In the developed world, Clostridium difficile infection (CDI) is the most important cause of nosocomial infectious diarrhea. In addition to providing epidemiological data and helping to indicate that a local outbreak may be occurring, laboratory tests are used to augment clinical decisions on individual patients. Very rarely do diagnostic tests provide results at the point of decision making; in the intervening period between requesting investigations on a patient with suspected CDI and return of the laboratory result, decisions must be made regarding patient isolation and treatment.

We describe the identification and control of an outbreak of gentamicin resistant, meticillin susceptible Staphylococcus aureus (GR-MSSA) on a 36-bed neonatal unit (NNU) in London. Control measures included admission and weekly screening for GR-MSSA, cohorting affected babies, environmental and staff screening, hydrogen peroxide vapour (HPV) for terminal disinfection of cohort rooms, and reinforcement of hand hygiene. Seventeen babies were affected by the outbreak strain over ten months; seven were infected and ten were asymptomatic carriers. The outbreak strain was gentamicin resistant and all isolates were indistinguishable by pulsed-field gel electrophoresis. The outbreak strains spread rapidly and were associated with a high rate of bacteraemia (35% of 17 affected patients had bacteraemia vs. 10% of 284 patients with MSSA prior to the outbreak, p=0.007). None of 113 staff members tested were colonised with GR-MSSA. GR-MSSA was recovered from 11.5% of 87 environmental surfaces in cohort rooms, 7.1% of 28 communal surfaces and 4.1% of 74 surfaces after conventional terminal disinfection. None of 64 surfaces sampled after HPV decontamination yielded GR-MSSA. Recovery of GR-MSSA from two high level sites suggested that the organism could have been transmitted via air. Occasional breakdown in hand hygiene compliance and contaminated environmental surfaces probably contributed to transmission.

Infection control for hospital pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) often takes the form of a package of interventions, including the use of patient isolation and decolonization treatment. Such interventions, though widely used, have generated controversy because of their significant resource implications and the lack of robust evidence with regard to their effectiveness at reducing transmission. The aim of this study was to estimate the effectiveness of isolation and decolonization measures in reducing MRSA transmission in hospital general wards. Prospectively collected MRSA surveillance data from 10 general wards at Guys and St. Thomas hospitals, London, United Kingdom, in 20062007 were used, comprising 14,035 patient episodes. Data were analyzed with a Markov chain Monte Carlo algorithm to model transmission dynamics. The combined effect of isolation and decolonization was estimated to reduce transmission by 64 (95 confidence interval: 37, 79). Undetected MRSA-positive patients were estimated to be the source of 75 (95 confidence interval: 67, 86) of total transmission events. Isolation measures combined with decolonization treatment were strongly associated with a reduction in MRSA transmission in hospital general wards. These findings provide support for active methods of MRSA control, but further research is needed to determine the relative importance of isolation and decolonization in preventing transmission.

Evidence that contaminated surfaces contribute to the transmission of hospital pathogens comes from studies modeling transmission routes, microbiologic studies, observational epidemiologic studies, intervention studies, and outbreak reports. This review presents evidence that contaminated surfaces contribute to transmission and discusses the various strategies currently available to address environmental contamination in hospitals. Copyright (c) 2013 by the Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

INTRODUCTION:Antimicrobial resistance and bacterial virulence factors may increase the risk of hematogenous complications during methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI). This study reports on the impact of increasing vancomycin minimum inhibitory concentrations (V-MICs) and MRSA clone type on risk of hematogenous complications from MRSA BSI during implementation of an effective MRSA control program.METHODS:In sum, spa typing, staphylococcal cassette chromosome mec allotyping, and vancomycin and teicoplanin MICs were performed on 821 consecutive MRSA bloodstream isolates from 1999 to 2009. Prospectively collected data, including focus of infection, were available for 695 clinically significant cases. Logistic and multinomial logistic regression was used to determine the association between clone type, vancomycin MIC (V-MIC), and focus of infection.RESULTS:MRSA BSIs decreased by ∼90% during the 11 years. Typing placed isolates into 3 clonal complex (CC) groups that had different population median V-MICs (CC30, 0.5 μg/mL [n = 349]; CC22, 0.75 μg/mL [n = 272]; non-CC22/30, 1.5 μg/mL [n = 199]). There was a progressive increase in the proportion of isolates with a V-MIC above baseline median in each clonal group and a disproportionate fall in the clone group with lowest median V-MIC (CC30). In contrast, there were no increases in teicoplanin MICs. High V-MIC CC22 isolates (1.5-2 μg/mL) were strongly associated with endocarditis (odds ratio, 12; 95% confidence interval, 3.72-38.9) and with a septic metastasis after catheter-related BSI (odds ratio, 106; 95% confidence interval, 12.6-883) compared with other clone type/V-MIC combinations.CONCLUSIONS:An interaction between clone type and V-MIC can influence the risk of endocarditis associated with MRSA BSI, implying involvement of both therapeutic and host-pathogen factors.

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 < 0.01), and pre-operative albumin levels <3.2 g/L (p = 0.012). There was a trend, though not significant, for increased infection in patients with high or low BMIs. The most common organisms isolated from clinical samples from infected patients were methicillin-resistant Staphylococcus aureus MRSA (43%), Pseudomonas aeruginosa (36%), Serratia marcescens, Proteus mirabilis and Enterococcus faecalis (7% each). All these organisms are typical hospital-acquired pathogens. Pseudomonas and Serratia were not covered by the prophylactic regime we used. The current antibiotic regime following SL is inadequate as the rate of infection is high. It would therefore seem logical to trial a separate antibiotic protocol of AP for patients undergoing SL that would include an extended course of antibiotics after the standard prophylaxis. In addition, infection rates may also be reduced by improving the metabolic state of patients pre-operatively by multi-disciplinary action. Steps should also be taken to reduce cross-infection with nosocomial pathogens in these patients. Other aspects of surgical management should be also taken in consideration.

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 …

A novel molecular assay for Clostridium difficile was developed using Linear-After-The-Exponential polymerase chain reaction (LATE-PCR). Single-stranded DNA products generated by LATE-PCR were detected and distinguished by hybridization to fluorescent mismatch-tolerant probes, as the temperature was lowered after amplification in 5(°)C intervals between 65°C and 25°C. Single-tube multiplex reactions for tcdA, tcdB, tcdC, and cdtB (binary toxin) sequences were initially optimized using synthetic targets and were subsequently done using genomic DNA; each target was detected and characterized by hybridization to one or more probes of a different fluorescent color. In the case of tcdC, three probes, each labeled with a Quasar fluorophore, hybridize to different locations with known mutations, including the deletion at nucleotide 117 in ribotype 027 strains and the premature stop codon mutation at nucleotide 184 in ribotype 078 strains, each of which is associated with hypervirulent infections. These and other tcdC mutations were distinguished from the reference sequence, as well as from each other by changes in the fluorescent contour generated from the combined Quasar-labeled probes. Specific variations in tcdA and tcdB were also identified in the multiplex assay, including those that identified strains lacking toxin A production. This single closed-tube assay generates substantially more information about virulent C. difficile than currently available commercial assays and could be further expanded to provide strain typing.

The production of binary toxin and presence of truncating mutations in the putative toxin repressor gene, tcdC, have been associated with the increased virulence and spread of Clostridium difficile, especially ribotype 027. We analysed the prevalence of binary toxin genes and tcdC mutations in 207 clinical C. difficile isolates collected between 2008–2010. The majority (83%) belonged to one of five tcdC types and 8% were ribotype 027. There was little evidence of epidemic spread but there was a high prevalence of both predicted tcdC truncating mutations (15%) and binary toxin genes (28%), which occurred in both 027 and other ribotypes. We measured risk factors (age and laboratory markers) and patient outcomes (severity of disease, ICU admission, mortality, recurrence and length of stay) for patients infected with C. difficile strains with and without these mutations and genes. There was a significantly higher serum C-reactive protein and total peripheral white cell count in the group with predicted tcdC truncating mutations, but no difference in patient outcome. The group with binary toxin genes had a significantly higher total peripheral white cell count and 30 day all cause mortality. We have demonstrated a high prevalence of both predicted tcdC truncating mutations and binary toxin genes in a variety of C. difficile ribotypes, however neither of these factors by themselves predicted clinical virulence. This and other work show that commonly described deletions and truncating mutations do not by themselves explain the virulence of ribotype 027 and other C. difficile strains and further work is required to explain why some isolates appear to produce more severe disease than others.

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.

We investigated methicillin-resistant Staphylococcus aureus (MRSA) environmental contamination in an inner city outpatient clinic and emergency department (ED). Moistened cotton-tipped swabs were used to sample 63 surfaces in the outpatient clinic and 69 surfaces in the ED. MRSA was identified on none of the 63 surfaces in the outpatient clinic and on 7% of the 69 surfaces in the ED. Our findings may have implications for cleaning and disinfection regimens in outpatient settings.

Studies in the 1970s and 1980s suggested that environmental surface contamination played a negligible role in the endemic transmission of healthcare-associated infections. However, recent studies have demonstrated that several major nosocomial pathogens are shed by patients and contaminate hospital surfaces at concentrations sufficient for transmission, survive for extended periods, persist despite attempts to disinfect or remove them, and can be transferred to the hands of healthcare workers. Evidence is accumulating that contaminated surfaces make an important contribution to the epidemic and endemic transmission ofClostridium difficile,vancomycin-resistant enterococci, methicillin-resistantStaphylococcus aureus, Acinetobacter baumannii, Pseudomonas aeruginosa,and norovirus and that improved environmental decontamination contributes to the control of outbreaks. Efforts to improve environmental hygiene should include enhancing the efficacy of cleaning and disinfection and reducing the shedding of pathogens. Further high-quality studies are needed to clarify the role played by surfaces in nosocomial transmission and to determine the effectiveness of different interventions in reducing associated infection rates.

Toxin enzyme immunoassays (EIAs) are inadequate for the diagnosis of Clostridium difficile infection (CDI) when used alone. In September 2010 we replaced toxin EIA with a two-step algorithm, testing first with glutamate dehydrogenase and confirming with polymerase chain reaction for toxin B gene. We compared this to the gold standard of toxigenic culture, observing a positive predictive value of 96% (laboratory prevalence of 4.7%). There was no deterioration in turnaround time but there was a decrease of 11% in repeat specimens sent from the same patients. The improved performance of the algorithm increased the laboratory positivity rate from 2.2% to 5.6%. This led to an increase in our Trust CDI rate reported under the Health Protection Agency's mandatory surveillance scheme. We investigated whether the change was due to increasing nosocomial transmission, environmental contamination or consumption of antimicrobials, but found no evidence of this. We conclude that it probably resulted from the change in testing algorithm. Although we have improved testing and enhanced patient safety, we are likely to be unfairly financially penalised because of our apparent (but not real) increase in CDI rates. Assessment of CDI rates should take testing methodology into account and national policies should be revised to reflect this.

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.

Over the past decade, community-associated meticillin-resistant Staphylococcus aureus (MRSA) has emerged in patients without health-care contact, especially in the USA. Although data are limited, the prevalence of community-associated MRSA in Europe seems to be low but is increasing. The organism has been reported in most European countries, including the Netherlands and Nordic countries, which have low rates of health-care-associated MRSA. In Greece, rates of community-associated MRSA in some centres approach those of the USA. By contrast with North America, where the USA300 clone (ST8-IV) predominates, community-associated MRSA in Europe is characterised by clonal heterogeneity. The most common European strain is the European clone (ST80-IV), although reports of USA300 are increasing. Several community-associated MRSA clones have arisen in Europe, most notably the ST398-V pig-associated MRSA clone in the Netherlands and Denmark. An understanding of the epidemiology of community-associated MRSA is essential to guide new control initiatives to prevent these organisms from becoming endemic in Europe.

ABSTRACT With inocula of 6 to 7 log 10 CFU, most vegetative bacteria and spores tested survived on surfaces for more than 5 weeks, but all were inactivated within 90 min of exposure to hydrogen peroxide vapor in a 100-m 3 test room even in the presence of 0.3% bovine serum albumin to simulate biological soiling.

ABSTRACT The clinical utility of real-time PCR screening assays for methicillin (meticillin)-resistant Staphylococcus aureus (MRSA) colonization is constrained by the predictive values of their results: as MRSA prevalence falls, the assay's positive predictive value (PPV) drops, and a rising proportion of positive PCR assays will not be confirmed by culture. We provide a quantitative analysis of universal PCR screening of critical care and emergency surgical patients using the BD GeneOhm MRSA PCR system, involving 3,294 assays over six months. A total of 248 PCR assays (7.7%) were positive; however, 88 failed to be confirmed by culture, giving a PPV of 65%. Multivariate analysis was performed to compare PCR-positive culture-positive (P+C+) and PCR-positive culture-negative (P+C−) assays. P+C− results were positively associated with a history of methicillin-sensitive Staphylococcus aureus infection or colonization (odds ratio [OR], 3.15; 95% confidence interval [CI], 1.32 to 7.54) and high PCR thresholds of signal intensity, indicative of a low concentration of target DNA (OR, 1.19 per cycle; 95% CI, 1.11 to 1.26). P+C− results were negatively associated with a history of MRSA infection or colonization (OR, 0.19; 95% CI, 0.09 to 0.42) and male sex (OR, 0.40; 95% CI, 0.20 to 0.81). P+C+ patients were significantly more likely to have subsequent positive MRSA culture assays and microbiological evidence of clinical MRSA infection. The risk of subsequent MRSA infection in P+C− patients was not significantly different from that in case-matched PCR-negative controls. We conclude that, given the low PPV and poor correlation between a PCR-positive assay and the clinical outcome, it would be prudent to await culture confirmation before altering infection control measures on the basis of a positive PCR result.