Barry Cookson

Staphylococcus aureus Isolates Carrying Panton-Valentine Leucocidin Genes in England and Wales: Frequency, Characterization, and Association with Clinical Disease

ABSTRACT Staphylococcus aureus isolates carrying the genes that encode for Panton-Valentine leucocidin (PVL), a highly potent toxin, have been responsible for recent outbreaks of severe invasive disease in previously healthy children and adults in the United States of America and Europe. To determine the frequency of PVL-positive isolates sent to the Staphylococcus Reference Unit (United Kingdom) for epidemiological purposes, we tested 515 isolates of S. aureus, and 8 (1.6%) were positive for the PVL locus. A further 470 isolates were selected to explore the association of PVL-positive S. aureus with clinical disease. Of these, 23 (4.9%) were PVL positive and most were associated with skin and soft tissue infections (especially abscesses). The PVL genes were also detected in isolates responsible for community-acquired pneumonia, burn infections, bacteremia, and scalded skin syndrome. Genotyping by pulsed-field gel electrophoresis and multilocus sequence typing revealed that the PVL-positive isolates were from diverse genetic backgrounds, although one prevalent clone of 12 geographically dispersed methicillin-resistant S. aureus (MRSA) isolates was identified (ST80). All 12 isolates were stapylococcal cassette chromosome mec type IVc, had an agr3 allele, and shared a common toxin gene profile (sea-see, seg-sej, eta, etb, and tst negative but etd positive). ST80 strains with similar genetic characteristics have been responsible for community-acquired infections in France and Switzerland. The remaining PVL-positive isolates were mostly methicillin-sensitive S. aureus and belonged to 12 different sequence types, including ST22 and ST30, which are closely related to the most prevalent MRSA clones in United Kingdom hospitals, EMRSA-15 and EMRSA-16, respectively.

Isolation measures in the hospital management of methicillin resistant Staphylococcus aureus (MRSA): systematic review of the literature

Abstract Objective To evaluate the evidence for the effectiveness of isolation measures in reducing the incidence of methicillin resistant Staphylococcus aureus (MRSA) colonisation and infection in hospital inpatients. Design Systematic review of published articles. Data sources Medline, Embase, CINAHL, Cochrane Library, System for Information on Grey Literature in Europe (SIGLE), and citation lists (1966-2000). Review methods Articles reporting MRSA related outcomes and describing an isolation policy were selected. No quality restrictions were imposed on studies using isolation wards or nurse cohorting. Other studies were included if they were prospective or employed planned comparisons of retrospective data. Results 46 studies were accepted; 18 used isolation wards, nine used nurse cohorting, and 19 used other isolation policies. Most were interrupted time series, with few planned formal prospective studies. All but one reported multiple interventions. Consideration of potential confounders, measures to prevent bias, and appropriate statistical analysis were mostly lacking. No conclusions could be drawn in a third of studies. Most others provided evidence consistent with a reduction of MRSA acquisition. Six long interrupted time series provided the strongest evidence. Four of these provided evidence that intensive control measures including patient isolation were effective in controlling MRSA. In two others, isolation wards failed to prevent endemic MRSA. Conclusion Major methodological weaknesses and inadequate reporting in published research mean that many plausible alternative explanations for reductions in MRSA acquisition associated with interventions cannot be excluded. No well designed studies exist that allow the role of isolation measures alone to be assessed. None the less, there is evidence that concerted efforts that include isolation can reduce MRSA even in endemic settings. Current isolation measures recommended in national guidelines should continue to be applied until further research establishes otherwise.

Guidelines for UK practice for the diagnosis and management of methicillin-resistant Staphylococcus aureus (MRSA) infections presenting in the community

These guidelines have been developed by a Working Party convened on behalf of the British Society for Antimicrobial Chemotherapy. Their aim is to provide general practitioners and other community- and hospital-based healthcare professionals with pragmatic advice about when to suspect MRSA infection in the community, when and what cultures should be performed and what should be the management options, including the need for hospitalization.

Evaluation of Molecular Typing Methods in Characterizing a European Collection of Epidemic Methicillin-Resistant Staphylococcus aureus Strains: the HARMONY Collection

ABSTRACT We analyzed a representative sample of methicillin-resistant Staphylococcus aureus (MRSA) from 11 European countries (referred to as the HARMONY collection) using three molecular typing methods used within the HARMONY group to examine their usefulness for large, multicenter MRSA surveillance networks that use these different laboratory methodologies. MRSA isolates were collected based on their prevalence in each center and their genetic diversity, assessed by pulsed-field gel electrophoresis (PFGE). PFGE groupings (≤3 bands difference between patterns) were compared to those made by sequencing of the variable repeats in the protein A gene spa and clonal designations based on multilocus sequence typing (MLST), combined with PCR analysis of the staphylococcal chromosome cassette containing the mec genes involved in methicillin resistance (SCCmec). A high level of discrimination was achieved using each of the three methodologies, with discriminatory indices between 89.5% and 91.9% with overlapping 95% confidence intervals. There was also a high level of concordance of groupings made using each method. MLST/SCCmec typing distinguished 10 groups containing at least two isolates, and these correspond to the majority of nosocomial MRSA clones described in the literature. PFGE and spa typing resolved 34 and 31 subtypes, respectively, within these 10 MRSA clones, with each subtype differing only slightly from the most common pattern using each method. The HARMONY group has found that the methods used in this study differ in their availability and affordability to European centers involved in MRSA surveillance. Here, we demonstrate that the integration of such technologies is achievable, although common protocols (such as we have developed for PFGE) may also be important, as is the use of centralized Internet sites to facilitate data analysis. PFGE and spa-typing data from analysis of MRSA isolates from the many centers that have access to the relevant equipment can be compared to reference patterns/sequences, and clonal designations can be made. In the majority of cases, these will correspond to those made by the (more expensive) method of choice—MLST/SCCmec typing—and these alternative methods can therefore be used as frontline typing systems for multicenter surveillance of MRSA.

Evaluation of the national Cleanyourhands campaign to reduce Staphylococcus aureus bacteraemia and Clostridium difficile infection in hospitals in England and Wales by improved hand hygiene: four year, prospective, ecological, interrupted time series study

Objective To evaluate the impact of the Cleanyourhands campaign on rates of hospital procurement of alcohol hand rub and soap, report trends in selected healthcare associated infections, and investigate the association between infections and procurement. Design Prospective, ecological, interrupted time series study from 1 July 2004 to 30 June 2008. Setting 187 acute trusts in England and Wales. Intervention Installation of bedside alcohol hand rub, materials promoting hand hygiene and institutional engagement, regular hand hygiene audits, rolled out nationally from 1 December 2004. Main outcome measures Quarterly (that is, every three months) rates for each trust of hospital procurement of alcohol hand rub and liquid soap; Staphylococcus aureus bacteraemia (meticillin resistant (MRSA) and meticillin sensitive (MSSA)) and Clostridium difficile infection for each trust. Associations between procurement and infection rates assessed by mixed effect Poisson regression model (which also accounted for effect of bed occupancy, hospital type, and timing of other national interventions targeting these infections). Results Combined procurement of soap and alcohol hand rub tripled from 21.8 to 59.8 mL per patient bed day; procurement rose in association with each phase of the campaign. Rates fell for MRSA bacteraemia (1.88 to 0.91 cases per 10 000 bed days) and C difficile infection (16.75 to 9.49 cases). MSSA bacteraemia rates did not fall. Increased procurement of soap was independently associated with reduced C difficile infection throughout the study (adjusted incidence rate ratio for 1 mL increase per patient bed day 0.993, 95% confidence interval 0.990 to 0.996; P<0.0001). Increased procurement of alcohol hand rub was independently associated with reduced MRSA bacteraemia, but only in the last four quarters of the study (0.990, 0.985 to 0.995; P<0.0001). Publication of the Health Act 2006 was strongly associated with reduced MRSA bacteraemia (0.86, 0.75 to 0.98; P=0.02) and C difficile infection (0.75, 0.67 to 0.84; P<0.0001). Trust visits by Department of Health improvement teams were also associated with reduced MRSA bacteraemia (0.91, 0.83 to 0.99; P=0.03) and C difficile infection (0.80, 0.71 to 0.90; P=0.01), for at least two quarters after each visit. Conclusions The Cleanyourhands campaign was associated with sustained increases in hospital procurement of alcohol rub and soap, which the results suggest has an important role in reducing rates of some healthcare associated infections. National interventions for infection control undertaken in the context of a high profile political drive can reduce selected healthcare associated infections.

Meticillin-resistant Staphylococcus aureus

Meticillin was introduced in 1959 to treat infections caused by penicillin-resistant Staphylococcus aureus. In 1961 there were reports from the UK of S aureus isolates that had acquired resistance to meticillin (meticillin-resistant S aureus, MRSA). Similar MRSA isolates were soon found in other European countries, and later from Japan, Australia, and the USA. Today MRSA is a major cause of hospital-acquired infections, and a serious public-health concern. In this forum, we present different perspectives from across the globe to better understand the complexity of the problem, and examine the challenges that individual countries face in trying to control the spread of MRSA

Methicillin-resistant Staphylococcus aureus in the community : New battlefronts, or are the battles lost?

Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of nosocomial infections worldwide. Interpretation of community MRSA trends is problematical, in that the term is ill-defined, and related data are difficult to put into context. There are four relevant battlefronts, all of interest to risk assessment and prevention. These comprise the following: the issues relating to an increasing pool of patients with MRSA discharged from hospitals into the community; MRSA spreading to patients in nursing and residential homes; and MRSA spreading from patients and healthcare workers to others in the community. There are often difficulties in determining whether the fourth issue, MRSA arising apparently de novo in the community, is in fact due to one of these other fronts. All these battlefronts are important and not yet lost. However, we must agree on definitions and design-appropriate surveillance strategies, so that we can best inform prevention and control activities to contain these emerged or emerging problems.

Rapid identification of methicillin-resistant Staphylococcus aureus from positive blood cultures by real-time fluorescence PCR.

ABSTRACT Methicillin-resistant Staphylococcus aureussepticemia is associated with significant morbidity and mortality and requires treatment with intravenous glycopeptides. For blood cultures positive for gram-positive cocci, 24 to 48 h is required for the detection of S. aureus bacteremia and the provision of antibiotic susceptibility testing results. We describe a molecular biology-based assay that requires 2 h from the time of initial positivity of blood cultures. The assay correctly detected 96% of the S. aureus isolates including all methicillin-resistant S. aureus isolates. Clinical data collected during the study suggest that 28% of patients with S. aureus bacteremia do not receive early and appropriate treatment and that 10% of patients may initially be receiving inappropriate glycopeptide treatment.

Trends among pathogens reported as causing bacteraemia in England, 2004–2008

The Health Protection Agency in England operates a voluntary surveillance system that collects data on bacteraemias reported by over 90% of laboratories in England. Trends in causative microorganisms reported between 2004 and 2008 were analyzed using a generalized linear model with a log link function for Poisson distribution. In 2008, 101,276 episodes of bacteraemia were reported; a rate of 189 per 100,000 population. More than one-half occurred in those aged over 65 years and males. The most common organisms reported were Escherichia coli (23%), coagulase-negative staphylococci (CNS) (16.9%) and Staphylococcus aureus (11.4%). Between 2004 and 2008, E. coli bacteraemia increased by 33% (p < 0.001); the species now accounts for more than 30% of bacteraemia in those aged over 75 years. There also were significant increases in bacteraemia caused by other Gram-negative pathogens and marked seasonal variation. Bacteraemia caused by S. aureus increased until 2005, with a decline after 2006 (p < 0.001) entirely due to methicillin-resistant strains. CNS bacteraemia have declined significantly since 2007. The renewed dominance of Gram-negative pathogens as major causes of bacteraemia in England is of particular concern because they are associated with a high morbidity and increasing resistance to antibiotics. Further investigation of the underlying causes and prevention strategies is a public health priority. Recent declines in methicillin-resistant S. aureus bacteraemia have not been reflected in other pathogens, including methicillin-susceptible S. aureus.

Decline of EMRSA-16 amongst methicillin-resistant Staphylococcus aureus causing bacteraemias in the UK between 2001 and 2007

OBJECTIVES Between 1998 and 2000, 95.6% of methicillin-resistant Staphylococcus aureus (MRSA) bacteraemias in the UK were due to two epidemic strains, namely EMRSA-15 or EMRSA-16 (60.2% and 35.4%, respectively). We sought to determine the proportions of these strains before and after the general decline in MRSA bacteraemia that began around 2004. METHODS Consecutive MRSA isolates collected in 2001, 2003, 2005 and 2007 by the BSAC Bacteraemia Surveillance Programme were categorized to multilocus sequence typing (MLST) clonal complex and to SCCmec type by PCR. MICs were determined by the BSAC method. Data trends were tested for significance using a generalized linear regression model. RESULTS Collectively, EMRSA-15 and EMRSA-16 consistently accounted for approximately 95% of MRSA studied between 2001 and 2007, but the proportions of EMRSA-16 declined from 21.4% in 2001 to 9% in 2007 (P < 0.05), whilst the proportion of EMRSA-15 rose commensurately, accounting for 85% of MRSA in 2007. Ciprofloxacin and erythromycin resistance were common amongst both EMRSA-15 and EMRSA-16. CONCLUSIONS EMRSA-15 and EMRSA-16 remain the main MRSA strains in bacteraemia in the UK, but the proportion of EMRSA-16 declined from the late 1990 s, thus preceding the general decline in MRSA bacteraemias that began in the middle of the present decade.