A double zone of inhibition was observed for vancomycin and teicoplanin. Local results were confirmed and the same double zone phenomenon was observed. In addition, the strain demonstrated a double zone for ampicillin Table 2. Colonies in the Etest double zones DZ of ampicillin, teicoplanin, and vancomycin were collected and tested separately. Two of 3 DZ isolates demonstrated identical susceptibility testing results by Etest, but the isolate subcultured from the DZ on the ampicillin strip isolate number 3 was susceptible to both vancomycin and teicoplanin Table 2.
Additional PCR tests [14] confirmed high-level gentamicin resistance and the species identifications, e. A plasmid analysis was performed and the van A samples presented an identical profile Figure 2 [15]. In spite of repeating the test several times and using different enzymes, we were not able to evaluate the plasmid analysis on isolate number 3 ampicillin DZ isolate.
Enterococcal infections can be associated with significant morbidity and mortality because they often occur in critically ill patients, especially those receiving organ transplants [1, 3].
If the strain reported here had caused a systemic infection, the treatment would have been very difficult. Isolates with high-level resistance to aminoglycosides are refractory to the synergistic effects that occur when these compounds are associated with cell-wall active drugs, such as b-lactams and glycopeptides. Multiple risk factors are related to infection by VRE, and colonization like the case reported here usually precedes the infection [16].
VRE carriage tends to be prolonged from 19 to days , and a patient whose gastrointestinal tract is colonized with VRE may function as a reservoir and facilitate the nosocomial dissemination of this pathogen. In addition, these patients will have a sustained risk for developing VRE infection [7, 17]. Over the last 3 years, our prospective VRE surveillance program has not identified any glycopeptide resistant strain [18].
Rectal swabs are obtained twice weekly from all ICU patients. The swab is plated on a selective agar screen plate. These isolates were identified as E. Despite the fact that one isolate had a distinct vancomycin susceptibility pattern by Etest, the PFGE and ribotyping results of all isolates analyzed were identical. The hypothesis of mixed culture was excluded because all isolates had identical PFGE and ribotyping patterns Figure 1.
However, as previously observed by Woodford, et al. These results reinforce the difficulties found in the characterization of VRE isolates. The fact that one of these isolates separated from the Etest double zones the ampicillin DZ isolate had a vancomycin MIC distinct from the other isolates with identical chromosomal patterns, may be explained by the loss of the plasmid containing van A gene, since we could not detect plasmid in this vancomycin-susceptible isolate.
A surveillance program is necessary to rapidly detect and control the appearance and dissemination of VRE on a nation-wide basis. The microbiology laboratories have an important role as the first line of defense by detecting these resistant strains accurately and quickly.
Measures for preventing the spread of VRE in hospitals include the application of strict isolation precautions and the implementation of effective antimicrobial use control programs.
In summary, the clinical laboratories in Brazil must be prepared to detect VRE, and infection control personnel should be prepared to contain potential outbreaks before the pathogen becomes endemic. We are very grateful to Ana C. Address for correspondence: Helio S. Sader, M. Rua Botucatu, E-mail: heliosader uol. Abrir menu Brasil.
Brazilian Journal of Infectious Diseases. Abrir menu. Cereda Helio S. Sader Ronald N. Machado Yara P. Zanatta Sinaida T. Rego Eduardo A. Medeiros About the authors. Enterococcus faecalis; glycopeptide resistance; vanA; initial case report; transplant.
Sastry V. Vancomycin-resistant enterococci: an emerging pathogen in immunosuppressed transplant recipients. Transplant Proc ; Cereda R. Braz J Infect Dis ; This surveillance system collects reports of VRE from device-associated infections, such as central-line associated bloodstream infections.
CDC works with healthcare facilities and state and local health departments to control outbreaks of resistant germs like VRE and to help devise and implement prevention strategies for facilities with high numbers of VRE infections. Skip directly to site content Skip directly to page options Skip directly to A-Z link. Section Navigation. Facebook Twitter LinkedIn Syndicate. Minus Related Pages.
On This Page. How common are these infections? Top of Page. Who is at risk? Those most likely to be infected include: people who have been previously treated with antibiotics, including vancomycin, for long periods of time people who are hospitalized, have undergone surgical procedures, or have medical devices inserted in their bodies such as catheters people with weakened immune systems, such as patients in intensive care units, or in cancer or transplant wards Top of Page.
The most common clinical sources of E. It is worth mentioning that the ratio of the total numbers of clinical E. Compared to other regions in Germany, in the West and Southwest slightly higher proportions of E.
The proportion of E. However, from onwards, the percentage of vancomycin-resistant clinical E. This finding is supported by univariable and multivariable analyses, which show that isolates collected after were increasingly more likely to be tested resistant against vancomycin than isolates in Table 2. A similar rise of VREF proportions between and was found in sensitivity analyses including E. Since bloodstream infections are of particular clinical interest, it is noteworthy that in the included hospitals the number of VREF blood isolates increased from 57 to between and accompanied by a marked rise in VREF proportions from Time trend of vancomycin-resistant E.
Regional analyses of E. VREF proportions are noticeably lower in the Northwest Uni- and multivariable regression analyses confirm that E. While in the Southwest and Southeast a pronounced increase of VREF proportions was observed between and , the northern regions do not show a rise of VREF during that same period.
This finding is supported by a multivariable analysis controlling for interaction between year and region Additional file 3 : Table S2. It is important to note that southern regions feature considerably higher VREF proportions than northern regions only from onwards.
Vancomycin-resistant E. The absolute number of VREF isolates in the ARS database continuously increased from to between and , suggesting that numbers of infections with vancomycin-resistant E. This trend is supported by our analysis of publicly available data from the hospital payment system based on fee-for-case on DRGs [ 20 ] that show a four-fold increase of diagnoses of glycopeptide-resistant E.
In order to study the influence of the patient age on vancomycin resistance patterns, VREF proportions were analysed for different age categories. The results displayed in Fig. Multivariable analyses reveal that E.
Further analyses of all age categories combined do not indicate that female and male patients differ in VREF proportions The resulting p-values were adjusted for multiple testing using a Bonferroni correction. Adjusted p-Values female vs. Since the frequency of drug-resistance pathogens can differ between infection sites, VREF proportions were analysed in different clinical specimens, including blood cultures, urine samples, wound material and swabs. No major differences in vancomycin resistance proportions were found between the analysed sampling sites blood: Therefore, no associations between clinical specimen and the likelihood of VREF resistance were found in uni- and multivariable regression analyses Table 2.
To study vancomycin resistance patterns in different hospital care types, VREF proportions were analysed for secondary care, tertiary care and specialist care hospitals as well as prevention and rehabilitation care centres. Univariable analyses show that E.
Interestingly, remarkably high proportions of VREF were observed in isolates from patients treated in prevention and rehabilitation care centres, where more than one third of all E. In line with that, the multivariable regression analysis identified prevention and rehabilitation care centres as an independent risk factor of increased likelihood of VREF resistance in relation to secondary care hospitals. By analysing data from the German Antibiotic Resistance Surveillance system the present study shows that from onwards the proportions of clinical E.
Regional analyses reveal that, in particular, southern regions of Germany have been affected by a pronounced rise of VREF proportions, whereas northern regions do not feature substantial increases of VREF. While VREF proportions do not differ between female and male patients in the whole dataset, subgroup analyses show that E. Rising proportions of vancomycin-resistant E. Since infections with VREF are associated with worse clinical outcomes compared to infections with vancomycin-sensitive strains [ 21 , 22 , 23 ], rising vancomycin resistance is of great clinical concern in the management of patients with nosocomial E.
Current German data show increasing trends of nosocomial infections with vancomycin-resistant Enterococci in German hospitals [ 13 , 25 ]. These findings are strongly supported by our analyses of publicly available data from German hospitals, which show a four-fold increase of diagnoses of infections or colonisations with glycopeptide-resistant E.
It is important to note that rising numbers of diagnoses of infections or colonisations with glycopeptide-resistant E. Interestingly, our data show that the ratio of clinical E. Analyses of resistance trends between different geographical regions in Germany between and reveal that VREF proportions significantly vary within Germany exhibiting a pronounced north-south disparity. Bender und Guido Werner, unpublished data. Therefore, the increase in VREF rates in certain regions in Germany might be associated with a preferred prevalence of certain strain types.
Increasing proportions of enterococci infections with vancomycin-resistant strains in Germany are also observed in data from the national Nosocomial infection surveillance system KISS. In contrast to our findings, KISS identified a belt of states with higher proportions of vancomycin-resistant enterococci infections in the centre of Germany spanning from west to east [ 13 ].
The different results to our surveillance system might be explained by different methodological approaches used in the KISS study, such as only inclusion of bloodstream and urinary tract infections from ICUs and wound infections from surgical departments.
The reasons for the regional differences observed in our study are largely unknown. However, a large representative population-based study analysing German antibiotic prescription data reported higher outpatient antibiotic prescription of fluoroquinolones in southwestern regions of Germany [ 31 ]. The extensive use of fluoroquinolones has been shown to be associated with the emergence of vancomycin-resistant enterococci in the hospital setting [ 32 ].
This finding underlines the importance of the implementing of interventions that improve outpatient antibiotic prescribing [ 33 ]. It is important to note that the analyses of regional resistance patterns are based on the location of the hospital rather than the residence of the patient. This suggests that the described regional VREF proportions are a true reflection of the acquisition of VREF in the respective regions, irrespective of whether they were acquired in the hospital or in the community.
Very little is known about factors associated with increased vancomycin resistance in clinical E. This study did not find any differences in VREF proportions between female and male patients. This finding is also reported in other studies from different regions in the world [ 35 , 36 , 37 , 38 ].
In contrast, a study analysing data from three New York hospitals found that isolates from female patients have a higher likelihood of being vancomycin-resistant than samples from men [ 39 ]. However, that particular study analysed infections with Enterococcus faecalis or Enterococcus faecium. Since it has been known that different age groups exhibit different microbial susceptibility proportions, VREF resistance patterns were analyzed for different age categories.
Similar age trends have been reported for other bacterial pathogens, including Staphylococcus aureus , Escherichia coli , Streptococcus pneumoniae , Pseudomonas aeruginosa, Helicobacter pylori and Klebsiella pneumonia [ 16 , 40 , 41 , 42 ].
A possible explanation is that older patients are more likely to be colonised with drug-resistant pathogens due to more frequent exposure to antibiotics throughout their lives, thereby promoting the selection of drug-resistant bacteria as described for enterococci [ 43 ]. In addition, in comparison to younger patients elderly patients are likely to have more comorbidities and are more likely to reside in nursing homes or other healthcare facilities, both factors that have been shown to be associated with increased antibiotic resistance [ 44 ].
Since nosocomial bloodstream infections are of particular public health relevance and are often associated with worse outcomes than other infection types [ 45 , 46 , 47 , 48 ], VREF proportions were analysed in clinical blood samples and other specimen.
Blood samples do not show higher VREF proportions compared with urine samples, wound material and swabs. Interestingly, it has been shown that vancomycin resistance does not further increase the risk of in-hospital mortality and infection-attributed hospital stay in bloodstream infections with E. This study indicates that VREF proportions are higher in specialist care hospitals and prevention and rehabilitation care centres, a finding that is possibly explained by the larger number of patients with comorbidities and other factors e.
Specialist care hospitals and prevention and rehabilitation care centres have also been identified as risk factors for antimicrobial resistance in Klebsiella pneumoniae in Germany [ 16 ]. This study used data from the ARS database which is the largest and most comprehensive surveillance system for antimicrobial resistance in Germany [ 14 , 50 ].
As of , ARS comprised of data from more than participating hospitals across all regions in Germany allowing for detailed analyses of epidemiological trends.
To our knowledge, with more than However, it is important to consider the limitations of this study. First, participation in ARS is voluntary, and thus, participating laboratories and hospitals are not equally distributed resulting in a clustering in certain regions.
In particular, northern regions are under-represented in the sample set, while the Western region is overrepresented. Therefore, statistical analyses were used that accounted for clustering effects.
Second, since information on underlying diagnoses is not collected in ARS, it is not possible to differentiate between colonisation and infection. To address this issue, isolates were excluded if they were likely collected for screening purposes. Third, although the analyses were restricted to hospitals that continuously participated in ARS between and , it cannot ruled out that changes in hospital structures and case mix might have biased the longitudinal observations results.
To account for these limitations the key finding of increasing VREF proportion and different regional patterns were confirmed by sensitivity analyses and regression analyses assessing the interaction between region and year which underlines the robustness of the results presented in this study. Proportions of vancomycin resistance in clinical E.
VREF proportions differ considerable among German regions with a particular focus of high vancomycin resistance in Southwest and Southeast Germany. Continued surveillance and implementation of effective infection prevention and control measures accounting for local resistance differences are needed to reduce the spread of vancomycin-resistant E.
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