Plasmid-mediated quinolone resistance in isolates obtained in german intensive care units.
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ABSTRACT:
SUBMITTER: Jonas D
PROVIDER: S-EPMC547280 | biostudies-literature | 2005 Feb
REPOSITORIES: biostudies-literature
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Plasmid-mediated quinolone resistance in isolates obtained in german intensive care units.
Jonas Daniel D Biehler Klaus K Hartung Doris D Spitzmüller Bettina B Daschner Franz D FD
Antimicrobial agents and chemotherapy 20050201 2
Screening of 703 isolates of Enterobacteriaceae, obtained from 34 German intensive care units (ICUs), revealed qnr-positive, integron-containing isolates of Enterobacter sp. and Citrobacter freundii from four patients in 2 German ICUs. This is one of the first reports of qnr-positive strains obtained from patients in Europe. ...[more]
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Project description:Three mechanisms for plasmid-mediated quinolone resistance (PMQR) have been discovered since 1998. Plasmid genes qnrA, qnrB, qnrC, qnrD, qnrS, and qnrVC code for proteins of the pentapeptide repeat family that protects DNA gyrase and topoisomerase IV from quinolone inhibition. The qnr genes appear to have been acquired from chromosomal genes in aquatic bacteria, are usually associated with mobilizing or transposable elements on plasmids, and are often incorporated into sul1-type integrons. The second plasmid-mediated mechanism involves acetylation of quinolones with an appropriate amino nitrogen target by a variant of the common aminoglycoside acetyltransferase AAC(6')-Ib. The third mechanism is enhanced efflux produced by plasmid genes for pumps QepAB and OqxAB. PMQR has been found in clinical and environmental isolates around the world and appears to be spreading. The plasmid-mediated mechanisms provide only low-level resistance that by itself does not exceed the clinical breakpoint for susceptibility but nonetheless facilitates selection of higher-level resistance and makes infection by pathogens containing PMQR harder to treat.
| S-EPMC4288778 | biostudies-other
Project description:Quinolone resistance encoded by the qnr gene and mediated by plasmid pMG252 was discovered in a clinical strain of Klebsiella pneumoniae that was isolated in 1994 at the University of Alabama at Birmingham Medical Center. The gene codes for a protein that protects DNA gyrase from quinolone inhibition and that belongs to the pentapeptide repeat family of proteins. The prevalence of the gene has been investigated by using PCR with qnr-specific primers with a sample of more than 350 gram-negative strains that originated in 18 countries and 24 states in the United States and that included many strains with plasmid-mediated AmpC or extended spectrum beta-lactamase enzymes. qnr was found in isolates from the University of Alabama at Birmingham only during 6 months in 1994, despite the persistence of the gene for FOX-5 beta-lactamase, which is linked to qnr on pMG252. Isolates from other locations were negative for qnr. The prevalence of mcbG in the same sample was also examined. mcbG encodes another member of the pentapeptide repeat family and is involved in immunity to microcin B17, which, like quinolones, targets DNA gyrase. A single clinical isolate contained mcbG on a transmissible R plasmid. This plasmid and one carrying the complete microcin B17 operon slightly decreased sparfloxacin susceptibility but had a much less protective effect than pMG252. Plasmid-mediated quinolone resistance was thus rare in the sample examined.
| S-EPMC151764 | biostudies-literature
Project description:Quinolones are potent antibacterial agents that specifically target bacterial DNA gyrase and topoisomerase IV. Widespread use of these agents has contributed to the rise of bacterial quinolone resistance. Previous studies have shown that quinolone resistance arises by mutations in chromosomal genes. Recently, a multiresistance plasmid was discovered that encodes transferable resistance to quinolones. We have cloned the plasmid-quinolone resistance gene, termed qnr, and found it in an integron-like environment upstream from qacE Delta 1 and sulI. The gene product Qnr was a 218-aa protein belonging to the pentapeptide repeat family and shared sequence homology with the immunity protein McbG, which is thought to protect DNA gyrase from the action of microcin B17. Qnr had pentapeptide repeat domains of 11 and 28 tandem copies, separated by a single glycine with a consensus sequence of A/C D/N L/F X X. Because the primary target of quinolones is DNA gyrase in Gram-negative strains, we tested the ability of Qnr to reverse the inhibition of gyrase activity by quinolones. Purified Qnr-His(6) protected Escherichia coli DNA gyrase from inhibition by ciprofloxacin. Gyrase protection was proportional to the concentration of Qnr-His(6) and inversely proportional to the concentration of ciprofloxacin. The protective activity of Qnr-His(6) was lost by boiling the protein and involved neither quinolone inactivation nor independent gyrase activity. Protection of topoisomerase IV, a secondary target of quinolone action in E. coli, was not evident. How Qnr protects DNA gyrase and the prevalence of this resistance mechanism in clinical isolates remains to be determined.
| S-EPMC122823 | biostudies-literature
Project description:Although quinolone resistance usually results from chromosomal mutations, recent studies indicate that quinolone resistance can also be plasmid mediated. The gene responsible, qnr, is distinct from the known quinolone resistance genes and in previous studies seemed to be restricted to Klebsiella pneumoniae and Escherichia coli isolates from the University of Alabama in Birmingham, where this resistance was discovered. In Shanghai, the frequency of ciprofloxacin resistance in E. coli has exceeded 50% since 1993. Seventy-eight unique ciprofloxacin-resistant clinical isolates of E. coli from Shanghai hospitals were screened for the qnr gene by colony blotting and Southern hybridization of plasmid DNA. Conjugation experiments were done with azide-resistant E. coli J53 as a recipient with selection for plasmid-encoded antimicrobial resistance (chloramphenicol, gentamicin, or tetracycline) and azide counterselection. qnr genes were sequenced, and the structure of the plasmid DNA adjacent to qnr was analyzed by primer walking with a sequential series of outward-facing sequencing primers with plasmid DNA templates purified from transconjugants. Six (7.7%) of 78 strains gave a reproducible hybridization signal with a qnr gene probe on colony blots and yielded strong signals on plasmid DNA preparations. Quinolone resistance was transferred from all six probe-positive strains. Transconjugants had 16- to 250-fold increases in the MICs of ciprofloxacin relative to that of the recipient. All six strains contained qnr with a nucleotide sequence identical to that originally reported, except for a single nucleotide change (CTA-->CTG at position 537) encoding the same amino acid. qnr was located in complex In4 family class 1 integrons. Two completely sequenced integrons were designated In36 and In37. Transferable plasmid-mediated quinolone resistance associated with qnr is thus prevalent in quinolone-resistant clinical strains of E. coli from Shanghai and may contribute to the rapid increase in bacterial resistance to quinolones in China.
| S-EPMC161834 | biostudies-literature
Project description:Although plasmid-mediated quinolone resistance (PMQR) was thought not to exist before its discovery in 1998, the past decade has seen an explosion of research characterizing this phenomenon. The best-described form of PMQR is determined by the qnr group of genes. These genes, likely originating in aquatic organisms, code for pentapeptide repeat proteins. These proteins reduce susceptibility to quinolones by protecting the complex of DNA and DNA gyrase or topoisomerase IV enzymes from the inhibitory effect of quinolones. Two additional PMQR mechanisms were recently described. aac(6')-Ib-cr encodes a variant aminoglycoside acetyltransferase with two amino acid alterations allowing it to inactivate ciprofloxacin through the acetylation of its piperazinyl substituent. oqxAB and qepA encode efflux pumps that extrude quinolones. All of these genes determine relatively small increases in the MICs of quinolones, but these changes are sufficient to facilitate the selection of mutants with higher levels of resistance. The contribution of these genes to the emergence of quinolone resistance is being actively investigated. Several factors suggest their importance in this process, including their increasing ubiquity, their association with other resistance elements, and their emergence simultaneous with the expansion of clinical quinolone resistance. Of concern, these genes are not yet being taken into account in resistance screening by clinical microbiology laboratories.
| S-EPMC2772364 | biostudies-literature
Project description:We have studied by PCR and DNA sequencing the presence of the qnrA, qnrB, qnrS, aac(6')-Ib-cr, qepA, intI1, and ISCR1 genes in 200 clinical isolates of Enterobacter cloacae (n = 153) and E. aerogenes (n = 47) consecutively collected between January 2004 and October 2005 in two hospitals located in Santander (northern Spain) and Seville (southern Spain). Mutations in the quinolone resistance-determining region of gyrA and parC also were investigated in organisms containing plasmid-mediated quinolone resistance genes. The isolates had different resistant phenotypes, including AmpC hyperproduction, extended-spectrum beta-lactamase production, resistance or decreased susceptibility to quinolones, and/or resistance to aminoglycosides. Among the 116 E. cloacae isolates from Santander, qnrS1, qnrB5, qnrB2, and aac(6')-Ib-cr were detected in 22 (19%), 1 (0.9%), 1 (0.9%), and 3 (2.6%) isolates, respectively. Twenty-one, 17, and 2 qnrS1-positive isolates also contained bla(LAP-1), intI1, and ISCR1, respectively. A qnrB7-like gene was detected in one E. aerogenes isolate from Santander. No plasmid-mediated quinolone resistance gene was detected in the isolates from Seville. The qnrS1-containing isolates corresponded to four pulsed-field gel electrophoresis patterns and showed various levels of resistance to quinolones. Six isolates were susceptible to nalidixic acid and presented reduced susceptibility to ciprofloxacin. The qnrS1 gene was contained in a conjugative plasmid of ca. 110 kb, and when the plasmid was transferred to recipient strains that did not have a specific mechanism of quinolone resistance, the ciprofloxacin MICs ranged from 0.047 to 0.125 microg/ml.
| S-EPMC2708531 | biostudies-literature
Project description:Plasmid-mediated resistance to quinolones is increasingly reported in studies of Enterobacteriaceae. Using a PCR-based strategy, a series of gram-negative species were screened for qnrA-like genes. Shewanella algae, an environmental species from marine and fresh water, was identified as its reservoir. This is a one of the very few examples of progenitor identification of an acquired antibiotic resistance gene.
| S-EPMC1196254 | biostudies-literature
Project description:A novel plasmid-mediated quinolone resistance gene, qnrB, has been discovered in a plasmid encoding the CTX-M-15 beta-lactamase from a Klebsiella pneumoniae strain isolated in South India. It has less than 40% amino acid identity with the original qnr (now qnrA) gene or with the recently described qnrS but, like them, codes for a protein belonging to the pentapeptide repeat family. Strains with qnrB demonstrated low-level resistance to all quinolones tested. The gene has been cloned in an expression vector attaching a polyhistidine tag, which facilitated purification to >or=95% homogeneity. As little as 5 pM of QnrB-His6 protected purified DNA gyrase against inhibition by 2 microg/ml (6 microM) ciprofloxacin. With a PCR assay qnrB has been detected in Citrobacter koseri, Enterobacter cloacae, and Escherichia coli isolates from the United States, linked to SHV-12 beta-lactamase and coding for a product differing in five amino acids from the Indian (now QnrB1) variety. The qnrB gene has been found near Orf1005 in some, but not all, plasmids and in association with open reading frames matching known chromosomal genes, suggesting that it too was acquired by plasmids from an as-yet-unknown bacterial source.
| S-EPMC1426915 | biostudies-literature
Project description:Background. Plasmid-mediated quinolone resistance (PMQR) has received considerable attention recently. Data analysis in Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER) revealed 75% of the Enterobacteriaceae isolates to be ciprofloxacin-resistant in 2012. Few reports regarding the prevalence of PMQR are available from India. Hence, the present study was carried out to ascertain the prevalence of PMQR genes among clinical isolates of ciprofloxacin-resistant Enterobacteriaceae in JIPMER. Methods. The study included 642 ciprofloxacin-resistant clinical Enterobacteriaceae isolates. JIPMER hospital's annual consumption data for fluoroquinolones were retrieved from the Department of Pharmacy. The test isolates were screened for the presence of qnr A, B, D, S and aac(6')-Ib-cr genes. PMQR-positive isolates alone were tested for the presence of class I (intI1) and class II (intI2) integrons. Randomly selected PCR amplicons were sequenced and analysed using MEGA software. A total of 30 PMQR strains chosen at random were assessed for the transferability of the PMQR genes. Results. A majority of the strains exhibited high MIC values with 106 strains exhibiting MIC values >256 µg/mL. The aac(6')-Ib-cr gene had the highest prevalence at 64% (414) while, qnrB and qnrS genes were present in 15% (97) and 10% (64) of the isolates respectively. None of the strains were positive for qnrA and qnrD. All PMQR-positive isolates were screened for class I (intI1) and class II (intI2) integrons. Class I integron was found to be predominant among the test isolates with a few of them carrying both the classes of integrons. Transferability of PMQR genes to transconjugants was identified. Conclusion. The incidence of PMQR genes in the tertiary-care setup of the JIPMER hospital was found to be high which could be probably due to the increased prescription of fluoroquinolones. Thus, there is a need for rational usage of fluoroquinolones.
| S-EPMC4860338 | biostudies-literature
Project description:BackgroundLittle is known about importance and implementation of end-of-life care (EOLC) in German intensive care units (ICU). This survey analyses preferences and differences in training between "medical" (internal medicine, neurology) and "surgical" (surgery, anaesthesiology) residents during intensive care rotation.MethodsThis is a point-prevalence study, in which intensive care medicine course participants of one educational course were surveyed. Physicians from multiple ICU and university as well as non-university hospitals and all care levels were asked to participate. The questionnaire was composed of a paper and an electronic part. Demographic and structural data were prompted and EOLC data (48 questions) were grouped into six categories considering importance and implementation: category 1 (important, always implemented), 2 (important, sometimes implemented), 3 (important, never implemented) and 4-6 (unimportant, implementation always, sometimes, never). The trial is registered at the "Deutsches Register für klinische Studien (DRKS)", Study number DRKS00026619, registered on September 10th 2021, www.drks.de .ResultsOverall, 194/ 220 (88%) participants responded. Mean age was 29.7 years, 55% were female and 60% had scant ICU working experience. There were 64% medical and 35% surgical residents. Level of care and size of ICU differed significantly between medical and surgical (both p < 0.001). Sufficient implementation was stated for 66% of EOLC questions, room for improvement (category 2 and 3) was seen in 25, and 8% were classified as irrelevant (category 6). Areas with the most potential for improvement included prognosis and outcome and patient autonomy. There were no significant differences between medical and surgical residents.ConclusionsEven though EOLC is predominantly regarded as sufficiently implemented in German ICU of all specialties, our survey unveiled still 25% room for improvement for medical as well as surgical ICU residents. This is important, as areas of improvement potential may be addressed with reasonable effort, like individualizing EOLC procedures or setting up EOLC teams. Health care providers as well as medical societies should emphasize EOLC training in their curricula.
| S-EPMC9115951 | biostudies-literature