Addenbrookes hospital in Cambridge (UK) have recently performed a point prevalence survey for antibiotic resistant bacteria. None of 540 patient samples grew CPE, but 130 (24%) grew VRE. So, why no CPE but so much VRE?
by Andreas Voss and Eli Perencevich,
During the recent ICPIC 2017 and a pre-meeting think tank, the sense and non-sense of RCTs looking at various infection control measures was a major point of discussion during many sessions. Data from well-designed quasi-experimental studies, epidemiological evidence, and logic seems to vanish, whenever a new RCT is published, even if the results are not applicable to situations that are non-endemic, have higher or lower compliance with the preventive measures in question, or whether the intended measures were actually applied within the intended patient group. Some studies seem to assume that the transmission during the first days of admission are of no consequence. Others assume that given endemicity and a high patient load, the intended measures such as single-room isolation can’t be applied, even if a patient was randomized to receive those measures.
A brave study from the Palmore/Frank group at NIH has opened the Pandora’s Box that is screening staff for MDROs, and, I’m delighted to say, firmly closed it with their findings! Only 3% of staff carried ESBLs, one carried a CPE, and none carried VRE, and this despite extensive contact with MDRO patients for many of the staff sampled!
It is great to see the long-awaited ‘Benefits of Terminal Room Disinfection’ (BETR-D) randomised controlled trial of a UVC automated room decon (ARD) system published, in the Lancet, no less! This study firms up the importance of environmental contamination in transmission, and demonstrates additional benefit of UVC over and above enhanced conventional methods for VRE, maybe for MRSA, but not for C. difficile.
What do you do to prevent VRE transmission?
…you are not alone, if the answer to this question is ‘nothing special’, based on survey published in ARIC! Dale Fisher’s team in Singapore put together a simple survey, asking the global IPC community what measures they have in place to prevent the transmission of VRE. There was a huge degree of variability, ranging from ‘nothing special’ to ‘the kitchen sink’!
Infection Prevention 2015, the annual conference of IPS, was held in Liverpool this year. I’m delighted to say that the abstracts from the submitted science are published Open Access in the Journal of Infection Prevention. This first instalment of my report will be “bug-focussed”, followed by another two on different themes:
Part I: Beating the bugs
The conference kicked off with fellow ‘Reflections’ blogger Prof Andreas Voss. By Andreas’ own admission, he was given a curve-ball of a title: ‘CRE, VRE, C. difficle or MRSA: what should be the priority of infection prevention?’ [No idea where that could have come from…] Andreas developed a framework for grading the priority of our microbial threats, accounting for transmissibility, virulence, antibiotic resistance, at-risk patients, feasibility of decolonisation, cost, and impact of uncontrolled spread. And the result? Any and all microbes that cause HCAI should be a priority of infection prevention. Even those that seem to have less clinical impact (such as VRE) are good indicators of system failure. If we focus too much on one threat, we risk losing sight of the bigger picture.
Cast your minds back to the 2010 HIS conference in Liverpool and Drs Stephanie Dancer and Stephan Harbarth debating the relative importance of contaminated hands vs. surfaces in the transmission of MDROs. I don’t remember the details of the debate, but I do remember the surprising lack of evidence on both sides. Back then, we had no real way to quantify the contribution of the environment to the transmission of MDROs, or to measure the relative importance of contaminated hands vs surfaces. The evidence has evolved to the extent that a group of US researchers have published a paper modeling the relative contribution of contaminated hands vs surfaces to the transmission of MDROs. I like the paper very much, and the authors should be congratulated for breaking new ground in understanding transmission routes of MDROs.
The model simulates patient-to-patient transmission in a 20-bed ICU. The values of the parameters that were used to build the model were sensible on the whole, although baseline hand hygiene compliance was set at 57-85% (depending on staff type and whether at room entry or exit), which seems rather generous when baseline environmental cleaning compliance was set at 40%. Also, the increased risk from the prior room occupant for MRSA and VRE was set at 1.4 (odds ratio) for both, whereas it probably should be higher for VRE (at least >2) based on a number of studies.
100 simulations were run for each pathogen, evaluating the impact of step-wise changes in hand hygiene or terminal cleaning compliance. The key finding is that improvements in hand hygiene compliance are more or less twice as effective in preventing the transmission of MDR A. baumannii, MRSA or VRE, i.e. a 20% improvement in terminal cleaning is required to ‘match’ a 10% improvement in hand hygiene compliance. Also, the relationship between improved terminal cleaning and transmission is more or less linear, whereas the relationship with hand hygiene shows relatively more impact from lower levels of hand hygiene compliance (see Figure, below). Thus, the line for improving hand hygiene or terminal cleaning would intercept and indeed cross over at around 40 or 50% improvement. The implication here is that hand hygiene is more important at low levels of compliance, whereas terminal cleaning is more important at high levels of compliance (although don’t forget the difference in the baseline compliance ‘setpoint’.
The study raises some important issues for discussion:
- It had not struck me before that the level of compliance with hand hygiene and environmental cleaning are nearly identical, on average, with only around 40% of hand hygiene opportunities met and 40% of environmental surfaces cleaned if human beings are left to their own devices. Both of these figures can be improved considerably with concerted effort, but the sustainability of these improvements without continued effort is rather disappointing.
- The models address MRSA, VRE and MDR A. baumannii transmission. It’s a little strange that C. difficile was not included, since most consider this to be the ‘most environmental’ hospital pathogen.
- The study only modeled the impact of terminal cleaning, whereas daily cleaning seems likely to also be an important factor (which is acknowledged as a limitation in the discussion). This seems especially important in light of data that touching a contaminated surface carries approximately the same risk of hand contamination as touching an infected or colonized patient.
- I am not certain that this assumption makes logical sense: ‘thoroughness of cleaning of 40% implies that, given a single cleaning opportunity, there is a 40% probability that the room will be cleaned sufficiently well to remove all additional risk for the next admitted patient’. This would be true if cleaning was performed to perfection 4 times out of 10, whereas it is actually performed with 40% efficacy 10 times out of ten! To this end, it would be interesting to insert the various automated room disinfection systems into the model to evaluate and compare their impact. Indeed, hydrogen peroxide vapour has been shown to mitigate and perhaps even reverse the increased risk from the prior room occupant (for VRE at least).
- In the introduction, the authors comment that ‘A randomized trial comparing improvements in hand hygiene and environmental cleaning would be unethical and infeasible.’ I see what they’re saying here, in that it would be unethical by modern standards to investigate the impact of no hand hygiene or no environmental cleaning (although this has been done for hand hygiene), but it would be useful, feasible and ethical to perform a cluster RCT of improving hand hygiene and environmental cleaning. It would look something like the classic Hayden et al VRE study, but with an RCT design.
- How useful is mathematical modeling in informing decisions about infection prevention and control practices? This is not the first mathematical model to consider the role of the environment. For example, researchers have used models to evaluate the relative importance of various transmission routes including fomites for influenza. But a model is only as good as the accuracy of its parameters.
- Does this study help us to decide whether to invest in increasing hand hygiene or terminal cleaning? To an extent yes. If you have awful compliance with both hand hygiene and terminal cleaning at your facility, this study suggests that improving hand hygiene compliance will yield more improvement than improving terminal cleaning (for A. baumannii, MRSA and VRE at least). However, if you have high levels of compliance with hand hygiene and terminal cleaning, then improving terminal cleaning will yield more.
In general, this study adds more evidence to the status quo that hand hygiene is the single most effective intervention in preventing the transmission of HCAI. However, in a sense, the hands of healthcare workers can be seen as high mobile surfaces that are often contaminated with MDROs and rarely disinfected when they should be!
Article citation: Barnes SL, Morgan DJ, Harris AD, Carling PC, Thom KA. Preventing the transmission of multidrug-resistant organisms: modeling the relative importance of hand hygiene and environmental cleaning interventions. Infect Control Hosp Epidemiol 2014; 35: 1156-1162.
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.