Month: September 2014

Universal vs. targeted interventions in infection prevention and control: the case for a targeted strategy

Jon Otter (@jonotter) Conferences , , , ,

Today, I participated in a debate with Professor Ian Gould on universal vs. targeted interventions for infection prevention and control at Infection Prevention 2014. I was arguing for a targeted approach, and you can download my slides here, and you can listen to a recording of the talks here.

Universal interventions are appealing: they make no discrimination between patients, there’s a clear message for staff, and you have no way of knowing reliably who is colonized anyway! However, for me to get behind a universal intervention, it would have to demonstrate short-term, long-term and cost-effectiveness.

Before getting into the details of my argument, it is worth defining what we mean by ‘universal’ or ‘targeted’ interventions (see Table 1, below). It’s important to note that an intervention can be targeted either to an individual (e.g. chlorhexidine given to decolonize the skin of a patient known to be colonized with MRSA) or targeted to a population (e.g. chlorhexidine given to all patients in high risk settings, such as the ICU). Screening is an interesting one. It’s easy to mistake screening as a universal strategy when it’s applied to all patients (as is common in the NHS), but it’s fundamentally a targeted strategy to identify patients for an intervention (such as isolation and / or decolonization). A truly universal strategy has no need of screening.

Table 1: defining universal and targeted interventions.universal vs. targeted definitions_cropped

Short-term effectiveness

Short-term effectiveness can be difficult to measure. What is the standard for demonstrating short-term effectiveness? Most common interventions lack accepted standards for demonstrating short-term effectiveness, and the results may well be different as setting and pathogen varies. However, there are some universal approaches that have effectively failed at the first hurdle and not demonstrated even short-term effectiveness. For example, ‘selective’ digestive decontamination has been applied to try to decolonize carriers of resistant Gram-negatives. Although this clearly has some impact, and reduces colonization, it seems to temporarily suppress the level of resistant bacteria in the gut flora, not decolonize the patient. Similarly, the use of universal gloves and gowns failed to meet the primary endpoint in a cluster randomized controlled study (the BUGG study).

Long-term effectiveness

A number of universal strategies that have demonstrated some level of short-term effectiveness fail in terms of long-term effectiveness due to the promotion of bacterial resistance (or reduced susceptibility). For example, selective digestive decontamination on a group of patients resulted in a sharp increase in gentamicin resistance, and perhaps more worryingly an increase in colistin resistance. Furthermore, a microbiomic analysis of a patient undergoing selective digestive decontamination identified a seven-fold increase in the abundance of aminoglycoside resistance genes in the ‘resistome’.

Another way in which universal strategies that are effective in the short-term may fail in the long-term is due to reliance on human beings to maintain compliance with protocols. This is relatively easy during studies, where staff have both support and scrutiny to drive performance. When the spotlight is off and they’re on their own, performance is less impressive. We can see this type of “reverse Hawthorne effect” in compliance with contact precautions, and in hand and environmental hygiene.

Cost effectiveness

Once a strategy has demonstrated both short-term and long-term effectiveness, it must demonstrate cost effectiveness before widespread adoption. Even if you disagree with me and consider screening to be a universal strategy for MRSA when applied to all patients at the time of admission, it has failed to demonstrate cost-effectiveness in almost all scenarios. Economic analysis using the standard threshold of £30,000 per Quality Adjusted Life Year (QALY) has shown that screening all admissions for MRSA is not effective for teaching or acute hospitals at current, high or low prevalence. Universal screening was only cost-effective for specialist hospitals (the vast minority), and then only at some levels of MRSA prevalence. For this reason, the Department of Health is going to reverse its recommendation for universal screening of all hospital admissions.

Summary

I can’t think of a single universal intervention that has demonstrated short-term, long-term and cost effectiveness (see Table 2). Decolonization using chlorhexidine comes close, but almost all studies of this intervention have been performed in an ICU setting, where this intervention is applied to a targeted population. I would be uncomfortable about using chlorhexidine for daily bathing of all hospital patients due to the risk of promoting reduced bacterial susceptibility.

Table 2: short-term, long-term and cost-effectiveness of universal interventions.universal vs targeted debate summary_cropped

Targeted interventions have been shown to be effective in reducing transmission, preserve the activity of our precious antimicrobial agents, require less modification of human behaviour, and are cheaper and less resource-intensive. So, on balance, I favour targeted interventions for infection prevention and control.

How to assess scientific posters: a practical guide

Jon Otter (@jonotter) Conferences , ,

Posters are a hugely important part of scientific congresses. The submitted abstracts that get accepted as oral presentations are always only a fraction of the science available at conferences. And which abstracts get selected as oral presentations are, to a degree, at the whim of the abstract assessment committee and procedures. So, there will be some gems amongst the posters that have the potential to change practice.

I gave a talk at IPS today: a practical guide to assessing scientific posters. You can download my slides here. But they will only tell part of the story. The idea was for the session to be a practical workshop to arm those who are new to infection prevention and control with the tools to maximize their conference experience in terms of accessing submitted science.

I covered the publication process: concept -> research -> abstract -> poster -> paper -> “post-publication peer review”. It was interesting to think in more detail about what makes a good poster. Clearly, first and foremost, a poster must be visual. If it doesn’t look good visually, then it’s not a good poster. That said, what looks “good” is somewhat subjective, but I think some basic themes emerge in terms of visual presentation:

  • Eye catching – draws the viewer in
  • Graphical, not text based
  • Not cluttered
  • Good use of colour
  • Clear ‘flow’ from one section to the next
  • Key findings communicated clearly
  • Contains more detailed information for those that want it
  • Correct size for the board (check the guidelines!)
  • Not an essay / epic; it’s designed to stimulate discussion
  • No intricate fonts that are difficult to read
  • Watch out for fuzzy low-res graphics
  • You can’t include all your data – be selective

And then there’s the scientific content. Really, this is the same question as what makes a good abstract or, indeed paper. The following criteria may be useful in this regard:

Table: what makes a good poster (or abstract, or paper) in terms of content?How to assess a poster_cropped

So, I hope the participants found this session useful.

Tending the human microbiome

Jon Otter (@jonotter) Antibiotic resistance , , ,

Atomic antibiotics

This isn’t hot off the press (a 2012 review article by Tosh & McDonald) but it’s probably more important now than when first published, given our rapid advances in understanding of the importance of the microbiome in human health over the last year or two.

A couple of clear principles emerge from the review:

  • A happy, healthy human microbiome is characterized by diversity (both in terms of number of different species, and diversity within the species), and composed mainly of bacteria that we’re not familiar with – Fermicutes and Bacteroidetes).
  • Antibiotics have a profound and sustained effect on the human microbiome (even those that are typically associated with no or few side effects). This results in a reduction in both diversity and change in composition, which is bad news for human health. In particular, this leave the gut more open to colonization with unwanted intruders aka antibiotic resistant bacteria.

The future of anti-infective therapy according to Tosh and McDonald is in:

(1)     Developing and using more microbiome-sparing antimicrobial therapy. The idea of ‘selective digestive decontamination’ flies in the face of this objective.

(2)     Developing techniques to maintain and restore indigenous microbiota. A lot of progress has been made here, for example, in the case of faecal microbiota transplantation (FMT) for the treatment of recurrent CDI.

(3)     Discovering and exploiting host protective mechanisms normally afforded by an intact microbiome.

Rather than obliterate our microbiome with overuse of antibiotic “Atomic bombs”, we need to carefully tend individual and collective microbiomes in order to make them resistant to the increasing queue of antibiotic resistant colonizers!

Article citation: Tosh PK, McDonald LC. Infection control in the multidrug-resistant era: tending the human microbiome. Clin Infect Dis 2012;54:707-713.

Image credit: Modified from ‘Mushroom cloud‘.

Not all resistant Gram-negative bacteria are created equal: Enterobacteriaceae vs. non-fermenters

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

apples and oranges

Apples and oranges. They’re both more or less spherical and classified as fruits, and that’s about whether the similarity ends. It’s the same for antibiotic-resistant Enterobacteriaceae (e.g. Klebsiella pneumoniae) and non-fermenters (e.g. Acinetobacter baumannii): they both share the same basic shape (more or less) and classification (Gram-negative), and that’s about where the similarity ends (see the Table below):

Table: Comparing the epidemiology of resistant Enterobacteriaceae and non-fermenters.3M webinar QA Not all created equal_table

I gave a webinar yesterday as part of a three part series on resistant Gram-negatives. You can download the slides here, and access the recording here (although you’ll have to register to do so). I am increasingly hearing people talking about ‘carbapenem-resistant organisms’ (CRO), used as a catch-all term to encompass both the Enterobacteriaceae and the non-fermenters. As you can see from the comparison table able, this doesn’t make a lot of sense given the key differences in their epidemiology. Indeed, MRSA is a CRO, so why don’t we lump that together with the Enterobacteriaceae and non-fermenters? Carbapenem-resistant Enterobacteriaceae and carbapenem-resistant non-fermenters are both emerging problems, but they are not the same problem.

I asked a few questions of the audience, which I’ve summarised below:

Figures: Questions asked of around 150 webinar participants, mainly from the USA.3M webinar QA Not all created equal Q13M webinar QA Not all created equal q23M webinar QA Not all created equal q3

I was not surprised that so few people felt comfortable explaining the difference between the Enterobacteriaceae and non-fermenters – and this rather justified the whole thrust of the webinar! I was a little surprised that the ‘prevalence’ of the two groups of resistant bacteria were so similar; I was expecting the Enterobacteriaceae to be more common (although I admit this wasn’t a brilliantly worded question). In terms of control interventions, it’s true that we still don’t really know what works to control resistant Gram-negative bacteria. But it does seem likely that the control interventions will be different for Enterobacteriaceae and non-fermenters, and this did come across in the responses. Hand hygiene was selected by most people (which makes sense), with screening & isolation, and stewardship more commonly selected for Enterobacteriaceae, and cleaning / disinfection for the non-fermenters.

Q&A

Following the webinar, the audience asked a few interesting questions:

  1. Can you get chlorhexidine resistant organisms? A number of studies have hinted that reduced susceptibility to chlorhexidine may be an emerging problem, (for example Batra, Otter, Lee and Suwantarat). But increases in bacterial MICs (for Gram-positive bacteria at least) appear to be a long way below the applied concentration. However, it’s worth noting that the measured CHG skin concentration in one study (15-312 mg/L before the daily bath and 78-1250 mg/L after the daily bath) was much lower than the applied CHG concentration (10,000 mg/L). This is around the CHG MIC for some Gram-negatives and potentially brings the subtly reduced susceptibility to CHG reported in MRSA into play. On balance though, the rationale and data on reduced susceptibility are cautionary but not enough to recommend against universal use in the ICU given the clinical upside.
  2. Do you think we should be doing universal chlorhexidine bathing? On our ICU in London, we have been using universal chlorhexidine decolonization for a decade combined with targeted screening and isolation, and have seen a dramatic reduction in the spread of MRSA. So yes, I think we should be doing universal chlorhexidine bathing, but the need to monitor carefully for the emergence of clinically-relevant reduced susceptibility.
  3. Can we discontinue contact precautions for CRE? The short answer is no. Quite a few studies have found that gut colonization with CRE typically lasts for at least 6 months to >1 year. And those that become spontaneously ‘decolonised’ sometimes revert to colonized, suggesting that they weren’t really decolonized at all – it’s just that their load of CRE at the time of sampling had fallen below the limit of detection. So I favour a “once positive, always positive” approach to CRE colonization.
  4. Which disinfectant would you recommend for resistant Gram–negatives? It does seem that the non-fermenters (and in particular A. baumannii) are “more environmental” than the Enterobacteriaceae. However, the Enterobacteriaceae (including CRE – especially K. pneumoniae) can survive on dry surfaces for extended periods. Therefore, I think enhanced disinfection – especially at the time of patient discharge – is prudent for both groups. Consider using bleach or hydrogen peroxide-based liquid disinfectants, and terminal disinfection may be a job for automated room disinfection systems, such as hydrogen peroxide vapour.
  5. Should we use objective tools to monitor cleaning? Effective tools are available to objectively monitor cleaning (e.g. ATP and fluorescent dyes), and these have been shown to improve surface hygiene. Therefore, we should all now be using these tools to performance manage our cleaning processes.

Image credit: ‘Apples and oranges’.

Acinetobacter contamination: is anywhere safe?

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

A study from New York City describes an environmental survey of contamination with antibiotic-resistant Gram-negative bacteria on surfaces in the community. The authors hypothesise that resistant Gram-negatives could be carried by staff, patients and visitors beyond the confines of the hospital.

Almost 500 environemntal samples were collected from surfaces in the public areas of six hospitals and surrounding communities (<1 mile from the hospital) (443 samples), with a further surfaces from communities >1.5 miles from any hospital as a control (50 samples). A total of 70 GNR were identified (Figure), mostly fairly inoccousous species from a human disease viewpoint. However, some potential human pathogens were identified (Table).

Figure: breakdown of Gram-negative rods identified from surfaces in public areas of the hospital and surrounding community.GNR contam

Table: potential human pathogens identified from surfaces in public areas of the hospital and surrounding community.

n % Species
15 3.0 Acinetobacter baumannii
3 0.6 Citrobacter freundii
2 0.4 Escherichia coli
2 0.4 Stenotrophomonas maltophilia
1 0.2 Enterobacter cloacae

Some other important findings:

  • All of the A. baumannii isolates were resistant to ceftazidime, and one was resistant to imipenem (i.e. carbapenem-resistant). Eleven of the 15 were clonally related to one another and to a patient isolate from one of the hospitals.
  • One of the S. maltophilia isolates carried an integron-encoded VIM carbapenemase, which is potentially transmissible to other Gram-negative species (including Enterobacteriaceae).  
  • Each sample was cultured in an enrichment broth, and the broth was probed for the presence of a range of beta-lactamase genes (including ESBLs and carbapenemases). No beta-lactamases were detected (other than the S. maltophilia isolate). I suspect the picture would have been rather difference in New Dehli!
  • Although the survey included both surfaces in public areas of hospitals and in the community, it seems that most of the A. baumannii were identified on surfaces in the community.

So, is it a surprise to see environmental contamination with antibiotic-resistant Gram-negatvies on touch-surfaces in the community? Not really, A. baumannii in particular can survive on surfaces for ages, and ‘mimics’ Gram-positive bacteria in terms of its environmental longevity (i.e. months / years). That said, I performed a similar study looking for MRSA on touch surfaces in the community in London, and didn’t find any. More importantly, do we need to do anything about this? As the authors state, A. baumannii can be virtually impossible to eliminate from hospital surfaces without resorting to hydrogen peroxide vapour. So is it time to roll hydrogen peroxide vapour into your local Pizza Hut? Clearly not. You’d hope that cleaning and disinfection protocols, which should deal with this sort of contamination, are already established in these public places, but it would be prudent to reinforce these basic hygienic practices. Also, I agree with the authors that these findings represent and opportunity for the promotion of hand hygiene in the community.

The authors use strong words to describe NYC as ‘plagued’ with resistant Gram-negative bacteria, and a ‘dismal failure to control A. baumannii.’ If this epidemic continues, we can expect to see the focus of the problem – and the target for our interventions – shift from the acute hospital setting to encompass the community.

Ebola: PPE and paranoia

Jon Otter (@jonotter) Ebola , , , ,

The contrast in the stringency of the CDC and UK Department of Health / Health and Safety Executive guidelines for infection prevention and control when dealing Ebola virus disease (EVD) patients is striking. This is particularly acute with regard to recommendations for Personal Protective Equipment (PPE) and terminal disinfection. Having recently reviewed both documents for a webinar on Ebola infection prevention and control (you can download the slides here, by the way), I thought I’d share the contrast:

Table: PPE and disinfection recommendations for dealing with patients with Ebola virus disease. Source: US CDC patient and environmental guidelines, and UK Department of Health. (Please note – this summary chart is designed to be illustrative rather than definitive.)Ebola ppe table

So is there any reason why the level of PPE and type of terminal disinfection required should be any different depending on which side of the Atlantic you happen to be? None whatsoever. So why the discrepancy? It’s difficult to say. This difference in recommendations has prompted the question of “To CDC or not to CDC” in terms of PPE for Ebola, and an opinion piece in Annals of Internal Medicine justifying the CDC approach. It is probably true that the level of PPE recommended by CDC is enough to block transmission, and that the risk of environmental contamination is low enough such that fumigation is not necessary. Probably. But is that good enough when Ebola is on the line? It is certainly true that you can be wearing all the PPE in the world but if you put in on incorrectly, don’t take care of it during use or remove it carelessly you will put yourself at risk.

When I came to decontaminate a room using hydrogen peroxide vapour following a case of Lassa fever in London some years ago, I wore all the PPE that I could lay my hands on (see below)!

Me illustrating the “belt and braces” (aka paranoid) approach to PPE (a la UK, not CDC recommendations).Lassa PPE me_annotated

Did this level of PPE match the risk of exposure to viable Ebola? Perhaps not, but it certainly made me feel a whole lot more secure about entering the room to do the job!