Adjunctive Clavulanic Acid Abolishes the Cefazolin Inoculum Effect in an Experimental Rat Model of Methicillin-Sensitive Staphylococcus aureus Endocarditis

William R. Miller; Kavindra V. Singh; Cesar A. Arias; Barbara E. Murray

doi:10.1128/AAC.01158-18

Adjunctive Clavulanic Acid Abolishes the Cefazolin Inoculum Effect in an Experimental Rat Model of Methicillin-Sensitive Staphylococcus aureus Endocarditis

William R. Miller, Kavindra V. Singh, Cesar A. Arias, Barbara E. Murray

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

Abstract

We tested the ability of clavulanic acid to restore the efficacy of cefazolin against Staphylococcus aureus TX0117, which exhibits the cefazolin inoculum effect (CzIE). In the rat infective endocarditis model, the coadministration of cefazolin plus clavulanic acid resulted in a significant reduction of bacterial counts (7.1 0.5 log₁₀ CFU/g) compared to that with cefazolin alone (2 0.6 log₁₀ CFU/g; P 0.0001). The addition of a -lactamase inhibitor may be a viable strategy for overcoming the CzIE.

Original language	English (US)
Article number	e01158-18
Journal	Antimicrobial Agents and Chemotherapy
Volume	62
Issue number	11
DOIs	https://doi.org/10.1128/AAC.01158-18
State	Published - Nov 2018

Keywords

Animal models
Cefazolin
Clavulanic acid
Infective endocarditis
Inoculum effect
Staphylococcus aureus

ASJC Scopus subject areas

Pharmacology
Pharmacology (medical)
Infectious Diseases

Divisions

Infectious Disease

Access to Document

10.1128/AAC.01158-18

Cite this

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title = "Adjunctive Clavulanic Acid Abolishes the Cefazolin Inoculum Effect in an Experimental Rat Model of Methicillin-Sensitive Staphylococcus aureus Endocarditis",

abstract = "We tested the ability of clavulanic acid to restore the efficacy of cefazolin against Staphylococcus aureus TX0117, which exhibits the cefazolin inoculum effect (CzIE). In the rat infective endocarditis model, the coadministration of cefazolin plus clavulanic acid resulted in a significant reduction of bacterial counts (7.1 0.5 log10 CFU/g) compared to that with cefazolin alone (2 0.6 log10 CFU/g; P 0.0001). The addition of a -lactamase inhibitor may be a viable strategy for overcoming the CzIE.",

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language = "English (US)",

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journal = "Antimicrobial Agents and Chemotherapy",

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publisher = "American Society for Microbiology",

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AU - Arias, Cesar A.

AU - Murray, Barbara E.

PY - 2018/11

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N2 - We tested the ability of clavulanic acid to restore the efficacy of cefazolin against Staphylococcus aureus TX0117, which exhibits the cefazolin inoculum effect (CzIE). In the rat infective endocarditis model, the coadministration of cefazolin plus clavulanic acid resulted in a significant reduction of bacterial counts (7.1 0.5 log10 CFU/g) compared to that with cefazolin alone (2 0.6 log10 CFU/g; P 0.0001). The addition of a -lactamase inhibitor may be a viable strategy for overcoming the CzIE.

AB - We tested the ability of clavulanic acid to restore the efficacy of cefazolin against Staphylococcus aureus TX0117, which exhibits the cefazolin inoculum effect (CzIE). In the rat infective endocarditis model, the coadministration of cefazolin plus clavulanic acid resulted in a significant reduction of bacterial counts (7.1 0.5 log10 CFU/g) compared to that with cefazolin alone (2 0.6 log10 CFU/g; P 0.0001). The addition of a -lactamase inhibitor may be a viable strategy for overcoming the CzIE.

KW - Animal models

KW - Cefazolin

KW - Clavulanic acid

KW - Infective endocarditis

KW - Inoculum effect

KW - Staphylococcus aureus

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Adjunctive Clavulanic Acid Abolishes the Cefazolin Inoculum Effect in an Experimental Rat Model of Methicillin-Sensitive Staphylococcus aureus Endocarditis

Abstract

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