MERS-CoV: a survival guide for you and your patients

This time last week, we were on red alert that a MERS-CoV pandemic was gathering pace. The news over the last few days has been more encouraging, with no new cases reported in Saudi Arabia, the epicenter of the MERS-CoV cases. However, there are still plenty of patients with MERS-CoV who need to be cared for around the world. Like SARS-CoV, but unlike the “usual suspects” that cause HCAI such as MRSA and C. difficile, MERS-CoV has the capacity to affect both healthcare workers and patients. Thus, I hope that this ‘survival guide’ will prove useful to those on the front line.

I presented a webinar on ‘MERS-CoV: coming to a hospital near you? Infection prevention and control challenges’. You can download the slides here. I came across a fantastic blog whilst preparing the webinar: ‘Virology Down Under’ by Dr Ian Mackay. I’ve used some of his excellent images in the slides, with his kind permission.

There are two transmission routes to consider for MERS-CoV: droplet / aerosol and contact / fomite. CDC recommends both airborne and contact isolation procedures to reflect these transmission routes. This involves placement of the patient in a negative pressure airborne infection isolation room, and the use of gloves, gowns, eye protection and N95 (FFP3) mask, and, of course, hand hygiene. PHE recommends a similar approach.

First and foremost, as a respiratory virus, inhalation of infected droplets is likely to be the most important transmission route. However, whilst not an ‘airborne’ virus (such as measles), aerosols can be generated by MERS-CoV patients that comprise small droplet nuclei that travel for long distances. A recent study of influenza suggests that the generation of aerosols is surprisingly common, to the extent that ‘living and breathing is an aerosol generating procedure’. Indeed, a recent study showed that a MERS-CoV aerosol diminished by only 7% over 10 minutes (compared with 95% for influenza). The use of an N95 (FFP3) mask will prevent direct inhalation of droplets / aerosols, and gloves, gowns and eye protection will prevent contact with mucous membranes and contamination of clothing or hands for subsequent nasal inoculation. But, if MERS-CoV aerosol is generated in the patient’s room (which seems likely), how long will it last and will the subsequent admission to the next room be at risk?

Let’s assume a patient sheds a MERS-CoV infectious aerosol of 6-log. I’m not aware of any infectious dose data for MERS-CoV yet, but for SARS-CoV it can be as low as <20 plaque forming units. Given the decay rate of 7% over 10 minutes, infectious aerosol above the infectious dose could be present after the discharge of the patient for a little under 26 hours! Even if the virus was shed at a lower titre, infectious aerosol times would still be considerable (Table). Could this be a job for automated room disinfection systems, which address both surface and airborne contamination? One such system, hydrogen peroxide vapour, has recently been shown to inactivate the SARS-CoV surrogate, TGEV.

Shed titre Time to reach 20 virus particles
1000000 26 hours
100000 20 hours
10000 15 hours
1000 9 hours
100 4 hours

Table: Relationship between shed titre of MERS-CoV and time to reach 20 virus particles.

Whilst respiratory viruses are not that great at surviving on surfaces compared with C. difficile spores and some vegetative bacteria, they can survive long enough to bring contact / fomite transmission into play. A number of reviews have concluded that contact / fomite transmission is an important route for influenza and other respiratory viruses such as rhinovirus. The SARS-CoV and surrogates exhibit unusual survival properties compared with other respiratory viruses, with survival times often measured in days, weeks or even months. Recent data suggests that MERS-CoV shares this property, surviving for >2 days when dried onto hard surfaces compared with only a few hours for influenza tested in the same study. Fortunately, these enveloped viruses are inactivated rapidly by usual hospital disinfectants, so I can understand the CDC’s recommendation for standard environmental disinfection.

So, how to protect yourself and your patients? The answer is simple for direct patient care: wear your gown, gloves, goggles and N95 (FFP3) mask, and wash your hands! It’s simple in theory, compliance with these measures in practice is not as good as you may expect. Prof Seto published a study in the Lancet in 2003 about compliance with personal protective equipment (PPE) and hand hygiene during the SARS epidemic. Remarkably, even when caring for patients known to be infected with SARS, <30% of healthcare workers self-reported that they wore a mask, glove, gown and washed their hands as they should have done. And this was self-reported, so you’d expect there to be a bias towards compliance! Most importantly, none of the healthcare workers who complied with all four measures became infected.

Seto Lancet SARS PPE

Figure: Healthcare worker compliance with mask, glove, gown use, and hand washing during the SARS epidemic, stratified by those who became infected with SARS.

To summarise: how to protect you and your patients from MERS-CoV:

  • Place patient in negative pressure airborne infection isolation room, where available.
  • Wear the correct PPE when in the room (gloves, gown, N95 / FFP3 mask, goggles), and wash your hands.
  • Pay attention to the potential for contaminated surfaces and air, particularly following the discharge of the patient.
  • Oh, and if you go on holiday to Saudi Arabia, don’t kiss any camels!

Perspective from ECCMID 2014 Part II: What to do about MDR-GNR?

 gram neg

I was hoping that the ECCMID 2014 session on ‘Outbreaks of MDR Gram-negative bacteria: what works and what does not work?’ would bring some answers from large, controlled studies to improve the evidence base for MDR-GNR control. I’m sorry to report that most of what was presented only served to highlight the limitations of the evidence base! There’s a bit of a Catch 22 here: in most settings, the problem lies in outbreaks, but the answers lie in large, adequately controlled cluster randomized studies in endemic settings.

  • Dr Weterings from NL provided a rather bleak start to the session, reporting an outbreak of carbapenem-resistant K. pneumoniae in a hospital and nursing home. Environmental cultures regularly grew the outbreak strain (including a shared glucose meter) and the control measures that were effective in the hospital were more challenging to implement in the nuring home.
  • Dr Gonzalez-Galan found a bundle of interventions dramatically effective to reduce the rate of endemic MDR A. baumannii. The bundle comprised surveillance, hand hygiene audit, and a checklist for environmental cleaning and contact precautions compliance. But which element of the bundle worked, and were any elements redundant?
  • Dr Cohen reported an MDR A. baumannii outbreak in Israel affecting 70% of ventilated patients at its peak, which forced colistin as the empiric VAP therapy. Proper disinfection of the ventilators brought the problem under control. Similarly, an endoscoy-associated ESBL K. pneumoniae outbreak in Norway (reminescient of the NDM outbreak in Chigago) was controlled by implementing proper endoscope disinfection.
  • Probably the most useful presentation of the session was from Dr Cataldo preseting a systematic review of interventions for MDR-GNR. Most studies (78% of the 86 included) were in outbreak settings, and plagued by low quality. Nonetheless, bundles were 2x more effective than single interventions (45% vs. 28%). The study struggled to determine convincingly which element of the bundles was most effective, but hand hygiene, contact precations and education came through as the pillars of effective bundles.
  • Dr Dettenkofer showed that an educational intervention improved compliance with standard precautions (especially hand hygiene and to a lesser extent the inappropriate use of examination gloves for some procedures). However, ‘standard precations’ are far from standard, and it seems that you need to go further than standard precautions to control MDR-GNR.
  • Dr Hussein showed that standing over healthcare workers and telling them to wash their hands improved compliance (unsurprisingly!). I venture that hospitals would only take this measure in extreme circumstances, although hand hygiene “enforcers” are not without precedent.
  • Dr Perencevich reported that the Hawthrone effect tends to strike after 15 mins of observation, so hand hygiene observations should be kept short and sweet. (Incidentally, hand hygiene compliance was higher among doctors than nurses in this study; I think it’s the first time I’ve ever seen it this way around!)
  • Dr Hansen presented data from the PROHIBIT collaborative, who found that alcohol based hand rub usage tracks the prevalence of antimicrobial resistance across Europe. However, the rate of red and yellow cards in the Euro 2008 football championships also correlates with antimicrobial resistance rates across Europe, and national consumption of chocolate correlates with the national rate of Nobel laureates: collelation doesn’t necessarily mean causation!
  • Finally, Dr Langelar reported that the Dutch national healthcare inspectorate visits were effective in raising standards. But was this papering the cracks or effecting culture change?
  • I am sure there were lots of good posters on this topic too, but I didn’t get very far with those. Perhaps somebody else did and would like to provide some additional information?

Dr Evelina Tacconnelli gave a thoughtful talk comparing the various international guidelines for MDR-GNR, reflecting on the recently published ESCMID version. The subject is broad, specifically in terms of which MDR-GNR, and in which setting. Guidelines for CRE in a general hospital population would look quite different to guidelines for CRAB in the ICU. Dr Tacconnelli focused on the areas of controvosy: isolation for ESBL carriers, how to prioritise limited side rooms (see useful ‘Lewisham’ isolation prioritization tool in Appendix 6 of these Irish guildelines), selective digestive decontamination, and the need for bundles. Finally, Dr Tacconnelli referenced a neat model for the effectiveness of various infection control interventions for controlling the spread CRKP. This is a clever study, and probably useful, but much like Berta (showing my age), incorrect inputs result in meaningless (or worse, misleading) outputs.

Dr Anna-Pelagia Magiarakos discussed some of the challenges of implementing guidelines, reminiscent of Dr Evonne Curren’s recent talk on a similar subject. One important point is to have some guidelines to implement! Countries lacking guidelines for the control of MDR-GNR tend to have higher rates (ECDC and PROHIBIT data). Once you have some guidelines, barriers to implementation need to be overcome: time, culture, resources, lack of understanding or belief that they will work, competence, habit, routines and “ivory tower” guidelines written by those detacted from the coal-face, to name but a few!

So are we any closer to knowing what works to control MDR-GNR following ECCMID 2014? Bundles are more effective than single interventions, but we still don’t know which elements of the bundle are most important, and this will vary by pathogen and setting. We need more studies like the commendable but complex MOSAR Lancet ID study.

You can view some other ‘Perspectives from ECCMID’ here.

Image credit: Iqbal Osman.

IFIC 2013 Conference Report

ific argentina logo

The 13th International Federation of Infection Control (IFIC) meeting took place in Buenos Aires, Argentina in October 2013. A colleague who attended sent me some notes from the meeting, which I was not able to attend. I found the notes useful, so thought I’d share them (albeit a little late)!

Pro-Con debates

The first was on government regulations in infection control. The Pro delivered by H Baguio from Uruguay and Con by M Borg from Malta. H Baguio gave examples where government regulations have had impact on infection rates, citing the case of MRSA in the UK and reductions in bacteraemia, UTI and KPC prevalence after governmental regulation and auditing introduced in Uruguay. M Borg gave examples were governmental interventions did not improve the situation:  for example, a 5x increase in the cost of medical waste disposal due to an insistence on considering it hazardous, when much could be considered non-hazardous. Also, there is a suggestion that since CLABSIs became non-refundable by the US government, many hospitals have started using peripheral lines over central lines to avoid financial loss. Another possible consequence is a less active attempt to detect infections in US hospitals, and a reticence to admit high-risk patients to avoid infection. However, in general the debate was not really pro-con as both admitted that some sort of government regulation is needed but they were not the only solution. This was reflected in the final results: 50% pro and 50% con.

The second debate was about universal vs. targeted MRSA screening. T. Boswell was arguing for universal screening, while E Lingaas of Norway was for targeted. There were good arguments from both sides but the vote suggested a swing towards targeted screening. I think the debate would have been more interesting if it as about universal screening for all pathogens of interests such as the emerging MDR Gram-negative bacteria. Whether you choose universal or targeted screening will depend on your country and healthcare setting. In countries with high carriage prevalence, universal screening will be more beneficial, especially when using quick and cheap diagnostic tests. For countries with low prevalence, targeting screening probably makes more sense. However, choose your targeted screening approach carefully: I performed a study recently where we found that reverting to our targeted screening approach would miss around 50% of carriers!

Selected talks

Stella Maimone (Buenos Aires, Argentina): “Infection control: the other side of the moon”

Stella was the first registered infection control nurse in Argentina. Most IC nurses in Argentina have been trained by her. She gave a general talk on IC in Latin America (LA) based mainly on the differences between Latin America and developed countries in IC. She noted that most LA countries ministries of health have some sort of infection surveillance systems including in Argentina. However, the data are not publicly available (at least in Argentina) which is a major difference between LA vs. USA and Europe.

Although LA countries are aware of the cost of HAIs, they have limited resources and it is not possible to reproduce the same IC policies that are implemented in US and UK (e.g. CDC guidelines) in LA. The reasons for that are: limited resources, different culture, LA people don’t like to be controlled (i.e. governmental regulations will have limited effect), and LA people think short term hence IC policies aimed at results in the distant future will not be adopted.

Hence for effective IC policies in LA, the limited resources of the countries/hospitals, the wider culture of society, and the ‘micro culture’ of the healthcare community must be taken into consideration.

Maria Clara Padoveze (University of Sao Paulo, Brazil): “Help! An outbreak!”

This was an interactive session with Q & A throughout. The informative talk covered outbreak definition and detection, but did not address outbreak control and infection control interventions in detail, which was a shame. Maria highlighted a useful website for performing quick literature reviews on various outbreaks from round the world: This gives you an up-to-date (ish) report of outbreaks from around the world. If you register (free) you can access advance search where you can search per country for example.

Celeste Lucero (Argentina): “MDROs: a new world war”

This helpful overview began with an overview of how organisms acquire multidrug resistance. Celeste mentioned the WHONET-Argentina, which is a WHO Collaborating Centre for Surveillance of Antimicrobial Resistance in the country. Celeste offered a few examples including the CTXM-2, which is endemic in Argentina, and the emergence of CTXM-15 and OXA-163. She also mentioned that many Acinetobacter baumannii are now only treatable by Tigicycline and Colistin, and that rates of KPC have been increasing since 2010. To compound matters, Argentina had its first reported NDM-1 in 2013. I left the talk without a clear picture of prevalence of MDROs in Argentia, which may reflect the paucity of accurate epi data.

Martin Kiernan (UK): “Taking infection prevention to the next level”

Martin gave a talk on the UK experience in IC, citing examples of the impressive reductions achieved in the UK for MRSA and C. difficile, and the various interventions to achieve these reductions. He mentioned that the problem now is MDR Gram-negatives such as E. coli and Klebsiella pneumoniae. His talk focused on how to change the IC culture in a hospital, including getting everyone engaged.

Syed Sattar (University of Ottawa, Canada): “The role of high-touch environmental surfaces in the spread of HAI: strategies to minimize the risks”

The talk began by outlining the factors that determine the risk of transmission from an environmental surfaces: probability of contamination; ability of pathogen to survive on the surface; transmission potential (e.g. porous surfaces are poor at transmitting pathogens, hence focus more on hard surfaces); location and frequency of direct contact with the surface (e.g. via hands or mucous membranes). He then went to define which pathogens to focus on. He warned not to focus on the high profile pathogens or the “pathogen of the month” such as HIV or H1N1 as these are less resistant in the environment and easily killed by disinfectants. Pathogens to focus on are: C. difficile spores; norovirus and other non-enveloped viruses such as rotavirus; MRSA; Acinetobacter; VRE.

The remainder of the talk was around liquid disinfectants and wiping. He specifically highlighted the problem with disinfectants/wipes, which are effective at spreading contamination if they don’t actually kill pathogens. He outlined the results of one of his studies, where they tested a number of disinfectants with wiping action and found that all except one did not kill all pathogens and also did spread them to other surfaces.

Some key papers mentioned in the conference:

1-   Zimlichman E, et al. Health Care-Associated Infections: A Meta-analysis of Costs and Financial Impact on the US Health Care System. JAMA Intern Med. 2013. Previously reviewed on the blog here.

2-   Limb M. Variations in collecting data on central line infections make comparison of hospitals impossible, say researchers. BMJ. 2012 Sep 21;345:e6377.

3-   Sattar SA, Maillard JY. The crucial role of wiping in decontamination of high-touch environmental surfaces: review of current status and directions for the future. Am J Infect Control. 2013 May;41(5 Suppl):S97-104.