In:
Journal of Clinical Microbiology, American Society for Microbiology, Vol. 60, No. 7 ( 2022-07-20)
Abstract:
We investigated the performance of the Xpert methicillin-resistant Staphylococcus aureus (MRSA)/ S. aureus skin and soft tissue (SSTI) quantitative PCR (qPCR) assay in SAATELLITE, a multicenter, double-blind, phase 2 study of suvratoxumab, a monoclonal antibody (MAb) targeting S. aureus alpha-toxin, for reducing the incidence of S. aureus pneumonia. The assay was used to detect methicillin-susceptible S. aureus (MSSA) and MRSA in lower respiratory tract (LRT) samples from mechanically ventilated patients. LRT culture results were compared with S. aureus protein A ( spa ) gene cycle threshold ( C T ) values. Receiver operating characteristic (ROC) and Youden index were used to determine the C T cutoff for best separation of culture- S. aureus -negative and S. aureus -positive patients. Of 720 screened subjects, 299 (41.5%) were S. aureus positive by qPCR, of whom 209 had culture data: 162 (77.5%) were S. aureus positive and 47 (22.5%) were S. aureus negative. Culture results were negatively affected by antibiotic use and cross-laboratory variability. An inverse linear correlation was observed between C T values and quantitative S. aureus culture results. A spa C T value of 29 (≈2 × 10 3 CFU/mL) served as the best cutoff for separation between culture-negative and culture-positive samples. The associated area under the ROC curve was 83.8% (95% confidence interval [CI], 78 to 90%). Suvratoxumab provided greater reduction in S. aureus pneumonia or death than placebo in subjects with low S. aureus load ( C T ≥ 29; relative risk reduction [RRR], 50.0%; 90% CI, 2.7 to 74.4%) versus the total study population (RRR, 25.2%; 90% CI, −4.3 to 46.4%). The qPCR assay was easy t o perform, sensitive, and standardized and provided better sensitivity than conventional culture for S. aureus detection. Quantitative PCR C T output correlated with suvratoxumab efficacy in reducing S. aureus pneumonia incidence or death in S. aureus -colonized, mechanically ventilated patients.
Type of Medium:
Online Resource
ISSN:
0095-1137
,
1098-660X
DOI:
10.1128/jcm.00347-22
Language:
English
Publisher:
American Society for Microbiology
Publication Date:
2022
detail.hit.zdb_id:
1498353-9
SSG:
12
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