Within-host genetic diversity of extended-spectrum beta-lactamase-producing Enterobacterales in long-term colonized patients.

Despite recognition of the immediate impact of infections caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales (ESBL-PE) on human health, essential aspects of their molecular epidemiology remain under-investigated. This includes knowledge on the potential of a particular strain to persist in a host, mutational events during colonization, and the genetic diversity in individual patients over time. To investigate long-term genetic diversity of colonizing and infecting ESBL-Klebsiella pneumoniae species complex and ESBL-Escherichia coli in individual patients over time, we performed a ten-year longitudinal retrospective study and extracted clinical and microbiological data from electronic health records. In this investigation, 76 ESBL-K. pneumoniae species complex and 284 ESBL-E. coli isolates were recovered from 19 and 61 patients. Strain persistence was detected in all patients colonized with ESBL-K. pneumoniae species complex, and 83.6% of patients colonized with ESBL-E. coli. We frequently observed isolates of the same strain recovered from different body sites associated with either colonization or infection. Antimicrobial resistance genes, plasmid replicons, and whole ESBL-plasmids were shared between isolates regardless of chromosomal relatedness. Our study suggests that patients colonized with ESBL-producers may act as durable reservoirs for ongoing transmission of ESBLs, and that they are at prolonged risk of recurrent infection with colonizing strains.

Epidemiology of patients harboring carbapenemase-producing bacteria and comparison with patients with detection of extended-spectrum beta-lactamase-producing Enterobacterales-A retrospective cohort study.

OBJECTIVE: We evaluated the epidemiology of carbapenemase-producing bacteria (CPB) in Switzerland by comparing risk factors between patients colonized with CPB and patients colonized with extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-PE). METHODS: This retrospective cohort study was conducted at the University Hospital Basel in Switzerland. Hospitalized patients with CPB in any sample between January 2008 and July 2019 were included. The ESBL-PE group consisted of hospitalized patients with detection of ESBL-PE from any sample between January 2016 and December 2018. Comparisons of risk factors for acquisition of CPB and ESBL-PE were performed by logistic regression. RESULTS: Inclusion criteria were met for 50 patients in the CPB group and 572 in the ESBL-PE group. In the CPB group, 62% had a travel history and 60% had been hospitalized abroad. When comparing the CPB group to the ESBL-PE group, hospitalization abroad (odds ratio [OR], 25.33; 95% confidence interval [CI], 11.07-57.98) and prior antibiotic therapy (OR, 4.76; 95% CI, 2.15-10.55) remained independently associated with CPB colonization. Hospitalization abroad (P < .001) and prior antibiotic therapy (P < .001) predicted CPB in the comparison of CPB with ESBL Escherichia coli, whereas hospitalization abroad was associated with CPB in comparison to ESBL Klebsiella pneumoniae. CONCLUSIONS: Although CPB still seem to be mainly imported from areas of higher endemicity, local acquisition of CPB is emerging, especially in patients with close and/or frequent contact with healthcare services. This trend resembles the epidemiology of ESBL K. pneumoniae, supporting mainly healthcare-associated transmission. Frequent evaluation of CPB epidemiology is required to improve detection of patients at risk of CPB carriage.

Risk factors for colonization with multiple species of extended-spectrum beta-lactamase producing Enterobacterales: a case-case-control study.

BACKGROUND: Approximately 11% of patients colonized with extended-spectrum beta-lactamase producing Enterobacterales (ESBL-PE) are colonized with more than one ESBL-producing species. We investigated risk factors associated with colonization with multiple ESBL-PE species. METHODS: We performed a case-case-control study at the University Hospital Basel, Switzerland, including hospitalized patients colonized with ESBL-PE between 01/2008 and 12/2018. Patients colonized with multiple species of ESBL-PE during the same hospitalization were assigned to group 1. Group 2 consisted of patients with ESBL-PE and a newly acquired ESBL-PE-species identified during subsequent hospitalization. Controls (i.e., group 3) were patients with only one species of ESBL-PE identified over multiple hospitalizations. Controls were frequency-matched 3:1 to group 2 cases according to time-at-risk (i.e., days between ESBL-PE detection during first and subsequent hospitalizations) to standardize the duration of colonization. ESBL was identified with phenotypic assay and the presence of ESBL genes was confirmed by whole genome sequencing. RESULTS: Among 1559 inpatients, 154 cases met eligibility criteria (67 in group 1, 22 in group 2, 65 in group 3). International travel within the previous 12 months (OR 12.57, 95% CI 3.48-45.45, p < 0.001) and antibiotic exposure within the previous 3 months (OR 2.96, 95% CI 1.37-6.41, p = 0.006) were independently associated with co-colonization with multiple ESBL-PE species. Admission from another acute-care facility was the only predictor of replacement of one ESBL-PE species with another during subsequent hospitalizations (OR 6.02, 95% CI 1.15-31.49, p = 0.003). CONCLUSION: These findings point to strain-related factors being the main drivers of co-colonization with different ESBL-PE and may support stratification of infection prevention and control measures according to ESBL-PE species/strains.

Infections in Patients Colonized With Extended-spectrum Beta-Lactamase-Producing Enterobacterales: A Retrospective Cohort Study.

We investigated relative proportions of extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-PE) versus non-ESBL-PE (nESBL-PE) infections in ESBL-PE colonized patients. ESBL-PE are not causative for the majority of infections in hospitalized patients colonized with ESBL-PE. Site of infection and patient-level exposures may be useful predictors of nESBL-PE infections, potentially guiding empiric treatment recommendations.

Independent, external validation of clinical prediction rules for the identification of extended-spectrum ß-lactamase-producing Enterobacterales, University Hospital Basel, Switzerland, January 2010 to December 2016.

BackgroundAlgorithms for predicting infection with extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-PE) on hospital admission or in patients with bacteraemia have been proposed, aiming to optimise empiric treatment decisions.AimWe sought to confirm external validity and transferability of two published prediction models as well as their integral components.MethodsWe performed a retrospective case-control study at University Hospital Basel, Switzerland. Consecutive patients with ESBL-producing Escherichia coli or Klebsiella pneumoniae isolated from blood samples between 1 January 2010 and 31 December 2016 were included. For each case, three non-ESBL-producing controls matching for date of detection and bacterial species were identified. The main outcome measure was the ability to accurately predict infection with ESBL-PE by measures of discrimination and calibration.ResultsOverall, 376 patients (94 patients, 282 controls) were analysed. Performance measures for prediction of ESBL-PE infection of both prediction models indicate adequate measures of calibration, but poor discrimination (area under receiver-operating curve: 0.627 and 0.651). History of ESBL-PE colonisation or infection was the single most predictive independent risk factor for ESBL-PE infection with high specificity (97%), low sensitivity (34%) and balanced positive and negative predictive values (80% and 82%).ConclusionsApplying published prediction models to institutions these were not derived from, may result in substantial misclassification of patients considered as being at risk, potentially leading to wrong allocation of antibiotic treatment, negatively affecting patient outcomes and overall resistance rates in the long term. Future prediction models need to address differences in local epidemiology by allowing for customisation according to different settings.

Persisting intrahospital transmission of multidrug-resistant Klebsiella pneumoniae and challenges for infection control.

In the past several decades, the incidence of Klebsiella pneumoniae harboring resistance mechanisms against multiple antibiotic agents has increased on a global scale. We discuss reasons for ongoing transmission of multidrug-resistant K. pneumoniae in healthcare settings, which has resulted in the successful spread and establishment of this pathogen. It is now one of the most important causes of healthcare-associated infections worldwide.

[CME: Zoonosis in Switzerland: Leptospirosis]. / CME: Zoonosen in der Schweiz: Leptospirose CME-Fragen.

CME: Zoonosis in Switzerland: Leptospirosis Abstract. Leptospirosis is worldwide a common zoonosis that also occurs in Switzerland. Frequently it presents as a self-limited, mild illness. The more severe presentation with jaundice and sever acute kidney injury (Weil's disease) is, however, associated with a high morbidity and mortality. In order to make the diagnosis, it is important to recognize the typical findings and perform the appropriate diagnostic workup. In this article, we discuss the clinical signs, diagnostic workup, therapy and prevention of leptospirosis and present the case of a 54-year-old patient with severe leptospirosis.