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.
Discussion
- 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.
Reflections on Infection Prevention and Control 
This is actually a threefold problem. The first has to do with how multidrug resistant organisms get selected in the first place. The second is how they’re maintained in a given environment, and the third question is how to keep from spreading them.
The first two questions are relatively easy to answer. We created these organisms with the indiscriminate use of the antibiotics in question. We maintain their prevalence by the same means that we create them, with the indiscriminate use of antibiotics.
People often think of bacteria the same way they think of some invading force, in terms of combat and warfare. That’s not the case. There are no storm-trooper bacteria, complete with tanks, brown shirts and little swastikas on their outer cell walls. The bacteria that become multidrug resistant are the survivors, the things that crawled out of their holes after we bombed them with multiple antibiotics that killed all their susceptible brethren. More often than not, they’re not particularly strong or efficient, either. The adaptations that made them resistant to the action of antibiotics only give them a survival advantage in environments full of those antibiotics.
Take a multidrug resistant Serratia, say, and put it in some broth media with some mixed drug susceptible E colis and Staphs with no antibiotics, let the culture go for a couple of days, plate the broth onto solid media and see how many of those Serratia there are in relation to the other bacteria that aren’t multidrug resistant. Do this with serial passes of the same combination in drug free media and you’ll soon see that the Serratia have been crowded out. They can’t compete with drug susceptible organisms in the absence of the selective pressure placed on the total population by the antibiotics.
One issue, then, is to control the amount and kinds of antibiotics in the environment. This needs supervision by experts. Certain antibiotics shouldn’t be available to any random physician. To a person, they will overdose their patients with multiple antibiotics, “just to be sure” and never double check when they get culture and susceptibility results to see if they can get by with fewer or different drugs. It’s pure intellectual sloth, but given all the other things ICU physicians need to know and do, it’s understandable sloth. That’s why there should be a specialist who knows the antibiotic resistance patterns in his facility, who can be the only person allowed to approve the use of certain antibiotics when there are no other better options or who has the authority to intervene and revise the antibiotic administration to more conservative regimens.
The final point, spreading the organisms around, well, good old soap, lots of running water and frequent changes of gloves, preferably between each patient contact are the best things you can do, far better than any kind of fancy disinfectants. Aerial UV lights to disinfect the air probably won’t help that much with the exception of organisms that stay in the air a long time, like M. tuberculosis.
In summary, stop slinging around so many antibiotics in pursuit of “broad spectrum coverage” after you can get reliable bacteriology reports, and keep on washing your hands and changing your gloves. Those are the best things you can do.
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Thanks Stanley, agree the problem is multifactorial, and demands a multifaceted approach. Restricting the use of all, and in particular high risk antibiotics will help, when applied in tandem with basic infection prevention and control measures. I have reservations about systemic use of antibiotics to ‘decolonise’ MDR-GNR carriers though http://www.micro-blog.info/2014/05/perspective-from-eccmid-2014-a-voice-against-selective-digestive-decontamination-sdd/
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Control of pathogen transfer will need to address 3 things- patient, provider and patient environment. Screening(conventional or rapid method), Isolation, hand hygiene, chlorhexidine bathing all address 2 aspects of the 3 causative factors. And environment has been proven to be more important than the other two. We have spent all our time, energy, money on the two and ignored the environment.
Patient environment is really important and this has been shown over and over and over again. This is the reason why just barrier precautions of gowns and gloves dont work. ICU Staff get tired and frustrated with this seemingly pointless step and it undergoes attrition. I think its good practice, so i am all for it.
To date, there is no scientific way to assess a patient room objectively prior placing them in that environment- It is cleaned, assumed to be thoroughly cleaned and there is no objectivity to this. I am aware there are lots of decontamination strategies but do we have a way to know the room is really clean prior placing a patient inside.
Its similar to saying- This antihypertensive medication is awesome- trust me, just dont check your blood pressure??!!!
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Murlikrishna thanks for the comment. I agree with you that this study addresses patient and provider, but doesn’t really address the patient environment (although chlorhexidine use does reduce shedding of pathogens into the environment). But there are some ways to objectively assess room cleaning and disinfection: principally ATP, fluorescent markers and aerobic colony counts. Another option is to use an automated room decontamination system for terminal disinfection of patient rooms, which takes the human element out of the process. These systems can be validated by biological or chemical indicators / cycle data to provide an objective measure of performance
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