It’s the most Chunderful time of the year (or maybe not). The Norovirus ‘season’ will still be on us and a few points are well worth reflecting on. A recent systematic review of Norovirus risk in high and middle-income countries asserts that there may be as many as 12.5 million infections annually these countries alone, with possibly as many as 2.2 million outpatient visits related to the illness. Personally I have always liked having a bit of norovirus around. Keeps the staff on their toes and gives a good indicator of how IPC is really being performed rather than another set of 99% compliant hand hygiene audits.
Shortly after the PHE Toolkit was published, I blogged some crude sums to size the burden of CRE admission screening a la Toolkit. I’m pleased to report that colleagues at Imperial have done a much better job of this, published in a letter in the Journal of Infection. The study provides some evidence that the recommendation in the PHE CRE Toolkit to perform pre-emptive isolation of suspected carriers whilst obtaining three negative screens is simply not feasible. The team then compare an alternate strategy – of applying the Tookit triggers to admissions to high risk specialties only (intensive care, nephrology, cardiothoracic surgery, neurosurgery and oncology).
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.
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).
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.
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.
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.
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.
Pat Cattini (Matron / Lead Specialist Nurse Infection Prevention and Control, Royal Brompton and Harefield NHS Foundation Trust) and I recently teamed up to present a webinar entitled: ‘Introduction to the identification and management of carbapenem-resistant Enterobacteriaceae (CRE)’. You can download our slides here, and here’s the recording:
The webinar covered the following ground:
- Why the fuss?
- What are CRE?
- Who do we screen?
- How do we screen?
- What happens if someone is positive?
- Key questions
CRE represent a combination of anitibiotic resistance, mortality and potential for rapid spread, so we need to be proactive in our approach to the detection and management of carriers. We simply can’t afford for CRE to become established in the same way that MRSA did, so now is the time of opportunity to develop the most effective prevention strategy. The recently published Public Health England Toolkit is useful, but it’s a set of tools to help construct a local policy, not a one-size-fits-all CRE policy. We hope that this webinar will assit you in developing your local CRE policies and plans.
Oh, and look out for the Premiere of ‘ISOLATION: THE ENEMY OF CRE’ (a Pat Cattini film)…
There seems to be a general movement away from targeted, pathogen-based precautions (principally screening and isolation) in the USA. This changing professional opinion was clear from the recent SHEA conference, where several leading experts gave what amounted to a collective justification for abandoning contact precautions for MRSA.
The update of the SHEA Compendium of Strategies to Prevent Healthcare-Associated Infections in Acute Care Hospitals is accompanied by a commentary from a group of leading US figures titled ‘Approaches for preventing HCAI: Go long or go wide’. In the commentary, the authors weigh the evidence and opinion for so-called ‘vertical’ (aka targeted) vs. ‘horizontal’ (aka universal) interventions (Table).
The commentary outlines the potential drawbacks of targeted approaches (such as fewer visits from healthcare workers and feelings of isolation), but doesn’t spend a lot of time discussing the potential drawbacks of universal approaches. For example, “isolation fatigue”, where a procedure loses its impact if it has to be applied to every patient. And then there’s the possibility of resistance when performing universal decolonization. This is particularly worrysome when using antibiotics, but could also be a problem when using biocides such as chlorhexidine.
I’m not ready to abandon pathogen-based targeted interventions just yet. Conceptually, it just does not make sense. If you have a patient with MRSA and a respiratory virus, chances are they will become a ‘super-spreader’. Those who favour universal approaches do make some provision for exceptional cases that really should be identified and isolated via a ‘syndromic’ approach to isolation: crudely, only isolate patients when they’re oozing. However, this syndromic approach would likely miss our ‘super-spreading’ patient, which may well result in an MRSA outbreak – that we could all do without.
Furthermore, if you have a patient who is colonized with CRE, are you brave enough to take no special precautions, as would be the case for a ‘universal only’ approach? The success of this strategy would depend on a high level of compliance with standard precautions such as hand hygiene and environmental cleaning and disinfection. Whilst sound in theory, this just doesn’t happen in the trenches; your facility is above average if your hand hygiene compliance rate is the right side of 40%. Whilst still not 100%, hand hygiene compliance is higher when patients are placed in isolation, most likely because there’s a stronger psychological trigger to comply with hand hygiene.
It’s important to note that targeted and universal approaches are by no means mutually exclusive. For example, 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, should we go long or go wide in the prevention of HCAI? The answer is both. We should optimize case for all patients, which means careful standard precations with liberal application of chlorhexidine and tight restriction of antibiotics. But we should also identify those with communicable pathogens and segregate them from others. In this regard, we have the weight of history on our side.
Image: Jeff Weese.
Not content with a single well-planned study to provide information on what works to control multidrug-resistant organisms (MDROs) in the ICU, the MOSAR study group published an interrupted time series and a cluster randomized trial of various interventions in the Lancet ID. This makes the study rather complex to read and follow, but there are a number of important findings.
Interrupted time series – ‘hygiene’ intervention (chlorhexidine and hand hygiene)
Following a 6-month pre-intervention period, a 6-month interrupted time series of a ‘hygiene’ intervention (universal chlorhexidine bathing combined with hand-hygiene improvement) was performed. The key outcomes were twofold: whether there was a change in trend during each phase, and whether there was a step-change between the phases. The hygiene intervention effected a trend change reduction in all MDROs combined and MRSA individually, but not in VRE or ESBLs (Table). However, there was no step-change compared with the baseline period.
Table: Summary of reduced acquisition of all MDROs combined, or MRSA, VRE and ESBLs individually.
Cluster RCT – screening and isolation
In the 12-month cluster RCT of screening and isolation, the 13 ICUs in 8 European countries were randomized to either rapid screening (PCR for MRSA and VRE plus chromogenic media for ESBL-Enterobacteriaceae) or conventional screening (chromogenic media for MRSA and VRE only). When analysed together, the introduction of rapid or conventional screening was not associated with a trend or step-change reduction in the acquisition of MDROs (Table). In fact, there was an increase in the trend of MRSA acquisition. When comparing rapid with conventional screening, rapid screening was associated with a step-change increase in all MDROs and ESBLs.
- The study suggests, prima facie, not to bother with screening and isolation. Indeed, the authors conclude: “In the context of a sustained high level of compliance to hand hygiene and chlorhexidine bathing, screening and isolation of carriers do not reduce acquisition rates of multidrug-resistant bacteria, whether or not screening is done with rapid testing or conventional testing”. However, the major limitation here is that many of the ICUs were already doing screening and isolation during the baseline and hygiene intervention phases! I checked the manuscript carefully (including the supplemental material) to determine exactly how many units were, but it is not disclosed. To make this conclusion, surely the cluster RCT should have been ‘no screening and isolation’ vs. ‘screening and isolation’.
- The increasing trend of MRSA associated with screening and isolation by either method, and step-change increases in all MDROs and ESBLs associated with rapid screening are difficult to interpret. Is an increase in acquisition due to screening and isolation plausible? Can more rapid detection of carriers really increase transmission (the turnaround time was 24 hours for rapid screening, and 48 hours for chromogenic screening)? The rapid screening arm also included chromogenic screening for ESBLs, whereas the conventional screening arm did not, so perhaps this apparent increase in acquisition is due to improved case ascertainment somehow?
- Looking at the supplemental material, a single hospital seemed to contribute the majority of MRSA, with an increasing trend in the baseline period, and a sharp decrease during the hygiene intervention. There’s a suspicion, therefore, that an outbreak in a single ICU influenced the whole study in terms of MRSA. Similarly, a single hospital had a sharp increase in the ESBL rate throughout the screening intervention period, which may explain, to a degree, the increasing trend of ESBL in the rapid screening arm.
- There was an evaluation of length of stay throughout the study phases, with a significant decrease during the hygiene intervention (26%), a significant increase during the rapid screening intervention, and no significant change during the conventional screening intervention. It seems likely that improved sensitivity of rapid screening identified more colonized patients who are more difficult to step down, resulting in an overall increase in length of stay.
- The carriage of qacA and qacB was compared in the baseline and hygiene intervention phase, finding no difference in carriage rate (around 10% for both). This does not match our experience in London, where carriage rates of qacA increased when we introduced universal chlorhexidine bathing. However, this was restricted to a single clone; the acquisition of genes associated with reduced susceptibility to chlorhexidine seems to be clone-specific.
- ICUs varied from open plan to 100% single rooms. Whilst the average proportion of patients in single rooms (15-22%) exceeded the average requirement of patients requiring isolation (around 10%), there was no measure of unit-level variation of single room usage. Since the study was analysed by cluster, the lack of single rooms on some units could have been more important than would appear from looking at the overall average. Put another way, a 100% open plan unit would have been forced to isolate all carriers on the open bay, and vice versa for a 100% single room unit.
- The impact of the various interventions was moderate, even though a ‘high’ MRDO rate was necessary for enrollment (MRSA bacteraemia rate >10%, VRE bacteraemia rate >5%, or ESBL bacteraemia rate >10%). Would the impact of screening and isolation be different on a unit with a lower rate of MDROs? It’s difficult to tell.
- Some of the microbiology is quite interesting: 8% of MRSA were not MRSA and 49% of VRE were not VRE! Also, 29% of the ESBLs were resistant to carbapenems (although it’s not clear how many of these were carbapenemase producers).
In summary, this is an excellent and ambitious study. The lack of impact on ESBL transmission in particular is disappointing, and may lead towards more frequent endogenous transmission for this group. The results do indicate screening and isolation did little to control MDRO transmission in units with improved hand hygiene combined with universal chlorhexidine. However, we need a ‘no screening and isolation’ vs. ‘screening and isolation’ cluster RCT before we ditch screening and isolation.
Article citation: Derde LP, Cooper BS, Goossens H et al. Interventions to reduce colonisation and transmission of antimicrobial-resistant bacteria in intensive care units: an interrupted time series study and cluster randomised trial. Lancet Infect Dis 2014; 14: 31-39.
The recent PHE CPE toolkit advocates implementing targeted screening and isolation of carriers. Reading the guidelines in a little more detail, the ‘triggers’ for screening a patient for CPE are, in the last 12 months: (a) an inpatient in a hospital abroad or (b) an inpatient in a UK hospital which has problems with spread of CPE (if known) or (c) a ‘previously’ positive case. Patients who screen positive should be placed in contact isolation; patients who screen negative should be placed in contact isolation until a further two consecutive negative screens have been taken. It’s important to note that the negative screens must be at least 48 hours apart. So, for patient who turns out to be negative will be in contact isolation for around 6 days (screens collection on days 0, 2 and 4, and a further day for the final negative screen result).
The number of patients who will meet the trigger for screening is currently unknown, but I have heard whispers of 25-50% of all admissions. This will place a considerable burden on already over-stretched isolation facilities, and bear substantial cost implications.
Single rooms in the NHS are already in very short supply. Indeed, recent press and commentary highlights the implications of running out of single rooms: patients shunted around “like parcels” in the middle of the night to relieve bed pressures.
Now, you could argue that patients who screen negative for CPE but are awaiting their confirmatory negative screens do not need to be isolated in a single room; they can be isolated in a bay. But if 25-50% of patients suddenly begin contact precautions, you’d quickly run into problems. Patients on contact precautions take longer to care for, and tend to get less attention than other patients resulting in more adverse events, as illustrated by a couple of recent Controversies blogs. Also, I fear you may begin to see ‘isolation fatigue’, where the procedure loses its impact if it has to be applied so broadly. And then there’s the cost. A recent US study calculated that contact precautions cost around £23 ($35) per patient day (not including the cost of disposal for all that additional waste!). If 25% of the 100,000 patients admitted to a London hospital Trust met the trigger for CPE screening and turned out to be negative, the price tag for isolation alone would be pushing £3.5m.
I support the PHE guidelines and agree that we need to “search and destroy” CPE above all else before it becomes endemic. However, are they feasible to implement in their current form?
Image: ‘Swabs’ by Frank Carey.
This isn’t exactly hot off the press (published in 2011) but I’ve only just come across it; it’s a great article and worth revisiting. Many hospitals worldwide suffer a chronic lack of single rooms to place patients requiring contact precautions, but also for patients with other needs such as increased privacy and dignity. There are pros and cons associated with increasing the proportion of single rooms, with a high proportion of single rooms usually requiring a higher staff:patient ratio, and patients in single rooms often having less staff contact and more likely to suffer feelings of isolation. The evidence that an increase in the proportion of single rooms reduces the transmission of healthcare-associated infection has been somewhat equivocal.
This Canadian study evaluated the impact of ‘privatization’ of an ICU. In March 2002, a 24-bed ICU (comprising two 10-bed rooms and four single rooms) was moved to a new 100% single room unit. A 25-bed ICU in a sister hospital (comprising 2, 5, 6 or 8-bed rooms) did not undergo any change in configuration and served as a comparison unit. Importantly, the two units shared the same infection control team, policies and practices. Patients admitted between 2000 and 2005 were studied for the acquisition of a range of pathogens. A unique and useful aspect of the study was to divide microbes into likely endogeneous or exogeneous acquisition. The key result reported was the change in rate ratio of the intervention ICU compared with the comparison ICU before and after the date of privatization of the intervention ICU. This was effectively an estimate of the percentage reduction in the rate in the intervention hospital associated with privatization.
Significant reductions where shown in most pathogens associated with exogenous acquisition, including C. difficile (43%), MRSA (47%) and Acinetobacter spp. (53%), and a substantial but non-significant reduction in Stenotrophomonas maltophilia (52%) (Figure). In addition, a combined analysis of C. difficile, MRSA and VRE also showed a significant reduction of 54%. Significant reductions were also shown for some pathogens in the exogenous/endogenous acquisition group, including Klebsiella spp. (38%). There was no significant change (4%) in the rate of coagulase-negative staphylococci and most other pathogens associated with endogenous acquisition. Perhaps not surprisingly, the authors also reported a reduction in the overall length of stay associated with the intervention.
Figure: Change in the acquisition rate ratio of the intervention vs. comparison ICU before and after before (2001-2002) vs. after (2003-2005) privatisation. (* Not statistically significant.)
As with all studies, this one is not without criticism. However, there are several aspects that I find particularly convincing. Firstly, whilst there were differences in the configuration of the two ICUs, the inclusion of a comparison unit was an important strength. Secondly, the authors evaluated all available pathogens, rather than focusing on an individual MDRO. Thirdly, and perhaps most convincingly, most pathogens associated with exogeneous infections were affected by the intervention whereas most pathogens associated with endogenous acquisition were not. Additional strengths include several “data-check” sensitivity analyses and an additional model to provide evidence that these were not transient reductions associated with moving to a new, clean unit. Many if not all of these important strengths are lacking from similar studies that have returned a negative result.
The simple equation that more single rooms = less acquisition of pathogens is firmly supported by this study. However, infection rates are not the only factors to be considered when contemplating a move to 100% single rooms. Staffing levels, patients views and up-front costs must be factored into the decision to move towards 100% single rooms.