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Summary 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

Summary 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 (SCC mec ) 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.

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.

Summary 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 (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.

Summary 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.

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.

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.

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 FSa2mw; CC8, CC88 and CC154 isolates harboured PVL-encoding elongated head-type phages; and some CC59 isolates harboured a FSa2958-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.

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is increasingly common in the USA, but rare in the UK. We compared CA-MRSA from the UK and USA to examine differences in the molecular epidemiology. We investigated patients presenting with MRSA in the first 72 h of hospital admission or in out-patient settings in a UK and a US hospital from January 2004 to March 2006. Fluoroquinolone susceptibility was used as a screening marker to select presumptive CA-MRSA. One hundred and eighteen and 49 such strains were identified, representing a prevalence of 0.1 and 0.2 isolates per 1,000 patient days in the UK and US respectively. Panton-Valentine leukocidin (PVL)-positive ST8-IVa (USA300)-type strains predominated among 43 surviving US isolates, whereas PVL-negative ST1-IVa predominated among 71 surviving UK isolates. There are striking differences between the molecular epidemiology of CA-MRSA in UK and US hospitals, which may have implications for control.

Despite increasing antimicrobial resistance and multiple drug resistance in clinical isolates of both Gram-positive and Gram-negative bacteria, there are few novel antimicrobial agents in development. The few new agents that have been recently licensed have tended to have narrow spectra of activity, focused on Gram-positive pathogens, especially methicillin-resistant Staphylococcus aureus (MRSA). This situation is rightly causing concern among clinicians and public health authorities worldwide. This article reviews available data on three new antibacterials currently in development. The cephalosporin ceftobiprole is active against MRSA, Enterococcus faecalis and penicillin-resistant Streptococcus pneumoniae, but otherwise has a spectrum of activity similar to that of other recent cephalosporins. In a clinical trial, ceftobiprole was non-inferior to vancomycin for the treatment of MRSA-associated complicated skin and skin structure infections (cSSSIs). Doripenem, a new carbapenem, has some activity against MRSA, but otherwise has an anti-Gram-positive spectrum of activity similar to that of imipenem and an anti-Gram-negative spectrum similar to that of meropenem. In a clinical trial, it was non-inferior to meropenem for the treatment of complicated intra-abdominal infections. Iclaprim is a dihydrofolate reductase inhibitor with greatly enhanced activity, as compared with trimethoprim, against a range of Gram-positive and Gram-negative pathogens. The limited literature concerning this agent has concentrated on its potential role in the treatment of infections with Gram-positive bacteria. A clinical trial has demonstrated the non-inferiority of iclaprim, as compared with linezolid, in the treatment of cSSSIs, including those associated with MRSA.

A commercial rapid polymerase chain reaction methicillin-resistant Staphylococcus aureus (MRSA) screening method (IDI-MRSA) is validated for the use with nasal swabs transported in liquid Stuart's medium. We investigated the use of IDI-MRSA for screening for MRSA in pooled nose, axilla, and groin swabs and in single swabs from skin puncture sites, wounds, throat, rectum, and groin using swabs transported in Amies medium without charcoal. We performed the IDI-MRSA test on swabs that had been used for routine MRSA broth culture and which were selected to be about 50% MRSA positive. We compared the IDI-MRSA result with the MRSA culture result. With 201 pooled sets, the sensitivity of IDI-MRSA was 85% and the specificity 95%. With 32 single screening swabs, sensitivity was 94% and specificity 80%. The method is not compromised by swab transport in Amies medium if an additional heating step is used. We had a low rate of initial inhibition (1.3%), which may have been due to the extra heating step used to liquefy gel from the Amies medium. Thus, in this study IDI-MRSA gives similar results to culture with pooled or single swabs from multiple screening sites.

Summary 1.From September 2003, acute National Health Service trusts in England have been required by the Department of Health to undertake mandatory surveillance of bacteraemias caused by glycopeptide-resistant enterococci (GRE). 2.In total, 4855 enterococcal bacteraemias (including 256 reports of ‘Group D streptococci') were reported through the voluntary reporting system to the Communicable Disease Surveillance Centre (CDSC) in England and Wales in 2002, and 8.9% of the reports that contained information on vancomycin susceptibility indicated that the isolate was resistant to vancomycin. Most hospitals reported fewer than five GRE bacteraemias per year to the CDSC, with only 13 hospitals reporting more than five episodes per year, although there is undoubtedly an element of under-reporting. 3.This Working Group was established to review the methods used to identify and test the susceptibility of enterococci to glycopeptides, and to make recommendations on the reporting of GRE bacteraemias, as there were indications that current methods would not provide a suitable basis for this surveillance. 4.A review of methods was undertaken, including a national questionnaire on methods, approaches to testing and risk factors for GRE bacteraemia. This, together with data from routine laboratory reports and special surveys, revealed the following. –A significant proportion of enterococci are not identified to species level. –There are problems with identification of enterococci. Commercially available kits do not identify some enterococcal species reliably. –Not all laboratories test vancomycin susceptibility of enterococci from bacteraemia. This does not allow a robust assessment of GRE bacteraemia rates because the prevalence of glycopeptide resistance will be underestimated if laboratories test teicoplanin alone or no glycopeptides against enterococci. –There are technical difficulties in detecting non-VanA resistance in enterococci and this will also contribute to under-reporting of glycopeptide resistance. 5.Clinically significant GRE infection is associated with a worse prognosis than infection with susceptible strains, but this factor has not been clearly separated from the possible influence of co-morbidities and antibiotic usage. 6.GRE bacteraemia occurs mainly on specialist units, particularly transplantation, renal, haematological malignancy and intensive care units. Hospitals with such units will inevitably have a higher risk of featuring prominently in surveillance studies. Hence, meaningful denominators for surveillance of GRE bacteraemia are required. Recommendations for GRE bacteraemia surveillance 1.As the mandatory surveillance of glycopeptide-resistant enterococci (GRE) bacteraemias has already started, this report recommends a phased approach to some of the developments, such as using meaningful denominators for the bacteraemia rates. 2.Rates of GRE bacteraemias in trusts should not be used as a performance indicator because the numbers are too small for valid analysis in this way. 3.GRE bacteraemias as a proportion of all clinically significant bacteraemias in the trust should be measured as an indicator of changing trends. 4.Since most GRE are likely to be associated with specialist units, reports of GRE bacteraemia should indicate the specialty in which the patient acquired the infection. 5.Data on clinical activity in the special units where patients acquired GRE bacteraemias should be obtained from trusts with more than five GRE bacteraemias in a year. 6.The significance of blood cultures containing GRE should be assessed clinically. If the bacteraemia that includes GRE is deemed to be clinically significant (according to the case definitions for bacteraemia), whether mono- or polymicrobial, it should be reported as a GRE bacteraemia. 7.Enterococci from blood cultures should be identified to species level to provide data on resistance rates in different species. 8.Biochemical identification should be augmented by antimicrobial susceptibility patterns. The identification is suspect if Enterococcus faecalis appears to be ampicillin resistant and/or quinupristin/dalfopristin susceptible, or if Enterococcus faecium appears to be ampicillin susceptible and/or quinupristin/dalfopristin resistant. The identification and susceptibility of such isolates should be checked and, if confirmed, the isolate should be sent to a reference laboratory for further investigation. 9.Enterococci from blood cultures should be tested for susceptibility to vancomycin. Teicoplanin is not an acceptable alternative to vancomycin for these purposes. 10.Standardized methods should be used for glycopeptide susceptibility testing of enterococci, and the technical requirements of the methods must be adhered to. 11.The situation should be reviewed after a year and the methodology should be amended as appropriate. Recommendations for further research 1.A group should be established to explore methods of data collection for global and individual risk factors for GRE bacteraemia. 2.Further studies on the performance of commercial identification kits with a range of enterococcal species are necessary. 3.Further studies to improve the reliability of susceptibility testing methods for detection of GRE are necessary.

The increase since the mid 1980s in glycopepetide resistant enterococci (GRE) raised concerns about the limited options for antimicrobial therapy, the implications for ever-increasing numbers of immunocompromised hospitalised patients, and fuelled fears, now realised, for the transfer of glycopeptide resistance to more pathogenic bacteria, such as Staphylococcus aureus. These issues underlined the need for guidelines for the emergence and control of GRE in the hospital setting. This Hospital Infection Society (HIS) and Infection Control Nurses Association (ICNA) working party report reviews the literature relating to GRE prevention and control. It provides guidance on microbiological investigation, treatment and management, including antimicrobial prescribing and infection control measures. Evidence identified to support recommendations has been categorized. A risk assessment approach is recommended and areas for research and development identified.

Due to increasing methicillin-resistant Staphylococcus aureus (MRSA) infection in cardiothoracic patients at St Thomas' Hospital, an enhanced infection control programme was introduced in September 2000. It was based on UK national guidelines on the control of MRSA and targeted additional identified risk factors for surgical site infection (SSI). It included recognition of the problem by senior staff and their taking responsibility for it; intensive support, education and advice from the infection control team; improved ward and theatre hygiene; pre-admission, admission and weekly MRSA screening; isolation and clearance treatment; nursing care pathways for MRSA colonized patients; and teicoplanin plus gentamicin surgical prophylaxis. The effectiveness of the programme was assessed by retrospective analysis of computerized patient data for the 16 months before and after the introduction of the programme. There was no significant change in the number of operations or the proportion of patients admitted with MRSA, although nine patients were cleared of carriage before admission. However, there were significant falls in the proportion of patients acquiring MRSA on the ward [38/1036 to 14/921, P=0.003, RR 2.4 (95%CI 1.32-4.42)] and in the rate of bloodstream MRSA infections [12/1075 to 2/956, P=0.014, RR 5.34 (95%CI 1.20-23.78)]. Sternal and leg wound infections both halved (from 28/1075 to 13/956 and 16/1075 to 7/956, respectively) but this did not reach statistical significance. These results demonstrate that an enhanced, targeted infection control programme based on the UK national guidelines, SSI prevention guidelines and local risk assessment can reduce the incidence of nosocomial MRSA acquisition and invasive infection in cardiothoracic patients in the face of continuing endemic risk.

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 a6 log(10) inoculum, relative susceptibility was 10% bovine serum albumin (BSA)TSB3% BSAsaline0.3% BSA = water. MRSA was not recovered after60 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.

Two aminoglycoside-resistant strains of Klebsiella pneumoniae caused an outbreak on the neonatal unit at St Thomas' Hospital. One, which affected 18 patients, was capsular type K18 and resistant to newer cephalosporins by the production of the extended-spectrum β-lactamase SHV-2; the other, which colonized four patients, was capsular non-typeable and did not produce extended-spectrum β-lactamase. Both strains were probably brought into the unit by carrier patients; the probable carrier of the non-typeable strain was transferred from another hospital but was negative on a single admission screen; the probable carrier of the K18 strain was not screened on admission because he had been born at St Thomas', but his mother had been transferred from another hospital. Despite intensive efforts to control the outbreak by standard methods of hand washing, screening, patient isolation and environmental cleaning, a total of 22 neonates on the unit eventually became colonized or infected. One of three patients with bacteraemia died. A small proportion of samples of expressed breast milk, electronic thermometers and oxygen saturation probes were contaminated by the K18 strain and may have contributed to some of the cross-infection, but this did not explain the extent of the outbreak. The outbreak was controlled only by opening a temporary ward for colonized neonates and another for newly born babies, which allowed the closure and cleaning of the main neonatal unit. Multiply antibiotic resistant klebsiellas may be highly epidemic and cause serious, difficult-to-control outbreaks on neonatal units. All patients, regardless of their admission history, should be screened on admission for carriage of multiply resistant enterobacteria by a sensitive method, and units should have plans for temporary ward closure should outbreaks occur.

Over a two-month period, two distinct types of Pseudomonas aeruginosa resistant to ceftazidime and azlocillin were isolated from bronchial specimens of ITU patients who had been previously bronchoscoped. The source of the outbreak was probably a faulty contaminated bronchoscope washer-disinfector which had been purchased a year earlier but not properly maintained. This paper describes the outbreak, the identification and elimination of the source, and the steps taken to prevent recurrence. Several automated, closed washer-disinfectors had been bought by the hospital in response to health and safety concerns about glutaraldehyde disinfection toxicity, but the operation and maintenance of these machines had not been supervised. Several other washer-disinfectors were also found to be faulty. The potential hazards of automated endoscope washer-disinfectors and the importance of controlled professional maintenance, servicing and training is discussed.

Enterococci have become important nosocomial pathogens, with Enterococcus faecalis and then Enterococcus faecium predominating. Because of the emergence of glycopeptide (vancomycin and teicoplanin) resistance in enterococci, laboratories have been required to screen for resistant strains and to identify them to the species level. This has resulted in the need for accurate identification of species less commonly associated with clinical infections, such as Enterococcus casseliflavus and Enterococcus gallinarum, which are inherently resistant to the glycopeptides. Studies evaluating commonly used commercial identification systems, have found error rates for enterococcal species identification of 2-21% for E. faecalis, 5-9% for E. faecium, and 14-79% for other species. Reporting errors may have adverse effects on the management of clinical infections, as well as in the control of multidrug-resistant strain outbreaks. The purpose of this document is to present a simplified approach to the identification of Enterococcus species that uses a combination of rapid, readily available, and inexpensive tests.

Between July and September 1997 a ceftazidime- and aminoglycoside-resistant strain of Klebsiella pneumoniae infected or colonized seven patients on three paediatric wards at Guy's Hospital in London. The patients were mostly neonates or infants recovering from cardiac surgery for congenital defects. The organism was probably introduced by an asymptomatic patient from Greece and the subsequent outbreak could largely be explained by person-to-person spread on individual wards and frequent transfers of patients between wards. The outbreak was controlled by patient isolation and attention to handwashing, and there were no fatalities. The organisms were non-typeable by serology but had a characteristic RAPD profile. They produced the extended-spectrum β-lactamase SHV-5 and the aminoglycoside-modifying enzymes AAC(6′) + probably AAC(3)II, encoded on a conjugative plasmid of approximately 160 kb. Two other patients had multi-resistant klebsiellas, one of them an SHV-5 producer and one a TEM-5 producer, but these could be distinguished from each other and from the outbreak strain by serological and RAPD typing and by the genetics and mechanisms of their resistances. Three other multi-resistant enterobacteria were isolated during the outbreak: an Escherichia coli that had acquired the 160 kb resistance plasmid from the epidemic klebsiella, a Citrobacter isolated from one of the patients with the klebsiella but which did not produce SHV-5, and a TEM-5-producing Enterobacter . This outbreak illustrates the importance of screening patients from high-risk areas for multiply-resistant organisms on admission, and the value of bacterial typing and analysis of resistance mechanisms to define the epidemiology of hospital infection.

We describe the epidemiology and control of a hospital outbreak of multi-drug-resistant tuberculosis (MDR-TB). A human immunodeficiency virus (HIV)-negative patient with drug-sensitive tuberculosis developed MDR-TB during a period of unsupervised therapy. She was admitted to an isolation room in a ward with HIV-positive patients, but the room, unbeknown to hospital staff, was at positive-pressure relative to the main ward. Seven HIV-positive contacts developed MDR-TB. The diagnosis in the second patient was delayed, partly because acid-fast bacilli in his sputum were assumed to be Mycobacterium avium-intracellulare. All the available Mycobacterium tuberculosis isolates were indistinguishable by molecular typing. Nearly 1400 staff and patient contacts were offered screening, but the screening programme detected only one of the cases. Despite therapy, the index patient and two of the contacts died. HIV-positive patients are more likely than others to develop tuberculosis after exposure, and the disease may progress more rapidly. In these patients the possibility that acid-fast bacilli may represent M. tuberculosis must always be considered. Patients with tuberculosis (suspected or proven) should not be nursed in the same wards as immunosuppressed patients, and should be isolated. MDR-TB cases must be isolated in negative-pressure rooms. Hospital side-rooms may be positive-pressure as a fire safety measure; infection control teams must be aware of the airflows in all isolation rooms, and must be consulted during the design of hospital buildings. Good communication between infection control teams and clinicians is important, and all medical and nursing staff must be aware of the principles of management of patients with proven or suspected tuberculosis and MDR-TB.

Increasing evidence implicates deoxycholic acid (DCA) in the pathogenesis of cholesterol-rich gallbladder stones. However, relatively little is known about the activities of the two intestinal bacterial enzymes (cholylglycine hydrolase and cholic acid 7alpha-dehydroxylase) responsible for the deconjugation and subsequent dehydroxylation of conjugated cholic acid (CA), to form DCA. We, therefore, established optimal reaction conditions for measuring the activities of these two enzymes in vitro, and applied these conditions to the determination of the enzymes in caecal aspirates from six subjects undergoing clinically-indicated colonoscopy. With respect to cholylglycine hydrolase activity: zero order kinetics were found over 20 min at 37 degrees C (pH optimum 4.0), with Km and Vmax values of 1.66 mmol/l and 0.90 mmol CA min(-1) mg prot(-1), respectively. For cholic acid 7alpha-dehydroxylation: zero order kinetics were found over 7.5 min at 37 degrees C, under anaerobic conditions (pH optimum 8.0), with Km and Vmax values of 5.23 x 10(-8) mol/l and 1.88 x 10(-7) mol DCA min(-1) mg prot(-1), respectively. Applying these reaction conditions to the caecal aspirates, endogenous cholylglycine hydrolase activities ranged from 0.49 to 2.43 units (mg protein[-1] min[-1]) and CA 7alpha-dehydroxylase activities from 1.75 to 5.82 x 10(-7) units (mg protein[-1] min[-1]). This study is unique in assaying quantitatively both the deconjugation and dehydroxylation enzyme activities in human caecal samples--an essential first step to further studies of intestinal bacterial enzymes in the pathogenesis of cholesterol gallstone disease.

Summary 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.

Salvage laryngectomy carries a high risk of post-operative infection with reported rates of 40–61%. The purpose of this study was to analyse infections in our own patients and review the potential impact of our current antibiotic prophylaxis (AP). A retrospective analysis of infection in 26 consecutive patients between 2000 and 2010 undergoing salvage total laryngectomy (SL) following recurrent laryngeal cancer after failed radiotherapy or chemo-radiation was undertaken. The antibiotic prophylaxis was intravenous teicoplanin, cefuroxime and metronidazole at induction and for the following 24 h. Infection was defined by Tabet and Johnson’s grade 5, categorized as pharyngocutaneous fistula. Fifteen patients (58%) developed a post-operative wound infection, which occurred on average at 12 days after surgery. Univariate analysis demonstrated three risk variables that had a significant correlation with infection: alcohol consumption (p = 0.01), cN stage of tumour (p

Glutamate dehydrogenase (GDH) is popular as a preliminary test for the detection of Clostridium difficile. Recent work has suggested that GDH sensitivity may vary according to ribotype and may be lower for ribotypes 002, 027, and 106 compared with polymerase chain reaction (PCR). We investigated this effect using a dilution series of 64 isolates tested by GDH and Cepheid GeneXpert PCR. PCR was significantly more sensitive than GDH overall; however, there was no difference in detection according to specific ribotype.

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 β-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.

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 ≥10 −6 ) strains were identified, with ciprofloxacin MICs of 0.25μg/mL, 8μg/mL and 64μg/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.

The Cepheid Xpert polymerase chain reaction assay (Sunnyvale, CA) had a sensitivity of 100%, specificity of 96.7%, and positive and negative predictive values of 90.5% and 100%, respectively, compared with toxigenic culture for the laboratory diagnosis of Clostridium difficile in diarrheal stool samples. This test appears to be a significant improvement to poorly performing enzyme immunoassays.

The public health burden caused by methicillin-resistant Staphylococcus aureus (MRSA) infections is now widely recognized, and is a cause of public alarm. Effective MRSA risk management in the healthcare system as well as in the community should rely on accurate detection of reservoirs and sources of transmission, as well as on close monitoring of the impact of interventions on disease incidence and bacterial dissemination. MRSA carrier screening and disease surveillance, coupled with molecular typing, are key information tools for integrated MRSA control and individual risk assessment. These tools should be tailored to the distinct needs of local interventions and national prevention programmes. Surveillance schemes should primarily inform local staff and serve as quality assurance about MRSA risk management. New technologies, including the use of selective culture media and real-time PCR assays, allow faster detection of MRSA carriers upon admission or during stay in healthcare institutions. More research is needed to ascertain their cost-effectiveness for MRSA control. Likewise, tremendous progress has been made concerning molecular typing methods, with optimization and standardization of sequence-based technologies offering broad applicability and high throughput. However, no single S. aureus typing method is yet providing fully reliable information within the range of discrimination needed for public health action. Further refinement of genotyping methods and international harmonization of surveillance and typing schemes must be achieved to facilitate global MRSA control.

OBJECTIVE: To determine whether introducing a rapid test for meticillin resistant Staphylococcus aureus (MRSA) screening leads to a reduction in MRSA acquisition on hospital general wards. DESIGN: Cluster randomised crossover trial. SETTING: Medical, surgical, elderly care, and oncology wards of a London teaching hospital on two sites. MAIN OUTCOME MEASURE: MRSA acquisition rate (proportion of patients negative for MRSA who became MRSA positive). PARTICIPANTS: All patients admitted to the study wards who were MRSA negative on admission and screened for MRSA on discharge. INTERVENTION: Rapid polymerase chain reaction based screening test for MRSA compared with conventional culture. RESULTS: Of 9608 patients admitted to study wards, 8374 met entry criteria and 6888 had full data (82.3%); 3335 in the control arm and 3553 in the rapid test arm. The overall MRSA carriage rate on admission was 6.7%. Rapid tests led to a reduction in median reporting time from admission, from 46 to 22 hours (P

We report the identification and control of an outbreak of a ciprofloxacin-susceptible strain of UK epidemic meticillin-resistant Staphylococcus aureus (EMRSA)-15 on a neonatal unit (NNU). All babies were screened for MRSA on admission using ciprofloxacin-containing media which did not detect the outbreak strain. The first identified case was a premature baby who developed MRSA bacteraemia with associated tibial osteomyelitis and multiple subcutaneous abscesses. The outbreak strain was subsequently identified in the nasopharyngeal secretions of a second child who was not clinically infected. Screening of all patients on the NNU using non-ciprofloxacin-media identified two other colonised babies. All four patient isolates were EMRSA-15, spa type t022, SCCmec IV, Panton-Valentine leucocidin (PVL) negative, indistinguishable by pulsed-field gel electrophoresis and susceptible to all non-beta-lactam antimicrobials tested. The outbreak strain was cultured from four of 48 environmental sites in a communal milk-expressing room. Unsupervised movement of mothers to and from the milk-expressing room may have contributed to the outbreak. Control measures included cohort isolation of affected babies, improved environmental cleaning, increased emphasis on hand hygiene and education of mothers. Ciprofloxacin-containing media should be used with caution for MRSA screening in settings where ciprofloxacin-susceptible strains (including community-associated MRSA) are increasing in prevalence.

A joint working party has produced evidence-based guidelines for the prophylaxis and treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections in the UK. These guidelines will help clinicians choose appropriate therapy and point to areas where further research is needed. This review summarizes the main recommendations and discusses their implementation into clinical practice.

In 2001, the UK Department of Health introduced mandatory surveillance of meticillin-resistant Staphylococcus aureus (MRSA) bacteraemias (blood-culture-positive episodes) in English hospitals. We performed enhanced surveillance in their hospital between April 2001 and March 2003 to determine the epidemiology of MRSA bacteraemia across different specialities. There were 267 MRSA-blood-culture-positive episodes, giving a rate of 0.37 per 1000 occupied bed-days (OBD). Thirty-three (12.4%) episodes were false positives due to contaminants and 15 (5.6%) originated in the community or at another institution. Thirty-one (11.6%) episodes were in outpatients or occurred after recent discharge and were designated 'hospital associated'. The remaining 188 cases were clinically significant hospital-acquired episodes in inpatients, with a rate of 0.26 per 1000 OBDs. The highest rates were in the intensive therapy unit (ITU; 2.74 per 1000 OBDs) and the high-dependency unit (HDU; 1.68 per 1000 OBDs). Fifty-five non-ITU, non-HDU episodes occurred in patients who had been discharged from ITU or HDU prior to the development of bacteraemia but during the same admission. The number of MRSA bacteraemias related to ITU/HDU suggests that these wards may be hubs of MRSA infection. Haematology, oncology and renal (HOR) patients had the greatest number of hospital-associated episodes. The most common source of MRSA bacteraemia was a vascular access device (VAD) (108 episodes, 57%, 64% of which were central lines). The high bacteraemia rates in ITU, HDU and HOR patients were associated with high usage of VADs. The majority of episodes occurred in patients who were newly colonized with MRSA after admission. Thus, in this hospital, VADs and stays in ITU or HDU are important risk factors for bacteraemia, and VAD care and prevention of cross-infection are priorities for intervention. We recommend that the mandatory national surveillance scheme should collect additional data on MRSA bacteraemia to provide information for a national strategy for MRSA control and to allow appropriate comparison between institutions.

We evaluated toxigenic Clostridium difficile detection by a lateral flow assay for antigen and toxin, an enzyme immunoassay, and two commercial PCR methods. Compared to the cell cytotoxicity neutralization assay and toxigenic culture, both toxin detection methods lacked sensitivity. PCR following combined antigen and toxin detection provided the most useful diagnostic information.

During a 1-month period in 1996, all inpatients and staff in the Zagreb Trauma Hospital were screened for methicillin-resistant Staphylococcus aureus (MRSA) carriage in order to control MRSA spread within the hospital. During the study period, 663 patients were admitted to the hospital, and screening prior to discharge revealed that 42 were colonised or infected with MRSA. Twenty-three (55%) of these would not have been detected if active screening had not been performed. Amongst 205 staff members, MRSA carriage was only found in one (0.5%) nurse. The prevalence and incidence of MRSA carriage varied significantly amongst the wards and was related to the length of hospital stay. One-third of the patients colonised or infected with MRSA had a history of previous admission to another hospital, and one-third were transferred to another institution after discharge. Thirty-nine of 42 MRSA isolates shared the same antibiotic sensitivity pattern, suggesting endemic spread of MRSA. However, randomly amplified polymorphic DNA molecular typing revealed four profiles, the most common involving 15 of 36 tested strains. There was no obvious clustering of epidemiological types by ward, except for the appearance of a single type on the burns unit, and it was likely that different strains had been introduced into the hospital by patient transfers from elsewhere. The results of this study indicate that a substantial proportion of MRSA carriers escape infection control measures if active screening is not performed. Based on the results of this study, steps have been taken to improve interhospital communication about the transfer of patients colonised with MRSA. Randomly amplified polymorphic DNA typing proved to be a useful aid to epidemiological investigations of MRSA.

The minimum inhibitory concentrations (MICs) of mupirocin were determined by the E test (AB Biodisk, Sweden) and the agar dilution method for 107 staphylococci. The organisms consisted of 34 coagulase-negative staphylococci and 73 methicillin-resistant Staphylococcus aureus. Polymerase chain reaction (PCR) primers designed to amplify a 456 bp region of the plasmid-borne isoleucyl tRNA synthetase gene (ileS-2), responsible for high-level mupirocin resistance in staphylococci, were used on DNA preparations from these isolates. Isolates with high-level mupirocin resistance due to the ileS-2 gene should be PCR positive. There was close correlation between the E test and agar dilution MIC values, with only two strains differing by more than two serial dilutions. Most (51 of 54 strains) of the high-level resistant strains (MIC>256 microg/ml) were resistant to the highest concentration of mupirocin tested (1024 microg/ml). PCR correctly classified all but four (96%) of the isolates in accordance with the results of agar dilution. All four isolates that gave discrepant results were methicillin-resistant Staphylococcus aureus. Two of these were PCR positive, yet the MIC of mupirocin for these strains was

Objective To establish the extent of inter-hospital spread of methicillin-resistant Staphylococcus aureus (MRSA) in Zagreb and to determine the most suitable method for typing local strains. Methods We analyzed a collection of 33 MRSA isolates from three Zagreb hospitals together with five unrelated British MRSA isolates by antibiogram typing, bacteriophage typing, randomly amplified polymorphic DNA (RAPD) analysis and pulsed-field gel electrophoresis (PFGE) after digestion with Sma I restriction endonuclease. Bacteriophage typing was done with the international set of S. aureus typing phages. RAPD and PFGE profiles were analyzed visually and by using the ‘GelCompar' computer program. Results Antibiogram typing provided eight profiles. Thirty (91%) of the 33 Croatian strains of MRSA were non-typable by phage typing. Visual analysis of RAPD products identified six, and visual analysis of PFGE fragments nine, distinct profiles. Computer analysis of RAPD data separated British isolates from the Croatian ones, but did not cluster the visually determined RAPD types. PFGE computer analysis separated British isolates and clustered isolates in concordance with visual interpretation. Thirty-one of the 38 isolates (82%) were visually grouped in the same clusters by both molecular methods. The dominant strain was present in each of the three hospitals. Conclusions Bacteriophage typing was unhelpful for the analysis of Croatian MRSA, since most strains were untypable with the international set of bacteriophages. RAPD and PFGE were more successful in typing the organisms and showed evidence of inter-hospital spread of one predominant MRSA strain in all three Zagreb hospitals. Thus RAPD and PFGE proved to be a useful aid in elucidating the epidemiology of MRSA infection in Zagreb hospitals and should be established in Croatia for typing MRSA.

Left to their own devices, doctors don’t always do the right thing Obstetricians were outraged when, in 1846, Ignaz Semmelweis reduced mortality from puerperal fever in Viennese women from 16% to 3% by making doctors and medical students disinfect their hands between performing postmortems and delivering babies: they could not accept any criticism of their professional practice. Semmelweis lost his job and died in a lunatic asylum, while his dirty, deluded, and dangerous colleagues abandoned his policies, continued with their distinguished careers, and returned puerperal mortality to its previous appalling level. Of course they did not know then, as we do now, that puerperal fever is caused by group A streptococcus, or that normal human skin is colonised by high concentrations of bacteria that transfer to the hands of staff during routine patient care and then on to other patients.1 2 They would have been shocked to discover that we now have incontrovertible evidence that hand decontamination significantly reduces the transfer of pathogens and the incidence of hospital and healthcare associated infections,2 and that Semmelweis has been vindicated. Between the 1890s and the 1950s, the epidemiology of common bacterial pathogens was elucidated. This led to the universal introduction of standard hygiene measures, such as handwashing, no touch technique, gloving and gowning, instrument sterilisation, environmental …