Year: 2014

ICHE special edition on CRE and MDROs

Jon Otter (@jonotter) Acinetobacter, Antibiotic resistance, CRE , , , , ,

CRE medium

Infection Control and Hospital Epidemiology have once again excelled themselves in putting together a fine special edition on CRE and MDROs. Around this time last year I posted an article on the ICHE special edition on the role of the environment, and this special edition is equally important. I strongly recommend that you read the special edition from cover to cover, but I’ve picked out a few of my personal highlights below:

  • A thoughtful editorial by Drs Lautenbach and Perencevich sets the scene. They reflect on our ‘woeful unpreparedness’ to address both current and future MDROs.
  • A number of articles provide updates on surveillance and prevalence. Brennan et al. report findings from a 6-month CRE point-prevalence survey based on voluntary reporting in the state of Michigan, finding a crude rate of 1.07 cases per 10,000 patient days. Interestingly, this rate was almost 3 cases per 10,000 patient days in long-term acute care facilities. Isolates were not collected and analyzed, so carbapenemase genes were not confirmed; the fact that close to 10% of isolates were susceptible to meropenem suggests that a good number of the CRE were not carbapenemase producers. Indeed, another state-level point-prevalence survey (Pfeiffer et al., from Oregon) found that only 3 of the 60 CRE isolates reported were carbapenemase producers. Another state-level survey of CRE (Johnson et al., from Michigan) identified regional clustering of CRE colonization of mechanically ventilated patients in the central region of the state.
  • Analysis through the SHEA Research Network found that contact isolation policies for multidrug-resistant Gram-negative rods (MDR-GNR) are surprisingly variable. Worryingly, almost 20% of facilities surveyed did not isolate patients infected or colonized with MDR Pseudomonas or Acinetobacter, and 6% do not isolate patients with CRE. Policies for de-escalation of contact precautions were equally variable. Contact isolation policies seem to be even more lax in long-term care facilities based on data from Pfeiffer et al., reporting that only half of patients colonized with MDROs are placed on contact precautions.
  • A number of studies evaluated risk factors for CRE. For example, Bhargava et al. identified high acute morbidity score, immunosuppression, presence of indwelling medical devices and prior antimicrobial exposures to be consistent risk factors for CRE in the various patient populations they evaluated.
  • A survey of the kitchen in a Swiss hospital identified ESBL-producing Enterobacteriaceae in 92% of raw chicken and 6% of rectal samples from food handlers.
  • The efficacy of chlorhexidine bathing for MDR-GNR has been questioned, so data from Lin et al. on this issue are particularly welcomed. In a study of 62 patients in a long-term acute care facility, daily chlorhexidine gluconate (CHG) bathing halved the chances of culturing CRE from the body sites analyzed. However, it’s worth noting that the measured CHG skin concentration (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 potentially brings the subtly reduced susceptibility to CHG reported in MRSA into play.
  • Several studies evaluated the potential for environmental contamination with MDR-GNR. Rosa et al. found that exposure to surfaces contaminated with MDR A. baumannii increased the risk of acquisition by almost 3-fold. Although the design of the study was fundamentally different, it is interesting to note that the increased risk from admission to a room previously occupied by a patient with MDR A. baumannii was also around 3-fold in a previous study. Havill et al. reported that the survival time for CRE (including K. pneumoniae) on dry surfaces is measured in weeks not days. Rock et al. carefully observed 220 unique interactions between healthcare workers (HCW) and patients with KPC or non-KPC producing K. pneumoniae, finding that HCW gloves or gowns became contaminated during 14% of the 220 interactions, and 26% of 43 environmental samples were positive. There was no significant difference between HCW or environmental contamination rates for KPC vs. non-KPC producing K. pneumoniae.
  • There was not much on therapy for CRE – perhaps because there is little to say for pan-drug resistant CRE! An article discussing the challenges of managing CRE infections by Drekonja et al. through surveying the CDC funded Emerging Infections Network highlighted the common problems due to toxicity from using “last-line” antimicrobials colistin and tigecycline.

It seems that the prevalence of CRE is patchy in the USA at present, and that long-term care, and long-term acute facilities are an integral part of the story. Given the limited evidence base, interventions need to cover all bases: active surveillance, rapid and accurate diagnostics, environmental (and perhaps food) hygiene, contact isolation and perhaps antiseptic decolonization, all combined with facility-wide education and communication initiatives. The most effective – and cost-effective – interventions to prevent and control the spread of CRE and other MDR-GNR are controversial so to this end I am looking forward to the SHEA ‘From MRSA to CRE: Controversies in MDROs’ and joint HIS / IPS ‘What’s that coming over the hill: rising to the challenge of resistant Gram-negative rods’ Spring meetings next month!

Photo credit: Enterobacter cloacae NDM-1 growing on Oxoid Brilliance CRE Agar by Nathan Reading.

A postcard from São Paulo, Brazil: thank goodness for the NHS

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

sao paulo traffic mediumI recently had the opportunity to spend a week in São Paulo, Brazil, to meet with some infection control and infectious diseases folks. I came away feeling pretty disturbed and very grateful for the NHS.

Brazil is a massive country, with almost 200m inhabitants. São Paulo is Brazil’s largest city, with more than 20m inhabitants making it the 7th largest city in the world. I have lived in London and close to New York, and spent quite some time in Tokyo but nothing comes close to the traffic in São Paulo. It took me 3 hours to travel the 30km from the airport to the hotel, not because it was the middle of the rush hour or because there was a problem, just because the volume of traffic is too big for the infrastructure to handle.

Brazil has around 7000 hospitals; 70% are private with a healthcare insurance system for those who can afford it. The public hospitals are the only option for those who cannot afford healthcare insurance. I visited a number of public and private hospitals and was struck by the following:

  • Rates of antibiotic resistance are eye-wateringly high. Around 40% of healthcare-associated Klebsiella pneuomoniae are carbapenem-resistant and of these, around 20% are colistin-resistant. More than 50% of K. pneumoniae produce ESBLs. The situation with Acinetobacter baumannii is even worse, with >80% resistant to carbapenems. Whilst there is usually some treatment option left, pan-drug resistant Gram-negative bacteria are a daily reality on the ICUs. To top it off, around 60% of S. aureus are MRSA, 80% of E. faecium are VRE and C. difficile is chronically under-reported due to lack of testing infrastructure and limited awareness about sending specimens. There’s an excellent 2011 review on antibiotic resistance in Brazil here, although a lot has happened since 2011.
  • The public hospitals are chronically overcrowded. This is best illustrated by a quick visit to the Emergency Department, where patients on stretchers line the corridors as far as the eye can see. These patients usually stay for days, not hours. The problem is so endemic that ICUs have been established in the ED. The wards are crowded too, with very small distances between beds. Plus, there are not enough staff to cover their beds, especially during nights and weekends. Following one meeting at a very large public hospital (2000 beds), we literally could not leave the building due to the sheer volume of patients trying to get in. Just like the roads, the volume of patients is too high for the infrastructure to handle.
  • The contrast between public and private hospitals is stark. Instead of being met by patients on stretchers when you arrive at public hospitals, you’re met by glass fronted healthcare insurance offices.

So, what can be done? The various strategies to curb the growing threat of antibiotic resistance are as relevant in Brazil as elsewhere: prevention is better than cure; reduce antibiotic use; improve accurate and timely diagnosis; perform surveillance for action; embrace novel solutions; highlight the financial burden; and develop new antibiotics. Some progress has been made, for example, antibiotics are no longer available without prescription over-the-counter. The commitment and enthusiasm of the infection control and infectious diseases folks that I have met here is inspiring. However, they are limited by poor healthcare infrastructure, virtually no investment in microbiology laboratory facilities, lack of national reporting, the widespread availability of poor-quality antibiotics and extensive use of antibiotics in the veterinary sector, which makes progress difficult.

Next time you have the misfortune of visiting an Accident & Emergency Department in an NHS hospital, rather than moan if you have to wait a few hours to access world-leading healthcare free at the point of care, instead be thankful for the NHS.

Photo credit: Fred Inklaar.

What can outbreaks of Salmonella from the 1950s tell us about CRE?

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

I recently came across a fascinating review article published in 1963 mainly about outbreaks of Salmonellosis during the 1950s. The review focuses on epidemics that were traced to contaminated surfaces, including ingested, contact and inhaled transmission routes. A number of interesting epidemics stand out:

  • An outbreak linked to contaminated neonatal respirators.
  • An outbreak linked to a contaminated chopping board (see Figure). In this outbreak, one of the investigators apparently contracted Salmonellosis after touching the chopping board during sampling and then having a cigarette before washing his hands.
  • An outbreak (of microbial endotoxin syndrome) linked to a contaminated mouthpiece of SCUBA equipment. Here, the outbreak occurred in naval diving academy and the pattern of lessons and cases was so regular, that the epidemiologist could predict precisely when to visit to see the next case.

chopping board 2

Figure: A chopping board at risk of persistent microbial contamination due to surface damage. 

Although most outbreaks covered in the review relate to ancient catering-related outbreaks of Salmonella, there may be some useful learning for hospital epidemiology today, specifically CRE. It’s rare although not unheard of to find Salmonella carrying a carbapeneamase (i.e. Salmonella CRE). However, Salmonella is a member of the Enterobacteriaceae, so the involvement of contaminated surfaces during outbreaks of Salmonella suggests that contaminated surfaces may also be important during outbreaks of CRE.

It’s interesting that even back in the 1960s contaminated surfaces were recognized as potentially important in epidemics, whereas by the 1980s, the role of contaminated surfaces in endemic transmission was considered negligible. It’s difficult to know whether experts of the 1960s (perhaps there are some reading this?) would have considered contaminated surfaces important in both epidemic and endemic transmission? I suspect so, and we just lost sight of that in the 1980s and 90s.

Article citation: Sanborn WR. The relation of surface contamination to the transmission of disease. Am J Public Health Nations Health 1963;53:1278-1283.

Image: Ben Hosking.

An overview of the options for antimicrobial surfaces in hospitals

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

surfaces

I’ve been asked to write a chapter providing an overview of options for antimicrobial surfaces in hospitals for a Springer book. As a result of the preliminary literature reviews for this chapter, I’ve summarized the various available options for antimicrobial surfaces in hospitals in this post.

A number of different interventions aimed at improving environmental hygiene have been evaluated. Switching from one disinfectant to a product with superior microbiological efficacy in particular has been shown to reduce transmission.1-6 However, one of the problems with available disinfectants is the lack of residual effect, meaning that recontamination occurs quickly.7,8 An attractive option is to somehow make surfaces antimicrobial to exert a continuous reduction in the level of contamination. A recent review by Prof Hilary Humphreys provides a useful overview of the various approaches to antimicrobial surfaces.9 There are several approaches to making a hospital surface ‘antimicrobial’:

  • Permanently ‘manufacture in’ an agent with antimicrobial activity (e.g. copper or a chemical).
  • Periodically apply an agent with antimicrobial activity (e.g. copper containing liquid agents, or chemical disinfectants with residual activity).
  • Physically alter the properties of a surfaces to make it less able to support microbial contamination or easier to clean (e.g. antibiofilm surfaces).

The table below provides an overview of the various options available to make a hospital surface antimicrobial.

Candidate Application Pros Cons
Metals
Copper Manufactured in / liquid disinfectant Rapidly microbicidal; large evidence-base; evidence of reduced acquisition. Sporicidal activity equivocal; cost, acceptability and durability may be questionable.
Silver Manufactured in / liquid disinfectant Broadly microbicidal. ? sporicidal; tolerance development; relies on leaching so surface loses efficacy over time.
Chemicals
Organosilane Liquid disinfectant Easy to apply. Limited microbicidal activity; questionable “real-world” efficacy.
Light-activated (e.g. titanium dioxide or photosensitisers) Manufactured in / liquid disinfectant Broadly microbicidal; can be activated by natural light. ? sporicidal; requires light source for photoactivation (some require UV light); may lose activity over time.
Quaternary ammonium compound based Liquid disinfectant Easy to apply. Limited microbicidal activity; largely untested real-world activity.
Triclosan Manufactured-in / liquid disinfectant Already adopted in some consumer markets. Resistance / tolerance development; relies on leaching so surface loses efficacy over time.
Polycationic e.g. polyhexamethylene biguanide, PHMB Liquid disinfectant Easy to apply. Limited microbicidal activity; questionable “real-world” efficacy.
Physical alteration of surface properties
“Liquid glass” (silicon dioxide) Liquid application Reduces deposition; improves ‘cleanability’. Not microbicidal; some evidence of reduced contamination; unknown required frequency of application.
Sharklet pattern Manufactured-in Reduces deposition; reduced. biofilms. Not microbicidal; not feasible to retrofit.
Advanced polymer coatings (e.g. polyethylene glycol PEG, superhydrophobic/philic, zwitterionic) Manufactured-in Reduces deposition; some can be ‘doped’ with copper or silver. Not microbicidal; may be expensive; scale up to large surfaces questionable; not feasible to retrofit.
Diamond-like carbon (DLC) films Manufactured-in Reduces deposition; can be ‘doped’ with copper or silver. Not microbicidal; likely to be expensive; feasibility of scale up to large surfaces questionable; not feasible to retrofit.

There are some other options not listed in the table, that could be considered candidates for antimicrobial surfaces, although they are currently at an early stage of development, including:

There is an impressive and rapidly emerging evidence-base for copper surfaces.13 The implementation of copper high-touch surfaces, which have a continuous biocidal action, results in a reduction in contamination and may reduce transmission.14-16 However, copper is expensive, difficult to retrofit and durability may be questionable.13,17 Thus, an effective disinfectant with a residual activity that does not compromise staff or patient safety or promote the development of reduced susceptibility is desirable. Several candidate disinfectants that have residual activity with a variety of active chemicals have emerged.18-22 These can be delivered through pre-existing cleaning and disinfection arrangements at little or no extra cost. However, there is very little published data on the microbiological or clinical impact of disinfectants with residual activity. A number of recent study suggest that promising in vitro activity may not translate into “real-world” impact: a recent study by Boyce et al. found that two organosilane products simply did not work as intended when applied to surfaces in a US hospital.22

During my research for this post, I came across a very useful presentation by Peter Hoffman from Public Health England, which can be downloaded here. Taking some of his ideas, plus a few of my own, the following points for discussion emerge:

  • Which is the optimal deployment mode – antimicrobial agents that are manufactured in or periodically applied, or ways to make the surface physically less able to support contamination or easier to clean?
  • If periodic application is selected, how frequently is a fresh application required (i.e. how durable is the antimicrobial coating)?
  • Which surfaces should be made antimicrobial? It’s probably not feasible to do them all, particular for antimicrobial options that need to be manufactured in.
  • Surfaces in hospitals are often dirty (obviously); it’s not clear how much the presence of organic matter would interfere with the activity of antimicrobial surfaces. Clearly, antimicrobial surfaces do not obviate the need for careful attention to hospital cleaning and disinfection. In fact, their continued effectiveness depends on it.
  • The deposition of contamination and potential acquisition of contamination through contact with surfaces often occurs in quick succession, so antimicrobial surfaces with a contact time measure in minutes (rather than seconds) may be too slow to be useful.
  • C. difficile spores represent a real challenge to antimicrobial surfaces. Copper seems to get closest to demonstrating inactivation, but even here data are somewhat equivocal.23 Could introducing an antimicrobial surface that is not effective against C. difficile “squeeze the balloon” and provide a selective advantage to C. difficile?
  • How effective will antimicrobial surfaces that rely on an active agent leaching from surfaces be in a dry environment?
  • How do we test – and compare efficacy – of antimicrobial surfaces? A standardized test has been proposed,24 but not yet adopted widely. Importantly, this methodology specifies an aerosol deposition of microbes whereas other proposed methodologies specify the deposition of microbes in a liquid suspension. Testing the ‘wet’ deposition of microbes may overestimate the antimicrobial potential of the surfaces, which would usually be challenged with dry deposition in the real world.
  • Much of the literature for antimicrobial surfaces is published in materials science journals, as illustrated in this useful review by Page et al.25 I, for one, find this pretty difficult to access; as a healthcare scientist, it’s a new and daunting language to learn.
  • The cost, and cost-effectiveness of implementing antimicrobial surfaces in the healthcare setting has not been rigorously assessed.

There’s a plethora of potential options and approaches to make a hospital surface ‘antimicrobial’. Copper is leading the way as a candidate, although other options are available. Making a surface less able to support contamination in the first place, and / or easier to clean is another tempting option, particularly if this can be combined with a level of antimicrobial activity. Finding and evaluating the optimal antimicrobial surface will require a multidisciplinary approach, requiring industrial partners, materials scientists, healthcare scientists and epidemiologists to refine and test the available options. More studies in the clinical setting, ultimately including those with a clinical outcome, are required.

Photo credit: Benjamin Hall.

References

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

2.       Donskey CJ. Does improving surface cleaning and disinfection reduce health care-associated infections? Am J Infect Control 2013; 41: S12-19.

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

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

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

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

7.       Hardy KJ, Gossain S, Henderson N et al. Rapid recontamination with MRSA of the environment of an intensive care unit after decontamination with hydrogen peroxide vapour. J Hosp Infect 2007; 66: 360-368.

8.       Otter JA, Cummins M, Ahmad F, van Tonder C, Drabu YJ. Assessing the biological efficacy and rate of recontamination following hydrogen peroxide vapour decontamination. J Hosp Infect 2007; 67: 182-188.

9.       Humphreys H. Self-disinfecting and Microbiocide-Impregnated Surfaces and Fabrics: What Potential in Interrupting the Spread of Healthcare-Associated Infection? Clin Infect Dis 2013;

10.     Shepherd SJ, Beggs CB, Smith CF, Kerr KG, Noakes CJ, Sleigh PA. Effect of negative air ions on the potential for bacterial contamination of plastic medical equipment. BMC Infect Dis 2010; 10: 92.

11.     Pangule RC, Brooks SJ, Dinu CZ et al. Antistaphylococcal nanocomposite films based on enzyme-nanotube conjugates. ACS Nano 2010; 4: 3993-4000.

12.     Markoishvili K, Tsitlanadze G, Katsarava R, Morris JG, Jr., Sulakvelidze A. A novel sustained-release matrix based on biodegradable poly(ester amide)s and impregnated with bacteriophages and an antibiotic shows promise in management of infected venous stasis ulcers and other poorly healing wounds. Int J Dermatol 2002; 41: 453-458.

13.     O’Gorman J, Humphreys H. Application of copper to prevent and control infection. Where are we now? J Hosp Infect 2012; 81: 217-223.

14.     Salgado CD, Sepkowitz KA, John JF et al. Copper surfaces reduce the rate of healthcare-acquired infections in the intensive care unit. Infect Control Hosp Epidemiol 2013; 34: 479-486.

15.     Schmidt MG, Attaway HH, Sharpe PA et al. Sustained reduction of microbial burden on common hospital surfaces through introduction of copper. J Clin Microbiol 2012; 50: 2217-2223.

16.     Rai S, Hirsch BE, Attaway HH et al. Evaluation of the antimicrobial properties of copper surfaces in an outpatient infectious disease practice. Infect Control Hosp Epidemiol 2012; 33: 200-201.

17.     Weber DJ, Rutala WA. Self-disinfecting surfaces. Infect Control Hosp Epidemiol 2012; 33: 10-13.

18.     Keward J. Disinfectants in health care: finding an alternative to chlorine dioxide. Br J Nurs 2013; 22: 926, 928-932.

19.     Hedin G, Rynback J, Lore B. Reduction of bacterial surface contamination in the hospital environment by application of a new product with persistent effect. J Hosp Infect 2010; 75: 112-115.

20.     Baxa D, Shetron-Rama L, Golembieski M et al. In vitro evaluation of a novel process for reducing bacterial contamination of environmental surfaces. Am J Infect Control 2011; 39: 483-487.

21.     Brady MJ, Lisay CM, Yurkovetskiy AV, Sawan SP. Persistent silver disinfectant for the environmental control of pathogenic bacteria. Am J Infect Control 2003; 31: 208-214.

22.     Boyce JM, Havill NL, Guercia KA, Schweon SJ, Moore BA. Evaluation of two organosilane products for sustained antimicrobial activity on high-touch surfaces in patient rooms. Am J Infect Control 2014;

23.     Wheeldon LJ, Worthington T, Lambert PA, Hilton AC, Lowden CJ, Elliott TS. Antimicrobial efficacy of copper surfaces against spores and vegetative cells of Clostridium difficile: the germination theory. J Antimicrob Chemother 2008; 62: 522-525.

24.     Ojeil M, Jermann C, Holah J, Denyer SP, Maillard JY. Evaluation of new in vitro efficacy test for antimicrobial surface activity reflecting UK hospital conditions. J Hosp Infect 2013; 85: 274-281.

25.     Page K, Wilson M, Parkin IP. Antimicrobial surfaces and their potential in reducing the role of the inanimate environment in the incidence of hospital-acquired infections J Mat Chem 2009; 19: 3819-3831.

 

What do we mean by ‘cleaning’ and ‘disinfection’?

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

clean definition 2

We urgently need to decide what we mean when we use the terms “clean” and “cleaning”.

In the last few years, the accumulated microbiological and epidemiological data (and prolonged heated debate) has lead us to conclude that  environmental surfaces need to be considered alongside hands, laundry etc so on, as part of a multibarrier approach to infection prevention and control in healthcare settings, and hygiene at home. Set against this however, our current approach of “what do we do to these surfaces to break the chain of infection transmission?” is both unscientific, and also highly misleading to the people we need to communicate with.  This part of the equation is fast becoming the weak link, preventing us from maximising health benefits from infection prevention and control measures.  This really hit home on reading the different contributions to the excellent 2013 AJIC supplement by Rutala and Webber which, on one hand showed just how much our thinking about environmental surface risks  has developed, but in many papers “environmental cleaning” was used interchangeably with “environmental disinfection” which made it confusing to know what the writer really meant.

From our IFH experience of home hygiene, we know what happens when advising consumers (or equally, hospital cleaning staff) to “clean” a surface e.g. after preparing raw poultry. They will clean until the visible dirt is gone – and we know that this is not necessarily enough.  For the home, we have data showing that after cleaning kitchen surfaces with soap and water following preparation of a chicken (in the UK 60% are contaminated with Campylobacter),  surfaces may LOOK squeaky clean, but the Salmonella or Campylobacter is now spread everywhere (and in numbers up to 103 or more).   We have similar data for surfaces contaminated with norovirus-containing faecal matter from an infected person (for which the infectious dose may be very small).

As a start, we need a term to advise/communicate “this surface needs to be cleaned to a level that breaks the chain of infection” and we currently have NO way to do this.   If we accept that the term “clean” means absence of visible dirt/soil, we need a term to describe “microbiologically safe clean”, not just for consumers or hospital cleaning professionals, but also for communicating with each other as scientists.

There is also another common misconception. Some people work on the basis that “clean” means visibly clean, and “microbiologically safe clean” means a chemical or thermal disinfectant has been used.  But then how can we communicate that hand washing can make hand surfaces microbiologically safe” without need for a disinfectant.  There is a notion that “cleaning” is hygienically inferior to disinfection – but data now shows that the log reduction by handwashing with soap can be equivalent to that achieved by alcohol handrubs if done properly, and you have access to running water.  We put much effort into hand hygiene compliance, but relatively little into stressing that handwashing technique to deliver hands which are “fit for purpose” is equally important.

We need to go back to the simple principles of what we are trying to achieve – namely to break the chain of onwards transmission of pathogens by treating surfaces (hands or environmental) to reduce germs to an “acceptable level” i.e. make a surface “fit for purpose”.  This can be done in 2/3 ways – removing them, inactivation, or a combination of both. For the last 14 years, IFH has successfully used the word “hygienically clean” to mean “microbiolgically safe”, and “hygienic cleaning”  to describe the process to achieve this – which could be soap and water with rinsing – or cleaning disinfection, or a combination of both.

Guest Blogger Bio

SBPHOTO

Dr Sally Bloomfield is an Honorary Professor at the London School of Hygiene and Tropical Medicine. She is also is the Chairman and Member of the Scientific Advisory Board of the International Scientific Forum on Home Hygiene (IFH).  Through these roles Professor Bloomfield continues to develop her work in raising awareness of the importance of home hygiene in preventing the transmission of infectious disease, and developing and promoting home hygiene practice based on sound scientific principles. She is also working to develop understanding of “hygiene issues” such as the “hygiene hypothesis” and “antimicrobial resistance”.

Professor Bloomfield’s background is in healthcare and infectious disease. She has a degree in Pharmacy, and PhD in Pharmaceutical Microbiology from the University of Nottingham. Sally was previously a Senior Lecturer in Pharmaceutical Microbiology at Kings College London (1995 – 1997) and a Hygiene Liaison manager at Unilever Research Port Sunlight UK (1997 – 2001).  She has published 100 research and review papers on the subject of home hygiene and the action and mode of action role of antimicrobial agents.

How much patient-to-patient spread of S. aureus occurs? Apparently, not much

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

I recently posted an article on surprising finds of a study suggesting that horizontal transmission of C. difficile from known symptomatic cases may be less common that we thought. A group of researchers from Oxford, Brighton and London in the UK applied similar methodology to Staphylococcus aureus transmission with similar findings: only a fifth of S. aureus acquisitions could be attributed to patient-to-patient transmission.

All patients admitted to a 16 bed ICU in Brighton were screened on admission and weekly to detect S. aureus colonization and acquisition. Each isolate was typed by spa and whole genome sequencing (WGS). The number of acquisitions that could be linked using conventional methods (spa typing combined with an analysis of overlapping stays) vs. WGS was evaluated.

Overall, 185 (16.7%) of 1109 admissions carried S. aureus; 59 carried MRSA (5.3%). 680 patients were on the unit for long enough to have a weekly screen and hence were eligible for assessing acquisition. Of these, 44 S. aureus (22 MRSA) acquisitions were detected in 41 patients. 35 of these acquisitions were in patients who were screen-negative on admission and 9 were acquisitions of different strains in patients who were already colonized on admission.

Only 14% (5/36) of the acquisitions available for typing were of the same spa type as another patient on the unit at the same time. All of these were MRSA. WGS discounted three of these apparent occurrences of patient-to-patient transmission, confirmed two and identified a further five (3 MRSA, 2 MSSA). So, in total, 7 / 36 (19%) of acquired isolates (5 MRSA and 2 MSSA) were linked to isolates from other patients (Figure).

Price MRSA WGSFigure: Source of S. aureus acquisitions identified through WGS.

The paper raises some interesting questions:

  • Principally, if almost 80% of patients did not acquire their S. aureus from other patients on the unit, where on earth did they acquire them from? In the C. difficile study, unrecognized importation of diverse strains from the community that would not be detected on admission since admission screening was not performed represents a plausible explanation for the surprisingly low incidence of horizontal transmission from known cases. This is not the case in this study, where all patients were screened on admission for S. aureus. So where were the diverse isolates acquired from? Staff carriers? Contaminated surfaces? S. aureus has the capacity to survive on surfaces for very long periods (more than 1 year), so an ancient environmental reservoir is possible. Furthermore, there was no ‘lead in’ period to the study, so it could be that S. aureus on the unit in the months before the study left an environmental reservoir that led to acquisition in some cases, which would not have been captured by this study. The fact that 4/7 patient-to-patient transmissions acquired the same strain of S. aureus without sharing time on the ICU together supports this, although could also be explained by staff carriers. It was a shame that 16% of the 329 S. aureus isolates (including 16% (7/44) of the acquired isolates) were not available for sequencing, which represents a substantial reservoir from which patient-to-patient transmission likely occurred in some cases.
  • It was interesting that some 20% (9/44) acquisitions that were detected occurred in patients who were already colonized on admission; these would have been missed altogether if molecular typing was not performed. I wonder how much ‘silent’ acquisition of this type occurs?
  • Assuming temporal relationship between strains assumes a constant mutation rate. The ‘speed of the mutation clock’ was assessed in this study through repeated sampling of the same patient. This exercise demonstrated minimal diversity, as was the case for C. difficile.
  • WGS is rapidly becoming the gold standard for transmission mapping. In this study, the conventional approach of evaluating spa typing with overlapping stays lacked both sensitivity and specificity for identifying transmitted isolates.

In summary, the major finding is that only 20% of patients who acquired S. aureus appeared to acquire it through horizontal spread from other patients. The next frontier of transmission mapping must be a more comprehensive evaluation of other potential sources: contaminated surfaces, contaminated air, nurses, doctors, cleaners, tea-tray deliverers and the list goes on…

Article citation: Price JR, Golubchik T, Cole K, Wilson DJ, Crook DW, Thwaites GE, Bowden R, Walker AS, Peto TE, Paul J, Llewelyn MJ. Whole-genome sequencing shows that patient-to-patient transmission rarely accounts for acquisition of Staphylococcus aureus in an intensive care unit. Clin Infect Dis 2014. Jan 9. [Epub ahead of print].

The Hospital Microbiome Project

Jon Otter (@jonotter) Contamination , ,

hosp microbiome

I recently came across the Hospital Microbiome Project, a multidisciplinary, multinational project designed to investigate the hospital microbiome. The science of ‘microbiomics’ (considering the whole microbial population rather than the small subset that can be cultured) is beginning to revolutionise our understanding of microbiology and human disease (1,2). Environmental studies tend to evaluate the presence of a particular microbe of interest. Few have begun to evaluate the microbiome of the hospital, and how it interacts with patients. Furthermore, antibiotic resistance genes can be shared between various species through horizontal transmission. Indeed, a study from our group at King’s College London found that ‘outbreaks of resistance’ across different species could be identified in the ICU (3). It is not known whether environmental surfaces represent a reservoir for antibiotic resistance genes and an environment in which horizontal transmission can occur (4-6). Thus, the ‘resistome’ of hospital surfaces warrants further evaluation (4-6). This point is particularly important for multidrug-resistant Gram-negative rods, which are multiply antibiotic resistant through a variety of resistance mechanisms (7-8).

The Hospital Microbiome Project uses methods to assess both the microbiome and the resistome of the hospital environment. Patient, staff, water and air will be sampled and sequencing of 16S and 18S ribosomal DNA has been used to identify bacteria and fungi, respectively, and an oligonucleotide array to detect a range of resistance genes. The initial studies are tracking the development of the hospital microbiome in a new Chicago hospital, and of a single patient room in a German military hospital (9). Some initial results already published on the Hospital Microbiome website are fascinating, explaining the microbial populations in a hospital under construction.

I look forward to seeing more results from the project in due course. There’s a chance the findings could change the way we think about contamination of the hospital environment.

References

  1. Blottiere HM, de Vos WM, Ehrlich SD, Dore J. Human intestinal metagenomics: state of the art and future. Curr Opin Microbiol 2013; 16: 232-239.
  2. Rajpal DK, Brown JR. Modulating the human gut microbiome as an emerging therapeutic paradigm. Sci Prog 2013; 96: 224-236.
  3. Vlek AL, Cooper BS, Kypraios T, Cox A, Edgeworth JD, Auguet OT. Clustering of antimicrobial resistance outbreaks across bacterial species in the intensive care unit. Clin Infect Dis 2013; 57: 65-76.
  4. Molin S, Tolker-Nielsen T. Gene transfer occurs with enhanced efficiency in biofilms and induces enhanced stabilisation of the biofilm structure. Curr Opin Biotechnol 2003; 14: 255-261.
  5. Warnes SL, Highmore CJ, Keevil CW. Horizontal transfer of antibiotic resistance genes on abiotic touch surfaces: implications for public health. MBio 2012; 3:
  6. Mkrtchyan HV, Russell CA, Wang N, Cutler RR. Could public restrooms be an environment for bacterial resistomes? PLoS ONE 2013; 8: e54223.
  7. Karah N, Sundsfjord A, Towner K, Samuelsen O. Insights into the global molecular epidemiology of carbapenem non-susceptible clones of Acinetobacter baumannii. Drug Resist Updat 2012; 15: 237-247.
  8. Munoz-Price LS, Poirel L, Bonomo RA et al. Clinical epidemiology of the global expansion of Klebsiella pneumoniae carbapenemases. Lancet Infect Dis 2013; 13: 785-796.
  9. Smith D, Alverdy J, An G et al. The Hospital Microbiome Project: Meeting Report for the 1st Hospital Microbiome Project Workshop on sampling design and building science measurements, Chicago, USA, June 7th-8th 2012. Stand Genomic Sci 2013; 8: 112-117.

Image credit: Hospital Microbiome Website.

Meeting up with ‘old friends’ keeps you healthy – especially when they’re worms

Jon Otter (@jonotter) Epidemiology , , ,

hookwormHigh income countries are undergoing a massive increase in chronic inflammatory disorders, at least partly due to a failure of immunoregulation. A review in PNAS from Prof Graham Rook at UCLH explores how exposure to the “right” microorganisms (so called ‘old friends’) is crucial for the development of an effective immune system.

Early microbial exposures teach the body how to differentiate friend and foe, fundamentally affect the development of the crucial gut microbiome and prime the development of a functional immune system. Without these exposures, the immune system may attack self (leading to autoimmune diseases), attack harmless airborne particles (leading to allergic disorders such as hay fever), attack gut contents (leading to inflammatory bowel disease), or not be able to turn off background inflammation (leading to cardiovascular disease).

So, what are the most useful early microbial exposures to prime the immune system? The “hygiene hypothesis” suggests that we are ‘too clean for our own good’. However, Dr Rook suggests that exposures to a diverse group of our microbiological ‘old friends’ is what the immune system needs to develop properly, not indiscriminate microbial exposure, which will result in unnecessary exposure to harmful pathogens. Exposure to some of our ‘old friends’ (such as the worm-like parasitic helmiths) has been lost altogether in developed countries, and exposure to other microorganisms has been changed fundamentally by our urban living. Put another way, we should not allow our children to lick the toilet bowl, but should not discourage them from eating a bit of soil occasionally!

Where could this lead? Perhaps we could develop synthetic ‘crapsules’ to augment microbially deficient youngsters (in the same way that vitamin D supplements can be useful)? Or maybe the careful administration of our worm-like parasite old friends (helminths) would help to halt the progression or even reverse the course of previously incurable diseases (such as multiple sclerosis)?

I love the description of a newborn human as a computer loaded with programs (genetics) but no data, and that the type of data entered will affect how the computer functions. Also, the idea that our limited understanding of the depth, breadth and complexity of the microbial world based on the microbes we can grow in the lab can be likened to ‘microbial dark matter’. Notwithstanding the substantial gaps in our understanding, it seems that exposure to our microbial ‘old friends’ early in life is the best way to reverse the worrying trend in chronic inflammatory disorders for future generations.

Photo credit: Jay Reimer.