Legislation aimed at controlling antimicrobial-resistant pathogens through the use of active surveillance cultures to screen hospitalized patients has been introduced in at least 2 US states. In response to the proposed legislation, the Society for Healthcare Epidemiology of America (SHEA) and the Association of Professionals in Infection Control and Epidemiology (APIC) have developed this joint position statement. Both organizations are dedicated to combating healthcare-associated infections with a wide array of methods, including the use of active surveillance cultures in appropriate circumstances. This position statement reviews the proposed legislation and the rationale for use of active surveillance cultures, examines the scientific evidence supporting the use of this strategy, and discusses a number of unresolved issues surrounding legislation mandating use of active surveillance cultures. The following 5 consensus points are offered. (1) Although reducing the burden of antimicrobial-resistant pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE), is of preeminent importance, APIC and SHEA do not support legislation to mandate use of active surveillance cultures to screen for MRSA, VRE, or other antimicrobial-resistant pathogens. (2) SHEA and APIC support the continued development, validation, and application of efficacious and cost-effective strategies for the prevention of infections caused by MRSA, VRE, and other antimicrobial-resistant and antimicrobial-susceptible pathogens. (3) APIC and SHEA welcome efforts by healthcare consumers, together with private, local, state, and federal policy makers, to focus attention on and formulate solutions for the growing problem of antimicrobial resistance and healthcare-associated infections. (4) SHEA and APIC support ongoing additional research to determine and optimize the appropriateness, utility, feasibility, and cost-effectiveness of using active surveillance cultures to screen both lower-risk and high-risk populations. (5) APIC and SHEA support stronger collaboration between state and local public health authorities and institutional infection prevention and control experts.
ABSTRACT mecA , the gene that mediates methicillin resistance, and its accompanying mec locus DNA, insert near the gyrA gene in Staphylococcus aureus . To investigate whether there is a similar relationship between mecA and gyrA in coagulase-negative staphylococci (CNS), mecA - and gyrA -specific DNA fragments were used to probe methicillin-resistant isolates of Staphylococcus epidermidis (MRSE) ( n = 11) and Staphylococcus haemolyticus (MRSH) ( n = 11). The gyrA probe hybridized to the same Sma I DNA fragment as the mecA probe in all strains tested. However, since the size of the Sma I fragments containing mecA and gyrA varied from 73 to 600 kb, the distance between the two genes was determined more precisely. Cloned mecA or gyrA fragments plus vector sequences each containing a Sma I site were introduced into the chromosome of three isolates each of MRSE and methicillin-resistant S. aureus (MRSA), and the sizes of the generated Sma I fragments were determined by pulsed-field gel electrophoresis. The distance between gyrA and mecA was found to be between 38 and 42 kb in both MRSE and MRSA, and the two genes were in the same relative orientation in all strains. Restriction fragment length polymorphism (RFLP) patterns around the gyrA gene in CNS were identical, but species specific, for all 10 MRSE and 10 MRSH isolates examined. In contrast, 8 of 11 methicillin-susceptible S. epidermidis isolates and 7 of 7 methicillin-susceptible S. haemolyticus isolates had different gyrA RFLP patterns. These data show that mecA is site and orientation specific, relative to gyrA , in both MRSE and MRSA. In addition, the local environment around gyrA in methicillin-resistant CNS, in contrast to methicillin-susceptible isolates, is similar, suggesting clonality or the requirement for specific DNA sequences with which the mec complex must interact for chromosomal integration to occur.
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Abstract Background: Clostridium difficile -associated diarrhea (CDAD) causes substantial healthcare-associated morbidity. Unlike other common healthcare-associated pathogens, little comparative information is available about CDAD rates in hospitalized patients. Objectives: To determine CDAD rates per 10,000 patient-days and per 1,000 hospital admissions at 7 geographically diverse tertiary-care centers from 2000 to 2003, and to survey participating centers on methods of CDAD surveillance and case definition. Methods: Each center provided specific information for the study period, including case numbers, patient-days, and hospital characteristics. Case definitions and laboratory diagnoses of healthcare-associated CDAD were determined by each institution. Within institutions, case definitions remained consistent during the study period. Results: Overall, mean annual case rates of CDAD were 12.1 per 10,000 patient-days (range, 3.1 to 25.1) and 7.4 per 1,000 hospital admissions (range, 3.1 to 13.1). No significant increases were observed in CDAD case rates during the 4-year interval, either at individual centers or in the Prevention Epicenter hospitals as a whole. Prevention Epicenter hospitals differed in their CDAD case definitions. Different case definitions used by the hospitals applied to a fixed data set resulted in a 30% difference in rates. No associations were identified between diagnostic test or case definition used and the relative rate of CDAD at a specific medical center. Conclusions: Rates of CDAD vary widely at tertiary-care centers across the United States. No significant increases in case rates were identified. The varying clinical and laboratory approaches to diagnosis complicated comparisons between hospitals. To facilitate benchmarking and comparisons between institutions, we recommend development of a more standardized case definition.
Previous microarray data (E. Mongodin, J. Finan, M. W. Climo, A. Rosato, S. Gill, and G. L. Archer, J. Bacteriol. 185:4638-4643, 2003) noted an association in two vancomycin-intermediate Staphylococcus aureus (VISA) strains between high-level, passage-induced vancomycin resistance, a marked increase in the transcription of purine biosynthetic genes, and mutation of the putative purine regulator purR. Initial studies to report on the possible association between vancomycin resistance and alterations in purine metabolism in one of these strains (VP-32) confirmed, by Western analysis, an increase in the translation of PurH and PurM, two purine pathway enzymes. In addition, PurR was identified, by knockout and complementation in a vancomycin-susceptible strain, as a repressor of the purine biosynthetic operon in S. aureus, and the PurR missense mutation was shown to inactivate the repressor. However, despite the apparent relationship between increased purine biosynthesis and increased vancomycin resistance in VP-32, neither the addition of exogenous purines to a defined growth medium nor the truncation or inactivation of purR improved the growth of vancomycin-susceptible S. aureus in the presence of vancomycin. Furthermore, the passage of additional vancomycin-susceptible and VISA strains to high-level vancomycin resistance occurred without changes in cellular purine metabolism or mutation of purR despite the development of thickened cell walls in passaged strains. Thus, we could confirm neither a role for altered purine metabolism in the development of vancomycin resistance nor its requirement for the maintenance of a thickened cell wall. The failure of biochemical and physiological studies to support the association between transcription and phenotype initially found in careful microarray studies emphasizes the importance of follow-up investigations to confirm microarray observations.
Clinical isolates of Staphylococcus aureus displaying intermediate resistance to vancomycin (VISA) have been identified. The objective of our study was to identify VISA colonization among patients known to be colonized or infected with vancomycin-resistant enterococci (VRE). Eight weekly point prevalence screening surveys for VRE and S. aureus were conducted on 5 hospital units. Of the 243 patients screened, 31 (12.8%) were colonized with VRE. In addition, 18 inpatients were already known to be VRE-positive. Fourteen (28.6%) of the 49 VRE-positive patients were co-colonized with S. aureus. All 30 S. aureus isolates from these 14 patients were methicillin-resistant (MRSA) but remained vancomycin-susceptible (minimal inhibitory concentration [MIC] range, 0.75–2 µg/mL). Population analysis profiling demonstrated no evidence of heteroresistant subpopulations that could grow on agar containing 3 µg/mL vancomycin for any of the MRSA isolates. Although 23 (77%) of 30 staphylococcal isolates had vancomycin MICs of 1.5 or 2 µg/mL, no VISA strains (MICs, 8–16 µg/mL) were recovered.
The genes mediating the conjugative transfer of the 52-kb staphylococcal plasmid pGO1 are within a 14.4-kb gene cluster designated trs. However, a clone containing trs alone cannot transfer independently and no candidate oriT has been found within or contiguous to trs. In this study, we identified a 1,987-bp open reading frame (ORF) 24 kb 3' and 13 kb 5' to trs that was essential for conjugative transfer: transposon insertions into the ORF abolished transfer and a plasmid containing the ORF could complement these transposon-inactivated pGO1 mutants for transfer. Analysis of the nucleotide sequence of this ORF revealed significant homology between the amino terminus of its predicted protein and those of several single-stranded endonucleases. In addition, a 12-bp DNA sequence located 100 bp 5' to the ORF's translational start site was identical to the oriT sequences of the conjugative or mobilizable plasmids RSF1010, pTF1, R1162, pSC101, and pIP501. The ability of the ORF, designated nes (for nicking enzyme of staphylococci), to generate a single-stranded nick at the oriT was demonstrated in Escherichia coli by alkaline gel and DNA sequence analysis of open circular plasmid DNA. Plasmids that could be converted to the open circular form by the presence of oriT and nes could also be mobilized at high frequency into Staphylococcus aureus recipients with a second plasmid containing only trs. We propose that the 14.4 kb of trs and the approximately 2.2 kb of the oriT-nes region, coupled with an origin of replication, make up the minimal staphylococcal conjugative replicon.
Fazit Die Studie belegt einige bekannte Fakten über Chlorhexidin: Erstens, es ist in der Lage, die Keimbelastung mit grampositiver Flora zu reduzieren, während es im gramnegativen Bereich weniger wirksam zu sein scheint. Zweitens, es ist gut hautverträglich und es findet keine nennenswerte Resistenzentwicklung auch bei breitflächiger Anwendung statt. Interessant sind auch die beobachteten Unterschiede in der MHK für MRSA und VRE, was die Frage aufwirft, ob andere Substanzen bei hoher VRE-Prävalenz besser wirksam sind. Trotz insgesamt geringer Anzahl konnte auch bei den katheterinduzierten Fungämien eine Reduktion beobachtet werden. Da es sich bei der Fungämie in der Regel um eine Komplikation bei Langliegern handelt, wirft diese Beobachtung die Frage des optimalen Zeitpunkts einer Chlorhexidinwaschung auf: Muss wirklich jeder Intensivpatient sein tägliches antiseptisches Bad von Anfang an erhalten, oder wäre ein gezielter Einsatz bei Langliegern genauso effektiv? Auch wenn sich Chlorhexidin selbst in der Studie als gut hautverträglich erwies und keine substanzspezifischen Nebenwirkungen beobachtet wurden, weist die Studie in der Nebenbeobachtung auf eine grundsätzliche Problematik desinfektionsmittelgetränkter Waschlappen hin: die mögliche primäre Kontamination mit desinfektionsmittelresistenten Organismen, in diesem Falle mit Burkholderia cepacia. Ähnliche Probleme sind auch von anderen vorgetränkten Pflegeprodukten bekannt, sodass diese in Ausbruchssituationen gerade von für die Station untypischen Erregern immer in die Differenzialdiagnostik mit einbezogen werden müssen. Zusammenfassend erscheint die tägliche Chlorhexidinwaschung bzw. eine gleichwertige antiseptische Waschung von Intensivpatienten zur Keimlastreduktion in Situationen mit hoher MRSA- und/oder VRE-Last und einer relevant hohen Rate von Blutstrominfektionen eine geeignete Interventionsmaßnahme zu sein.
ABSTRACT Nosocomial oxacillin-resistant Staphylococcus aureus (ORSA) bloodstream isolates were tested to determine the prevalence of vancomycin heteroresistance. We screened 619 ORSA nosocomial bloodstream isolates from 36 hospitals between 1997 and 2000. Only one isolate exhibiting heterotypic resistance was detected. Thus, vancomycin heteroresistance in clinical bloodstream isolates remains rare in the United States.