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In vitro activity of cefepime, imipenem, tigecycline, and gentamicin, alone and in combination, against extended-spectrum beta-lactamase-producing Klebsiella pneumoniae and Escherichia coli.
Pharmacotherapy. 2008 Mar; 28(3):295-300.P

Abstract

STUDY OBJECTIVE

To evaluate the activity of cefepime, imipenem, tigecycline, and gentamicin, alone and in combination, against extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae and Escherichia coli.

DESIGN

In vitro susceptibility and time-kill analysis.

SETTING

University-affiliated research laboratory. ISOLATES: Ten K. pneumoniae and 10 E. coli clinical strains known to produce ESBL.

MEASUREMENTS AND MAIN RESULTS

Minimum inhibitory concentration (MIC) testing was performed at 5.5 and 7.0 log(10) colony-forming units (cfu)/ml. Time-kill studies were performed over 24 hours with a high inoculum of 7.0 log(10) cfu/ml for cefepime, imipenem, tigecycline, and gentamicin at 1 times MIC. Combination studies were tested for cefepime plus tigecycline, cefepime plus imipenem, imipenem plus tigecycline, and for adjunctive gentamicin with cefepime, imipenem, or tigecycline. At the high inoculum, the MIC ranges for cefepime, imipenem, tigecycline, and gentamicin were 0.25-256 (MIC for 90% of tested strains [MIC(90)] = 32), 0.125-2 (MIC(90) = 1), 0.25-16 (MIC(90) = 4), and 0.25-4 mg/L (MIC(90) = 1), respectively, for all isolates. At the higher inoculum, MICs shifted for cefepime, imipenem, and tigecycline. Change in log(10) cfu/ml from baseline to 24 hours for cefepime, imipenem, and tigecycline alone ranged from 4.85-0.71, 5-4.22, and 3.5-1.01, respectively, for all isolates. Bactericidal activity was observed for cefepime alone (10 [50%] of 20 isolates), imipenem alone (20 [100%] of 20), and tigecycline alone (3 [15%] of 20). Combination studies with cefepime plus tigecycline resulted in synergy against 4 (20%) of 20 isolates. Combination studies with gentamicin resulted in synergy against 6 isolates (30%) with cefepime and 4 isolates (20%) with tigecycline. No synergy was observed with imipenem combinations. No antagonism was observed. With the exception of cefepime, correlations were observed between MIC and terminal densities for studied agents.

CONCLUSIONS

Cefepime exhibited bactericidal activity but was unrelated to susceptibility. Tigecycline exhibited predictable bacteriostatic activity and synergy in combination against a subset of study isolates. Imipenem exhibited predictable bactericidal activity against all isolates. The utility of combination regimens with novel agents requires further exploration.

Authors+Show Affiliations

Anti-infective Research Laboratory, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan 48201, USA. r.cha@wayne.edu

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

18294108

Citation

Cha, Raymond. "In Vitro Activity of Cefepime, Imipenem, Tigecycline, and Gentamicin, Alone and in Combination, Against Extended-spectrum Beta-lactamase-producing Klebsiella Pneumoniae and Escherichia Coli." Pharmacotherapy, vol. 28, no. 3, 2008, pp. 295-300.
Cha R. In vitro activity of cefepime, imipenem, tigecycline, and gentamicin, alone and in combination, against extended-spectrum beta-lactamase-producing Klebsiella pneumoniae and Escherichia coli. Pharmacotherapy. 2008;28(3):295-300.
Cha, R. (2008). In vitro activity of cefepime, imipenem, tigecycline, and gentamicin, alone and in combination, against extended-spectrum beta-lactamase-producing Klebsiella pneumoniae and Escherichia coli. Pharmacotherapy, 28(3), 295-300. https://doi.org/10.1592/phco.28.3.295
Cha R. In Vitro Activity of Cefepime, Imipenem, Tigecycline, and Gentamicin, Alone and in Combination, Against Extended-spectrum Beta-lactamase-producing Klebsiella Pneumoniae and Escherichia Coli. Pharmacotherapy. 2008;28(3):295-300. PubMed PMID: 18294108.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In vitro activity of cefepime, imipenem, tigecycline, and gentamicin, alone and in combination, against extended-spectrum beta-lactamase-producing Klebsiella pneumoniae and Escherichia coli. A1 - Cha,Raymond, PY - 2008/2/26/pubmed PY - 2008/6/5/medline PY - 2008/2/26/entrez SP - 295 EP - 300 JF - Pharmacotherapy JO - Pharmacotherapy VL - 28 IS - 3 N2 - STUDY OBJECTIVE: To evaluate the activity of cefepime, imipenem, tigecycline, and gentamicin, alone and in combination, against extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae and Escherichia coli. DESIGN: In vitro susceptibility and time-kill analysis. SETTING: University-affiliated research laboratory. ISOLATES: Ten K. pneumoniae and 10 E. coli clinical strains known to produce ESBL. MEASUREMENTS AND MAIN RESULTS: Minimum inhibitory concentration (MIC) testing was performed at 5.5 and 7.0 log(10) colony-forming units (cfu)/ml. Time-kill studies were performed over 24 hours with a high inoculum of 7.0 log(10) cfu/ml for cefepime, imipenem, tigecycline, and gentamicin at 1 times MIC. Combination studies were tested for cefepime plus tigecycline, cefepime plus imipenem, imipenem plus tigecycline, and for adjunctive gentamicin with cefepime, imipenem, or tigecycline. At the high inoculum, the MIC ranges for cefepime, imipenem, tigecycline, and gentamicin were 0.25-256 (MIC for 90% of tested strains [MIC(90)] = 32), 0.125-2 (MIC(90) = 1), 0.25-16 (MIC(90) = 4), and 0.25-4 mg/L (MIC(90) = 1), respectively, for all isolates. At the higher inoculum, MICs shifted for cefepime, imipenem, and tigecycline. Change in log(10) cfu/ml from baseline to 24 hours for cefepime, imipenem, and tigecycline alone ranged from 4.85-0.71, 5-4.22, and 3.5-1.01, respectively, for all isolates. Bactericidal activity was observed for cefepime alone (10 [50%] of 20 isolates), imipenem alone (20 [100%] of 20), and tigecycline alone (3 [15%] of 20). Combination studies with cefepime plus tigecycline resulted in synergy against 4 (20%) of 20 isolates. Combination studies with gentamicin resulted in synergy against 6 isolates (30%) with cefepime and 4 isolates (20%) with tigecycline. No synergy was observed with imipenem combinations. No antagonism was observed. With the exception of cefepime, correlations were observed between MIC and terminal densities for studied agents. CONCLUSIONS: Cefepime exhibited bactericidal activity but was unrelated to susceptibility. Tigecycline exhibited predictable bacteriostatic activity and synergy in combination against a subset of study isolates. Imipenem exhibited predictable bactericidal activity against all isolates. The utility of combination regimens with novel agents requires further exploration. SN - 0277-0008 UR - https://www.unboundmedicine.com/medline/citation/18294108/In_vitro_activity_of_cefepime_imipenem_tigecycline_and_gentamicin_alone_and_in_combination_against_extended_spectrum_beta_lactamase_producing_Klebsiella_pneumoniae_and_Escherichia_coli_ DB - PRIME DP - Unbound Medicine ER -