Details

Autor(en) / Beteiligte

• Tarlton, Nicole J
• Petrovic, Danka-Florence
• Frazee, Bradley W
• Borges, Clarissa A
• Pham, Emily M
• Milton, Aubrianne K
• Jackson, Nicole
• deBoer, Tara R
• Murthy, Niren
• Riley, Lee W

Titel

A Dual Enzyme-Based Biochemical Test Rapidly Detects Third-Generation Cephalosporin-Resistant CTX-M-Producing Uropathogens in Clinical Urine Samples

Ist Teil von

• Microbial drug resistance (Larchmont, N.Y.), 2021-04, Vol.27 (4), p.450-461

Ort / Verlag

United States

Erscheinungsjahr

2021

Quelle

MEDLINE

Beschreibungen/Notizen

• Extended-spectrum β-lactamase (ESBL)-producing Gram-negative bacteria (GNB) are increasingly identified as the cause of both community and healthcare-associated urinary tract infections (UTIs), with CTX-Ms being the most common ESBLs identified. CTX-M-producing GNB are resistant to most β-lactam antibiotics and are frequently multidrug-resistant, which limits treatment options. Rapid diagnostic tests that can detect ESBL-producing GNB, particularly CTX-M producers, in the urine of patients with UTIs are needed. Results from such a test could direct the selection of appropriate antimicrobial therapy at the point-of-care (POC). In this study, we show that a chromogenic, dual enzyme-mediated amplification system (termed DETECT [dual-enzyme trigger-enabled cascade technology]) can identify CTX-M-producing GNB from unprocessed urine samples in 30 minutes. We first tested DETECT against a diverse set of recombinant β-lactamases and β-lactamase-producing clinical isolates to elucidate its selectivity. We then tested DETECT with 472 prospectively collected clinical urine samples submitted for urine culture to a hospital clinical microbiology laboratory. Of these, 118 (25%) were consistent with UTI, 13 (11%) of which contained ESBL-producing GNB. We compared DETECT results in urine against a standard phenotypic method to detect ESBLs, and polymerase chain reaction and sequencing for CTX-M genes. DETECT demonstrated 90.9% sensitivity and 97.6% specificity (AUC, 0.937; 95% confidence interval, 0.822-1.000), correctly identifying 10 of 11 urine samples containing a clinically significant concentration of CTX-M-producing GNB (including , , and ). Our results demonstrate the clinical potential of DETECT to deliver diagnostic information at the POC, which could improve initial antibiotic selection.