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1.
BMC Infect Dis ; 15: 212, 2015 May 12.
Article in English | MEDLINE | ID: mdl-25963025

ABSTRACT

BACKGROUND: Typhoid fever is an acute, invasive, and potentially fatal systemic infection caused by Salmonella enterica subspecies enterica serotype Typhi (S. Typhi). Drug resistance to antimicrobials such as ciprofloxacin is emerging in developing countries, threatening the efficacy of treatment of patients in endemic regions as well as of travellers returning from these countries. METHODS: We compared the antimicrobial resistance profiles of 192 S. Typhi isolated from patients over a time span of twelve years. Susceptibility testing was done by the disk diffusion method. A representative selection of isolates (n = 41) was screened by PCR for mutations in the quinolone resistance-determining regions (QRDRs) of the gyrA and parC genes and all 192 isolates were screened for plasmid-mediated quinolone resistance (PMQR) genes. Multilocus sequence typing (MLST) was used to investigate the sequence type of isolates from patients with a known history of international travel. RESULTS: Resistance rates for nalidixic acid increased from 20 % to 66.7 % between 2002 and 2013. Resistance to ciprofloxacin was detected in 55.6 % of the isolates by 2013. Ciprofloxacin resistance was predominantly associated with the triple substitutions Ser83 → Phe and Asp87 → Asn in GyrA and Ser80 → Ile in ParC. The plasmid-mediated resistance gene qnrS1 was detected in two isolates. Sequence type ST1 was associated with the Indian subcontinent, while ST2 was distributed internationally. Multidrug resistance was noted for 11.5 % of the isolates. CONCLUSIONS: Fluoroquinolone resistant S. Typhi constitute a serious public health concern in endemic areas as well as in industrialized countries. Increased surveillance of global patterns of antimicrobial resistance is necessary and the control of resistant strains is of the utmost importance to maintain treatment options.


Subject(s)
Anti-Infective Agents/pharmacology , Ciprofloxacin/pharmacology , Salmonella typhi/drug effects , Anti-Infective Agents/therapeutic use , Ciprofloxacin/therapeutic use , DNA Gyrase/genetics , Drug Resistance, Bacterial/genetics , Humans , Microbial Sensitivity Tests , Multilocus Sequence Typing , Polymerase Chain Reaction , Salmonella typhi/genetics , Salmonella typhi/isolation & purification , Switzerland/epidemiology , Travel , Typhoid Fever/epidemiology
2.
PLoS One ; 9(4): e95864, 2014.
Article in English | MEDLINE | ID: mdl-24755830

ABSTRACT

Sixty extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli isolated from rivers and lakes in Switzerland were screened for individual strains additionally exhibiting a reduced quinolone susceptibility phenotype. Totally, 42 such isolates were found and further characterized for their molecular (fluoro)quinolone resistance mechanisms. PCR and sequence analysis were performed to identify chromosomal mutations in the quinolone resistance-determining regions (QRDR) of gyrA, gyrB, parC and parE and to describe the occurrence of the following plasmid-mediated quinolone resistance genes: qepA, aac-6'-Ib-cr, qnrA, qnrB, qnrC, qnrD and qnrS. The contribution of efflux pumps to the resistance phenotype of selected strains was further determined by the broth microdilution method in the presence and absence of the efflux pump inhibitor phe-arg-ß-naphthylamide (PAßN). Almost all strains, except two isolates, showed at least one mutation in the QRDR of gyrA. Ten strains showed only one mutation in gyrA, whereas thirty isolates exhibited up to four mutations in the QRDR of gyrA, parC and/or parE. No mutations were detected in gyrB. Most frequently the amino-acid substitution Ser83→Leu was detected in GyrA followed by Asp87→Asn in GyrA, Ser80→Ile in ParC, Glu84→Val in ParC and Ser458→Ala in ParE. Plasmid-mediated quinolone resistance mechanisms were found in twenty isolates bearing QnrS1 (4/20), AAC-6'-Ib-cr (15/20) and QepA (1/20) determinants, respectively. No qnrA, qnrB, qnrC and qnrD were found. In the presence of PAßN, the MICs of nalidixic acid were decreased 4- to 32-fold. (Fluoro) quinolone resistance is due to various mechanisms frequently associated with ESBL-production in E. coli from surface waters in Switzerland.


Subject(s)
Anti-Bacterial Agents/pharmacology , Escherichia coli Proteins/metabolism , Escherichia coli/enzymology , Quinolines/pharmacology , Water Microbiology , beta-Lactamases/metabolism , Amino Acid Substitution , DNA Gyrase/genetics , DNA Gyrase/metabolism , DNA Topoisomerase IV/genetics , DNA Topoisomerase IV/metabolism , Escherichia coli/drug effects , Escherichia coli Proteins/genetics , Lakes/microbiology , Microbial Sensitivity Tests , Rivers/microbiology , Switzerland , beta-Lactam Resistance
3.
Antimicrob Agents Chemother ; 58(6): 3560-3, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24733466

ABSTRACT

Human isolates of Salmonella enterica serovars Hadar, Kentucky, Virchow, Schwarzengrund, and the monophasic variant of S. Typhimurium, Salmonella enterica subsp. enterica serovar 4,5,12:i:- were examined for mutations within the quinolone resistance target genes gyrA, gyrB, parC, and parE and for plasmid-mediated resistance genes. Differences were observed among the serovars. A novel variant of qnrD, qnrD2, was detected in an S. Hadar isolate.


Subject(s)
Anti-Bacterial Agents/pharmacology , DNA Gyrase/genetics , Drug Resistance, Bacterial/genetics , Quinolones/pharmacology , Salmonella enterica/genetics , Base Sequence , Humans , Microbial Sensitivity Tests , Nalidixic Acid/pharmacology , Plasmids/genetics , Salmonella enterica/drug effects , Sequence Analysis, DNA , Serogroup , Switzerland
5.
Microb Drug Resist ; 19(5): 362-9, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23611297

ABSTRACT

The aim of this study was to gain knowledge of the local epidemiology of extended-spectrum cephalosporin-resistant bacteria in primary care patients in a Swiss community. Fecal swabs were obtained from 291 primary care patients. Phenotyping and genotyping methods were used for further characterization of the isolates. Risk factors associated with carriage of ß-lactam-resistant strains were determined. Extended-spectrum cephalosporin-resistant Enterobacteriaceae were detected in 15 (5.2%) of the primary care patients. Thirteen isolates were CTX-M producers, one produced SHV-12, and three carried CMY-2. The pathogenic pandemic clone Escherichia coli ST131 was detected in 26.6% of the patients. Two patients (13.3%) carried two distinct strains simultaneously. There was a statistically significant risk of carriage of resistant strains for persons with a history of antibiotic therapy 4 months before sampling (p=0.05), markedly for therapy with ß-lactam (p=0.01). Age, gender, or history of hospitalization 4 months before sampling was not a risk factor for the acquisition of resistant bacteria in the analyzed patients. The relatively low prevalence of extended-spectrum cephalosporin-resistant strains in the community reflects the nationwide restrictive policy of antibiotic prescription as well as local implementation thereof. Nevertheless, our study shows that a potent antimicrobial resistance reservoir is present in primary care patients.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Cephalosporins/therapeutic use , Enterobacteriaceae Infections/drug therapy , Enterobacteriaceae Infections/epidemiology , Enterobacteriaceae/drug effects , Feces/microbiology , Adult , Aged , Aged, 80 and over , Bacterial Typing Techniques , Cross-Sectional Studies , Enterobacteriaceae/enzymology , Enterobacteriaceae/genetics , Enterobacteriaceae/isolation & purification , Enterobacteriaceae Infections/microbiology , Female , Humans , Male , Middle Aged , Primary Health Care , Switzerland/epidemiology , beta-Lactam Resistance/drug effects , beta-Lactam Resistance/genetics , beta-Lactamases/genetics , beta-Lactamases/metabolism
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