C. difficile

Contaminated surfaces contribute to transmission; the question is, how much?

Jon Otter (@jonotter) Contamination, Disinfection , , , ,

mop

I’ve been asked to write a chapter on the role of the environment in transmission in an Springer book (on the potential role for antimicrobial surfaces in healthcare). So, I’ve been busy updating my 2011 ICHE literature review on a similar topic, drawing on an excellent recent AJIC review by Dr Donskey.

There are some epidemiological associations that suggest an important role for contaminated surfaces in transmission. Most compelling are the studies showing that admission to a room previously occupied by a patient with certain environmentally-associated pathogens increases the risk of acquisition for incoming patients, presumably due to residual contamination. However, in order to really nail a scientific association, an intervention is required. Hence, the environmental intervention studies provide the highest quality evidence evaluating the role of the environment in transmission (see the Table below).

These studies have shown that switching to more effective agents, improving the cleaning / disinfection process or turning to automated “no-touch” room disinfection systems (NTD) can reduce transmission in endemic settings. It’s important to note that some studies report an ineffective environmental intervention. These are important to publish to avoid publication bias. Looking under the bonnet of these studies usually offers an explanation as to why they did not show a significant reduction in transmission. For example:

  • Wilcox 2003. There was virtually no impact on the frequency of C. difficile environmental contamination on the wards using bleach, so it’s surprising that they saw any reduction in CDI!
  • Valiquette 2007. The bundle of interventions, some of which were environmental, was only given a few months to be effective.
  • Wilson 2011. This one is more difficult to explain. Perhaps it was underpowered to detect a clinical impact in the declining prevalence of MRSA in the UK?
  • Dharan 1999. The intervention was focused mainly on improving the cleaning and disinfection floors, which are not exactly a high-touch, high-risk sites.

Believe it or not, I still occasionally meet people who tell me that contaminated surfaces do not contribute to transmission. That rather dated viewpoint is becoming increasingly untenable as the volume and quality of data evaluating the role of the environment in transmission continues to increase. For me, the question has now moved on to how much contaminated surfaces contribute to transmission, and how best to address contamination of the hospital environment.

Table. Intervention studies evaluating the role of contaminated surfaces in the endemic transmission of nosocomial pathogens.

Reference Setting, location Organism Study design Key findings
Mayfield 2000 1 Three units, USA C. difficile 18-month before-after study of a switch from QAC to bleach disinfection. Significant reduction in CDI incidence on the highest risk unit from 8.6 to 3.3 cases per 1000 patient-days.
Wilcox 2003 2 Two units, UK C. difficile 2-year ward cross-over study of a switch from detergent to bleach disinfection. Significant reduction in CDI incidence on one of the units (from 8.9 to 5.3 cases per 100 admissions), but not on the other.
McMullen 2007 3 MICU and SICU, USA C. difficile 2-month before-after evaluation of bleach disinfection of CDI rooms on SICU and 4-month evaluation of bleach disinfection of all rooms on MICU in a hyper-endemic setting. Significant reduction in CDI incidence on both units (10.4 to 3.9 cases per 1000 patient days on SICU; 16.6 to 3.7 cases per 1000 patient days on MICU).
Valiquette 2007 4 Hospital-wide, Canada C. difficile 5-month evaluation of enhanced infection control and disinfection, including a switch to bleach, and a subsequent switch to ‘accelerated’ hydrogen peroxide. Neither environment intervention made a significant impact on the incidence of CDI; a reduction in the use of high-risk antibiotics significantly reduced the incidence of CDI.
Boyce 2008 5 Hospital-wide, USA C. difficile 20-month before-after study on the use of HPV disinfection for terminal disinfection of CDI rooms. Significant reduction in CDI incidence on five high incidence units (from 2.3 to 1.3 cases per 1000 patient-days). Lesser reduction in CDI incidence hospital wide.
Hacek 2010 6 Three hospitals, USA C. difficile 3-year before-after study on switching from QAC to bleach for terminal disinfection of CDI rooms. Significant reduction in the incidence of CDI (from 0.85 to 0.45 per 1000 patient days).
Orenstein 2011 7 Two medical units, USA C. difficile 2-year before-after study on switching to bleach wipes for daily and terminal disinfection of all rooms. Significant reduction in the incidence of CDI (from 24.2 to 3.6 per 1000 patient days).
Manian 2013 8 Hospital-wide, USA C. difficile 3-year before-after study on enhanced terminal disinfection of CDI rooms using HPV and bleach. Significant reduction in the incidence of CDI (from 0.88 to 0.55 cases per 1000 patient days).
Hayden 2006 9 ICU, USA VRE 9-month before-after study on educational improvement of cleaning and hand hygiene. The frequency of environmental contamination and patient acquisition of VRE were reduced  from 33 to 17 acquisitions per 1000 patient-days during the improved cleaning phase.
Datta 2011 10 ICU, USA VRE / MRSA 3-year before-after study of an intervention (fluorescent markers, “bucket method” and education) to enhance daily and terminal cleaning. Significant reduction of MRSA (3.0% to 1.5% of admissions) and VRE (3.0% to 2.2% of admissions) acquisitions; intervention significantly reduced the increased risk from the prior occupant for MRSA but not VRE.
Perugini 2011 11 Hospital-wide, Brazil VRE 4-year before-after study of an educational and observational intervention for cleaners. Significant reduction in VRE infection (from 7.7 to 1.9 per 1000 patient days) and environmental contamination.
Grabsch 2012 12 Hospital-wide, Australia VRE 18-month before-after study of a multimodal intervention (switch to bleach, improved monitoring of cleaners, modification of VRE contact isolation, periodic ‘super-clean-disinfection’ of high-risk wards). Significant reduction of VRE colonization (from 10.7% to 8.0% of patients) and VRE environmental contamination.
Passaretti 2013 13 ICU, USA VRE / all MDROs 30-month cohort study on the impact of HPV decontamination. Patient admitted to rooms disinfected using HPV significantly less likely to acquire an MDRO (15.7 to 6.2 per 1000 patient days) and VRE (11.6 to 2.4 per 1000 patient days).
Mahamat 2007 14 Hospital-wide, UK MRSA 8-year interrupted time series analysis of multiple infection control interventions. Introduction of bleach disinfection, environmental sampling, alcohol gels and admission screening all reduced the prevalence of MRSA.
Dancer 2009 15 Two wards, UK MRSA 12-month cross over-study on the impact of one extra cleaner. Enhanced cleaning was associated with significant reductions surface contamination, hygiene fails and MRSA acquisition.
Wilson 2011 16 ICU, UK MRSA 12-month randomized crossover study on the impact of additional twice daily cleaning of hand contact surfaces. Significant reduction in the detection of MRSA on surfaces and hands, but no significant change in MRSA acquisition was detected.
Dharan 1999 17 5 medical wards, Switzerland – 4-month controlled study where 3-wards received an intervention (including an active oxygen based compound) and 2 wards continued current practice. Intervention associated with reduced contamination but not reduced nosocomial infection or MRSA infection / colonization.

HPV = hydrogen peroxide vapour.

 

References

1.       Mayfield JL, Leet T, Miller J, Mundy LM. Environmental control to reduce transmission of Clostridium difficile. Clin Infect Dis 2000; 31: 995-1000.

2.       Wilcox MH, Fawley WN, Wigglesworth N, Parnell P, Verity P, Freeman J. Comparison of the effect of detergent versus hypochlorite cleaning on environmental contamination and incidence of Clostridium difficile infection. J Hosp Infect 2003; 54: 109-114.

3.       McMullen KM, Zack J, Coopersmith CM, Kollef M, Dubberke E, Warren DK. Use of hypochlorite solution to decrease rates of Clostridium difficile-associated diarrhea. Infect Control Hospital Epidemiol 2007; 28: 205-207.

4.       Valiquette L, Cossette B, Garant MP, Diab H, Pepin J. Impact of a reduction in the use of high-risk antibiotics on the course of an epidemic of Clostridium difficile-associated disease caused by the hypervirulent NAP1/027 strain. Clin Infect Dis 2007; 45 Suppl 2: S112-121.

5.       Boyce JM, Havill NL, Otter JA et al. Impact of hydrogen peroxide vapor room decontamination on Clostridium difficile environmental contamination and transmission in a healthcare setting. Infect Control Hosp Epidemiol 2008; 29: 723-729.

6.       Hacek DM, Ogle AM, Fisher A, Robicsek A, Peterson LR. Significant impact of terminal room cleaning with bleach on reducing nosocomial Clostridium difficile. Am J Infect Control 2010; 38: 350-353.

7.       Orenstein R, Aronhalt KC, McManus JE, Jr., Fedraw LA. A targeted strategy to wipe out Clostridium difficile. Infect Control Hosp Epidemiol 2011; 32: 1137-1139.

8.       Manian FA, Griesnauer S, Bryant A. Implementation of hospital-wide enhanced terminal cleaning of targeted patient rooms and its impact on endemic Clostridium difficile infection rates. Am J Infect Control 2013; 41: 537-541.

9.       Hayden MK, Bonten MJ, Blom DW, Lyle EA, van de Vijver DA, Weinstein RA. Reduction in acquisition of vancomycin-resistant enterococcus after enforcement of routine environmental cleaning measures. Clin Infect Dis 2006; 42: 1552-1560.

10.     Datta R, Platt R, Yokoe DS, Huang SS. Environmental cleaning intervention and risk of acquiring multidrug-resistant organisms from prior room occupants. Arch Intern Med 2011; 171: 491-494.

11.     Perugini MR, Nomi SM, Lopes GK et al. Impact of the reduction of environmental and equipment contamination on vancomycin-resistant enterococcus rates. Infection 2011; 39: 587-593.

12.     Grabsch EA, Mahony AA, Cameron DR et al. Significant reduction in vancomycin-resistant enterococcus colonization and bacteraemia after introduction of a bleach-based cleaning-disinfection programme. J Hosp Infect 2012; 82: 234-242.

13.     Passaretti CL, Otter JA, Reich NG et al. An evaluation of environmental decontamination with hydrogen peroxide vapor for reducing the risk of patient acquisition of multidrug-resistant organisms. Clin Infect Dis 2013; 56: 27-35.

14.     Mahamat A, MacKenzie FM, Brooker K, Monnet DL, Daures JP, Gould IM. Impact of infection control interventions and antibiotic use on hospital MRSA: a multivariate interrupted time-series analysis. Int J Antimicrob Agents 2007; 30: 169-176.

15.     Dancer SJ, White LF, Lamb J, Girvan EK, Robertson C. Measuring the effect of enhanced cleaning in a UK hospital: a prospective cross-over study. BMC Med 2009; 7: 28.

16.     Wilson AP, Smyth D, Moore G et al. The impact of enhanced cleaning within the intensive care unit on contamination of the near-patient environment with hospital pathogens: a randomized crossover study in critical care units in two hospitals. Crit Care Med 2011; 39: 651-658.

17.     Dharan S, Mourouga P, Copin P, Bessmer G, Tschanz B, Pittet D. Routine disinfection of patients’ environmental surfaces. Myth or reality? J Hosp Infect 1999; 42: 113-117.

The pitfalls of PCR for detecting pathogens on surfaces

Jon Otter (@jonotter) C. difficile, Contamination, MRSA , , , ,

PCR has proven an invaluable tool for the rapid diagnosis of a range of pathogens, including MRSA and C. difficile. Several studies have evaluated the potential use of PCR for the detection of pathogens on surfaces and have identified some issues that, frankly, seem pretty terminal for this application using currently available commercial PCR kits.

A study from Cleveland evaluated the use of a commercial RT-PCR test for detecting C. difficile on hospital surfaces. Three composite sites were sampled in 22 patient rooms, 41% of which housed a patient with CDI with the remaining 59% sampled after terminal cleaning and disinfection. Two swabs and a gauze were collected from each site; one swab was cultured directly onto selective agar and the other was tested using PCR. The gauze was cultured using broth enrichment. C. difficile that grew on the selective agar were tested for toxin production and only toxigenic C. difficile were included.

Overall, 23 (35%) of the 66 sites grew toxigenic C. difficile and only 4 of these were detected using the standard RT-PCR assay (sensitivity 17%, specificity 100%). The sensitivity of RT-PCR in rooms that had been cleaned and disinfected was even worse (10%). Increasing the CT threshold of the assay (making it less stringent) improved the overall sensitivity to 52% and did not affect the specificity.

The study has several important limitations. The RT-PCR assay detected only the Toxin B gene, whereas the toxigenic culture methodology would detect both Toxin A and B producers. More importantly, there was a crucial difference in sampling methodology: the gauzes used for broth enrichment culture had a 50% higher positivity rate than the swabs (in line with other findings), but only swabs were tested by both PCR and culture. Thus, if the gauzes are a more effective sampling device, this would make the RT-PCR methodology seems worse than it is. I would have liked to have seen the sensitivity of the RT-PCR assay for detecting C. difficile cultured from the swabs only, but I could not derive this from the data in the paper.

An older study from New Haven, Connecticut provides a contrasting view of the use of PCR to detect pathogens from surfaces. Here, 10 standardized sites were sampled in the rooms of 10 patients infected or colonized with MRSA, and 5 rooms of patients not known to be infected or colonized with MRSA. Swabs were directly plated onto selective agar for MRSA, then DNA was extracted from the swabs before a broth enrichment procedure using the same swabs. In this study, 40 (27%) of the 150 surfaces were positive by culture, but 90 (60%) were positive by PCR (sensitivity 93%, specificity 51%).

Deshpande 2013

Figure 1. Contrasting sensitivity and specificity when using PCR to detect C. difficile and MRSA on hospital surfaces.

It seems then that the sensitivity of PCR is too low for the environmental detection of C. difficile but the specificity is too low MRSA (figure 1). How could this be? Assuming that this is not due to experimental differences between the studies, it could be that the standard extraction procedure used for the C. difficile assay was not robust enough to liberate DNA from the mature environmental spores, resulting in low sensitivity. Conversely, the PCR assay was detecting DNA from dead MRSA on surfaces, resulting in low specificity.

So, in summary, the MRSA assay was too sensitive and the C. difficile assay was not sensitive enough! While the use of these “off the shelf” commercial assays doesn’t seem to be useful for detecting pathogens on surfaces, there may be hope for a PCR assay tailored specifically for an environmental application.

Article citations:

Deshpande A, Kundrapu S, Sunkesula VC, Cadnum JL, Fertelli D, Donskey CJ. Evaluation of a commercial real-time polymerase chain reaction assay for detection of environmental contamination with Clostridium difficile. J Hosp Infect 2013;85:76-78.

Otter JA, Havill NL, Boyce JM. Evaluation of real-time polymerase chain reaction for the detection of methicillin-resistant Staphylococcus aureus on environmental surfaces. Infect Control Hosp Epidemiol 2007;28:1003-1005.

Is superoxidised water destined to be an environmental superhero?

Jon Otter (@jonotter) Disinfection , ,

OLYMPUS DIGITAL CAMERA

Anything that with claims that are too good to be true usually is. But the data coming out about superoxidised water does seem very impressive. The latest research study, coming from the Cleveland VA, evaluated an electrochemically activated saline solution, also known as ‘superoxidized water’. Surprisingly, the novel disinfectant performed comparably to 10% bleach in vitro. VRE, MRSA and C. difficile spores were dried onto surfaces and exposed to 10% bleach or superoxidised water (Sterilox). The superoxidised water matched the bleach log for log (both achieving a 5-6 log reduction with no organic load and a 3-4 log reduction with organic load present). This was true even for the C. difficile spores. The team also evaluating the efficacy of spraying superoxidised water on wall-mounted equipment, finding that 12% of 66 cultures grew C. difficile before treatment, compared with none of the matched sites after treatment.

Superoxidised water lacks some of the drawbacks associated with 10% bleach, principally compatibility with electronic equipment as demonstrated in this study. This agent should be prioritized for further evaluation.

Article citation: Fertelli D, Cadnum JL, Nerandzic MM, Sitzlar B, Kundrapu S, Donskey CJ. Effectiveness of an electrochemically activated saline solution for disinfection of hospital equipment. Infect Control Hosp Epidemiol 2013;34:543-544.

Improved terminal disinfection using hydrogen peroxide vapour (HPV) or bleach to control C. diff

Jon Otter (@jonotter) C. difficile, Disinfection , , , , ,
A prospective before-after study at the 900 bed St. John’s Mercy Medical Center evaluated the impact of an HPV intervention focused on the terminal disinfection of rooms used by patients with multidrug-resistant organisms and C. difficile. HPV was introduced on a priority scale accounting for the target pathogen and the risk associated with the unit. Due to local prevalence, most of the rooms decontaminated using HPV were vacated by patients with C. difficile infection (CDI). Hence, the authors evaluated the impact of introducing HPV on the rates of CDI.
The rate of CDI was static prior to the introduction of HPV, with no significant change in rate from 2007 to 2008 (Figure). Hence, this study was performed in a truly endemic setting in contrast to a previous study of a similar design by Boyce et al., which was performed in a “hyper-endemic” setting. When HPV was introduced in 2009 (along with enhanced conventional methods comprising quadruple bleach disinfection for rooms that could not be disinfected using HPV), the rate of CDI fell by 37% from 0.9 to 0.5 cases per 1000 patient days (p<0.0001) (see chart below).
Chart showing the rate of C. difficile infection before and after the implementation of HPV or quadruple bleach disinfection for the terminal decontamination of patient rooms.
Micro Blog Jan 2013
Recent data have shown that patients admitted to rooms previously occupied by a patient with C. difficile are at an increased risk of developing C. difficile infection. Thus, it seems logical that improving the efficacy of terminal disinfection would result in reduced rates of CDI. Furthermore, the scale of reduction in CDI incidence was remarkably similar to the study by Boyce et al. (37% vs. 39%), though in this previous study, the 39% hospital wide reduction was not statistically significant.
The major criticism of the study is that HPV and quadruple bleach disinfection were implemented more or less simultaneously so it’s not possible to attribute the reduction to HPV alone. This is complicated by the fact that quadruple bleach disinfection was implemented for all C. difficile rooms in mid-2008, 6 months prior to the introduction of HPV. So, it is possible in theory to do a sub-analysis of corresponding months during the period when quadruple bleach disinfection alone compared with HPV plus quadruple bleach disinfection was in operation. However, this sub-analysis was not performed. A previous study by the same group showed that quadruple bleach disinfection was necessary to eliminate A. baumannii and MRSA from surfaces, and that HPV was microbiologically superior to quadruple bleach disinfection. Thus, since HPV has time and efficiency savings compared with quadruple bleach disinfection, it is cost effective to use HPV in this setting.
The authors undertook a careful evaluation of hand hygiene and glove / gowning compliance, showing that these were not significantly different comparing the pre-intervention and intervention periods. They also evaluated the use of key antimicrobial agents and found that there were small but statistically significant changes in antimicrobial usage, which may have confounded the association with improved disinfection. However, levofloxacin use (one of the high risk CDI drugs) increased significantly in 2009 and there was still a significant reduction in CDI.
The paper includes some useful data on feasibility and safely aspects of implementing HPV, and the ‘priority scale’ (Appendix) for deciding which rooms were disinfected using HPV is rational and will help other hospitals decide on a similar priority scale.
Several other points of interest are reported. For example, the significant reduction in CDI was achieved whilst adhering to US C. difficile control guidelines, which recommend the use of gloves and alcohol based hand products (rather than hand washing with soap and water) for treating patients with CDI in endemic settings. They also held patients who had CDI in contact precautions for the duration of their stay, not just until symptoms resolved.
This study shows that more effective removal of C. difficile spores from the rooms of patients when they are discharged through enhanced conventional methods combined with the implementation of HPV reduces the hospital-wide incidence of CDI. The authors conclude: ‘implementation of an enhanced hospital-wide terminal cleaning program revolving around HPV decontamination of targeted hospital rooms was practical, safe, and associated with a significant reduction in the endemic rate of CDI at our hospital.’
Article citation: Manian FA, Griesnauer S, Bryant A. Implementation of hospital-wide enhanced terminal cleaning of targeted patient rooms and its impact on endemic Clostridium difficile infection rates. Am J Infect Control in press.

Why boys and girls should keep the toilet seat down

Jon Otter (@jonotter) C. difficile , , ,

blog_toilet

A charming study evaluated the risk of aerosolisation of Clostridium difficle spores through toilet flushing and the potential for resulting environmental contamination. Sure enough, using a faecal suspension to simulate diarrhea caused by C. difficile, investigators found that air and surfaces surrounding the toilet were contaminated with C. difficile spores when the toilet was flushed with the lid up. So, the advice is to close the lid when you flush the toilet to avoid aersolisation spread of gastrointestinal pathogens. One added complication though: many hospital toilets do not have lids, so the authors concluded by discouraging the use of lidless toilets.

Article citation: Best EL, Sandoe JA, Wilcox MH. Potential for aerosolization of Clostridium difficile after flushing toilets: the role of toilet lids in reducing environmental contamination risk. J Hosp Infect 2012; 80: 1-5.