Point-of-care universal screening for meticillin-resistant Staphylococcus aureus: a cluster-randomized cross-over trial.

BACKGROUND: Meticillin-resistant Staphylococcus aureus (MRSA) is frequently endemic in healthcare settings and may be transmitted by person-to-person spread. Asymptomatic MRSA carriers are potential, unsuspected sources for transmission and some of them may be identified by admission screening. AIM: To assess whether rapid point-of-care screening (POCS) for MRSA at hospital admission may be associated with a reduction in MRSA acquisition rates when compared with slower laboratory-based methods. METHODS: A cluster-randomized cross-over trial was conducted in four admission wards of an acute London tertiary care hospital. Polymerase chain reaction-based POCS screening was compared with conventional culture screening. Patients were screened on ward admission and discharge, and the MRSA acquisition rate on the admission wards was calculated as the primary outcome measure. RESULTS: In all, 10,017 patients were included; 4978 in the control arm, 5039 in the POCS arm. The MRSA carriage rate on admission was 1.7%. POCS reduced the median reporting time from 40.4 to 3.7 h (P < 0.001). MRSA was acquired on the admission wards by 23 (0.46%) patients in the control arm and by 24 (0.48%) in the intervention arm, acquisition rates of 5.39 and 4.60 per 1000 days respectively. After taking account of predefined confounding factors, the adjusted incidence rate ratio (IRR) for change in trend for MRSA acquisition was 0.961 (95% confidence interval: 0.766-1.206). The adjusted IRR for step change for MRSA acquisition was 0.98 (0.304-3.162). CONCLUSION: POCS produces a significantly faster result but has no effect on MRSA acquisition on admission wards compared with culture screening. Where compliance with infection prevention and control is high and MRSA carriage is low, POCS has no additional impact on MRSA acquisition rates over the first one to four days of admission compared with conventional culture screening.

Implications of targeted versus universal admission screening for meticillin-resistant Staphylococcus aureus carriage in a London hospital.

Universal admission screening for meticillin-resistant Staphylococcus aureus (MRSA) has been performed in England since 2010. We evaluated the predictive performance of a regression model derived from the first year of universal screening for detecting MRSA at hospital admission. If we had used our previous targeted screening policy, 75% fewer patients (21,699 per year) would have been screened. However, this would have identified only ~55% of all MRSA carriers, 65% of healthcare-associated MRSA strains, and 40% of community-associated strains. Failing to identify ~45% of patients (262 per year) carrying MRSA at hospital admission may have implications for MRSA control.

Low prevalence of meticillin-resistant Staphylococcus aureus carriage at hospital admission: implications for risk-factor-based vs universal screening.

BACKGROUND: There is debate over the optimal policy for detecting meticillin-resistant Staphylococcus aureus (MRSA) colonization at hospital admission. The emergence of community-associated (CA)-MRSA may compromise targeted screening strategies based on risk factors for healthcare-associated (HA)-MRSA. AIM: To determine the prevalence of MRSA colonization at admission, and the genotype and molecular epidemiology of the strains involved. METHODS: A 12-month observational study was performed at a 1200-bed London tertiary referral hospital from 1 April 2008 to 1 March 2009. All available MRSA isolates were genotyped by spa and staphylococcal cassette chromosome mec (SCCmec) typing. FINDINGS: The overall MRSA colonization rate was 2.0% of 28,892 admissions (range 6.6% in critical care to 0.8% in obstetrics/gynaecology/neonatology). The overall frequency of previously unknown carriage of MRSA on admission was 1.4%. Most colonizing strains were epidemic HA-MRSA-15 and -16. However, heterogeneous CA strains accounted for 18% of recovered isolates, including 37.5% of MRSA from accident and emergency and 23.1% of MRSA from surgery. The CA-MRSA strain types had significantly different epidemiological associations from the HA-MRSA strains, so risk factors used for the identification of HA-MRSA may not detect CA-MRSA reliably. CONCLUSION: The low rate of HA-MRSA in the UK increases the relative proportion due to CA-MRSA, for which conventional risk-factor-based screening strategies may be less effective. Cost-benefit analyses of universal MRSA admission screening will need to take account of this new epidemiology.

The role of 'no-touch' automated room disinfection systems in infection prevention and control.

BACKGROUND: Surface contamination in hospitals is involved in the transmission of pathogens in a proportion of healthcare-associated infections. Admission to a room previously occupied by a patient colonized or infected with certain nosocomial pathogens increases the risk of acquisition by subsequent occupants; thus, there is a need to improve terminal disinfection of these patient rooms. Conventional disinfection methods may be limited by reliance on the operator to ensure appropriate selection, formulation, distribution and contact time of the agent. These problems can be reduced by the use of 'no-touch' automated room disinfection (NTD) systems. AIM: To summarize published data related to NTD systems. METHODS: Pubmed searches for relevant articles. FINDINGS: A number of NTD systems have emerged, which remove or reduce reliance on the operator to ensure distribution, contact time and process repeatability, and aim to improve the level of disinfection and thus mitigate the increased risk from the prior room occupant. Available NTD systems include hydrogen peroxide (H(2)O(2)) vapour systems, aerosolized hydrogen peroxide (aHP) and ultraviolet radiation. These systems have important differences in their active agent, delivery mechanism, efficacy, process time and ease of use. Typically, there is a trade-off between time and effectiveness among NTD systems. The choice of NTD system should be influenced by the intended application, the evidence base for effectiveness, practicalities of implementation and cost constraints. CONCLUSION: NTD systems are gaining acceptance as a useful tool for infection prevention and control.

Impact of the suspending medium on susceptibility of meticillin-resistant Staphylococcus aureus to hydrogen peroxide vapour decontamination.

Several factors influence the in vitro susceptibility of microbes to disinfectants. We evaluated the impact of various suspending media on the susceptibility of meticillin-resistant Staphylococcus aureus (MRSA) to hydrogen peroxide vapour (HPV) decontamination. From a >6 log(10) inoculum, relative susceptibility was 10% bovine serum albumin (BSA) < TSB < 3% BSA < saline < 0.3% BSA = water. MRSA was not recovered after >60 min exposure to HPV for all suspensions. These findings indicate that the suspending medium has an effect on the in vitro susceptibility of MRSA to HPV, which may have implications in the case of suboptimal cleaning.

Lack of enhanced effect of a chlorine dioxide-based cleaning regimen on environmental contamination with Clostridium difficile spores.

Spores of Clostridium difficile may play a significant role in transmission of disease within the healthcare environment and are resistant to a variety of detergents and cleaning fluids. A range of environmental cleaning agents has recently become available, many of which claim to be sporicidal. We investigated the effect of changing to a chlorine dioxide-based cleaning regimen on C. difficile environmental contamination and patient infection rates. The prevalence of environmental contamination was unaffected with a rate of 8% (9/120) before and 8% (17/212) following the change. Rates of patient infection were also unchanged during these periods.

Clinical negligence, litigation and healthcare-associated infections.

BACKGROUND: Litigation costs resulting from clinical negligence claims involving healthcare-associated infections are a significant but underappreciated cost to healthcare organizations. In England these claims are handled on behalf of the National Health Service (NHS) organizations by the NHS Litigation Authority (NHSLA). The total number of claims and the amounts awarded have increased significantly in recent years. AIM: To determine whether the recent significant reductions in meticillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI) and Clostridium difficile infections in England have had an effect on the number and value of NHSLA claims relating to these infections. METHODS: Data obtained from the NHSLA relating to claims mentioning C. difficile or MRSA from 2003 to 2010 were correlated with mandatory surveillance data from the Health Protection Agency for these infections. FINDINGS: The rate of NHSLA claims for MRSA has decreased in line with reductions in BSI for this infection (0.007 per BSI between 2003/4-2006/7 to 0.0017 per BSI between 2007/8 and 2010/11), but there was no significant change in claims relating to C. difficile infection. Overall the amounts awarded for successful claims have decreased significantly from a total of £76,846 for the period 1997/8-2006/7 to £24,821 for the period 2007/8-2010/11. CONCLUSIONS: The number of litigation claims involving MRSA has recently decreased significantly in line with surveillance data. There was no observed effect on claims involving C. difficile. The amounts awarded for successful claims for both infections have also fallen, although the reasons for this are not clear.

Community-associated meticillin-resistant Staphylococcus aureus: the case for a genotypic definition.

BACKGROUND: New distinct strains of community-associated meticillin-resistant Staphylococcus aureus (CA-MRSA) have emerged as a cause of infection in previously healthy individuals in community settings. It is important to identify CA-MRSA for clinical management, epidemiological analysis, infection prevention and control, and regulatory reporting, but definitions and nomenclature of these strains are confused. AIM: To review attempts to define CA-MRSA and propose a new definition. METHODS: Non-systematic review. FINDINGS: Epidemiological definitions were useful for differentiating CA-MRSA and healthcare-associated (HA)-MRSA strain types in the past. However, although HA-MRSA strain types are rarely transmitted in the community, CA-MRSA strains have started to be transmitted in healthcare facilities, so epidemiological definitions are breaking down. CA-MRSA are community strains of S. aureus that have acquired the meticillin resistance gene, mecA. They are distinct from HA-MRSA and should be defined genetically. This may be done by combining genotypic typing by multi-locus sequence or spa with analysis of the staphylococcal cassette chromosome mec. Carriage of Panton-Valentine leukocidin or antimicrobial susceptibility profiles can be useful indicators of CA-MRSA but should not be used for their definition. CONCLUSION: For full assessment of their epidemiology, MRSA infections should be characterized as: (1) caused by HA- or CA-MRSA strain types; (2) acquired in community or healthcare settings; and (3) onset in the community or healthcare facility.

Diagnostic testing for Clostridium difficile: a comprehensive survey of laboratories in England.

Recent studies have shown poor performance of commonly used toxin enzyme immunoassays (EIAs) for laboratory testing for Clostridium difficile infection (CDI). In 2009-2010, the UK Health Protection Agency and the European Society of Clinical Microbiology and Infectious Diseases stated that toxin EIA testing alone is suboptimal, and recommended a two-step testing protocol (i.e. screening with one method and confirming the results with another method). All acute English National Health Service trusts were surveyed to determine their testing methods and positivity rates using freedom of information requests. Replies were received from 168 of 170 trusts (99% response rate). Seventy percent of trusts were using a toxin EIA as a standalone testing method, with positive predictive values (PPVs) as low as 20% in some cases. The mean positivity rate decreased from 6.45% in 2008 to 4.47% in 2009, which will have a negative effect on the PPVs of these tests. The UK Department of Health publishes CDI rates as a measure of quality of care and good infection control practice. However, this may not provide valid comparisons because of the wide disparity between testing methods. The present study demonstrates wide variation in testing practices for CDI in England, and laboratories should reconsider their current testing strategies.

Community-associated meticillin-resistant Staphylococcus aureus strains as a cause of healthcare-associated infection.

Community-associated meticillin-resistant Staphylococcus aureus (CA-MRSA) was first noticed as a cause of infection in community-based individuals without healthcare contact. As the global epidemic of CA-MRSA has continued, CA-MRSA strain types have begun to emerge as a cause of healthcare-associated infections (HAIs) and hospital outbreaks have occurred worldwide. In areas where CA-MRSA clones have become established with high prevalence, for example USA300 (ST8-IV) in the USA, CA-MRSA are beginning to supplant or overtake traditional healthcare-associated MRSA strains as causes of HAI. The emergence of CA-MRSA as a cause of HAI puts a wider group of hospitalised patients, healthcare workers and their community contacts potentially at risk of MRSA infection. It also exposes CA-MRSA strains to the selective pressure of antibiotic use in hospitals, potentially resulting in increased antibiotic resistance, challenges traditional definitions of CA-MRSA and hampers control efforts due to the constant re-introduction of MRSA from an emerging community reservoir. There is thus an urgent need to clarify the definitions, prevalence and epidemiology of CA-MRSA and to develop systems for the identification and control of these organisms in the community, in hospitals and other healthcare facilities, and at the community-hospital interface.

Prevalence and role of efflux pump activity in ciprofloxacin resistance in clinical isolates of Klebsiella pneumoniae.

We investigated the prevalence and role of efflux pump activity and possible drug influx resistance in ciprofloxacin susceptibility amongst 26 distinct clinical isolates of Klebsiella pneumoniae of varying ciprofloxacin susceptibilities and known quinolone resistance-determining region (QRDR) genotypes. Cellular [(14)C]ciprofloxacin accumulation patterns and the amount of cell-associated [(14)C]ciprofloxacin of mid-logarithmic phase cells were determined before and after challenging with the efflux pump inhibitor carbonyl cyanide 3-chlorophenylhydrazone (CCCP). Most isolates (24/26), and all with ciprofloxacin minimum inhibitory concentrations (MICs) >1 µg/ml, had efflux activity that could extrude up to 90% of cell-associated [(14)C]ciprofloxacin; none had significant influx resistance. In isolates with no QRDR mutations, efflux alone reduced ciprofloxacin susceptibility. In isolates with QRDR mutations, the efflux activity varied: in one isolate with no efflux activity, the most common fluoroquinolone resistance-causing QRDR mutation did not bring about clinically significant ciprofloxacin resistance; isolates with multiple mutations had high MICs and, usually, high levels of efflux activity. Fluoroquinolone efflux activity is much more common in clinical isolates of K. pneumoniae than previously reported and it can contribute to decreased ciprofloxacin susceptibility.

Utility of antimicrobial susceptibility-based algorithms for the presumptive identification of genotypically-defined community-associated methicillin-resistant Staphylococcus aureus at a London teaching hospital.

PURPOSE: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) strains are classically characterised by susceptibility to most non-ß-lactam antimicrobial agents. We sought to determine whether antimicrobial susceptibility (AMS)-based algorithms could be used to presumptively identify CA-MRSA in a hospital MRSA collection. METHODS: Over a three-month period, all MRSA were tested for AMS, staphylococcal cassette chromosome mec (SCCmec) type, presence of the Panton-Valentine leukocidin (PVL) genes and spa type. CA-MRSA isolates were defined genotypically using a combination of spa and SCCmec type. AMS based algorithms were developed and tested for their sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). RESULTS: Ciprofloxacin susceptibility (p < 0.001) and fusidic acid resistance (p = 0.044) were independent predictors of CA-MRSA in a multivariate model. Although 98.5% of HA-MRSA were ciprofloxacin resistant, so too were 36.6% of CA-MRSA. Algorithms based on ciprofloxacin-susceptibility and fusidic acid resistance performed best, with specificity and NPV >90% and sensitivity and PPV >70%. CONCLUSIONS: Our data indicate that while ciprofloxacin-susceptible isolates are likely to be CA-MRSA, the use of ciprofloxacin-susceptibility as a marker of CA-MRSA would miss approximately one third of CA-MRSA isolates. Therefore, AMS patterns have limited utility for the identification of genetically-defined CA-MRSA in our setting.

The continuing crisis in antibiotic resistance.

The emergence of antibiotic resistance in bacterial pathogens is an inevitable consequence of antibiotic use. Despite repeated warnings, negligent antibiotic use and poor infection-control practice have led to the continuing development of extensive resistance problems worldwide. Multidrug-resistant pathogens are now characterized by their heterogeneity, increasing virulence, resistance even to reserve agents and spread within and between hospitals and the community. Examples are glycopeptide-resistant meticillin-resistant Staphylococcus aureus (MRSA) and enterococci, extended-spectrum ß-lactamase- and carbapenemase-producing coliforms, and toxin-hyperproducing Clostridium difficile. Effective national and international programmes of control to combat these problems are urgently needed. The potential for success of such coordinated efforts has been demonstrated by the recent dramatic reductions in MRSA and C. difficile infections in England.

Hypermutability in clinical isolates of Klebsiella pneumoniae is uncommon and is unrelated to ciprofloxacin resistance.

We investigated hypermutability in Klebsiella pneumoniae and its association with ciprofloxacin resistance and mutations in the quinolone resistance-determining region (QRDR). Sixty-four strains of K. pneumoniae isolated in London, UK, between 1995 and 2002 with widely differing ciprofloxacin minimum inhibitory concentrations (MICs) and known gyrA and parC sequences were tested for mutation frequencies by selection with rifampicin. Only three hypermutable (frequency >or=10(-6)) strains were identified, with ciprofloxacin MICs of 0.25 microg/mL, 8 microg/mL and 64 microg/mL. There was no relationship between hypermutation and the ciprofloxacin MIC or QRDR mutations. Screening selected strains with streptomycin did not reveal any hypermutators, and screening with ciprofloxacin identified only two of the three hypermutators identified by rifampicin. Hypermutation in K. pneumoniae is uncommon and does not contribute to accumulation of QRDR mutations or directly to ciprofloxacin resistance.

Panton-Valentine leukocidin-encoding bacteriophage and gene sequence variation in community-associated methicillin-resistant Staphylococcus aureus.

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) often produce Panton-Valentine leukocin (PVL), which is encoded by two co-transcribed genes located on lysogenized bacteriophages. Six PVL-encoding temperate phages have been described and single nucleotide polymorphisms (SNPs) in the PVL genes have been reported. In the present study, 22 PVL-positive CA-MRSA isolates were chosen to reflect the diversity of multilocus sequence type (MLST) clonal complexes (CC) identified in our hospital. Isolates were characterized by antimicrobial resistance profile, staphylococcal cassette chromosome mec (SCCmec) and spa type, pulsed-field gel electrophoresis profile and MLST. Primers were designed to sequence the lukSF-PV genes. PVL-encoding phages were characterized using a PCR-based assay. SNPs were identified at seven locations in the lukSF-PV genes, which varied with S. aureus MLST lineage. One SNP was nonsynonymous. All CC80 and some CC1 isolates carried PhiSa2mw; CC8, CC88 and CC154 isolates harboured PVL-encoding elongated head-type phages; and some CC59 isolates harboured a PhiSa2958-like phage. Novel or variant phages were present in CC5 and some CC1 and CC59 isolates. The PVL gene sequence and the PVL-encoding phage varied with lineage. Further work is required to determine whether PVL sequence and/or phage variations result in biological differences.

Two-step glutamate dehydrogenase antigen real-time polymerase chain reaction assay for detection of toxigenic Clostridium difficile.

Current diagnosis of Clostridium difficile infection (CDI) relies upon detection of toxins A/B in stool by enzyme immunoassay [EIA(A/B)]. This strategy is unsatisfactory because it has a low sensitivity resulting in significant false negatives. We investigated the performance of a two-step algorithm for diagnosis of CDI using detection of glutamate dehydrogenase (GDH). GDH-positive samples were tested for C. difficile toxin B gene (tcdB) by polymerase chain reaction (PCR). The performance of the two-step protocol was compared with toxin detection by the Meridian Premier EIA kit in 500 consecutive stool samples from patients with suspected CDI. The reference standard among samples that were positive by either EIA(A/B) or GDH testing was culture cytotoxin neutralisation (culture/CTN). Thirty-six (7%) of 500 samples were identified as true positives by culture/CTN. EIA(A/B) identified 14 of the positive specimens with 22 false negatives and two false positives. The two-step protocol identified 34 of the positive samples with two false positives and two false negatives. EIA(A/B) had a sensitivity of 39%, specificity of 99%, positive predictive value of 88% and negative predictive value of 95%. The two-step algorithm performed better, with corresponding values of 94%, 99%, 94% and 99% respectively. Screening for GDH before confirmation of positives by PCR is cheaper than screening all specimens by PCR and is an effective method for routine use. Current EIA(A/B) tests for CDI are of inadequate sensitivity and should be replaced; however, this may result in apparent changes in CDI rates that would need to be explained in national surveillance statistics.

Methods for screening for methicillin-resistant Staphylococcus aureus carriage.

Screening patients for methicillin-resistant Staphylococcus aureus (MRSA) carriage at hospital admission is widely accepted as an essential part of MRSA control programmes. It is assumed, although not proven, that rapid reporting of screening results will improve MRSA control, provided that a clear action plan for positive cases is in place and is being followed. An effective culture screening method is direct inoculation of pooled nose, throat and perineal swabs on a well-performing MRSA-selective chromogenic agar; presumptive MRSA colonies can be confirmed rapidly by latex agglutination with antibodies directed against penicillin-binding protein 2a. This method will usually produce a positive result after 24 h of incubation in >95% of true-positive cases, and will be sufficient for most initial treatment and infection control decisions; full antimicrobial susceptibilities will be available on the next day. Inoculation of selective enrichment broth containing a colorimetric growth indicator is an alternative overnight culture method, but there may be problems with overgrowth of other organisms, such as enterococci. PCR methods are now available that can produce same-day results, provided that samples reach the laboratory in time for batch processing, but cultures are required for susceptibility testing. In comparison with culture-based methods, PCR tests are costly, and some have relatively high false-positivity rates; definitive evidence of their clinical cost-effectiveness is lacking. New point-of-care PCR tests are being introduced that are potentially even more rapid but are even more expensive; studies on the clinical cost-effectiveness of these very rapid tests are awaited.