Author: Jon Otter (@jonotter)

This is what happens when norovirus “sprays” from a toddler

Jon Otter (@jonotter) Contamination, Norovirus , ,

baby changeAn outbreak report in the Journal of Infectious Diseases tells the fascinating story of a norovirus outbreak in a car (auto*) dealership in Oregon that was initially thought to be foodborne, but was eventually traced to contaminated surfaces on a baby changing table (diaper changing station*) in a public toilet (restroom*). The outbreak had a startlingly high attack rate, affecting 75% of 16 employees who attended a team meeting. A thorough investigation of the restaurant that provided the sandwiches for lunch turned out to be a blind alley following the recollection of a staff member of a toddler with “spraying” diarrhoea using the baby changing table in the public toilet of the dealership. The (generous) mother left the mess for the staff member to clean up, which was accomplished using, wait for it, dry paper towels.

The environmental investigation included samples from the baby changing table in the dealership and some ‘control’ samples from 14 baby changing tables in public toilets throughout the state. Norovirus of the same genotype as the outbreak strain was identified from the baby changing table in the car dealership, but norovirus was not identified from the control baby changing tables.

Some limitations of the outbreak include the fact that it is difficult to disentangle the relative importance of the environmental reservoir and secondary transmission via contaminated food. The PCR method used for environmental sampling does not assure that the norovirus RNA identified on the baby changing table was viable. Also, the environmental norovirus isolates could not be sequenced meaning that they could not be sequence-matched with the patient isolates.

Perhaps the most shocking part of the story is that the image of visible soiling on the baby changing table (after two rounds of cleaning) was consistently viewed on baby changing tables in public toilets. Or perhaps it’s even more shocking that only 3 of the 12 affected individuals actually took time off work. As a “survivor” of a norovirus outbreak that swept through the Otter household in 2012, I can vouch for the fact that a) you need to take time off work and b) you ought to take time off work!

One important discussion point was the finding of Dr Carling’s group that baby changing tables were least likely to be cleaned on cruise ships, a setting in which persistent norovirus outbreaks are common. This outbreak report and Dr Carling’s earlier work highlight an important deficiency in how to clean and disinfect baby changing tables in public toilets. As a frequent user over the past 14 months, I can vouch for the fact that, much like a hospital bed, turnover is high which pressurizes effective terminal disinfection! I agree with the authors that disinfection with a chlorine-containing disinfectant would be ideal, but question whether this is feasible in practice.

There’s surprisingly little data supporting the role of environmental contamination in the transmission of norovirus. I’m persuaded by the various outbreaks affecting separate cohorts of patients / staff on cruise ships or aeroplanes, but this outbreak is even more compelling due to the environmental findings. Quantifying the role of the environment in the transmission of norovirus is difficult to study because it always occurs in outbreaks (hence difficult to perform a controlled study). But I’d be interested to see whether the “prior room occupancy” concept that has been established for other environmentally-associated pathogens holds true for norovirus.

Article citation: Repp KK, Hostetler TP, Keene WE. A norovirus outbreak related to contaminated surfaces. J Infect Dis 2013;208:295-298.

Also, take a look at Dr Repp’s blog.

* = for my American readers! Current data indicates that around 40% of the readers of this blog are US based, 40% are UK based and 20% are rest of world!

ICPIC 2013 Conference Report

Jon Otter (@jonotter) Conferences ,

icpic2013_banner

My head is full and my wallet is light following an enjoyable week in Geneva for the 2nd ICPIC conference (25th – 28th June 2013). I missed out on the inaugural ICPIC in 2011, so I was pleased to make the 2nd ICPIC. I was a little concerned that it would be a “hand hygiene fest”, but the programme had a good balance between hand hygiene and other areas of infection prevention and control. The conference had more than 900 delegates from 89 nations with 97 oral presentations and 427 posters. Congratulations to the organizing committee for arranging an interesting and stimulating conference. The conference abstracts are freely available in an ARIC supplement and the slides can be purchased by contacting the conference organizers.

Sadly I was unable to clone myself and attend every session, but this will give you a flavour…

TUES 25TH JUNE – OPENING SESSION

The opening session focused on viruses with pandemic potential, with an impressive introduction from some Genève luminaries and a personal video from Dr Margaret Chan (WHO Director General).

David Heymann – The legacy of SARS

Dr Heyman presented an engaging first-hand overview of the early reports of SARS, illustrating that it was predominately a healthcare-associated infection. The legacy of SARS according to David Heymann:

  1. Improved global surveillance, for example, the advent of new surveillance methods and networks such as Google outbreak software.
  2. “Research ready” capacity. The emergence of new microbial threats promotes the requirement for a research network ready and waiting to swing into action, such as the Oxford University Institute for Emerging Infections.
  3. Economic impact. SARS cost Hong Kong 4% of GDP.
  4. Understanding animal reservoirs. HIV, SARS, Avian Influenza, MERS-CoV (?) and most other pathogens with pandemic potential have emerged from animal reservoirs.

Wing Hong Seto – Infection control before and after SARS

Dr Seto’s thesis was that the spread of SARS in hospitals was due to poor basic infection control practice, evidenced by his own institution’s low rate of staff infection stemming from his enthusiastic education and awareness campaign. Put another way, sloppy infection control cost healthcare professional’s their lives. Dr Chan stated earlier that “the thermometer won the war against SARS”, which resonated with Dr Seto’s “getting the basics right” message. The experience of SARS has resulted in an increase in focus on infection control in Asia region, resulting in more investment, higher infection control staff : bed ratios and centralized expert committees. However, there has been some overreaction too, with very expensive structural changes to hospitals without proper consultation. Dr Seto’s  enthusiasm truly lit up the stage.

Laurent Kaiser – influenza, coronavirus and emerging viruses: can we predict the unexpected?

A detailed overview of the genetic basis of these pandemic viruses that are associated with respiratory disease, aerosol / droplet spread, seasonal patterns, an RNA genome and rapidly emerging strains. The most interesting part of the talk for me was a consideration of how long it takes to “humanize” an animal virus. Whilst it’s difficult to be sure, it seems that it takes decades (or perhaps even centauries) for the necessary amount of recombination and mutation to occur for a virus to jump to humans and spread efficiently. For example, the H1N1 virus seems to be a mosaic of three viruses that may trace its origins to the 1918 pandemic. In this age of almost instant phylogeny, it may not be long before we can start watching viruses evolve in real time.

Keiji Fukuda – Latest news from MERS-CoV and H7N9

Dr Fukuda (WHO) gave a brief historical view of HIV, SARS, H5N1 and H1N1 to illustrate how a pandemic response looks in relation to the two current threats: H7N9 and MERS-CoV. A relatively small number of N7N9 (132) and MERS-CoV (70) cases have been reported so far, but their high mortality rates are alarming. Interesting unanswered questions:

  1. Are we at a suitable level of readiness to respond?
  2. How should we name pandemic viruses?
  3. How do we handle intellectual property that emerges during pandemic response?

Robert Wachter – Embedding infection prevention into medical training and the patient safety agenda

Dr Wachter explained that the patient safety movement began with infection control, but is now predominant in the US. Infection control should seek to embed itself within the core values of patient safety: quality and value. Dr Wachter explained some seminal moments in the development of the patient safety movement: the realization that medical errors were killing the equivalent of a jumbo jet of Americans each day and that zero is possible. Perhaps it would be helpful to see non-compliance with hand hygiene as a medical error?

WEDS 26th JUNE

Hyde Park corner debate: decrease of MRSA in the UK successful infection control or natural decrease? Stone v Wylie

Unusually, I found myself in disagreement with both the pro and con position presented in this debate!

Dr Stone laid out the case for the pro, largely based on this study. The main conclusions from the study were that MRSA bacteraemia and C. difficile rates fell in association with increased use of alcohol based hand products and soap, respectively, but MSSA bacteraemia rates did not fall; and that the Department of Health Implementation Teams and the Healthcare Act were associated with MRSA bacteraemia. It’s odd that rates of MSSA bacteraemia did not fall in conjunction with the increased use of alcohol based hand products. Also, I wonder whether a “breakpoints” type model would have been more suitable for this dataset?

Dr Wylie tried to convince us that the national reduction in MRSA was due to natural variation. He used the wax and wane of an unusual MRSA clone in the 1970s in Denmark as evidence that clones come and go. However, this was controlled by a focused national intervention, which rather defeated Dr Wylie’s argument. He offered three alternative plausible explanations:

  1. Incompletely understood interventions. [Not an alternative explanation per se, just saying that the decline was associated with the interventions, just not in the way that Dr Stone said.]
  2. Changes in host immunity.
  3. Changes in antibiotic use.

The one alternative explanation that Dr Wylie mentioned only in passing was increased use of chlorhexidine. This seems to be a much more plausible alternative explanation, so I’m not sure why this was not explored in more detail. It would also go some way to explain the relatively rapid decline in EMRSA-16 vs. EMRSA-15.

It just seems totally implausible that a national campaign to control MRSA would happen to correspond with a natural decline in MRSA. There will always be some uncertainty in interpreting epidemiological trends. Bradford-Hills famous criteria are oft cited, but worth noting that Bradford-Hill once said “my criteria cannot provide indisputable evidence – they help us to make up our minds”.

The impact of the US Veterans Affairs initiative: too nice to be true? Samore v Bonten

Dr Samore presented a robust case that the interventions throughout the VA network in the US explained the reductions in this NEJM study by Jain et al. He included a fair overview of the study limitations (principally no control group!). Interesting to note that the admission prevalence of MRSA was around 15% in the Jain study, compared with just 2% in London. Whilst there are important differences in the patient groups admitted to VA hospitals in the USA and a London teaching hospital, the magnitude of the difference is striking and may explain in part the large reductions in transmission achieved.

Dr Bonten took the opportunity to play devil’s advocate for several recent high-profile MRSA papers. I would have preferred a more detailed critique of the Jain et al. study, which was, after all, the subject of the debate! Dr Bonten’s group have published a reanalysis of the Jain data challenging their findings. Dr Bonten concluded, rather depressingly, that we still don’t have any proven interventions to control MRSA, apart from universal mupirocin and chlorhexidine, or “selective digestive decontamination”. Neither strategy get my vote due to the obvious risk of the development of resistance; we need to work harder to evaluate the most effective ways to target our precious remaining antibiotics in order to preserve their activity.

Antoine Andremont – The gut microbioma: mother of all troubles?

This fascinating lecture outlined the challenges associated with resistant bacteria in the gut. The gut houses a phenomonial number of bacteria (up to 1014 cfu per mL), predominantly non-pathogenic anaerobes (1010), other commensals (106-109) and resident enterobacteria (106). To qualify these numbers, the population of Paris is around 106 (number of enterobacteria) whereas the number of humans that have lived on earth for the past 3 million years is 1010 (number of non-pathogenic enterobacteria).

Antibiotic resistant enterobacteria can be found in the gut, comprising somewhere between 0 to 100% of all enterobacteria, which varies over time with diet and antibiotic usage. The presence of resistant enterbacteria is likely to result in widespread shedding into the environment based on VRE data.

The carriage of resistant bacteria in the gut is probably impossible to eliminate, but could be addressed by the following:

  1. Reduce the use of antibiotics.
  2. Increase hygiene and sanitation.
  3. Decolonization (although attempts to decolonize using antibiotics and probiotics have failed thus far).
  4. Moderate counts of resistant bacteria in the gut. There are several approaches here, for example the co-administration of a recombinant enzyme to inactivate antibiotics in the gut or the use of an “antibiotic sponge”.

George Daikos – The how’s and where’s of colistin resistance

Dr Daikos explained how polymyxins have been ‘reinvented’ to tackle multidrug-resistant Gram-negative rods, citing data from this Medscape report:

Colistin interest

The antibiotic works through electrostatic interaction with the cell membrane predominately via lipopolysaccharides which facilitates the update of colistin and subsequent cell death. Resistance can be intrinsic, adaptive or acquired, and heteroresistance has been reported. Heteroresistance could be greatly underreported: a recent SENTRY study found that 23% of multidrug resistant Acinetobacter were heteroresistant to colistin.

Colistin resistance is emerging fast in certain areas; 23% of K. pneumoniae are now resistant to colistin in Greece. The fact is, we still have a lot to learn about how to use colistin most effectively, it’s mode of action, resistance mechanisms and how to detect reduced susceptibility in the clinical lab.

Matthew Samore – C. difficile in the community: community-onset or silent reservoir?

Dr Samore began with some entertaining analogies to illustrate the various ways to understand the interchange between hospital and community C. difficile: Gwyneth Paltrow in Contaigon, an Iceberg, a Straw Man and a Bathtub! Several studies identify apparently rising rates of CDI in the community yet carriage by healthy community members remains rare (2-3%). Combined with the finding that C. difficile colonization increases with length of stay make me think that CDI remains a predominantly hospital problem with some community-onset cases. Indeed, the recent JAMA Intern Med study of apparent CA-CDI only evaluated healthcare-exposure for three months prior to the CDI episode, and most patients had some healthcare exposure. I was surprised that Dr Samore did not mention high rates of carriage in neonates, which seems to be a genuine community-based reservoir doubtless resulting in a background of community acquisition of C. difficile.

There’s perhaps a parallel with MRSA here. For a long time, people talked about “community-acquired” MRSA, when it was really MRSA transmitted in the hospital manifesting in the community. However, there did come a phase shift in the epidemiology of MRSA with the emergence of distinct CA-MRSA strains that began to transmit outside of hospitals. So, we shouldn’t rule out CA-CDI as a possibility, but I don’t think we’re there yet.

Walter Zingg – C. difficile control in the hospital

Dr Zingg considered the various factors in the transmission of C. difficile: contamination of patients’ skin, hands, air and surfaces; proximity to other patients and colonization pressure. The control interventions highlighted were isolation, hand washing, single use thermometers, environmental disinfection using a sporicide (including adjunctive hydrogen peroxide vapour where feasible) and antibiotic restriction. I was surprised not to hear of the role of molecular diagnostics in C. difficile control. The switch to more accurate molecular diagnostics has facilitated improved identification of infected patients, and hence more successful isolation.

Innovation Academy

Or should I say, the ‘Infection Control Dragon’s Den’. Just like the TV show, 15 innovations were granted a 3 minute pitch followed by two minutes of quick-fire questioning from the expert panel and audience. Prof Pittet ensured that each presenter stuck to their 3 minutes, which was entertaining in itself. Five finalists were selected for an extended pitch the following day and a winner selected by the expert panel. A classic quote from Einstein set us off: “If at first the idea is not absurd, it is not good”! I’ve listed the finalists below along with some details of all 15 pitches:

  1. The winner: ‘A novel immediate pre-operative decolonization strategy reduces surgical site infections.’ Pre-operative decolonization using photodisinfection combined with chlorhexidine bathing. High compliance, well tolerated and saved money. My only problem is that it was difficult to delineate the relative impact of photodisinfection (novel innovation) from chlorhexidine (already well established). Nonetheless, a worthy winner!
  2. Second place: ‘A novel antiviral technology for air filtration.’ An external antiviral layer for masks. The agent is only effective against enveloped viruses and the need was not well defined. Is this to prevent penetration of infected viruses through the mask or to reduce the risk of hand contamination when removing the mask?
  3. Third place: ‘A novel antibacterial material for transparent dressings.’ A small trial (n=10) of a polyurethane dressing with antimicrobial properties.
  4. Fourth place: ‘Can Dav132, a medical device targeting an adsorbent to the late ileum, decrease significantly the impact of antibiotics on the fecal microbiota?’ A medical device to “mop-up” antibiotics in the gut with huge potential to suppress resistant gut flora.
  5. Fifth place: ‘Infection Control Enclosure (ICE) pod: meeting the need for more single rooms’. [COI – I am listed as a co-author on this one!] A way to increase single room capacity in a multi-occupany bay setting.

The other pitches:

  • ‘Reduction of resistance by sublingual administration of antimicrobials.’ A gutsy musical presentation of an old paper from the 1970s. The only problem was, not a shred of data to support the innovation!
  • ‘A new generation of hybrid biomaterials for antimicrobial medical devices.’ Impregnated silicon for medical devices to reduce bacterial adhesion.
  • ‘Electronic hand hygiene monitoring for the WHO 5-moments method.’ An automated way to monitor hand hygiene compliance by placing a chip in each dispenser to measure usage in real-time and compare with expected usage patterns generated by an algorithm.
  • ‘Evaluation of the efficacy of a novel hydrogen peroxide cleaner disinfectant concentrate.’ ‘Accelerated’ hydrogen peroxide is an impressive product, but it’s been around for a long time so has no place in the innovation academy!
  • ‘A new genre of surface disinfectant with long residual bactericidal activity.’ A polymer antimicrobial surface film that can be impregnated with various antimicrobials (I think – wasn’t particularly clear on this point)!
  • ‘Development of an electronic dashboard to assist surveillance’. The e-dashboard ticks some important boxes for me, not least because it’s free! However, how does it compare with proprietary systems in terms of functionality?
  • ‘Combining electronic contacts data and virological data for studying the transmission of infections at hospital.’ Tagging patients and staff with RFID badges to track movements and then trace proximity (though not contact per se). Useful Harry Potter “Marauders’ Map” style technology.
  • ‘New holistic approach to determine the infection risk profile of a hospital; visualized in an easy-to-read plot’. A way to produce a visual, fairly intuitive ward-level report to easily identify areas for improvement. A useful tool, but lacks the novelty of other contenders.
  • ‘Organisational transformation – the application of novel change techniques & social media understanding to motivate infection-prevention activists.’ A pitch from the Infection Prevention Society using collaboration focused on social media to effect organizational change following a “pre-mortem” self-assessment.

I particularly enjoyed the Innovation Academy. The Dav132 antibiotic gut “sponge” got my vote as the most important innovation.

THURS 27th JUNE

Meet the experts (Boyce and Dettenkofer): Controversial issues about environmental cleaning and disinfection

Dr Dettenkofer began with a framework for understanding hospital cleaning and disinfection needs. His position is that low-level disinfection is the main requirement. However, the presence of C. difficile spores means that a sporicide (i.e. high-level disinfectant) is necessary on occasion. So, is the requirement for hospital disinfection high or low level disinfection? Dr Dettenkofer talked briefly about the debate over whether surface disinfection is required at all in hospitals, when cleaning (without the use of a chemical disinfectant) is often sufficient. Interesting to hear that Dr Dettenkofer has begun to use a liquid hydrogen peroxide disinfectant in his hospital. Finally, the question of whether a two-step process (cleaning followed by disinfection) is necessary. It’s difficult enough to get good compliance with one round of cleaning or disinfection, let alone assuring adequate coverage of first a cleaning agent, then a disinfectant. Effective combination products are required urgently.

Dr Boyce discussed:

  • What is the ‘best’ surface disinfectant? He considered aldehydes, QACs, phenolics, chlorine releasing agents, hydrogen peroxide and peracetic acid. The conclusion: all have pros and cons!
  • So, how to assess cleaning performance? Visual assessment, microbiological cultures, ATP or fluorescent markers. These are not mutually exclusive and, again, all have pros and cons.
  • Finally, which “no-touch” room disinfection system to use? Hydrogen peroxide vapour, aerosolized hydrogen peroxide, UVC, pulsed-xenon UV and other systems are available. You guessed it, all have pros and cons!

Control of hyperendemic Carbapenem-resistant Enterobacteriacae

Abdul Ghafur – The Indian perspective

A passionate presentation by Dr Ghafur beginning with 50% attributable mortality in his neutropaenic patients due to CRE resulting from carbapenem and colistin abuse; mortality for pan resistant CRE approached 100%. Dr Ghafur discussed some of the underlying problems in India: poor sanitation, high rates of carriage of resistant bacteria (80% CR Acinetobacter and 40% CR Klebsiella), reflecting on the fact that tight local antimicrobial prescription will not save you if everyone else is sloppy. How to treat pan-drug resistant CRE? “Pentatherapy” using a 5 drug cocktail and a prayer. (Actually, there is probably some synergy between colistin and other antibiotics so pentatherapy isn’t as daft as it sounds.)

Yehuda Carmeli – An Israeli perspective

Israel experienced a dramatic initially clonal national outbreak of CRE (KPC CC258) in 2006. Analysis of data from the outbreak indicated that compliance with cohorting correlated tightly with CRE transmission; more data that getting the basics right works. The risk-based screening that was implemented detected a low prevalence of carriage (5% from long-term care facilities, 0.5% from other high risk groups) but was considered worthwhile to prevent outbreaks. Dr Carmelli raised several points for discussion:

  • Media interest. It seems to me that the media can be a friend or foe in dealing with outbreaks and wider healthcare issues. If left unbriefed, they will be a foe. But if properly briefed, they can be a powerful ally.
  • Emergence of different CRE genes (OXA-48 and NDM-1) in Israel with different epidemiological associations than KPC.
  • Dealing with the long-term care facility reservoir.
  • Non-compliance with basic infection control.
  • “Eye off the ball” syndrome, where hospital administrators only respond to current threats.

The national successful response in Israel is an encouraging success story. However, Israel has a population of 8 million, with only 31 hospitals. Can successful national control strategies be implemented in larger countries with an inferior healthcare infrastructure and national debt problems such as Greece and Italy?

Achilles Gikas – The Greek perspective on CRE: from surveillance to control

Dr Gikas described the development of the CRE epidemic in Greece with overlapping outbreaks of VIM and KPC carriers, and how CRE is now a “frequent flyer” travelling around the world. Reassuringly, there are some local success stories in Greece where focused interventions have reduced rates of CRE, but, mindful of Dr Kulakkattil’s comment that “no hospital is an island”, concerted national efforts are required to grasp this rampaging Hellenic bull by the horns.

Environmental decontamination with hydrogen peroxide vapor – does the effect evaporate over the Atlantic? Perl v Huttner

Having spent some 10 years researching this particular topic, needless to say I was looking forward to this debate. The debate was not particularly well framed. Was this about most of the studies of HPV (and all of the controlled studies with a clinical outcome) coming from US hospitals? Or that many European countries have a lower proportion of single rooms, which makes the application of HPV more challenging? Or a wider debate about whether to consider “no-touch” disinfection (NTD) systems at all? I felt that Dr Perl addressed the more general questions while Dr Huttner focused on HPV studies, which rather took the wind out of the sails of the debate.

Dr Perl summarized data that pathogens are shed into the environment, they survive for extended periods, persist despite conventional cleaning and disinfection and improving conventional methods helps, but transmission continues. Hence, NTD systems and specifically HPV are warranted in some circumstance. Dr Perl acknowledged the lack of RCTs but showed convincing data that HPV eliminates pathogens from surfaces and reduces transmission, and fulfils Bradford-Hill’s criteria of causation.

Dr Huttner began like Dr Perl by considering some things that evaporate over the Atlantic: big cars, big guns and flavoured coffee to name but a few! His American wife gives him an unusually sharp perspective on trans-Atlantic issues. Dr Huttner had clearly done his homework and read the various HPV studies in detail. He presented a series of good points, although I didn’t feel that he constructed a particularly coherent argument. To address some specific points:

The short debate (30 mins) did not allow time for the authors to present a rebuttal, which was a shame, but it was a stimulating session.

FRI 28th JUNE

Controlling ESBLs – a global perspective

Jean-Christophe Lucet – Europe

Dr Lucet began by demonstrating a startling increase in the proportion of invasive isolates that carry ESBLs in Europe comparing 2005 with 2011. He reviewed data that ESBL-producing K. pneumoniae is much more likely to be transmitted in hospitals than ESBL-producing E. coli, perhaps due to an increased capacity for environmental survival. Effective interventions are difficult to recommend due to lack of RCTs, outbreak settings (and regression to the mean), publication bias and control bundles. However, Dr Lucet concluded:

  • Hand hygiene: yes.
  • Active surveillance cultures and contact precautions: equivocal.
  • Cohorting: yes during outbreaks.
  • Environmental control: less important than for other pathogens.
  • Selective digestive decontamination (SDD) / universal use of chlorhexidine: equivocal. My view is that SDD should not be used – the indiscriminate use of antibiotics will drive further resistance.

Wing-Hong Seto – Far East / Asia

Carriage rates of ESBLs in E. coli and K. pneumoniae are alarmingly high in parts of Asia, reaching >50% in India and Vietnam. Dr Seto suggested that single room isolation is more important for Gram-positive vs. Gram-negative bacterial pathogens based on relatively higher recovery of Gram-positive bacteria from the hospital environment. However, lactose non-fermenting Gram-negatives such as Acinetobacter seem to ‘mimic’ Gram-positive bacteria in terms of their environmental survival, and even the Enterobacteriaceae can survive for days to weeks to months on surfaces. So, I would argue that priority for single room isolation should be dictated by an assessment of local epidemiology and risk, not the survival properties of various bacteria.

Andrew Stewardson – Australia

Carriage rates of ESBL-producing bacteria are lower in Australia than in nearby Asian countries (<10% in the hospital population and <5% in the community). Dr Stewardson presented some interesting Australian data showing that rigorous implementation of standard precautions and antibiotic restriction programmes can result in impressive reductions of ESBL producing K. pneumoniae in hospitals.

Final reflections

My first ICPIC was an enjoyable experience. Highlights included the opening session learning lessons from SARS, the entertaining innovation academy and some grim updates on the ‘rampaging Hellenic bull’ that is CRE. Regretfully, I didn’t get to see a single poster and missed few concurrent sessions (including the review of best papers by Eli Perencevich and Andreas Widmer – they’ve published their slides here). Of all the analogies presented at the conference, I think the most useful was the ‘Infection Control Football Club’ by Dr Sheldon Stone. Hand hygiene is the goal keeper (i.e. last line of defence). But you won’t have a winning football team with just a goal keeper. No matter how good they are, they will never stop every shot.

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.