+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Comparative study of the effects of ceftizoxime, piperacillin, and piperacillin-tazobactam concentrations on antibacterial activity and selection of antibiotic-resistant mutants of Enterobacter cloacae and Bacteroides fragilis in vitro and in vivo in mixed-infection abscesses



Comparative study of the effects of ceftizoxime, piperacillin, and piperacillin-tazobactam concentrations on antibacterial activity and selection of antibiotic-resistant mutants of Enterobacter cloacae and Bacteroides fragilis in vitro and in vivo in mixed-infection abscesses



Antimicrobial Agents and ChemoTherapy 48(5): 1688-1698



The effects of ceftizoxime (CZX), piperacillin (PIP), and PIP-tazobactam (PT) concentrations on the antibacterial activity and selection of resistant mutants of Bacteroides fragilis and Enterobacter cloacae were investigated in vitro in a mixed-culture anaerobic time-kill study and in vivo in a mixed-infection abscess model. Mixed cultures were incubated for 24 h with 0.125 to 512 micro g of CZX per ml or 0.125 to 2,048 micro g of PIP or PT per ml. Mice were treated every 2 h for 24 h with CZX at 6 to 1,536 mg/kg/day or with PIP or PT at 24 to 6,144 mg/kg/day starting 30 min before inoculation with different B. fragilis-E. cloacae combinations. There was a good correlation between the in vitro and in vivo activities of the antibiotics and their MICs obtained with high inocula (10(8) CFU/ml). The respective 50% effective doses (milligrams per kilogram per day) with B. fragilis and E. cloacae 22491 were 771 and 521 for CZX, 416 and 643 for PIP, and 85 and 554 for PT, and with the B. fragilis-E. cloacae 032349 combination, they were 81 and 21 for CZX and 77 and 766 for PT. Resistant mutants of E. cloacae 22491 were preferentially selected in vitro with 2 to 64 micro g of CZX per ml and in vivo with CZX at 12 to 384 mg/kg/day. There was no preferential selection of CZX-resistant B. fragilis or E. cloacae 032349. For CZX-resistant E. cloacae 22491, we found a 16- to 512-fold increase in the MIC of CZX and increased MICs of other expanded-spectrum cephalosporins, owing in part to the production of a stably derepressed cephalosporinase. In vitro and in vivo, PT did not select resistant mutants of E. cloacae and B. fragilis. Results demonstrate the adverse microbiological outcome of choosing an expanded-spectrum cephalosporin like CZX for empirical treatment of mixed infections involving a susceptible Enterobacter strain.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 011880621

Download citation: RISBibTeXText

PMID: 15105122

DOI: 10.1128/aac.48.5.1688-1698.2004


Related references

Effect of dosing and dosing frequency on the efficacy of ceftizoxime and the emergence of ceftizoxime resistance during the early development of murine abscesses caused by Bacteroides fragilis and Enterobacter cloacae mixed infection. Antimicrobial Agents and ChemoTherapy 51(10): 3605-3611, 2007

The importance of TMIC to the emergence of ceftizoxime resistance during the early development of Bacteroides fragilis /Enterobacter cloacae mixed infection murine abscesses. Abstracts of the Interscience Conference on Antimicrobial Agents & Chemotherapy 43: 22, 2003

In vitro selection of ertapenem and piperacillin/tazobactam-resistant strains of Bacteroides fragilis and analysis of their virulence in gnotobiotic mice. Journal of ChemoTherapy 22(4): 259-263, 2010

In vitro pharmacodynamics of piperacillin, piperacillin-tazobactam, and ciprofloxacin alone and in combination against Staphylococcus aureus, Klebsiella pneumoniae, Enterobacter cloacae, and Pseudomonas aeruginosa. Antimicrobial Agents and ChemoTherapy 39(8): 1711-1716, 1995

Effect of dosing and dosing frequency on the efficacy of ceftizoxime development of murine abscesses caused by Bacteroides fragilis and Enterobacter cloacae mixed infection. 2007

In vitro activity of piperacillin/tazobactam and ertapenem against Bacteroides fragilis and Escherichia coli in pure and mixed cultures. Journal of Medical Microbiology 56(Pt 6): 798-802, 2007

In vitro activity of ertapenem and Piperacillin/Tazobactam against Bacteroides fragilis and Escherichia coli in single or in mixed culture. 2006

Comparative activity of ertapenem and piperacillin tazobactam in a murine systemic infection model with Bacteroides fragilis and Escherichia coli. Journal of Medical Microbiology 56(Pt 11): 1576-1579, 2007

Comparative in vitro activity of piperacillin, piperacillin-sulbactam and piperacillin-tazobactam against nosocomial pathogens isolated from intensive care patients. Clinical Microbiology and Infection 9(11): 1128-1132, 2003

In Vitro-In Vivo Discordance with Humanized Piperacillin-Tazobactam Exposures against Piperacillin-Tazobactam-Resistant/Pan-β-Lactam-Susceptible Escherichia coli. Antimicrobial Agents and ChemoTherapy 60(12): 7527-7529, 2016

In Vitro-In Vivo Discordance with Humanized Piperacillin-Tazobactam Exposures against Piperacillin-Tazobactam-Resistant/Pan-β-Lactam-Susceptible Klebsiella pneumoniae Strains. Antimicrobial Agents and ChemoTherapy 61(7):, 2017

In vitro activities of clindamycin, imipenem, metronidazole, and piperacillin-tazobactam against susceptible and resistant isolates of Bacteroides fragilis evaluated by kill kinetics. Antimicrobial Agents and ChemoTherapy 56(6): 3413-3416, 2012

Pharmacodynamics of piperacillin alone and in combination with tazobactam against piperacillin-resistant and -susceptible organisms in an in vitro model of infection. Antimicrobial Agents and ChemoTherapy 38(10): 2351-2356, 1994

Serum bactericidal activity of piperacillin/tazobactam against Staphylococcus aureus, piperacillin-susceptible and piperacillin-resistant Escherichia coli and Pseudomonas aeruginosa. ChemoTherapy 50(1): 27-30, 2004

Piperacillin/tazobactam (YTR 830) combination. Comparative antimicrobial activity against 5889 recent aerobic clinical isolates and 60 Bacteroides fragilis group strains. Diagnostic Microbiology and Infectious Disease 12(6): 489-494, 1989