Influence of Antimicrobial Stewardship and Molecular Rapid Diagnostic Tests on Antimicrobial Prescribing for Extended-Spectrum Beta-Lactamase- and Carbapenemase-Producing Escherichia coli and Klebsiella pneumoniae in Bloodstream Infection

Abstract

ABSTRACT The objective of this study was to evaluate whether the addition of the Verigene BC-GN molecular rapid diagnostic test to standard antimicrobial stewardship practices (mRDT + ASP) decreased the time to optimal and effective antimicrobial therapy for patients with extended-spectrum beta-lactamase (ESBL)- and carbapenemase-producing Escherichia coli and Klebsiella pneumoniae bloodstream infections (BSI) compared to conventional microbiological methods with ASP (CONV + ASP). This was a multicenter, retrospective cohort study evaluating the time to optimal antimicrobial therapy in 5 years of patients with E. coli or K. pneumoniae BSI determined to be ESBL- or carbapenemase-producing by mRDT and/or CONV. Of the 378 patients included (mRDT + ASP, n = 164; CONV + ASP, n = 214), 339 received optimal antimicrobial therapy (mRDT + ASP, n = 161; CONV + ASP, n = 178), and 360 (mRDT + ASP, n = 163; CONV + ASP, n = 197) received effective antimicrobial therapy. The mRDT + ASP demonstrated a statistically significant decrease in the time to optimal antimicrobial therapy (20.5 h [interquartile range (IQR), 17.0 to 42.2 h] versus 50.1 h [IQR, 27.6 to 77.9 h]; P < 0.001) and the time to effective antimicrobial therapy (15.9 h [IQR, 1.9 to 25.7 h] versus 28.0 h [IQR, 9.5 to 56.7 h]; P < 0.001) compared to CONV + ASP, respectively. IMPORTANCE Our study supports the additional benefit of molecular rapid diagnostic test in combination with timely antimicrobial stewardship program (ASP) intervention on shortening the time to both optimal and effective antimicrobial therapy in patients with ESBL- or carbapenemase-producing Escherichia coli and Klebsiella pneumoniae bloodstream infections, compared to conventional microbiological methods and ASP. Gram-negative infections are associated with significant morbidity and mortality, often resulting in life-threatening organ dysfunction. Both resistance phenotypes confer resistance to many of our first-line antimicrobial agents with carbapenemase-producing Enterobacterales requiring novel beta-lactam and beta-lactamase inhibitor combinations or other susceptible non-beta-lactam antibiotics for treatment. National resistance trends in a cohort of hospitalized patients at U.S. hospitals during our study period demonstrate the increasing incidence of both resistance phenotypes, reinforcing the generalizability and timeliness of such analysis.

Keywords

• molecular rapid diagnostic test
• antimicrobial stewardship program
• extended-spectrum beta-lactamase-producing Enterobacterales
• carbapenemase-producing Enterobacterales