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

Publication ,  Journal Article
Rincon, S; Carvajal, LP; Gomez-Villegas, SI; Echeverri, AM; Rios, R; Dinh, A; Pedroza, C; Ordoñez, KM; Nannini, E; Sun, Z; Fowler, VG; Diaz, L ...
Published in: J Clin Microbiol
March 19, 2021

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-β-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 ≥16 μg/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 ≥32 μg/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.

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Published In

J Clin Microbiol

DOI

EISSN

1098-660X

Publication Date

March 19, 2021

Volume

59

Issue

4

Location

United States

Related Subject Headings

  • Staphylococcus aureus
  • Staphylococcal Infections
  • Microbiology
  • Microbial Sensitivity Tests
  • Methicillin
  • Latin America
  • Humans
  • Diagnostic Tests, Routine
  • Cefazolin
  • Anti-Bacterial Agents
 

Citation

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Rincon, S., Carvajal, L. P., Gomez-Villegas, S. I., Echeverri, A. M., Rios, R., Dinh, A., … Reyes, J. (2021). A Test for the Rapid Detection of the Cefazolin Inoculum Effect in Methicillin-Susceptible Staphylococcus aureus. J Clin Microbiol, 59(4). https://doi.org/10.1128/JCM.01938-20
Rincon, Sandra, Lina P. Carvajal, Sara I. Gomez-Villegas, Aura M. Echeverri, Rafael Rios, An Dinh, Claudia Pedroza, et al. “A Test for the Rapid Detection of the Cefazolin Inoculum Effect in Methicillin-Susceptible Staphylococcus aureus.J Clin Microbiol 59, no. 4 (March 19, 2021). https://doi.org/10.1128/JCM.01938-20.
Rincon S, Carvajal LP, Gomez-Villegas SI, Echeverri AM, Rios R, Dinh A, et al. A Test for the Rapid Detection of the Cefazolin Inoculum Effect in Methicillin-Susceptible Staphylococcus aureus. J Clin Microbiol. 2021 Mar 19;59(4).
Rincon, Sandra, et al. “A Test for the Rapid Detection of the Cefazolin Inoculum Effect in Methicillin-Susceptible Staphylococcus aureus.J Clin Microbiol, vol. 59, no. 4, Mar. 2021. Pubmed, doi:10.1128/JCM.01938-20.
Rincon S, Carvajal LP, Gomez-Villegas SI, Echeverri AM, Rios R, Dinh A, Pedroza C, Ordoñez KM, Nannini E, Sun Z, Fowler VG, Murray BE, Miller WR, Palzkill T, Diaz L, Arias CA, Reyes J. A Test for the Rapid Detection of the Cefazolin Inoculum Effect in Methicillin-Susceptible Staphylococcus aureus. J Clin Microbiol. 2021 Mar 19;59(4).

Published In

J Clin Microbiol

DOI

EISSN

1098-660X

Publication Date

March 19, 2021

Volume

59

Issue

4

Location

United States

Related Subject Headings

  • Staphylococcus aureus
  • Staphylococcal Infections
  • Microbiology
  • Microbial Sensitivity Tests
  • Methicillin
  • Latin America
  • Humans
  • Diagnostic Tests, Routine
  • Cefazolin
  • Anti-Bacterial Agents