Occurrence of quinolone resistance in Staphylococcus aureus from nosocomial infection.
TL;DR: The phenotypic association of quinolone resistance and MRSA is rather likely due to a higher frequency of spontaneous resistant mutants which are present in natural populations of MRSA.
Abstract: Among 63 Staphylococcus aureus isolates (one isolate per one patient) counted from infections (from August to November 1991) in hospital T., eight exhibited resistance to fluoroquinolones. Seven of these quinolone-resistant isolates were multiply- and methicillin-resistant S. aureus (QR-MRSA). The results of phage-, plasmid- and genotyping (pulsed field electrophoresis) revealed that six different strain-clones of these MRSA were spread in the hospital. In vitro spontaneous mutants resistant to fluoroquinolones are 10-100-fold more frequent in MRSA than in other S. aureus when selected on isosensitest-agar containing 1 microgram/ml of ciprofloxacin. However, the same mutant frequencies were found in strain 8325-4 with and without the mecA-determinant. The resistance phenotype was stable over 30 generations of subculture in nutrient broth as well in natural quinolone resistant MRSA as in mutants of other types of S. aureus selected in vitro. The phenotypic association of quinolone resistance and MRSA is rather likely due to a higher frequency of spontaneous resistant mutants which are present in natural populations of MRSA. Data of chemotherapy prior to the isolation of S. aureus show that three of seven patients from whom QR-MRSA were isolated were treated with a quinolone. In eight cases of infections with non-MRSA and quinolone treatment the isolated S. aureus strains were in vitro sensitive to quinolones.
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TL;DR: In this article, the authors highlighted the importance of careful use of these agents in appropriate patients and doses, as well as careful infection-control practices, and emphasized the utility of a valuable class of antimicrobial agents.
Abstract: Summary Resistance to fluoroquinolones among Gram-positive cocci has emerged as these antimicrobial agents have become extensively used in clinical medicine. Resistance is effected by changes in the bacterial target enzymes DNA gyrase and topoisomerase IV, which reduce drug binding, and by action of native bacterial membrane pumps that remove drug from the cell. In both cases, quinolone exposure selects for spontaneous mutants that are present in large bacterial populations, and which contain chromosomal mutations that alter the target protein or increase the level of pump expression. Resistance among clinical isolates has been greatest in Staphylococcus aureus and particularly among meticillinresistant strains, in which both selection by quinolone exposure and transmission of clonal strains in health-care settings have contributed to high prevalence. Resistance in Streptococcus pneumoniae has also emerged in the community. Fluoroquinolone resistance has arisen in multidrug-resistant clones and its prevalence has been especially high in Hong Kong and Spain. Further spread and selection of such resistance could compromise the utility of a valuable class of antimicrobial agents, a point that emphasises the importance of the careful use of these agents in appropriate patients and doses, as well as careful infection-control practices.
297 citations
TL;DR: It is difficult to assess whether the percentage of NIs due to cross-transmission determined for this ICU may be the crucial explanation for the relatively high infection rate in comparison to other surgical ICUs.
Abstract: OBJECTIVE: To determine the percentage of cross-transmissions in an intensive care unit (ICU) with high nosocomial infection (NI) rates according to the data of the German Nosocomial Infection Surveillance System. SETTING: A 14-bed surgical ICU of a 1,300-bed, tertiary-care teaching hospital. METHOD: Prospective surveillance of NIs during a period of 9 months. If an NI was present, the isolates of the following indicator pathogens were stored and typed by species: Staphylococcus aureus, Enterococcus species, Escherichia coli, Pseudomonas aeruginosa, Acinetobacter baumannii, and Enterobacter species. Pulsed-field gel electrophoresis was performed for typing of S. aureus strains and arbitrarily primed polymerase chain reaction was applied for the other pathogens. The presence of two indistinguishable strains in two patients was considered as one episode of cross-transmission. RESULTS: Two hundred sixty-two patients were observed during a period of 2,444 patient-days; 96 NIs were identified in 59 patients and the overall incidence density of NI was 39.3 per 1,000 patient-days. For 104 isolates, it was possible to consider typing results. Altogether, 36 cross-transmissions have lead to NIs in other patients. That means at least 37.5% of all NIs identified were due to cross-transmissions. CONCLUSION: Because of the method of this study, the percentage of NIs due to cross-transmission identified for this ICU is an at least number. In reality, the number of cross-transmissions, and thus the number of avoidable infections, may have been even higher. However, it is difficult to assess whether the percentage of NIs due to cross-transmission determined for this ICU may be the crucial explanation for the relatively high infection rate in comparison to other surgical ICUs.
116 citations
TL;DR: Isolates with heterogenous and homogeneous phenotypes, fell into clearly distinct clusters and thus formed two clonally related MRSA strains, and differences were seen with phage and biochemical typing, and antimicrobial resistance patterns.
37 citations
TL;DR: Six commercially available agglutination tests for the detection of meticillin-sensitive S. aureus (MSSA) and mecA-positive MRSA strains were evaluated and only the Dry Spot Staphytect Plus test correctly identified all 52 MRSAusters.
Abstract: Most routine laboratory detection of Staphylococcus aureus isolates is based on rapid agglutination test systems. Failure of agglutination assays to identify meticillin-resistant S. aureus strains (MRSA) has been demonstrated. The aim of this study was to evaluate six commercially available agglutination tests for the detection of meticillin-sensitive S. aureus (MSSA) and mecA-positive MRSA strains. The Dry Spot Staphytect Plus test (Oxoid), the Pastorex Staph Plus test (Bio-Rad), the Slidex Staph-Kit and Slidex Staph Plus test (bioMerieux), the Staphaurex Plus test (Remel) and the Staphylase Test (Oxoid) were used. As determined by pulsed field gel electrophoresis, 52 distinct MRSA strains from five countries, 83 MSSA strains and 150 coagulase-negative staphylococci were included. Species identification and determination of susceptibility patterns were performed using colony morphology, Gram stain, catalase testing, tube coagulase testing, DNase testing, mannitol fermentation, susceptibility testing towards oxacillin by Etest, coagulase gene PCR, fibrinogen receptor gene PCR and PCR of the mecA gene. Sensitivity of the agglutination tests ranged from 82.7 to 100.0 % for MRSA strains and 92.8 to 100.0 % for MSSA strains, respectively. Specificity of the test systems ranged from 91.3 to 99.1 %. None of the six agglutination assays produced correct reactions for all staphylococci tested. Only the Dry Spot Staphytect Plus test correctly identified all 52 MRSA strains. For the other tests kits, sensitivity of MRSA detection was lower than for MSSA isolates. Depending upon the local MRSA prevalence and the parameter of interest (sensitivity or specificity), these test systems may be useful for routine diagnostic purposes.
33 citations
Cites methods from "Occurrence of quinolone resistance ..."
...Contourclamped homogeneous electric field electrophoresis was performed as described (Witte & Grimm, 1992) based on a previously published method (Chu et al., 1986)....
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TL;DR: Clonal dissemination of two different MRSA strains, both clumping factor negative, has been observed in Germany for more than a year and each exhibits a characteristic genomic DNA fragment pattern.
Abstract: SUMMARY Clonal dissemination of two different MRSA strains, both clumping factor negative, has been observed in Germany for more than a year. Both strains possess the mec-A determinant and each exhibits a characteristic genomic DNA fragment pattern. One strain has spread in the north, the other in the south-west of Germany. Intensive care units are mainly affected by MRSA-infections and probably play a special role in further intra- and inter-hospital spread.
30 citations
References
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TL;DR: Thirty-seven patients with methicillin-resistant Staphylococcus aureus infections and/or colonization were treated with oral ciprofloxacin (750 mg twice a day), and clinical cure or improvement of infections occurred in 91% of the patients, and bacteriologic cure occurred in 60%.
Abstract: Thirty-seven patients with methicillin-resistant Staphylococcus aureus infections and/or colonization were treated with oral ciprofloxacin (750 mg twice a day). Clinical cure or improvement of infections occurred in 91% of the patients, and bacteriologic cure occurred in 60%. Ciprofloxacin therapy suppressed methicillin-resistant S. aureus colonization in 55% of the patients. Ciprofloxacin-resistant strains emerged in 6 of the 37 patients.
85 citations
TL;DR: Ciprofloxacin is a highly effective drug and a breakthrough in several areas of medical interest, relatively safe and side-effects are usually mild or moderate in intensity and transient.
Abstract: During the clinical trials 8,861 patients have been treated with ciprofloxacin worldwide. 3,822 of the therapeutic courses were valid for analysis of efficacy according to FDA standards. The following dosages were usually administered: UTI: 100 to 500 mg twice daily orally or 100 mg twice daily intravenously; RTI: 250 to 1000 mg twice daily orally or 200 mg twice daily intravenously; septicemia: 200 mg intravenously twice daily; gonorrhea: 250 to 500 mg single tablet orally; all other infections: 500 to 1000 mg twice daily orally or 200 mg twice daily intravenously. Ciprofloxacin was administered to 762 courses of lower RTI, 88 courses of upper RTI, 108 courses of bacteremia, 766 courses of skin structure infection, 142 courses of bone and joint infections, 149 courses of intra-abdominal infections, 33 courses of gastrointestinal infections, 1,633 courses of UTI, 49 courses of pelvic infections, 279 courses of STD, mainly gonorrhea, and three courses of meningitis. The clinical response was resolution in 76%, improvement in 18% and failure in only 6%. Bacteriologic response by all sites evaluable: pathogens were eradicated from 74%, markedly reduced in 2%, persisted in 10%. Relapse occurred in 4% and reinfection was observed in another 6%. The overall response was favourable for 90% of the patients. Drug safety was established on a data base of 8,861 courses worldwide. The following side-effects according to COSTART terminology were observed: digestive 5%, metabolic nutritional 4.6%, central nervous 1.6%, skin 1.4%, hemic and lymphatic 1%, cardiovascular 0.4%, body as a whole 0.4%, urogenital 0.3%, special senses 0.3%, musculo-skeletal 0.1%, respiratory 0.08%. Several courses had more than one reaction. Thus the total incidence of side-effects for the treated patient population was 10.2%. Ciprofloxacin is a highly effective drug and a breakthrough in several areas of medical interest. It is relatively safe and side-effects are usually mild or moderate in intensity and transient.
84 citations
TL;DR: Cd2+ resistance was based on an efflux mechanism for Cd2+.
Abstract: Apparently chromosomally located mercury resistance determinants in five methicillin-resistant Staphylococcus aureus strains of different geographical origin were structurally homologous to plasmid-located mercury resistance determinants in S. aureus. These were all located on a 6.3-kilobase (kb) Bg/II fragment, as evident from Southern hybridization experiments with the 6.3-kb Bg/II fragment of plasmid pI258 as the probe. These methicillin-resistant S. aureus strains exhibited similar phage susceptibility patterns and biochemical reactions. They differed, however, in the DNA location of the mercury resistance determinants, as evidenced by neighboring cleavage sites for restriction endonucleases EcoRI, HindIII, and PstI. In an environmental (nonhospital) strain in which mercury resistance was also apparently chromosomally conferred, these determinants were also homologous to pI258 DNA, but they were located on a 6.6-kb Bg/II fragment. Cadmium resistance determinants in the five methicillin-resistant S. aureus strains and the environmental S. aureus strain were not similar to the known plasmid-located determinants cadA and cadB. Cd2+ resistance was based on an efflux mechanism for Cd2+. However, no parallel resistance to zinc was conferred. The 3.2-kb XbaI-Bg/II fragment obtained from plasmid pI258 and used as a cadA-specific probe did not hybridize to total DNA digests of the strains with apparently chromosomally determined cadmium resistance.
82 citations
Additional excerpts
...For strain 8325-4 med A (BB 270) see [9], for strains 1309 and 108/83, 253/86 and 524/86 see [10]....
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TL;DR: Five gentamicin-resistant clinical isolates of Staphylococcus aureus were found to contain self-transmissible plasmids of 32 to 37 megadaltons in size, suggesting the significant contribution of common conjugal plasmid contributions to the emergence of gentamicIn resistance in S. aUREus populations.
Abstract: Five gentamicin-resistant clinical isolates of Staphylococcus aureus were found to contain self-transmissible plasmids of 32 to 37 megadaltons in size. Restriction endonuclease digests of the plasmids were markedly similar to those of reference plasmids of unrelated geographical origin, thus suggesting the significant contribution of common conjugal plasmids to the emergence of gentamicin resistance in S. aureus populations.
81 citations
"Occurrence of quinolone resistance ..." refers methods in this paper
...Plasmid-profiles were established by use of the 'boiling method' [13]....
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TL;DR: No antagonistic drug interactions were seen in vivo when combination therapy with ciprofloxacin and gentamicin was evaluated in a model of E. coli thigh muscle infection in neutropenic mice.
Abstract: The in vitro activities of antibiotic combinations containing ciprofloxacin and either gentamicin, sisomicin, netilmicin, amikacin, or tobramycin were evaluated by checkerboard assay (agar dilution method). A total of 220 strains of Enterobacteriaceae and Pseudomonas aeruginosa (11 species, 20 strains each) were tested. Synergistic or antagonistic effects were observed in less than 1% of the tests performed; they appeared to represent method-dependent fluctuations rather than true antibiotic interactions. No significant differences among the five aminoglycosides tested were seen. Time-kill experiments performed with three representative strains of Escherichia coli and Serratia marcescens showed additive combination effects with respect to the kill rates and inhibition of bacterial regrowth. Exposure of Serratia strains to either ciprofloxacin or gentamicin before the addition of the second drug had little influence on the combination effects observed. No antagonistic drug interactions were seen in vivo when combination therapy with ciprofloxacin and gentamicin was evaluated in a model of E. coli thigh muscle infection in neutropenic mice. Comparable therapeutic effects were obtained, regardless of whether the two compounds were administered simultaneously or sequentially at 1- or 2-h intervals.
60 citations