A Test for the Rapid Detection of the Cefazolin Inoculum Effect in Methicillin-Susceptible Staphylococcus aureus

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Autores organización

Autores

  • Gomez-Villegas SI
  • Rios R
  • Dinh A
  • Pedroza C
  • Ordoñez KM
  • Nannini E
  • Sun Z
  • Fowler VG
  • Murray BE
  • Miller WR
  • Palzkill T
  • Diaz L
  • Arias CA

Grupos de investigación

Resumen

The cefazolin inoculum effect (CzIE) has been associated with therapeutic failures and mortality in invasive methicillin-susceptible Staphylococcus aureus (MSSA) infections. A diagnostic test to detect the CzIE is not currently available. We developed a rapid (;3 h) CzIE colorimetric test to detect staphylococcal-b-lactamase (BlaZ) activity in supernatants after ampicillin induction. The test was validated using 689 bloodstream MSSA isolates recovered from Latin America and the United States. The cefazolin MIC determination at a high inoculum (107 CFU/ml) was used as a reference standard (cutoff $16mg/ml). All isolates underwent genome sequencing. A total of 257 (37.3%) of MSSA isolates exhibited the CzIE by the reference standard method. The overall sensitivity and specificity of the colorimetric test was 82.5% and 88.9%, respectively. Sensitivity in MSSA isolates harboring type A BlaZ (the most efficient enzyme against cefazolin) was 92.7% with a specificity of 87.8%. The performance of the test was lower against type B and C enzymes (sensitivities of 53.3% and 72.3%, respectively). When the reference value was set to $32mg/ml, the sensitivity for isolates carrying type A enzymes was 98.2%. Specificity was 100% for MSSA lacking blaZ. The overall negative predictive value ranged from 81.4% to 95.6% in Latin American countries using published prevalence rates of the CzIE. MSSA isolates from the United States were genetically diverse, with no distinguishing genomic differences from Latin American MSSA, distributed among 18 sequence types. A novel test can readily identify most MSSA isolates exhibiting the CzIE, particularly those carrying type A BlaZ. In contrast to the MIC determination using high inoculum, the rapid test is inexpensive, feasible, and easy to perform. After minor validation steps, it could be incorporated into the routine clinical laboratory workflow. Copyright © 2021 American Society for Microbiology. All Rights Reserved.

Copyright © 2021 American Society for Microbiology.

Datos de la publicación

ISSN/ISSNe:
0095-1137, 1098-660X

Journal Of Clinical Microbiology  American Society for Microbiology

Tipo:
Article
Páginas:
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Enlace a otro recurso:
www.scopus.com

Citas Recibidas en Web of Science: 6

Citas Recibidas en Scopus: 11

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Keywords

  • Anti-Bacterial Agents; Cefazolin; Diagnostic Tests, Routine; Humans; Latin America; Methicillin; Microbial Sensitivity Tests; Staphylococcal Infections; Staphylococcus aureus; ampicillin; beta lactamase; cefazolin; cephalosporin; nitrocefin; antiinfective agent; cefazolin; meticillin; Article; bacterial genome; bacterium detection; bacterium isolate; bloodstream infection; colorimetry; controlled study; diagnostic test; endocarditis; enzyme activity; gene sequence; genetic variability; human; methicillin susceptible Staphylococcus aureus; methicillin susceptible Staphylococcus aureus infection; nonhuman; phylogeny; predictive value; priority journal; sensitivity and specificity; diagnostic test; genetics; microbial sensitivity test; South and Central America; Staphylococcus aureus; Staphylococcus infection

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