Extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae (EPE) in urine or feces is a substantial risk factor for subsequent EPE-bloodstream infection (BSI), according to a study recently published in Clinical Infectious Diseases.
The prevalence of EBSL-producing Escherichia coli and Klebsiella pneumoniae increased in clinical isolates in Europe between 2013 and 2016. In 2016, 22 countries reported >10% resistance to third-generation cephalosporin drugs among invasive E coli isolates. In the United States, 1700 deaths were attributed to BSI with EPE in 2013. A meta-analysis has estimated that the mortality rate from EPE-BSI is approximately double that for BSI with Enterobacteriaceae that are sensitive to third-generation cephalosporin drugs. Urinary tract infections are the most common clinical manifestations of ESBL-producing E coli. EPE normally reside in the gut and there is currently a global surge in intestinal colonization. Case-control studies report that colonization and previous use of antibiotics (fluoroquinolones and cephalosporins specifically) increase the risk for subsequent EPE-BSI. Currently, there are no large-scale cohort studies that assess the long-term risk or associated risk factors for severe infections with EPE in previously colonized individuals.
This study used a Public Health Agency of Sweden nationwide EPE register (SmiNet) to investigate the incidence of EPE-BSI up to 6 years after EPE-positive feces (n=5513) or urine (n=17189) culture compared with the incidence in the general population. In addition, this study investigated the influence of sociodemographic factors, comorbidities, and antibiotic use on subsequent EPE-BSI risk in individuals with a previous finding of EPE. Study subjects were followed until the occurrence of either study outcome, emigration, death, or end of the study period (December 31, 2012). The outcome was defined as the first EPE-positive blood culture. Outcomes <30 days of the positive urine/feces culture were defined as prevalent and ≥30 days after the culture were defined as incident.
The cumulative 6-year EPE-BSI incidence was 3.8%, 1.6%, and 0.02% in the urine, feces, and reference cohorts, respectively. Individuals with a previous documented EPE finding in urine or feces have a 61- and 32-fold increased risk, respectively, for incident EPE-BSI compared with the general population. This risk remains increased for approximately 3 years following a positive fecal culture and 5 years following a positive urine culture. Notably, investigators assert this risk diminishes significantly during the first 6 months and the first year after a positive fecal culture and a positive urine culture, respectively. Among EPE-exposed subjects, urologic disorders were associated with the highest adjusted cause-specific hazard ratio for subsequent EPE-BSI: 3.40. The adjusted cause-specific hazard ratios were between 1.62 and 2.20 for male sex, immunosuppression, diabetes, malignancy, lung disease, baseline urine source, and presence of K pneumoniae compared with E coli baseline sample. For example, a male with a urologic disorder and previous finding of ESBL-producing K pneumoniae has a 14-fold increased relative risk for subsequent EPE-BSI compared with a woman without urologic disorder and a previous finding of ESBL-producing E coli in feces. Furthermore, antibiotics with selective activity against gram-negative bacilli but not EPE (trimethoprim-sulfamethoxazole, fluoroquinolones, oral cephalosporins, and penicillins with extended spectrum), and pivmecillinam were associated with a two-fold increase in EPE-BSI risk during 3 months after antibiotic course.
Overall, the investigators conclude that, “We have identified high-risk populations that can become targets for interventions such as eradication therapy and antibiotic stewardship programs.”
Isendahl J, Giske CG, Hammar U, et al. Temporal dynamics and risk factors for bloodstream infection with extended-spectrum β-lactamase-producing bacteria in previously colonized individuals: national population-based cohort study [published online June 29, 2018]. Clin Infect Dis. doi: 10.1093/cid/ciy539