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.
Citations
More filters
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)....
[...]
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
More filters
TL;DR: Ciprofloxacin demonstrates normal linear pharmacokinetics, the rise in serum concentrations and the values of the total area under the serum concentration curve were proportional to the increase in the oral doses.
Abstract: The pharmacokinetics of ciprofloxacin were evaluated after increasing single oral doses of 100, 250, 500 and 1000 mg, and an intravenous dose of 100 mg given to each of 12 healthy volunteers (6 females and 6 males). Concentrations in serum and urine were determined by microbiological assay. The rise in peak serum concentrations and the values of the total area under the serum concentration curve were proportional to the increase in the oral doses. As the oral dose increased a slight increase was observed in the apparent time lag before absorption from 0.34 h after 100 mg to 0.53 h after 1000 mg. The serum half-life after the intravenous dose was 3.2 h. After the oral doses shorter apparent half-life values were observed. The intravenous dose showed an elimination phase distribution volume of 2.761/kg and total body clearance of 40.7 1/h. The total urinary excretion was 42.2 ± 15.6% of the dose after the intravenous dose; the figure was lower after the oral doses. The bioavailability of the 100 mg oral dose was 83.7% as calculated from the value of the total area under the serum curve after the same oral and intravenous dose in all 12 subjects. Ciprofloxacin thus demonstrates normal linear pharmacokinetics, the rise in serum concentrations being proportional to the dose.
49 citations
TL;DR: During the first twelve months after ciprofloxacin was introduced for clinical use at this institution, 65 new patients were found to be either infected or colonized by methicillin-resistant Staphylococcus aureus (MRSA) which were also cIProfl oxacin resistant (CR-MRSA).
Abstract: During the first twelve months after ciprofloxacin was introduced for clinical use at our institution, 65 new patients were found to be either infected or colonized by methicillin-resistant Staphylococcus aureus (MRSA) which were also ciprofloxacin resistant (CR-MRSA). Only 18 of these patients (28%) had been previously exposed to this antibiotic. Nine (50%) of the 18 patients had received ciprofloxacin for treatment for a pathogen other than MRSA. Although the initial cases of colonization or infection with CR-MRSA can be directly related to ciprofloxacin use, many of the subsequent cases of colonization and infection were not the consequence of ciprofloxacin therapy but rather hospital transmission of existing CR-MRSA.
44 citations
"Occurrence of quinolone resistance ..." refers result in this paper
...According to the report by Smith and co-workers [17], the majority of patients with quinolone-resistant MRSA (QRMRSA) did not receive this antibiotic....
[...]
TL;DR: Although the inoculum size had no effect on the rate of killing by ciprofloxacin, an increase in turbidity was noted when a high inoculum was tested, which could be misinterpreted as bacterial growth and result in a false report of an elevated MIC.
Abstract: Ciprofloxacin exhibited good in-vitro activity for methicillin-resistant Staphylococcus aureus with a MIC90 of 0.5 mg/l. The postantibiotic effect was 2.16 h. When ciprofloxacin was evaluated in combination studies with an aminoglycoside, none of the strains met the criterion of synergy as defined by FIC or FBC interaction indices of less than or equal to 0.25. However, killing kinetic experiments indicated that the combination of ciprofloxacin was synergistic for two of 12 strains with gentamicin and three of 12 strains with amikacin. Although the inoculum size had no effect on the rate of killing by ciprofloxacin, an increase in turbidity was noted when a high inoculum was tested. This increase in turbidity was due to the swelling of the staphylococci to several times their normal size and the formation of clusters of multicellular, incompletely divided staphylococci. If a high inoculum is used for susceptibility testing, this increase in turbidity could be misinterpreted as bacterial growth and could result in a false report of an elevated MIC.
38 citations
"Occurrence of quinolone resistance ..." refers background in this paper
...DISCUSSION Development of quinolone-resistance in MRSA was already reported during the investigational period of this antibiotic; there are reports for this development during the course of chemotherapy [15, 16]....
[...]
TL;DR: A similar study with repeated doses extending over 24 h, also including measurements of ciprofloxacin in pleural tissue and exudate is made, in contrast to the study by Schlenkhoff et al, which was measured by an HPLC method.
Abstract: Data recently published in this journal by Schlenkhoff et al. (1) give evidence for a marked penetration of ciprofloxacin into human lung tissue, but these authors measured ciprofloxacin only over a period of 4 h. We therefore have made a similar study with repeated doses extending over 24 h, also including measurements of ciprofloxacin in pleural tissue and exudate. In contrast to the study by Schlenkhoff et al., ciprofloxacin was measured by an HPLC method. Sixteen patients undergoing lung surgery mainly because of cancer participated in the study after they had given their written informed consent. The age of the patients ranged between 47 and 76 years (mean 52 + 15 years), their bodyweight ranged from 47 to 92 kg (average 66.0 + 12.2 kg). They received three i.v. infusions of 200 mg ciprofloxacin at 12 h intervals, each infusion lasting 30 min. Surgical procedures started 1 h (nine patients) or 2 h (seven patients) after the first application of ciprofloxacin. Samples of serum, tissues and pleural exudate were obtained at the following time points: serum 1 or 2 h after the beginning of the first and just prior to the second and third infusions; lung and pleurat tissue during the course of surgery 1 and 2 h after the first infusion; pleural
30 citations
TL;DR: To limit ciprofloxacin resistance, a reappraisal is necessary of fluoroquinolone usage against methicillin-and gentamicin-resistantStaphylococcus aureus.
Abstract: A total of 112Staphylococcus aureus strains resistant to methicillin and gentamicin were collected from 31 centres in 22 countries worldwide. Many strains were multi-resistant. In tests to determine the susceptibility of the organisms to ciprofloxacin 16 strains (14.3%), originating from France, the FRG, Israel and Italy, were shown to be resistant to this agent. To limit ciprofloxacin resistance, a reappraisal is necessary of fluoroquinolone usage against methicillin-and gentamicin-resistantStaphylococcus aureus.
24 citations