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2007 Annual Review

1. Virulence determinants in CA-MRSA

Most CA-MRSA carry the Panton-Valentine Leukocidin (PVL), but some do not. The status quo is that PVL is a virulence factor, which gives CA-MRSA a selective advantage. However, conflicting studies have been published investigating the role of PVL in the CA-MRSA disease process in 2007. Voycich et al. (2006) found that PVL was not a key virulence determinant using mouse models of mortality, abscess formation and in vitro studies using leukocytes (Voyich et al. 2006). In contrast, Labandeira-Ray et al. (2007) found that PVL is a virulence factor in a mouse model of necrotising pneumonia and further, that PVL is a global regulator affecting the expression of other genes (Labandeira-Rey et al. 2007). To confuse matters further, a recent Nature paper has demonstrated that over-expression of newly-described Phenol-Soluble Modulins (PSMs) could be the key virulence determinant in CA-MRSA (Wang et al. 2007). It is tempting to speculate that PVL acts as a global regulator increasing the expression of PSMs. Expect to see more high-quality research on virulence determinants in CA-MRSA in 2008!

2. USA300 CA-MRSA reaches Europe

USA300 CA-MRSA is running rampant in parts of the USA and even beginning to take over as the leading cause of healthcare-associated MRSA infection (Patel et al. 2007). In contrast, most CA-MRSA infection in Europe has been caused by the ST80, PVL-positive “European” clone. A recent study reported the sinister emergence of USA300 CA-MRSA in Denmark, and what seems to be the beginning of an exponential increase with 2 cases in 2003, 11 in 2004 and 28 in 2005 (Larsen et al. 2007). Watch out for more USA300 CA-MRSA in Europe in 2008.

3. CA-MRSA surface contamination in a community setting

Environmental contamination with CA-MRSA during an outbreak in an outpatient setting has been reported previously (Johnston et al. 2006). An outbreak of USA300 CA-MRSA affected 24 people in a religious community in the USA, with a high attack rate of 14% (Coronado et al. 2007). The outbreak strain was cultured from a computer keyboard and the sauna bench, representing 2 (4%) of the 47 sites sampled and sauna use along with prior antimicrobial use were significantly associated with infection. The outbreak was controlled through improved personal and environmental hygiene, demonstrating the need for environmental hygiene outside of the hospital setting for the control of S. aureus transmission.

4. MRSA environmental contamination is important!

An excellent review in the Lancet Infectious Diseases has established once and for all that environmental contamination with MRSA and, indeed, S. aureus, is important for transmission (Dancer 2007a)! The review establishes the transmission cycle of S. aureus focussing on the often under-emphasised role of environmental contamination. A short review in the Journal of Hospital Infection also published in 2007 discusses the role of the environment in the transmission of various organisms including MRSA, VRE and C. difficile (Boyce 2007).

5. Microbial environmental contamination in hospitals

Surface contamination with MRSA continues to be reported from around the world. Small prospective UK studies have identified MRSA on 10% of 50 tourniquets (Franklin et al. 2007), 12% of 70 bed-control hand-sets (Brady et al. 2007) and 6% of 50 case-notes for MRSA-positive patients (Hamza et al. 2007). A US study reported that patients with heavy gastrointestinal colonization with MRSA accompanied by diarrhoea contaminated their environment 2.5-fold more frequently than patients without MRSA gastrointestinal colonization but with MRSA colonization at other sites (Boyce et al. 2007). This suggests that patients with MRSA gastrointestinal colonisation and diarrhoea cause widespread environmental contamination and may require additional isolation and decontamination measures. MRSA is not the only microbe to contaminate hospital surfaces. A 2007 Greek study has reported widespread contamination of air and surfaces with potentially pathogenic fungi (Panagopoulou et al. 2007).

6. Bleach cleaning reduces the incidence of CDAD

A 19-bed medical ICU (MICU) and 24-bed surgical ICU (SICU) at a 1400 bed university-affiliated tertiary care facility in St. Louis, Missouri, experienced acute outbreaks of C. difficile-associated disease (CDAD) in late 2002 (McMullen et al. 2007). Both units implemented bleach cleaning; the bleach was implemented unit-wide on the MICU and in rooms occupied by CDAD patients only on the SICU. Statistically significant reductions in the rate of CDAD sustained over two years on both wards were noted (16.6 to 3.7 cases per 1000 patient-days on the MICU and 10.4 to 3.9 cases per 1000 patient-days on the SICU by the end of the intervention period). The authors report several limitations: no environmental sampling was conducted, a hospital-wide hand hygiene initiative was implemented in the hospital (though this was after the intervention phase) and feedback of CDAD rates to the wards may have increased compliance with infection control measures. In addition, antimicrobial prescription and consumption were not reported. Despite these limitations, this study provides further data supporting the role of contaminated environmental surfaces in the transmission of C. difficile.

7. Screening for asymptomatic C. difficile colonization: the way forward?

In a study from Cleveland, OH in the USA, 51% of 68 patients were found to be asymptomatically colonized with toxigenic C. difficile (Riggs et al. 2007). 59% of the environmental sites in the rooms of patients with C. difficile colonization were contaminated with C. difficile compared with 24% of sites in the rooms of patients who were not colonized. Crucially, spores on the skin of asymptomatic patients were transferred easily to the hands of researchers, suggesting that transmission from colonized patients via the hands of healthcare workers is likely. This study opens the “Pandora’s box” of whether to routinely screen patients for C. difficile colonization. With isolation facilities already at a premium, especially in the UK, the identification of widespread C. difficile colonization would place further operational strain on healthcare facilities!

8. HPV effective for the deactivation of Mycobacterium tuberculosis

A collaborative study between the Mayo Clinic in the USA and BIOQUELL published this year in the Journal of Clinical Microbiology demonstrates the efficacy of hydrogen peroxide vapour (HPV) for the deactivation of Mycobacterium tuberculosis (Hall et al. 2007). A relatively low inoculum was used to represent a spillage post manual disinfection to reflect local procedures. The study showed that the M. tuberculosis dried onto metal discs was deactivated within 30 minutes HPV exposure in time-course studies in a biological safety cabinet (BSC) and within the shortest cycle tested (90 minutes) when distributed throughout a laboratory room, including inside a drawer left ajar. The study concludes ‘HPV provides an alternative to traditional methods, such as formaldehyde fumigation, for the decontamination of laboratories used to handle M. tuberculosis. HPV could also be applied in the health care setting for the terminal decontamination of isolation facilities used to care for patients with tuberculosis.’

9. Recontamination following HPV

Several studies have been published in the Journal of Hospital Infection this year discussing recontamination following HPV decontamination. In a study from Birmingham Heartlands hospital, UK, MRSA was cultured from surfaces in a 9-bed ICU before cleaning, after cleaning but not after HPV and total bacterial counts showed a similar trend (Hardy et al. 2007). Recontamination with patient strains of MRSA returned to pre-cleaning levels within 24 hours. Healthcare worker hand contamination was not monitored at any stage so cannot be ruled out as a confounding factor. In a study from North Middlesex Hospital, London, UK, HPV decontamination virtually eradicated MRSA, VRE and Gram-negative rods (GNR) that had persisted despite terminal cleaning. When a patient colonised with MRSA and GNR was re-admitted into the room, MRSA recontamination occurred to pre-cleaning levels and GNR recontamination occurred towards post-cleaning levels within one week, although the patient was not colonised or infected with the GNR species recontaminating the environment. The findings of these studies suggest that MRSA recontamination may be rapid (with a few days) if MRSA-positive patients are re-admitted but that Gram-negative recontamination may be less rapid. Re-admitted MRSA-positive patients need to be treated in isolation for HPV decontamination to have a sustained impact.

10. And finally…

Another year of quirky articles including really scary Jack O’Lanterns (Nagano et al. 2006), an expose on long-standing problems in Medical Publishing (Dancer 2007b), the politicising of hospital infection in the UK (McConnell 2007) and some unexpected risks associated with adopting children (Gustafsson et al. 2007), attending a rave (Miller et al. 2007a), visiting the barber (Moore and Miller 2007) and even gardening (Russell et al. 2007)!

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References

Boyce,J.M. (2007) Environmental contamination makes an important contribution to hospital infection. J Hosp Infect 65, 50-54.

Boyce,J.M., Havill,N.L., Otter,J.A. and Adams,N.M. (2007) Widespread environmental contamination associated with patients with diarrhea and methicillin-resistant Staphylococcus aureus colonization of the gastrointestinal tract. Infect Control Hosp Epidemiol 28, 1142-1147.

Brady,R.R., Kalima,P., Damani,N.N., Wilson,R.G. and Dunlop,M.G. (2007) Bacterial contamination of hospital bed-control handsets in a surgical setting: a potential marker of contamination of the healthcare environment. Ann R Coll Surg Engl 89, 656-660.

Coronado,F., Nicholas,J.A., Wallace,B.J., Kohlerschmidt,D.J., Musser,K., Schoonmaker-Bopp,D.J., Zimmerman,S.M., Boller,A.R., Jernigan,D.B. and Kacica,M.A. (2007) Community-associated methicillin-resistant Staphylococcus aureus skin infections in a religious community. Epidemiol Infect 135, 492-501.

Dancer,S.J. (2007a) Importance of the environment in meticillin-resistant Staphylococcus aureus acquisition: the case for hospital cleaning. Lancet Infect Dis in press.

Dancer,S.J. (2007b) The Trouble with Medical Journals. J Hosp Infect 66, 98-99.

Franklin,G.F., Bal,A.M. and McKenzie,H. (2007) Phlebotomy tourniquets and MRSA. J Hosp Infect 65, 173-175.

Gustafsson,E., Ringberg,H. and Johansson,P. (2007) MRSA in children from foreign countries adopted to Swedish families. Acta Paediatr 96, 105-108.

Hall,L., Otter,J.A., Chewins,J. and Wengenack,N.L. (2007) Use of Hydrogen Peroxide Vapor for Deactivation of Mycobacterium tuberculosis in a Biological Safety Cabinet and a Room. J Clin Microbiol 45, 810-815.

Hamza, N., Bazoua, G., Al-Shajarie, Y., Kubiak, E., James, P. and Wong, C. (2007) A prospective study of the case-notes of MRSA-positive patients: a vehicle of MRSA spread. Ann R Coll Surg Engl 89, 665-667.

Hardy,K.J., Gossain,S., Henderson,N., Drugan,C., Oppenheim,B.A., Gao,F. and Hawkey,P.M. (2007) Rapid recontamination with MRSA of the environment of an intensive care unit after decontamination with hydrogen peroxide vapour. J Hosp Infect 66, 360-368.

Johnston,C.P., Cooper,L., Ruby,W., Carroll,K.C., Cosgrove,S.E. and Perl,T.M. (2006) Epidemiology of community-acquired methicillin-resistant Staphylococcus aureus skin infections among healthcare workers in an outpatient clinic. Infect Control Hosp Epidemiol 27, 1133-1136.

Labandeira-Rey,M., Couzon,F., Boisset,S., Brown,E.L., Bes,M., Benito,Y., Barbu,E.M., Vazquez,V., Hook,M., Etienne,J., Vandenesch,F. and Bowden,M.G. (2007) Staphylococcus aureus Panton-Valentine leukocidin causes necrotizing pneumonia. Science 315, 1130-1133.

Larsen,A., Stegger,M., Goering,R., Sorum,M. and Skov,R. (2007) Emergence and dissemination of the methicillin resistant Staphylococcus aureus USA300 clone in Denmark (2000-2005). Euro Surveill 12.

McConnell,J. (2007) Public reporting in the UK of hospital infections. J Hosp Infect 65 Suppl 2, 189-190.

McMullen,K.M., Zack,J., Coopersmith,C.M., Kollef,M., Dubberke,E. and Warren,D.K. (2007) Use of hypochlorite solution to decrease rates of Clostridium difficile-associated diarrhea. Infect Control Hosp Epidemiol 28, 205-207.

Moore,J.E. and Miller,B.C. (2007) Skin, hair, and other infections associated with visits to barber's shops and hairdressing salons. Am J Infect Control 35, 203-204.

Nagano,Y., Millar,B.C., Loughrey,A., Goldsmith,C.E., Rooney,P.J., Moore,J.E. and Elborn,J.S. (2006) Jack o'Lantern--scarier than you think! Am J Infect Control 34, 680-681.

Panagopoulou,P., Filioti,J., Farmaki,E., Maloukou,A. and Roilides,E. (2007) Filamentous fungi in a tertiary care hospital: environmental surveillance and susceptibility to antifungal drugs. Infect Control Hosp Epidemiol 28, 60-67.

Patel,M., Kumar,R.A., Stamm,A.M., Hoesley,C.J., Moser,S.A. and Waites,K.B. (2007) USA300 genotype community-associated methicillin-resistant Staphylococcus aureus as a cause of surgical site infections. J Clin Microbiol 45, 3431-3433.

Riggs,M.M., Sethi,A.K., Zabarsky,T.F., Eckstein,E.C., Jump,R.L. and Donskey,C.J. (2007) Asymptomatic carriers are a potential source for transmission of epidemic and nonepidemic Clostridium difficile strains among long-term care facility residents. Clin Infect Dis 45, 992-998.

Russell,K., Waghorn,D. and Devi,R. (2007) The potential perils of a visit to botanical gardens in a patient with a central intravascular device. J Hosp Infect 66, 402-404.

Voyich,J.M., Otto,M., Mathema,B., Braughton,K.R., Whitney,A.R., Welty,D., Long,R.D., Dorward,D.W., Gardner,D.J., Lina,G., Kreiswirth,B.N. and DeLeo,F.R. (2006) Is Panton-Valentine Leukocidin the Major Virulence Determinant in Community-Associated Methicillin-Resistant Staphylococcus aureus Disease? J Infect Dis 194, 1761-1770.

Wang,R., Braughton,K.R., Kretschmer,D., Bach,T.H., Queck,S.Y., Li,M., Kennedy,A.D., Dorward,D.W., Klebanoff,S.J., Peschel,A., Deleo,F.R. and Otto,M. (2007) Identification of novel cytolytic peptides as key virulence determinants for community-associated MRSA. Nat Med 13, 1510-1514.

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