Suchergebnisse

BACKGROUND: We evaluated data from isolates of nursing home (NH) patients sent to the Swiss centre for antibiotic resistance (ANRESIS). We focussed on carbapenem-resistance (CR) among Gram-negative pathogens, extended-spectrum cephalosporin-resistant (ESC-R) Escherichia coli/Klebsiella pneumoniae, methicillin-resistant Staphylococcus aureus (MRSA), and glycopeptide-resistant enterococci (GRE). METHODS: NH patient isolates from 01/2007 to 10/2017 were extracted. Temporal trends in resistance were described and risk factors associated with ESC-R and MRSA were assessed. For every administrative subdivision in Switzerland (i.e. canton), we calculated a coverage rate, defined as number of beds of governmentally-supported nursing homes, which sent ≥1 isolate in each 2014, 2015, and 2016, divided by the total number of supported beds. RESULTS: We identified 16'804 samples from 9'940 patients. A majority of samples (12'040; 71.6%) originated from the French/Italian speaking part of Switzerland. ESC-R E. coli increased from 5% (16/299) in 2007 to 22% (191/884) in 2017 (P < 0.01), whereas MRSA decreased from 34% (35/102) to 26% (21/81) (P < 0.01). Provenience from the German (vs. French/Italian) speaking part of Switzerland was associated with decreased risk for ESC-R (OR 0.5, 95% CI 0.4-0.7) and for MRSA (OR 0.1, 95% CI 0.1-0.2). CR among Pseudomonas aeruginosa was 10% (105/1096) and showed an increasing trend over time; CR among Enterobacteriaceae (37/12'423, 0.3%) and GRE (5/1'273, 0.4%) were uncommon. Overall coverage rate was 9% (range 0-58% per canton). There was a significant difference between the French/Italian (median 13%, interquartile range [IQR] 4-43%) and the German speaking cantons (median 0%, IQR 0-5%) (P = 0.02). CONCLUSIONS: ESC-R among E. coli is emerging in Swiss NHs, whereas MRSA show a declining trend over time. A minority of NHs are represented in ANRESIS, with a preponderance of institutions from the French/Italian speaking regions. Efforts should be undertaken to improve resistance surveillance in this high-risk setting.

BACKGROUND: Efflux pumps mediate antimicrobial resistance in several WHO critical priority bacterial pathogens. However, most available data come from laboratory strains. The quantitative relevance of efflux in more relevant clinical isolates remains largely unknown. METHODS: We developed a versatile method for genetic engineering in multi-drug resistant (MDR) bacteria, and used this method to delete tolC and specific antibiotic-resistance genes in 18 representative MDR clinical E. coli isolates. We determined efflux activity and minimal inhibitory concentrations for a diverse set of clinically relevant antibiotics in these mutants. We also deleted oprM in MDR P. aeruginosa strains and determined the impact on antibiotic susceptibility. FINDINGS: tolC deletion abolished detectable efflux activity in 15 out of 18 tested E. coli strains, and modulated antibiotic susceptibility in many strains. However, all mutant strains retained MDR status, primarily because of other, antibiotic-specific resistance genes. Deletion of oprM altered antibiotic susceptibility in a fraction of clinical P. aeruginosa isolates. INTERPRETATION: Efflux modulates antibiotic resistance in clinical MDR isolates of E. coli and P. aeruginosa. However, when other antimicrobial-resistance mechanisms are present, inhibition of MDR efflux pumps alone is often not sufficient to restore full susceptibility even for antibiotics with a dramatic impact of efflux in laboratory strains. We propose that development of novel antibiotics should include target validation in clinical MDR isolates. FUND: Innovative Medicines Initiative of European Union and EFPIA, Schweizerischer Nationalfonds, Swiss National Research Program 72, EU Marie Skłodowska-Curie program. The funders played no role in design, data collection, data analysis, interpretation, writing of the report, and in the decision to submit the paper for publication.

BACKGROUND: The risk of tuberculosis outbreaks among people fleeing hardship for refuge in Europe is heightened. We describe the cross-border European response to an outbreak of multidrug-resistant tuberculosis among patients from the Horn of Africa and Sudan. METHODS: On April 29 and May 30, 2016, the Swiss and German National Mycobacterial Reference Laboratories independently triggered an outbreak investigation after four patients were diagnosed with multidrug-resistant tuberculosis. In this molecular epidemiological study, we prospectively defined outbreak cases with 24-locus mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) profiles; phenotypic resistance to isoniazid, rifampicin, ethambutol, pyrazinamide, and capreomycin; and corresponding drug resistance mutations. We whole-genome sequenced all Mycobacterium tuberculosis isolates and clustered them using a threshold of five single nucleotide polymorphisms (SNPs). We collated epidemiological data from host countries from the European Centre for Disease Prevention and Control. FINDINGS: Between Feb 12, 2016, and April 19, 2017, 29 patients were diagnosed with multidrug-resistant tuberculosis in seven European countries. All originated from the Horn of Africa or Sudan, with all isolates two SNPs or fewer apart. 22 (76%) patients reported their travel routes, with clear spatiotemporal overlap between routes. We identified a further 29 MIRU-VNTR-linked cases from the Horn of Africa that predated the outbreak, but all were more than five SNPs from the outbreak. However all 58 isolates shared a capreomycin resistance-associated tlyA mutation. INTERPRETATION: Our data suggest that source cases are linked to an M tuberculosis clone circulating in northern Somalia or Djibouti and that transmission probably occurred en route before arrival in Europe. We hypothesise that the shared mutation of tlyA is a drug resistance mutation and phylogenetic marker, the first of its kind in M tuberculosis sensu stricto. FUNDING: The Swiss Federal Office of Public Health, the University of Zurich, the Wellcome Trust, National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC), the Medical Research Council, BELTA-TBnet, the European Union, the German Center for Infection Research, and Leibniz Science Campus Evolutionary Medicine of the Lung (EvoLUNG).