Micro Blog Summer 2013 Update

Jon Otter (@jonotter) Updates

summer

Dear Readers,

It’s been a good few months on the blog with lots of comments. Please keep them coming; we enjoy the interaction.

The following articles have been posted since the spring update:

And finally… are you gearing up to go to a festival this summer? Then you would be wise to be on the look out for the following according to this article: Cryptosporium parvum, Campylobacter spp., Escherichia coli, Salmonella enterica, Shigella sonnei, Staphylococcus aureus, hepatitis A virus, influenza virus, measles virus, mumps virus and norovirus. Most are associated with faecal-oral transmission, which says something about music festivals, don’t you think?

Don’t forget, you can subscribe to the blog to receive a notification via email each time a new article is published, or look out for updates on twitter here.

Saber and I both have the privilege of visiting ICPIC in Geneva this week. We plan to write a conference report on the blog next week.

Regards

Jon and Saber.

Eight solutions from the G8 summit to curb antibiotic resistance

Jon Otter (@jonotter) Antibiotic resistance , ,

G8

As effective therapy using antibiotics becomes increasingly difficult due to resistance, the emphasis must move from cure to prevention of bacterial infection. There is an urgent need to take internationally coordinated action to curb the further development of antibiotic resistance. The steps required are complex and will require engagement on a national and international level. So, it’s encouraging to see antibiotic resistance on the G8 agenda. Here’s eight solutions that have been discussed by G8 summit science ministers:

  1. Get antibiotic resistance on the agenda. The fact that the issue is being discussed at all demonstrates that the problem is being recognized. The recent rhetoric from Dame Sally Davies (“antibiotic resistance as big a risk as terrorism”) and the US CDC (“deadly, untreatable superbugs”) will help.
  2. Reduce overuse (abuse) of antibiotics in medical, veterinary and other applications. Antibiotics simply should not be used to fatten up animals and stop barnacles attaching to ship hulls!
  3. Restrict the availability of antibiotics where they are currently available over the counter. According to Dame Sally Davies, 83% of Russian families use antibiotics inappropriately at home.
  4. Stimulate the discovery of new antibiotics, and streamline the testing and approvals required to bring a new antibiotic to market. Drugs are expensive to discover and then bring to market. Pharmaceutical companies are not currently focused on developing new antibiotics and need to be incentivized.
  5. Improve and share surveillance efforts. National and international surveillance systems should be established for emerging resistant strains.
  6. Highlight the financial burden of antibiotic resistance ($21bn-$34bn a year in the US, £10bn a year in the UK).
  7. Stop selling antibiotics at the cost of Smarties. Otherwise they will be consumed like Smarties. Generic antibiotics can be very cheap indeed; increasing the price of generic antibiotics will provide a financial barrier to inappropriate over-the-counter use.
  8. Develop rapid diagnostics to reduce the universal or empiric use of inappropriate / ineffective agents. This does not sit well with the proposed universal use of antibiotics.

There’s no simple solution to the problem of increasing antibiotic resistance. The problem is long-standing, multi-factorial and global. However, international collaboration can make real progress is curbing the increase in antibiotic resistance rates and perhaps even begin to reverse the trend.

The terms 'horizontal' and 'vertical' intervention leave me feeling upside down, confused

Jon Otter (@jonotter) Epidemiology , , , , , ,

horizontal vertical

I am no expert in HIV, but I know that ‘vertical transmission’ means something very specific:

Vertical transmission: the transmission of a disease from mother to child either during pregnancy, childbirth, or by breastfeeding.

Similarly, the definition of ‘horizontal transmission’ is well defined:

Horizontal transmission: the transfer of an infection from person to person.

So, when I read about ‘vertical’ and ‘horizontal’ interventions in a recent New England Journal of Medicine Editorial and the Controversies blog, I began to get a little confused. I have a PhD in epidemiology so don’t consider myself easy to confuse (in this particular domain), but I would have thought that a ‘horizontal intervention’ would be directed towards preventing horizontal spread of an infectious agent and a ‘vertical intervention’ would be directed towards preventing the vertical transmission of an infectious agent. But this is not how these terms are being applied. Instead, a ‘horizontal intervention’ is being used to describe an intervention applied to every patient (such as chlorhexidine bathing or hospital-wide hand hygiene interventions) whereas a ‘vertical intervention’ is being used to describe an intervention designed to reduce colonization or infection due to a specific pathogen (such as active screening and isolation to prevent the spread of MRSA). The use of the term ‘vertical intervention’ seems especially confusing, since it’s a ‘vertical intervention’ to prevent the horizontal transmission of a specific pathogen!

I fail to see how the terms ‘vertical’ or ‘horizontal’ intervention are useful when there are such well-established definitions for horizontal and vertical transmission. I think that ‘universal intervention’ (such as universal screening or decolonization) and ‘targeted intervention’ (such as active screening and isolation to prevent the spread of MRSA) make a lot more sense. These terms are already in common circulation, so I would urge those who favour the use of ‘vertical’ or ‘horizontal’ intervention to reconsider their terminology.

Is treating surfaces rather than patients with colistin a good idea?

Jon Otter (@jonotter) Antibiotic resistance, Antimicrobial surfaces , , , ,

PillsAntimicrobial resistance is a worldwide problem and the emergence of multi-drug resistant (MDR) bacteria and the lack of therapeutic options have led to the revival of old antibiotics such as colistin.1 This antibiotic is now considered as a “last line” antibiotic used to treat infection with MDR strains especially those cause by Gram-negative pathogens.2 Unfortunately, resistance to colistin has already been documented among a number of problematic pathogens such as Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae, although the exact mechanism of resistance is not yet well defined.3

Within this context, I was surprised to come across a study4 presented at the 23nd European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) conference held in Berlin in April 2013, by a Portuguese group aimed at covalently immobilizing colistin on biomaterials to prevent biomaterial-associated infection.

The use of antimicrobial materials and materials coated or impregnated with antimicrobial agents in healthcare settings is a flourishing field of research. This is driven by an increased recognition of the role of environmental surfaces in the transmission of nosocomial pathogens5 as well as the age old problem of bacterial colonisation of indwelling medical devices.6  With few exceptions, such materials have yet to be proven effective in reducing infection in practice. In addition, the possibility of the development of resistance to the active agents within these materials and surfaces has not yet been well investigated.

The Portuguese study,4 successfully covalently immobilized colistin onto a polycarbonate surface using a polydopamine dip-coating methodology. They used two strains of P. aeruginosa to test for the ability of the bacteria to attach to these colistin coated surfaces and the antimicrobial activity of these surfaces. The results showed that colistin coated surfaces had no effect on bacterial attachment and that the majority (but not all) of the bacterial cells were killed. So, some cells were still viable after 24 hr incubation on the colistin coated surfaces. The concentration of colistin used was not reported, but it is clearly not sufficient to inactivate all the cells on the surfaces which can potentially lead to the development of resistance to the drug, especially in a versatile organism such as P. aeruginosa.

I believe that in an era of MDR and pan-resistant strains and virtually untreatable bacterial infections, the idea of using one of our last line antibiotics to coat biomedical surfaces potentially breading colistin and other antimicrobial resistant strains is the last thing the healthcare community needs.

References

  1. Bergen PJ, Landersdorfer CB, Lee HJ, Li J, Nation RL. ‘Old’ antibiotics for emerging multidrug-resistant bacteria.Curr Opin Infect Dis. 2012 Dec;25(6):626-33
  2. Biswas S, Brunel JM, Dubus JC, Reynaud-Gaubert M, Rolain JM. Colistin: an update on the antibiotic of the 21st century. Expert Rev Anti Infect Ther. 2012 Aug;10(8):917-34.
  3. Lim LM, Ly N, Anderson D, Yang JC, Macander L, Jarkowski A 3rd, Forrest A, Bulitta JB, Tsuji BT. Resurgence of colistin: a review of resistance, toxicity, pharmacodynamics, and dosing. Pharmacotherapy. 2010 Dec;30(12):1279-91
  4. Alves D, Lopes S, Pereira MO. A colistin coating to prevent biomaterial-associated infections. ECCMID. 2013. Berlin. Abstract P1105.
  5. Otter JA, Yezli S, French GL. The role played by contaminated surfaces in the transmission of nosocomial pathogens. Infect Control Hosp Epidemiol. 2011 Jul;32(7):687-99
  6. Nicolle LE. Urinary catheter-associated infections. Infect Dis Clin North Am. 2012 Mar;26(1):13-27.

Universal MRSA decolonization will tend towards universal resistance

Jon Otter (@jonotter) MRSA , , , , ,

swabA seminal study recently published in the New England Journal of Medicine evaluated the impact of universal decolonization vs. targeted screening and / or decolonization to prevent ICU infection. The study has the potential to fundamentally change practice in ICUs around the world. However, I have two major problems with the study, namely mupirocin and chlorhexidine.

Study design and results. The authors describe their design as a ‘pragmatic’ randomized controlled trial, which should serve as a model for other studies. There were several variables that the authors could not change, for example, the fact that some US states mandate universal screening whereas others do not. They were able to cleverly incorporate this into their stratified randomization process so that the integrity of the study was not compromised.

The study was large, with 74,256 patients admitted to 74 ICUs in 43 hospitals randomized to the following groups during the intervention phase:

Group 1: Targeted screening and isolation.

Group 2: Targeted screening, isolation and decolonization (using intranasal mupirocin and chlorhexidine bathing).

Group 3: Universal decolonization (using intranasal mupirocin and chlorhexidine bathing).

The study compared the hazard ratio for MRSA clinical cultures, all-pathogen bloodstream infections and MRSA bloodstream infections in the 12 month pre-intervention vs. the 18 month intervention period for each of the groups. The main finding was that universal decolonization (Group 3) was associated with significantly lower rates of MRSA clinical cultures and all-pathogen bloodstream infection, and reduced rates of MRSA bloodstream infection (Chart). Target screening and isolation (Group 1) was the least effective strategy and targeted screening, isolation and decolonization (Group 2) had intermediate effectiveness (Chart).

Huang 2013

[Chart: hazard ratios and 95% confidence intervals comparing the pre-intervention with the intervention period in each of the three groups. Group 1: Targeted screening and isolation; Group 2: Targeted screening, isolation and decolonization; Group 3: Universal decolonization.]

Major problems: My major issue with the study is the universal (aka indiscriminate) use of mupirocin and, to a lesser extent, chlorhexidine. MRSA are able to acquire low-level resistance to mupirocin through mutations in ileS or high-level resistance through the acquisition of mupA. I can’t help thinking that the authors underestimate the risk of driving mupirocin resistance with their comment in the discussion: ‘Mupirocin resistance has been reported in some studies of MRSA decolonization, but not all such studies.’  It is frankly naive to think that universal use of mupirocin for each ICU admission will not result in the widespread development of mupriocin resistance. Thus, the comment in the accompanying editorial urging caution in implementing the universal use of mupirocin is warranted.

The situation is not as clear-cut with chlorhexidine. Clinically significant reduced susceptibility to chlorhexidine in S. aureus has been hard to define for a number of reasons:

  1. There is no generally agreed methodology for detecting reduced chlorhexidine susceptibility.
  2. Population MICs vary considerably making a meaningful breakpoint difficult to determine.
  3. Higher MICs displayed by some isolates (4–16 mg/L) are still well below the effective chlorhexidine concentration applied to skin (10000–40000 mg/L).
  4. Although genes encoding membrane efflux pumps have been identified in S. aureus, including qacA, these have an unclear relationship with reduced susceptibility.
  5. Other mechanisms of reduced susceptibility, such as decreased uptake of chlorhexidine, may confound the apparent effect of efflux pumps.
  6. Although many studies have reported on qacA carriage or reduced chlorhexidine susceptibility in S. aureus isolates, few have evaluated clinically relevant outcomes.

Notwithstanding these limitations, it is clear that the implementation of chlorhexidine based decolonization drives an increase in the carriage of genes associated with reduced susceptibility to chlorhexidine, and this may be clinically relevant based on studies from London and Geneva. For example, a recent article from my research lab in London found that the implementation of universal chlorhexidine-based decolonization was associated with the selection of qacA linked with a higher chlorhexidine MIC in one dominant endemic MRSA clone (CC22), but not another (CC30). The slower reduction in the CC22 MRSA bloodstream infection rate suggests that carriage of qacA confers a selective advantage.

So, will the introduction of universal decolonization result in resistance to mupirocin and chlorhexidine? The answer for mupirocin is a resounding yes; the answer for chlorhexidine is currently not clear.

Other limitations: It’s always easy to snipe at a high-profile study, but there do seem to be some important limitations. First, nasal screens alone were performed in patients admitted to Groups 1 and 2. The sensitivity of nasal screens alone can be as low as 50%, so the inclusion of other screening sites are preferable to improve sensitivity. The implications of missing many carriers on admission in Groups 1 and 2 are obvious.

Second, although the trend was in the same direction, there was no significant reduction on MRSA bloodstream infections for patients in Group 3. In fact, the crude rate of MRSA bloodstream infection was rather high in all three groups (0.5 to 0.7 per 1000 patient days in all groups during the baseline and intervention periods). For reference, the rate of MRSA bloodstream infection at Guy’s and St. Thomas’ NHS Foundation Trust in London was lower than this at the peak of the MRSA problems in 2003, approximately 10 times lower by 2008 and has fallen further since then. So, why the relatively high rate of MRSA bloodstream infection across the board in this study?

Third, while randomization is the “gold standard” in terms of study design, by chance, three of four hospitals that performed bone marrow and solid organ transplantation ended up in Group 3, which skewed this population somewhat. The study was large enough to “smooth out” this skew, but small studies that attempt randomization should take note. In a recent study with Johns Hopkins, we only had 6 units to play with so decided not to randomize but instead roughly “matched” the units in the two arms, which may be a better approach in smaller studies.

Fourth, it does not seem that any attempt was made to ensure that patients in Groups 1 and 2 were bathed daily. While bathing with chlorhexidine impregnated cloths has been shown to be superior to bathing with soap and water, it is not possible to determine whether daily bathing or chlorhexidine were most important.

Finally, compliance will never be 100%. Only 81% of patients in Group 3 actually received chlorhexidine and 86% received mupriocin, and only approximately 90% of patients in Group 2 that were due decolonization received chlorhexidine and mupriocin. However, the authors did achieve a very high compliance (in the high 90s) with admission screening in Groups 1 and 2.

Summary: The authors should be complimented for performing such a detailed and useful study. Unfortunately, the protocol was not configured to assess the relative contribution of mupirocin and chlorhexidine to the reductions in infection. Given the likely emergence of mupirocin resistance, future studies should drop the universal use of mupirocin all together and see how far universal chlorhexidine alone can go; recent data suggest it will go a long way. Indeed, the UK has managed to make a dramatic, national reduction in the rate of MRSA bloodstream infection without implementing universal mupirocin.

I have grave concerns about the universal use of mupirocin for all ICU admissions and, perish the thought, for all hospital admissions. To decide on implementing universal mupriocin use with a plan to keep an eye on resistance rates seems remiss (to put it politely) since the likelihood of widespread resistance is so high. I am less concerned about the universal use of chlorhexidine, although reduced susceptibility needs to be monitored carefully.

The accompanying editorial was entitled ‘Screening inpatients for MRSA – the case is closed’. For me, the only closed case emerging from this study is that universal, indiscriminate use of mupriocin is a bad idea. Antibiotics have caused the problem; they are not the solution.

Article citation: Huang et al. Targeted versus universal decolonization to prevent ICU infection. New Engl J Med 2013 May 29. [Epub ahead of print].

Dissecting the CRE epidemic in Italy

Jon Otter (@jonotter) CRE , , , , ,

Italy flagCarbapenem-resistant Enterobacteriaceae (CRE) present unique challenges to infection prevention and control. Firstly, unlike MRSA and C. difficile, CRE can be caused by multiple genetic determinants (typically KPC, VIM, NDM and OXA-48 types) in multiple species. The combination of resistance determinants and species may have distinct characteristics with transmission and control implications. Further, there is a larger pool of resistance determinants for horizontal transfer. Secondly, CRE colonize the gastrointestinal tract, so deconlonization therapy is likely to be limited to suppressing the amount of CRE in the gut; elimination of the carrier state, which has been a mainstay of prevention and control interventions for MRSA, seems unlikely. Thirdly, pan-drug resistant CRE has already been reported and the pipeline for new agents is virtually empty, meaning that effective therapeutic options will be increasingly limited.

Data from EARS-Net suggests that the prevalence of CRE among bloodstream infections is low in most parts of Europe, with a gradual year-on-year increase. In Greece though, rates are exceptionally high, with the proportion of K. pneumoniae invasive isolates resistant to carbapenems increasing from 27.8% in 2005 to 68.2% in 2011. Also, rates in Cyprus are on the rise with 0% reported in 2006 up to to 15.7% in 2011. In the UK, rates of carbapenem resistance amongst K. pneumoniae have remained consistently <1% for the same period. Disturbingly, there has been a dramatic increase in the prevalence of carbapenem-resistant K. pneumoniae in the last few years in Italy, from 1% in 2009 to 15% in 2010 to 27% in 2011.

CRE Europe [Chart: Changes in proportion of carbapenem resistance in K. pneumoniae invasive isolates. Data from EARS-Net.]

A recent Eurosurveillance article reports a national survey of carbapenem resistance in Italy. 25 laboratories across the country participated and analyzed all consecutive, non-duplicate Enterobacteriaceae clinical isolates for six weeks in mid 2011. A total of 7,154 isolates were collected from inpatients and 6,595 isolates from outpatients. The highlight findings are:

  • 3.5% of inpatient isolates and 0.3% of outpatient isolates carbapenem resistant.
  • Carbapenem-resistant K. pneumoniae (CR-KP) the most problematic CRE, with 11.9% of K. pneumoniae isolates CR.
  • Substantial geographical variation in resistance rate, ranging from 0 to 33% for CR-KP.
  • KPC accounted for 90% of CRE enzymes; one CR-KPC clone predominated (CC-258).
  • Resistance to other agents was common amongst KPC-producing K. pneumoniae; 22% were resistant/non-susceptible to colistin, 21% to tigecycline and 16% to gentamicin; 1.5% were non-susceptible to all three.

This study raises several challenging questions. What do you do with a CR-KP isolate causing an infection that is also resistant to colistin, gentamicin and tigecycline? This seems to be true pan-resistance, with supportive care the only option.

Why is KP the outstanding CRE, specifically the CC-258 clone? What does it have that the other CRE lack? K. pneumoniae seems to survive better on surfaces that other Enterobacteriaceae, and has been associated with more hospital outbreaks than other Enterobacteriaceae historically. However, further research is required to answer this question.

Can the worrying trend of CRE in Italy be reversed? An aggressive, national intervention was successful in Israel, and there are some local success stories in Italy. However, brining the situation under control in Italy will require an aggressive, national programme that must be implemented immediately. Otherwise, CR-KP will quickly become endemic and probably impossible to bring under control.

The authors should be complimented for performing a timely study, but I do wonder whether the situation is considerably worse now, 12 months later, given the shape of the national epi curve.

Citation: Giani T, Pini B, Arena F, Conte V, Bracco S, Migliavacca R, the AMCLI-CRE Survey Participants, Pantosti A, Pagani L, Luzzaro F, Rossolini GM. Epidemic diffusion of KPC carbapenemase-producing Klebsiella pneumoniae in Italy: results of the first countrywide survey, 15 May to 30 June 2011. Euro Surveill 2013;18(22):pii=20489.

Image permission: Original image obtained from http://www.freestock.ca.

Three good reasons why not to “copperize” your hospital surfaces

Jon Otter (@jonotter) Antimicrobial surfaces , , ,

I recently received an email from the Copper Development Association entitled “Five Good Reasons to Install Antimicrobial Copper Touch Surfaces”. The five reasons are as follows:

  1. “Continuous and significant bioburden reduction, 24/7.
  2. Improved patient outcomes.
  3. A supplement to standard hygiene practices.
  4. Simple, cost-effective intervention.
  5. Payback in less than one year.”

I agree with all of these points in principle, and like the recently published copper study a lot, but I recently had two experiences that gave me three good reasons why not to “copperize” a hospital room.

Firstly, I was kindly given a copper pen at a conference. I’ve had it for a few months now and it’s beginning to look slightly the worse for wear (note the tarnishing where my grubby mits have been holding it, and the bright shiny part that has had less exposure to air underneath the swivel top). Is this how a bedrail would look after a few months of use?

copper pen annotated

Secondly, the pen works well but my hands smell of metal after using it. Would it be the same after touching my copper bedside table?

Thirdly, we had a new boiler installed last year resulting in a small pile of scrap copper pipes. I eventually got around to taking the copper pipes to the scrap metal merchant last weekend, expecting to get nothing for them and he gave me £50. So, exactly how much would it cost to “copperize” a hospital room, and would you really see ‘payback in less than one year’?

I appreciate that much of this may have to do with the composition of the copper alloy. I would imagine that reducing the amount of copper in the alloy would mean lower cost, less smell and less tarnishing. However, it would also reduce the ability to inactivate microbes deposited on the surfaces, so the research data really only applies to the composition of the copper alloy in the items that were tested. Also, there’s been some academic criticism of the copper study on the Controversies in Hospital Infection Prevention blog which is worth reading.

There are still a lot of questions around the implementation of copper surfaces in hospital rooms, and there are other options to consider. But I do think we should be thinking seriously about evaluating the clinical impact and cost-benefit of implementing antimicrobial surfaces.

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.

SHEA 2013 environment track – conference report

Jon Otter (@jonotter) Conferences ,

When I started doing research in this area a little over 10 years ago, the role of the environment in transmission was rarely mentioned at international conferences. So, to see an entire conference dedicated to discussing the role of the environment in transmission (SHEA 2013, in Atlanta) was a mouthwatering prospect.

SHEA Logo

I’d like to congratulate the organizing committee for putting together such an engaging and entertaining programme. At times, it was true ‘edutainment’.  The slides are available here for delegates.

Stephanie Dancer – plenary

The conference began with a plenary lecture by Dr Stephanie Dancer. Irrepressible as ever, Dr Dancer made a good case for improving hospital cleaning (yes, cleaning using detergent and water – not disinfectants). She highlighted some useful older literature, like this paper from 1963 demonstrating that the role of the environment was considered important once upon a time! She also mentioned a useful initiative that she has been involved with in Scotland, mapping visually where contamination occurs in hospital rooms (amongst other things). Dr Dancer finished by covering some of the newer frontiers in the research area, for example resistance plasmids knocking around in the environment, the role of contaminated air in transmission. I enjoyed Dr Dancer’s presentation very much, although contend that detergent and water cleaning is not always enough, now more so than ever as C. difficile and resistant Gram-negatives continue to cause problems around the globe.

Daniel Morgan – fomites

Next up, Dr Daniel Morgan discussed the role of fomites in transmission. I initially thought that this would overlap with the previous and subsequent presentations, but Dr Morgan stuck carefully to his title and considered the role of individual fomites in transmission. Blood pressure cuffs, stethoscopes (or should we say “staphoscope”!), mobile devices and ties (“neck ties” in American English!) were the subject of his reviews. He performed a literature review on each fomite, identifying a surprising amount of literature. I think that contamination of mobile devices is a large and increasing problem, and regular disinfection should be recommended. Dr Morgan also mentioned the interesting looking ‘hospital microbiome’ study in Chicago. Finally, look out for women’s purses (handbags in English English!) as a potential fomite site!

Tara Palmore – water

Waterborne infections were Dr Palmore’s subject. She began by challenging audience perceptions by claiming that all hospitals have had a waterborne infection in the past 12 months. Dr Palmore described an outbreak of Legionnaires’ disease associated with a fountain in a radiology department. Speaking to staff from another hospital after the talk who have had the exact same problem recently makes me wonder how widespread this problem is! The recent problems with Pseudomonas in ICUs in the UK illustrates the potential ramifications of a contaminated water supply. However, we shouldn’t expect sterile water coming out of the taps. If you need sterile water for a patient, use sterile water!

Rekha Murthy – air

Dr Murthy was considering the role of air in the transmission of nosocomial pathogens. She began with a useful classification scheme for pathogens (inspired by this paper) as “obligate”, “preferential” or “opportunistic” in terms of airborne transmission. We know a lot about “obligate” and “preferential” airborne pathogens like TB and ‘flu. It’s the likely “opportunistic” airborne pathogens that are most interesting to me, such as norovirus, MRSA and C. difficile. Sampling indicates that you can find these pathogens in the air, but is contaminated air a vector, and intermediary between the patient and the surface or an innocent bystander?

Curtis Donskey – impact of environmental interventions

Dr Donskey evaluated the evidence that improving environmental disinfection reduces HAIs. He began by drawing a clever parallel between antimicrobial stewardship and environmental hygiene interventions: you can choose to switch product, educate or automate. Dr Donskey demonstrated ample evidence that switching product, educating and automating environmental disinfection has evidence of reducing HAIs. However, he also discussed the potential problem of publication bias, challenging that we don’t like publishing negative findings due to the perception that we’re “admitting defeat”. Publication bias is a real problem in the scientific literature (see, for example, this study showing publication bias in studies of publication bias!). Another potential problem is that, C. difficile aside, almost all studies include the acquisition of colonization rather than the development of infection due to powering issues. This has implications for the cost-benefit of interventions since infections are where most of the cost of MDROs is accrued.

John Boyce – how to culture the environment

Dr Boyce presented everything that you need to know about culturing the environment. He performed a comprehensive literature review and outlined the options: swabs, sponges, enrichment, contact plates, media and other options. My own preferred method is a swab (which can do regular or irregular objects) that is plated direct (to give a quantitative measure of contamination) and then incubated in broth (to give a qualitative but more sensitive measure). With so much heterogeneity in sampling methods, comparison between studies is almost impossible. More standardization in this area would be useful.

Silvia Munoz-Price – measuring cleaning performance

Dr Munoz-Price considered the options for measuring hospital cleaning, presenting her experience with several UV fluorescent markers and ATP bioluminescence. The experience of Dr Munoz-Price is fascinating, finding that the use of environmental cultures along with fluorescent markers was required to drive compliance with cleaning protocols in their ICU. Markers alone lacked credibility (in the eyes of some ICU staff) and cultures alone were not feasible. Also, Dr Munoz-Price’s experience indicates that one fluorescent marking system was better than another since one was more visible under normal light.

David Weber – new technology

Dr Weber covered recent work on some new disinfectant formulations and “no-touch” automated room disinfection (NTD) systems. He presented some impressive data on improved hydrogen peroxide liquid disinfectants, some of which has been published recently by his group. Then, onto NTD systems. Dr Weber began with some useful criteria for adopting NTD systems: firstly they must be demonstrably safe, secondly they must reduce bioburden, thirdly they must reduce infections and finally they must be cost-beneficial. Dr Weber considered the evidence for the four principle NTD options currently available: hydrogen peroxide vapour (HPV) or hydrogen peroxide aerosol, UVC and pulsed-xenon UV (PX-UV). There’s evidence of safety and bioburden reduction for all systems, and evidence of reduced infections (and/or colonization) for HPV. No cost-effectiveness studies published as yet. So, which NTD system to choose? All systems have their pros and cons, so it will depend on your objectives outlined in this recent review, cited by Dr Weber.

James Steinberg and Craig Zimring – the built environment

Engineering solutions to make the hospital environment more amenable to cleaning and disinfection are an attractive option. With a little planning and thought, new hospitals can be built with infection prevention and control in mind at no (or minimal) additional cost. Also, altering the built environment in existing facilities can yield infection prevention and control benefits. Unfortunately, I missed this lecture, but I suspect the content was similar to their recent review article in the ICHE special edition.

Hilary Humphreys – antimicrobial surfaces

Prof Humphreys gave an accessible overview of the various options to implement antimicrobial surfaces in hospitals. There are various options to consider: metals (principally copper and silver), chemicals or physical changes to surfaces to reduce microbial deposition and/or make them more cleanable. Prof Humphreys mentioned a European testing standard for antimicrobial surfaces that is currently in development and will supersede some (rather wacky) standards that are currently out there. Another problem is that many of the studies supporting the use of antimicrobial surfaces are in engineering journals that seem to speak a different language to the medical literature. Prof Humphreys’ talk helped in interpreting these studies, but more are required in the medical literature. The recently published copper study provides some compelling reasons to prioritize antimicrobial surfaces for further evaluation.

Bill Rutala – disinfectants and microfiber

Dr Rutala presented a convincing case that we should use disinfectants routinely, not just detergents. The main arguments for using disinfectants over detergents for ‘non-critical’ surfaces is that they are more effective at reducing contamination and may have persistent activity, and detergents can become contaminated and spread microbes. It seems that microfiber cloths are better than cotton cloths at removing microbes, but they do harbor them for longer if not disinfected appropriately. So, the evidence for the use of microfiber is somewhat equivocal.

Susan Huang – chlorhexidine bathing

Dr Huang presented three compelling randomized controlled studies evaluating chlorhexidine (CHX) bathing published recently in Lancet, New England Journal of Medicine and one of hers this is not yet published (but doubtless destined for a high-impact journal). The studies seem clear: the introduction of CHX daily patient bathing results in less acquisition, less hand contamination and less environmental contamination. I left the lecture thinking why would you not do this? The potential for reduced susceptibility to CHX is probably the only thing that will stop daily patient bathing using CHX rapidly becoming the standard of care.

Thorny issue #1 – best paths to improve the thoroughness of cleaning (Anne Matlow, Mark Rupp, Larry Nation)

Dr Matlow presented some useful social science exploring the motivations and barriers to compliance with cleaning protocols. Educational deficiencies were identified, for example, almost 40% of housekeepers didn’t think the environment harbored germs that can cause disease. Motivations were explored and it seems that achievement and recognition are more important than pay and advancement.

Dr Rupp presented on the successes and challenges of using audit and feedback to improve compliance with cleaning protocols. Dramatic gains are possible, but it is difficult to sustain the gain. Dr Rupp identified some “positive outliers” during the course of this research. Some would term this group “positive deviants”, but Dr Rupp rightly points out the connotations of this phase are all wrong! There is a potential that these “positive outliers” (if judged by fluorescent markers) are the ones who have clocked the location of the marks and simply spot clean them. Exploring this group in detail will help to confirm that they really are the effective cleaners, and, if so, learn what sets them apart.

Larry Nation is a practicing environmental services director, so was able to provide a complimentary view. His team have moved from visual assessment of cleaning efficacy to a combination of fluorescent marking, ATP and visual assessment to measure the cleaning process and its impact.

All presenters agreed that audit and feedback are essential in setting a path toward improving the thoroughness of cleaning, so Thorny Issue #1 was not all that spiky!

Thorny issue #2 – resistance to disinfectants – Wilcox v Harbarth

Dr Wilcox presented the pro case. Biocide use is gargantuan compared with antibiotic use. However, there is a lot of fear and not much data surrounding biocide resistance. Serial passage of microbes to sub-lethal doses of biocides can induce tolerance, and triclosan is most susceptible to resistance. An area with much equivocal data is the possibility of resistance or reduced susceptibly to skin antiseptics such as CHX. The widespread and most likely increasing use of CHX means that reduced susceptibility would be problematic to say the least. Dr Wilcox presented some compelling data (including some from Dr Harbarth!) that reduced susceptibility to CHX is a problem.

Dr Harbarth presented the con case, although conceded that resistance to skin antiseptics could be a major problem in the future. Dr Harbath argued that antiseptics are a major part of the solution to controlling resistant micro-organisms, not driving the development of the problem! There is very limited evidence of the interaction between antibiotic and biocide resistance and evidence of small reductions in susceptibility that are well below the in-use concentration are not relevant.

On balance, an entertaining debate, and both speakers agree that reduced susceptibility to skin antiseptics is the most likely risk. There is some evidence that small reductions in CHX susceptibility may be relevant even when well below in-use concentrations, and that this may have implications for antibiotic cross-resistance (buried deep in Table 4 of Vali et al. 2008 – look what happened to EMRSA-16 after 48 hours sub-lethal exposure to CHX).

Thorny issue #3 – sporicides for C. difficile – McDonald v Dubberke

Dr McDonald took the pro position, and presented the evidence underpinning the CDC recommendation to use an EPA-registered sporicide for disinfection of rooms potentially contaminated with C. difficile spores. Whilst removal of spores (rather than chemical inactivation) is an important part of the disinfection process, the use of sporicidal disinfectants prevents the dispersal of spores around the room on contaminated cloths. Overall, the evidence for the use of a sporicide to control the spread of C. difficile is overwhelming.

Dr Dubberke presented a rather unenviable con position, given the volume of data supporting the use of a sporicide. However, he did put together a coherent case, highlighting the academic limitations of studies supporting the use of a sporicide, reiterating the risk of publication bias and that practice is more important than product.

Both authors agree that introducing a sporicide will not solve your C. difficile problems; you need to consider all aspects of transmission for that (antimicrobial stewardship, patient susceptibility factors and others). However, the con case presented by Dr Dubberke was not persuasive enough to convince me to abandon the use of a sporicide to help control C. difficile.

Thorny issue #4 – hands v environment – Edmond v Anderson

This debate has been run at several recent conferences so I was concerned that it would be a little “old hat”. How wrong I was.

Dr Boyce (who was chairing) polled the audience at the start of the debate, finding that around 90% thought that hand hygiene is more important than environmental disinfection in preventing HAIs.

Dr Edmond began with the pro. He began by a “thought experiment”, showing that a cluster RCT to compare the impact of the two interventions is not feasible. Dr Edmond acknowledged that there is more and better evidence for environmental interventions than for hand hygiene, but argued that hand hygiene makes a larger contribution to prevention and control. He evaluated the prior room occupancy studies and concluded that the increased risk from the prior occupant only accounts for a small minority of all transmissions.

Dr Anderson’s presentation for the con was outstanding; full of thoughtful, well-constructed arguments. He began with some quotes including the classic “I got 99 problems but the [bleach] ain’t one”; I suspect it was lost on a fair proportion of the audience, but a highlight of the conference for me! Dr Anderson’s argument focused on the fact that there is more and higher quality evidence for environmental interventions than for increased hand hygiene, having scoured the lengthy hand hygiene guidance documents to find a small handful of high-quality studies. In contrast, there are now a number of high-quality studies demonstrating the impact of environmental interventions.

The post-debate vote indicated a swing towards the importance of environmental disinfection, but still the majority concluding that hand hygiene is most important. There can be little doubt that hand hygiene prior to patient contact is the single most important intervention to prevent the spread of hospital pathogens, but it seems that the contribution of the contaminated environment is considerably greater than we thought.

Some points for discussion currently on my mind, mainly prompted by meeting:

  • Should we have a standardized set of environmental sites to sample and a standardized way to sample them to make studies more comparable? (A suggestion by Prof Hilary Humphreys.) I like this idea very much. The only problem is that it may result in widespread “targeting” of these sites only by housekeepers!
  • “The ward is very big; your swab is very small” (Dr Dancer). Are we sampling a large enough surface area? The CDC sponge method will help with this.
  • Can the introduction of single rooms in multi-occupancy bays contain pathogens more effectively (prompted by this image from Dr Weber)?
  • What is the contribution of contaminated air in “opportunistic” airborne pathogens (such as norovirus, MRSA and C. difficile)?
  • How much of a problem is publication bias? Do we really all have negative environment studies that we have not got around to publishing as suggested by Dr Donskey?
  • When are NTD systems warranted, and which NTD system is suitable for the intended application?
  • Should CHX ‘source control’ be implemented universally across the hospital?
  • Are antimicrobial surfaces going to be useful in preventing transmission, and, if so, which is the most effective?

An environmental odyssey

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

Research from the Cleveland VA published in the ICHE special edition tells a fascinating story of sequential interventions to reduce environmental contamination with C. difficile. The research includes pretty much the whole battery of environmental interventions at our disposal: education of housekeepers, the introduction of a specially trained “A” team, ATP bioluminescence, fluorescent markers and UVC for “no-touch” disinfection. About the only thing missing is copper surfaces!

Before we get to the interventions, let’s just reflect on the fact that somewhere between 60-70% of rooms were contaminated with C. difficile after terminal disinfection in the baseline period. It’s little wonder that admission to a room previously occupied by a patient with C. difficile increased the chances of developing C. difficile infection! Related to this, there’s some interesting thoughts at the beginning of the discussion about whether there could be a “safe” level of C. difficile contamination. I discussed this in a previous blog post here.

The introduction of fluorescent marking with feedback did not eliminate the C. difficile environmental contamination, with 50-60% of cultures remaining contaminated. Similarly, the introduction of a UVC “no-touch” room disinfection system for terminal disinfection did not solve the problem, with 30-40% of cultures remaining contaminated. Only when daily disinfection was performed by a dedicated team and terminal disinfection was performed by EVS supervisors and/or the infection control team was the problem finally solved and C. difficile could no longer be cultured from surfaces. It’s disappointing that the intervention that worked in eliminating C. difficile room contamination comprised improvements in both daily and terminal cleaning, so it’s not possible to determine which was most important. It seems likely that a combination of the two did the trick.

environmental-odyssey2

Figure: sequential interventions to tackle environmental contamination with C. difficile.

The study used robust microbiology methods to sample the environment, comprising swabs plated directly onto selective agar, and gauze pads from the same surfaces cultured through broth enrichment. The % positive sites from the enriched gauzes was approximately double the swabs inoculated directly onto agar, demonstrating the value of broth enrichment for environmental sampling.

Another important study finding was that the effectiveness of room cleaning prior to UVC room disinfection was sub-optimal, indicating that the housekeepers were placing too much faith in the automated system, which is designed only to disinfect and not to clean.

So what does this odyssey mean? Firstly that a combination of interventions can be useful, and secondly, the extraordinary lengths required to eliminate C. difficile spores from the environment.

Article citation:

Sitzlar B, Deshpande A, Fertelli D, Kundrapu S, Sethi AK, Donskey CJ. An Environmental Disinfection Odyssey: Evaluation of Sequential Interventions to Improve Disinfection of Clostridium difficile Isolation Rooms. Infect Control Hosp Epidemiol 2013;34:459-465.