Are the epidemiology and microbiology of methicillin-resistant Staphylococcus aureus changing?
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Biomedical subjects
Publications and source records attributed to J M Boyce.
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VRE have spread rapidly since their initial description in 1988. Although much has been learned about the epidemiology of VRE, further studies are needed to establish the reservoirs of the organism and the relative importance of various modes of transmission. There is considerable anecdotal evidence that nosocomial transmission of VRE can be thwarted by using measures such as those recommended by HICPAC, especially if they are implemented promptly after VRE have been introduced into hospitals.
OBJECTIVE: To study the possible role of contaminated environmental surfaces as a reservoir of methicillin-resistant Staphylococcus aureus (MRSA) in hospitals. DESIGN: A prospective culture survey of inanimate objects in the rooms of patients with MRSA. SETTING: A 200-bed university-affiliated teaching hospital. PATIENTS: Thirty-eight consecutive patients colonized or infected with MRSA. Patients represented endemic MRSA cases. RESULTS: Ninety-six (27%) of 350 surfaces sampled in the rooms of affected patients were contaminated with MRSA. When patients had MRSA in a wound or urine, 36% of surfaces were contaminated. In contrast, when MRSA was isolated from other body sites, only 6% of surfaces were contaminated (odds ratio, 8.8; 95% confidence interval, 3.7-25.5; P < .0001). Environmental contamination occurred in the rooms of 73% of infected patients and 69% of colonized patients. Frequently contaminated objects included the floor, bed linens, the patient's gown, overbed tables, and blood pressure cuffs. Sixty-five percent of nurses who had performed morning patient-care activities on patients with MRSA in a wound or urine contaminated their nursing uniforms or gowns with MRSA. Forty-two percent of personnel who had no direct contact with such patients, but had touched contaminated surfaces, contaminated their gloves with MRSA. CONCLUSIONS: We concluded that inanimate surfaces near affected patients commonly become contaminated with MRSA and that the frequency of contamination is affected by the body site at which patients are colonized or infected. That personnel may contaminate their gloves (or possibly their hands) by touching such surfaces suggests that contaminated environmental surfaces may serve as a reservoir of MRSA in hospitals.
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Patients frequently develop nosocomial infections that are caused by normal flora colonizing the patient at the time of admission, or by exogenous pathogens that are acquired and subsequently colonize the patient after admission to the hospital. To prevent nosocomial infections, a variety of strategies have been used either to prevent colonization from occurring, to eradicate colonizing organisms, or to prevent the progression from colonization to infection. These strategies include implementation of infection control measures designed to prevent acquisition of exogenous pathogens, eradication of exogenous pathogens from patients or personnel who have become colonized, suppression of normal flora, prevention of colonizing flora from entering sterile body sites during invasive procedures, microbial interference therapy, immunization of high-risk patients, and modification of antibiotic utilization practices. Because strategies that require widespread use of antimicrobial agents to suppress or eradicate colonizing organisms tend to promote emergence of multidrug-resistant pathogens, greater emphasis should be given to those strategies that prevent colonization from occurring or employ techniques other than administration of prophylactic antibiotics to eradicate colonization. Restricting inappropriate use of antibiotics should reduce the frequency with which patients become colonized and infected with multidrug-resistant organisms.
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In hospitals with 200 to 300 beds, hospital epidemiologists serve primarily as medical and epidemiology consultants to the infection control practitioners, as advocates for the infection control programs, and as chairpersons of the infection control committees. Because smaller hospitals often have limited resources for infection control, surveillance and control activities must focus on issues that have caused problems for the facility and on compliance with mandates and recommendations made by healthcare agencies. The clinical microbiology laboratory plays an important role in ongoing surveillance activities and often is responsible for performing cultures obtained during point prevalence culture surveys or outbreak investigations. Because laboratory support often is limited, the indications for obtaining a culture from patients, personnel, or the inanimate environment for infection control purposes must be reviewed and discussed carefully with the clinical laboratory in advance.
After controlling an epidemic of vanB-type vancomycin-resistant Enterococcus faecium (VRE), we contained a subsequent vanA E faecium outbreak by using prospective laboratory-based surveillance, placing patients with VRE in private rooms, requiring the use of both gowns and gloves by all personnel entering the patients' rooms, and conducting prevalence surveys of patients on affected wards.
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In areas where the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) is very low, aggressive strategies, which appear to have been effective, such as those used in the Netherlands and western Australia, may be feasible. In hospitals where MRSA is epidemic or highly endemic, less rigorous strategies are appropriate. However, which isolation techniques and barrier precautions are optimal is controversial. In addition, there is no consensus regarding the epidemiological importance of environmental contamination. Rapid detection of MRSA, prompt implementation of barrier precautions and prospective surveillance are essential components of a successful control programme. Eradicating nasal carriage of MRSA among patients and personnel can be useful during epidemics, but the cost-effectiveness of using this approach in hospitals where the prevalence of MRSA is low is unknown. Additional studies of this issue need to include surveillance for mupirocin-resistant strains.
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Enterococci expressing resistance to antimicrobial agents are increasingly important nosocomial pathogens. Effective strategies to prevent or abort outbreaks of resistant enterococcal infection will rely on an accurate understanding of the mechanisms by which these organisms spread. A 1065-bp insertion-like sequence (IS6770) is present in varying copy numbers in > 90% of enterococcal strains thus far examined. Hybridization patterns resulting from hybridization of enterococcal genomic DNA with an internal IS6770 probe vary considerably between unrelated strains and correlate well with results of pulsed-field gel electrophoresis and field-inversion gel electrophoresis in identifying clonal relationships among enterococcal isolates. IS6770 analysis of several outbreaks of resistant enterococci has confirmed the spread of single resistant clones rather than the emergence of resistance within the resident flora. These results suggest that IS6770 hybridization will be a useful tool for tracing the epidemiology of nosocomial enterococcal infections.
Calnexin is a membrane-bound protein of the ER in animal cells (Wada et al., 1991). It shows considerable similarity to the major calcium-sequestering protein of the ER lumen, calreticulin, with two calcium-binding regions--a high-affinity, low-capacity region in the ER lumen and a low-affinity, high-capacity region in the cytoplasm. The protein is postulated to act as a calcium-regulated chaperone during protein maturation (Ou et al., 1993). We have isolated a genomic sequence showing significant homology to the animal gene over the predicted coding sequence (Table I). A partial cDNA from Zea mays was isolated from an expression library made from 6-d coleoptiles (Clontech, Palo Alto, CA). The library was screened using a monoclonal antibody raised against a small number of microsomal proteins resulting from a partial purification of plasma membrane Ca2+ ATPase (Briars et al., 1988). The partial cDNA showed sequence homology to the calcium-binding region common to calreticulin and calnexin. The fragment was used to screen a genomic library constructed from Arabidopsis thaliana (cv Larasbonerecta), and a 15-kb fragment was isolated and subcloned and the relevant subfragments were sequenced. The coding region contains five introns, two in the N-terminal region and three in the C-terminal region. The predicted amino acid sequence shows a high level of homology with the animal calnexin, although the terminal highly acidic calcium-binding region is shorter. A cDNA for a putative homolog of calnexin was isolated from A. thaliana (cv Columbia) by Huang et al.(1993); our coding sequence shows 85% identity and 92% similarity determined by FASTA (Wisconsin Genetics Computer Group package); however, the differences are greater than would be expected between cultivars of the same species. A Southern blot probed with DNA from the central calcium-binding region shows multiple bands. This, combined with the sequence heterogeneity, suggests that calnexin belongs to a family of related genes.
Enterococcus faecium strains resistant to ampicillin, high levels of gentamicin, and vancomycin but susceptible to teicoplanin (vanB class vancomycin resistance) were recovered from 37 patients during an outbreak involving a 250-bed university-affiliated hospital. Three isolates with vancomycin MICs ranging from 8 to 256 micrograms/ml all hybridized with a vanB probe. Restriction endonuclease analysis of chromosomal and plasmid DNA suggested that all isolates tested were derived from a single clone. Vancomycin resistance was shown to be transferable. Risk factors for acquiring the epidemic strain included proximity to another case patient (P, 0.0005) and exposure to a nurse who cared for another case patient (P, 0.007). Contamination of the environment by the epidemic strain occurred significantly more often when case patients had diarrhea (P, 0.001). Placing patients in private rooms and requiring the use of gowns as well as gloves by personnel controlled the outbreak. These findings suggest that multidrug-resistant E. faecium strains with transferable vanB class vancomycin resistance will emerge as important nosocomial pathogens. Because extensive environmental contamination may occur when affected patients develop diarrhea, barrier precautions, including the use of both gowns and gloves, should be implemented as soon as these pathogens are encountered.
Active calcium transport in higher plant cell membranes involves both H(+)-linked antiport (at the tonoplast) and direct (P-type) calcium pumping ATPases. Both systems act to remove calcium from the cytoplasm either by pumping it into intracellular stores or into the apoplast. This chapter considers recent advances in our knowledge of the calcium-pumping ATPases of the plant cell, located both at the plasma membrane and in intracellular membranes. Progress in characterising the types of Ca2+ pump in plant cells is particularly important as it becomes increasingly clear that designations applicable to other eukaryotic Ca2+ pumps ('PM-type' and 'SR/ER type') are much less relevant for plant cells. Responses of plant Ca2+ pumps to mammalian Ca2+ pump inhibitors and differences in estimated relative molecular mass also underline the differences between plant and animal Ca2+ pumps. Molecular cloning has resulted in the identification of an SR/ER type Ca2+ pump in plants strongly homologous to that of mammals. These advances are put into the context of research aims in characterising the function and mechanisms of the plant Ca2+ pumps, and their role not only in regulating cytosolic free calcium concentrations, but also in providing intracellular signalling pools and in the regulation of secretion is discussed.
Cerebrospinal fluid (CSF) lactate values were measured in 26 children with meningitis (12 bacterial, 9 aseptic, 5 partially treated) and five children with meningococcaemia without meningitis. A reference range (0.5-3.2 mmol/l) was established from 100 control children. Amounts of lactate were significantly raised in bacterial meningitis (mean 6.5, range 4.5-10.2) compared with aseptic meningitis (mean 2.6, range 1.1-4.0) but this finding gave little practical help as the bacterial origin of the meningitis was clear from other CSF findings. High values (5.7) in a case of tuberculous meningitis (TBM) suggest that the test may be helpful when other CSF findings are inconclusive. Unless the CSF lactate is raised, the test is of minimal value in partially treated meningitis (mean 3.4, range 1.4-6.2). The previously unobserved finding of increased CSF lactate in meningococcaemia without meningitis (mean 3.9, range 3.1-5.0) supports the view that raised CSF lactate values in bacterial meningitis are not solely due to the presence of neutrophils. Literature relating to CSF lactate is reviewed.
A dramatic increase in the incidence of methicillin-resistant Staphylococcus aureus at a teaching hospital was documented to be due to three factors: a hospital-wide outbreak of 32 cases caused by an epidemic strain, an increase in the number of nosocomial cases caused by several other strains, and an increase in the number of patients admitted carrying strains acquired at other institutions. Case patients with the epidemic strain were significantly more likely than control patients to have had previous exposure to a respiratory therapist (P = .005) who had chronic sinusitis due to the epidemic strain. The plasmid DNA of isolates from the implicated respiratory therapist and affected patients yielded the same patterns on restriction endonuclease digestion. Implementation of general control measures and eradication of the respiratory therapist's sinusitis and nasal carriage terminated the epidemic. Establishing the importance of the infected health care worker by epidemiological methods led to control of the outbreak without the institution of wide-scale culture of specimens from personnel and the environment or other expensive and labor-intensive measures.