WHO have just released some guidelines for the prevention and control of carbapenem-resistant Enterobacteriaceae, Acinetobacter baumannii, and Pseudomonas aerugionsa. This guideline builds on the excellent WHO core components for IPC guidelines.
The UK guidelines for the prevention and control of multidrug-resistant Gram-negative bacteria (MDR-GNB) are published this week. It’s useful that the publication of these guidelines coincides with Antibiotic Awareness Week because MDR-GNB are brining us ever closer to the end of antibiotics. Although the guidelines don’t cover the treatment of MDR-GNB (this will be addressed in a forthcoming guideline), these highly resistant MDR-GNB leave few therapeutic options. Even when they remain susceptible to some antibiotics, these antibiotics are not front-line antibiotics for a reason (including poor tissue penetration and side effects). Furthermore, we are already seeing resistance to last-line (aka end of the golden-antibiotic-road) antibiotics e.g. colistin. Therefore, the old adage that ‘prevention is better than cure’ has never been so true!
I recently had a review published in CMI comparing EU guidelines for controlling multidrug-resistant Gram-negative bacteria (MDR-GNB). I included the following guidelines in my review: ECCMID 2014, Irish MDRO, PHE CPE, HPS CPE, ECDC systematic review on CPE (not strictly a guideline, but did include some recommendations). A couple of important points arise:
I was privileged to be asked to speak at the inaugural Healthcare Infection Society Middle East Summit in Dubai this week on ‘European approaches to MDR-GNR prevention and control’. You can download my slides here.
I began with a (probably too lengthy) preamble outlining some overall points:
- CRE is a big deal in Europe, especially in the UK, and has prompted unprecedented action on a national level in the form of a Toolkit, a Patient Safety Alert and a letter to all CEOs requesting (demanding?) an action plan. The political picture is similar elsewhere in Europe and in the USA. Although this level of government scrutiny can be challenging, on the whole I think it’s beneficial, and is probably a sizeable factor in the successes achieved with MRSA and CDI.
- Do we go universal or targeted? There’s been much discussion recently about abandoning traditional targeted (aka vertical) approaches in favour of universal (aka horizontal). Interesting, all guidelines that I could lay my hands on favoured a targeted approach for MDR-GNR, centred around screening and isolation of carriers.
- Where is the evidence? We are hamstrung by the lack of high quality studies telling us with any certainty what works to control MDR-GNR. Pretty much all studies to date are either performed in an outbreak setting (regression to the mean…) or include multiple interventions (which worked?), or both. The few studies that evaluated a single intervention in an endemic setting are underpowered to deliver a meaningful conclusion. So, we need bigger and better studies!
- How do you produce good guidelines – who is on the guideline writing dream team, and what are the key pitfalls to avoid. Plus, importantly, how to good guidelines translate through a good policy into good practice?
I gave a talk today at a meeting on combating carbapenem-resistant organisms. My angle was to clearly differentiate the epidemiology of the Enterobacteriaceae (i.e. CRE) from the non-fermenters (most importantly carbapenem-resistant A. baumannii – CRAB), and you can download my slides here.
I’ve blogged before about how confusing the terminology surrounding multidrug-resistant Gram-negative rods has become. Non-expert healthcare workers have little chance in distinguishing CRE from CPE from CRO from CPO. So we need to help them by developing some clear terminology, given the gulf in epidemiology between CRE and CRAB (see below).
So, I think we should talk in terms of CRE (and CPE for confirmed carbapenemase carriers), and CRNF (or CRAB for A. baumannii and CRPA for P. aeruginosa). I don’t think that CRO is a useful term – in fact, I find it rather confusing. Carbapenem resistance in Enterobacteriaceae (CRE) and A. baumannii (CRAB) are both emerging problems, but they are not the same problem.
During the webinar, I provided an overview of the available guidelines to control CRE and other resistant Gram-negative bacteria. I then identified gaps in the guidelines, in terms of definitions of standard precautions, outbreak epidemiology and who should be on the guidelines writing dream team. Finally, I discussed some controversial areas in terms of effective interventions: patient isolation, staff cohorting and selective digestive decontamination.
One of the most important points when considering infection prevention and control guidelines is the issue of ‘standard precautions’. What do we apply to every patient, every time? As you can see from Figure 1 below, ‘standard precautions’ is far from standardized. This is problematic when developing and implementing prevention and control guidelines.
Figure 1: differences in the definition of ‘standard precautions’.
I had the opportunity to ask the webinar audience a few questions throughout the webinar, which are outlined in Figure 2.
Figure 2: response to the questions from the 120 or so participants.
I was somewhat concerned but not that surprised that more than a quarter of the audience did not know where to access control guidelines for MDR-GNR. I suppose this means that we need to do a better job of signposting the location of the various guidelines available. Here’s a non-exhaustive list for starters:
- US CDC CRE Toolkit.
- US AHRQ CRE Toolkit.
- UK Public Health England CPE Tookit.
- UK ESBL guidelines.
- ECDC risk assessment on the spread of spreading (CPE).
- Canadian guidelines for carbapenem resistant GNB.
- Australian recommendations for CRE control.
- ESCMID MDR-GNR control guidelines.
There was a fairly even split between active and passive surveillance to detect outbreaks. The problem with relying on passive surveillance (i.e. clinical cultures) is that there’s a good chance that the ‘horse will have bolted’, and you have a large outbreak on your hands, before a problem is detected. For this reason, I favour active surveillance.
But who to screen? In the case of CRE, I was pleased to see that virtually nobody said nobody. There was a pretty even split between everybody, high-risk individuals or all individuals in high-risk specialties. Accurately identifying individuals who meet screening triggers is operationally challenging, as outlined by the “backlash” to the UK toolkit, so I think screening all patients in high-risk specialties (e.g. ICU) makes most sense.
So, what works to control MDR-GNR transmission? We don’t really know, so are left with a “kitchen sink” (aka bundle approach) (more on this in my recent talk at HIS). We need higher quality studies providing some evidence as to what actually works to control MDR-GNR. Until then, we need to apply a healthy dose of pragmatism!
Guest bloggers Dr. Rossana Rosa and Dr. Silvia Munoz-Price (bios below) write…
In everyday practice of those of us who work in intensive care units, a scenario frequently arises: a patient has a surveillance culture growing carbapenem-resistant Acinetobacter baumannii (CRAB). While the ultimate course of action we take will be dictated by the patient’s clinical status, that surveillance culture, in the appropriate context, can provide us with valuable information.
For this study1, we looked at a cohort of patients admitted to a trauma intensive care unit, and sought to identify the risk factors for CRAB infections. We found that patients who had surveillance cultures positive for CRAB had a hazard ratio of 16.3 for the development of clinical infections with this organism, compared to patient’s who remained negative on surveillance, even after adjusting for co-morbidities and antibiotic exposures. Since our results were obtained as part of a well-structured surveillance program, we know that colonization preceded infection. Unfortunately for some of our patients, the time from detection of colonization to development of clinical infections was a matter of days. With therapeutic options for the effective treatment of infections with CRAB limited to tigecycline and polymixins, the consequences of delaying therapy are often fatal. As described by Lee et al, a delay of 48 hour in the administration of adequate therapy for CRAB bacteremia can result in a 50% difference in mortality rate2.
Surveillance cultures are not perfect, and may not detect all colonized patients, but they can be valuable tools in the implementation of infection control strategies3, and as we found in our study, can also potentially serve to guide clinical decision that impact patient care and even survival.
Dr. Silvia Munoz-Price (centre left) is an Associate Professor of Clinical Medicine at the Institute for Health and Society, Medical College of Wisconsin, currently serving as the Enterprise Epidemiologist for Froedert & the Medical College of Wisconsin. Dr. Rossana Rosa (centre right) is currently an Infectious Diseases fellow at Jackson Memorial Hospital-University of Miami Miller School of Medicine. She hopes to continue developing her career in Hospital Epidemiology and Infection Control.
- Latibeaudiere R, Rosa R, Laowansiri P, Arheart K, Namias N, Munoz-Price LS. Surveillance cultures growing Carbapenem-Resistant Acinetobacter baumannii Predict the Development of Clinical Infections: a Cohort Study. Clin Infect Dis. Oct 28 2014.
- Lee HY, Chen CL, Wu SR, Huang CW, Chiu CH. Risk factors and outcome analysis of Acinetobacter baumannii complex bacteremia in critical patients. Crit Care Med. May 2014;42(5):1081-1088.
- Munoz-Price LS, Quinn JP. Deconstructing the infection control bundles for the containment of carbapenem-resistant Enterobacteriaceae. Curr Opin Infect Dis. Aug 2013;26(4):378-387.