinase that had accumulated and was thus protecting cefepime in the extr...Continue Reading
References
Jun 1, 1979·Antimicrobial Agents and Chemotherapy·C C Sanders, W E Sanders
Dec 1, 1992·Antimicrobial Agents and Chemotherapy·B J McGrathM J Rybak
Jan 1, 1992·Antimicrobial Agents and Chemotherapy·B GiwercmanN Høiby
Nov 1, 1991·Antimicrobial Agents and Chemotherapy·M J PucciT J Dougherty
Apr 1, 1991·Antimicrobial Agents and Chemotherapy·J A BossoJ M Matsen
Jan 1, 1991·Antimicrobial Agents and Chemotherapy·G L DaikosG G Jackson
Feb 1, 1990·Antimicrobial Agents and Chemotherapy·H NikaidoE Y Rosenberg
Apr 1, 1990·The Journal of Antibiotics·Y SakuraiT Sawai
Aug 1, 1990·The Journal of Infectious Diseases·G L DaikosD M Livermore
Feb 1, 1990·The Journal of Antimicrobial Chemotherapy·M AkovaD M Livermore
Apr 1, 1989·Antimicrobial Agents and Chemotherapy·J Fung-TomcR E Kessler
Jan 1, 1988·Clinical Microbiology Reviews·K Bush
Sep 1, 1986·Antimicrobial Agents and Chemotherapy·M L GatesW E Sanders
Nov 1, 1988·Antimicrobial Agents and Chemotherapy·H C NeuA Novelli
Apr 1, 1986·The Journal of Antimicrobial Chemotherapy·H C NeuP Labthavikul
Dec 1, 1986·Antimicrobial Agents and Chemotherapy·C C SandersE S Moland
May 1, 1986·Antimicrobial Agents and Chemotherapy·D J PhelpsR E Kessler
Feb 1, 1985·Antimicrobial Agents and Chemotherapy·R E KesslerF Leitner
May 1, 1985·Antimicrobial Agents and Chemotherapy·P C FuchsC Thornsberry
Jul 1, 1985·Antimicrobial Agents and Chemotherapy·D A ConradM I Marks
Jan 1, 1985·The Journal of Antimicrobial Chemotherapy·J BlaserS H Zinner
Apr 1, 1972·Antimicrobial Agents and Chemotherapy·C H O'CallaghanA H Shingler
Sep 1, 1982·Antimicrobial Agents and Chemotherapy·K BushR B Sykes
Jun 1, 1995·Antimicrobial Agents and Chemotherapy·K BushA A Medeiros
Citations
Dec 26, 2001·Antimicrobial Agents and Chemotherapy·Philip D Lister
Nov 8, 2002·American Journal of Pharmacogenomics : Genomics-related Research in Drug Development and Clinical Practice·Philip D Lister
Jul 16, 2004·The Kaohsiung Journal of Medical Sciences·Yen-Hsu ChenTyen-Po Chen
Jun 28, 2013·Pharmacological Reviews·Elisabet I Nielsen, Lena E Friberg
Aug 18, 2017·Medicinal Research Reviews·Lena DecuyperStanislav Gobec
Jan 28, 2005·Antimicrobial Agents and Chemotherapy·Amy Sarah GinsburgWilliam R Bishai
Feb 16, 2005·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Philip D Lister, Daniel J Wolter
Nov 15, 2011·Expert Opinion on Drug Safety·Mao HagiharaDavid P Nicolau
Aug 30, 2019·Clinical Microbiology Reviews·Juan P HorcajadaSantiago Grau
Mar 16, 2001·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·P D Lister
Jun 24, 2016·The Journal of Antimicrobial Chemotherapy·Christopher Ramsey, Alasdair P MacGowan
Nov 30, 2018·The Pediatric Infectious Disease Journal·Jamie L MillerRobert C Welliver
Jun 27, 2019·Scientific Reports·Thanyaluck SiriyongPeter J Coote
May 1, 1999·Antimicrobial Agents and Chemotherapy·P D Lister, C C Sanders
Apr 2, 1999·Antimicrobial Agents and Chemotherapy·P D ListerC C Sanders
Mar 3, 2004·Journal of Infection and Chemotherapy : Official Journal of the Japan Society of Chemotherapy·Daisuke Kataoka, Yoshinori Tanaka
Jul 10, 2003·Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases·E BernardG Potel