Chlorhexidine bathing outside the ICU: Await the ABATE!

Daily chlorhexidine (CHG) bathing has become routine in many ICUs. Given that more healthcare-associated infections (HAIs) (including more central-line associated bloodstream infections (CLABSIs)) occur outside of the ICU, many hospitals have also implemented this practice on general medicine and surgical wards. However, to this point there are few data to support the effectiveness of CHG bathing outside of ICUs. 

So I was very excited to hear Susan Huang present the results of the Active Bathing to Eliminate Infection (ABATE) study at IDWeek last week. Similar to the REDUCE MRSA study, this 53 hospital cluster-randomized trial took place in the Hospital Corporation of America (HCA) system. Units were randomized to routine care or decolonization (this consisted of daily CHG [4% rinse-off shower or 2% leave-on bed bath] with addition of mupirocin nasal ointment for 5 days if + for MRSA by history or culture/screen) for a 21-month intervention period (after collecting baseline data for 12 months). The primary outcome was MRSA or VRE clinical isolates, and the main secondary outcome was any bloodstream isolate attributed to the unit (for common commensals, 2 or more + cultures).

With the requisite reminder that it is always best to wait for the peer-reviewed publication to make firm conclusions, the results presented at IDWeek suggest the likely take-home from this study: No measurable benefit in the entire population, but significant reductions in MRSA/VRE clinical cultures and bloodstream infection in the subgroup with devices (central lines, midlines, and lumbar drains). This subgroup represented 12% of the study population but accounted for 34% of all MRSA/VRE events and 59% of bloodstream infections. The additional reductions in the decolonization arm for this subgroup (compared with routine care) were 32% for MRSA/VRE cultures and 28% for BSI (both highly statistically significant). 

Once published, these findings will leave infection prevention programs with some interesting decisions. A quick take might be, “OK, let’s just use CHG in those non-ICU patients with devices (or just central lines).” However, this isn’t what the ABATE trial evaluated—it showed a substantial reduction in MRSA/VRE/BSI outcomes in patients with devices when everyone else was also receiving CHG (+/- mupirocin). To assume that the decolonization of the non-device population had no beneficial effect on those with devices is to discount any potential role for reduction in pathogen transmission between non-device and device patients. Another tricky question has to do with the role of mupirocin—adding this agent to CHG for known MRSA carriers without knowing how important this component of the intervention was adds some logistical complexity, cost, and antimicrobial resistance concerns (the investigators are also doing the microbiology work to assess for CHG and mupirocin resistance emergence). 

We’ll revisit this study once it is published and all the details are available. For now we should congratulate Susan and the entire ABATE trial team for another tremendous contribution!

Screening, Decolonization and Environmental Decontamination for MRSA in Nursing Homes Doesn't Work

Just in the past couple of weeks, we've written about pneumonia prevention bundles, MDRO prevention bundles, and spread of S. aureus - all in nursing homes.  It's like no one cares about acute care facilities any more! (humor) There is now more great data for those charged with managing infection control in nursing homes.

Cristina Bellini and colleagues from Lausanne University Hospital in Switzerland just published the results of cluster-randomized trial of an MRSA prevention bundle in 104 nursing homes (53 intervention, 51 control) in the April ICHE. All residents in intervention and control nursing homes (NH), who gave consent, were screened for MRSA carriage at study entry and 12 months thereafter on a single day in each NH. Newly admitted or readmitted residents were screened when admitted to the NH. Screening included nasal, groin and ulcer swabs along with urine cultures if residents had an indwelling catheter. In the intervention NHs MRSA colonized residents underwent decolonization along with environmental decontamination.

The primary decolonization bundle included 5 days of nasal mupirocin, 5 days of CHG oral rinse twice per day, 5 days of CHG showers including CHG shampoo on day 1 and 5. Environmental disinfection included daily clothing changes for 5 days, new linens on day 1 and day 5, and daily bed/table/phone/remote/wheelchair/walker disinfection with 70% alcohol. A lot of steps.

Unfortunately, the MRSA decolonization and decontamination bundle was not successful. The baseline prevalence of MRSA was 8.9% in both groups. The rate declined in intervention units to 5.8% in the intervention unit and 6.6% on the control units after 12 months (p=0.66) Full stratified results are in Table 3 below, and as you can see, no matter how they analyzed the intervention, the MRSA bundle intervention did not reduce MRSA prevalence compared to controls. This was despite the fact that the participation rate was 87%.

A limitation of this study was that they only measured prevalence and not individual level acquisition of MRSA. It is possible that by measuring prevalence they missed detecting benefits of the intervention related to reduced patient-to-patient transmission of MRSA. In any case, as I said last week about the study in CID, congratulations to the authors and journal (this time ICHE) for publishing this important negative study.

CRE decolonization: Can we? Should we?

There's a new paper in American Journal of Infection Control which poses an interesting question: can CRE (carbapenem-resistant Enterobacteriaceae) be eradicated from the gut? Given the increasing problems with these organisms, decolonization could play an important role in their control.

This study was performed at a large tertiary care hospital in Israel where active surveillance is performed on admission and weekly in targeted populations. Unfortunately the design of the study makes it difficult to interpret. There were 4 study arms: treatment with oral gentamicin, treatment with oral colistin, treatment with oral gentamicin + oral colistin, or no treatment. In part, the susceptibility of the colonizing strain dictated the study arm (e.g., patients with a colistin-resistant, gentamicin-susceptible strain were treated with gentamicin, unless they did not consent to treatment, in which case they were assigned to the control group). If the patient's isolate was susceptible to both drugs, they were randomized to either drug or to combination therapy. Treatment was given for 60 days or until eradication (defined as 3 consecutive negative rectal cultures with PCR performed on the 3rd negative sample), whichever came first. In the end, 26 patients received gentamicin alone, 16 colistin alone, 8 received both, and 102 were untreated. Eradication occurred in 42% for gentamicin, 50% for colistin and 37% for combined treatment. Only 7% of the untreated patients spontaneously decolonized.

What conclusions can we draw?

1. Spontaneous decolonization is a rare event.
2. It appears that some patients (one-half or less) can potentially be decolonized or at least suppressed while on treatment. Of note, 2 patients in the gentamicin arm, 4 in the colistin arm, and 2 in the combo arm relapsed. It would be interesting to know whether patients who had CRE eradicated remained culture negative for the long-term (e.g., 3 months or 6 months after treatment). 
3. Given that colistin remains one of the most important drugs for treatment of these infections, it worries me that widespread use of this drug for decolonization could result in resistance. Indeed, colistin resistance was reported in 1 of 16 treated patients, and 6 of 26 patients in the gentamicin arm developed gentamicin resistance.

In the end, how do we use the data from this study? I suppose if I practiced in a hospital with high rates of CRE colonization, I would be tempted to try decolonization for very high risk patients (e.g., neutropenic leukemic patients). I would favor use of gentamicin if the isolate were susceptible. But it would make me very nervous.

Photo: Klebsiella pneumoniae, CDC

A bundled intervention to decrease surgical site infections: A Video Abstract

Last week we discussed a recent BMJ meta-analysis of SSI prevention intervention studies in cardiac and orthopedic surgery. Who better to tell you about the important results than the authors themselves. Loreen Herwaldt and Marin Schweizer offer their thoughts. Enjoy!

Perry Mason and REDUCE MRSA: Another "Case of the Positive Negative"

This guest post is by Marc-Oliver Wright, MT(ASCP), MS, CIC
 from NorthShore University HealthSystem
 in Evanston, IL 

"We need Perry Mason. Someone to put you in place." – Ozzy Osbourne

This week’s articles in the NEJM (Huang et al. “Targeted versus Universal Decolonization to Prevent ICU Infection”) and accompanying editorial (Edmond and Wenzel “Screening Inpatients for MRSA-Case Closed”) left me reminiscing of classic TV courtroom dramas where the well intentioned and sophisticated district attorney has finished presenting his/her case but Perry Mason has just cleared his throat and Matlock is still shining his ankle boots.


For those of you who missed it, Huang and colleagues randomized 74 intensive care units (ICUs) at 43 Hospital Corporation of America hospitals to one of 3 interventions among 2 cohorts.

1. Cohort one: States with mandatory MRSA screening (n=5)
     a. MRSA screening and isolation for ICU admissions (3)
     b. MRSA screening, isolation and decolonization for ICU admissions (2)
2. Cohort two: States without mandatory MRSA screening (38)
     a. MRSA screening and isolation for ICU admissions (13)
     b. MRSA screening, isolation and decolonization for ICU admissions (12)
     c. No screening, decolonization for all ICU admissions (13)

Decolonization included 5 days of intranasal mupirocin therapy and daily baths with chlorhexidine gluconate (CHG) for the duration of their stay in the ICU.

Adjusted hazard ratios for clinical cultures of MRSA with both decolonization strategies netted confidence intervals that were less than 1.0. Ditto for bloodstream infections with any pathogen (not just MRSA). When the authors selected out bloodstream infections caused by MRSA the findings were not significant. In the pairwise analysis universal decolonization attained statistical significance over screening/isolation/decolonization in the unadjusted analysis for bloodstream infection due to any pathogen. The authors conclude that universal decolonization is superior to either targeted decolonization or screening and isolation without decolonization.

This was a large, rather well designed, certainly well coordinated evaluation of multiple ICUs across the country. But the case is far from closed.

Defense exhibit one: Follow the blood. This article further affirms an already well conducted study by some of the same authors that demonstrated CHG bathing of ICU patients reduced bloodstream infections in ICU patients (Arch Intern Med. 2007;167:2073-9, ICHE 2009;30:959-63). There’s ample biological plausibility for this and in general, the horizontal (as opposed to vertical one MDRO at a time) approach is more logical. However, this effect in all likelihood has nothing to do with mupirocin, which has never been independently associated with a reduction in bloodstream infections. CHG reduces all-pathogen bloodstream infections in ICU patients: no objection your honor.

Defense exhibit two: An eyewitness-I see you. MRSA infections are not restricted by the boundaries of the unit. An APCHE score is not a pre-requisite to acquiring an MDRO. According to the evidence, ICU patients are at higher risk for MRSA infection, but many of prior studies were conducted in large academic medical centers where and when the case mix was different from today. Arguably, it’s operationally easier to limit intervention and research studies by geography.

Illinois was the first state to succumb to MRSA screening legislation; the legislation which reads that such screening will be performed on patients in “all intensive care units, and other at-risk patients identified by the hospital.” We, in the Land of Lincoln, have all, by design, implemented the former, but the latter is a hodge podge ranging from denial (only ICU patients are high-risk) to the assumed, evidentiary but not all-encompassing (patients from LTC are high-risk) to the near complete (70+ variable model built decision support module embedded in the EMR). The VA as well as my own organization deployed MRSA prevention strategies in ICU as well as non-ICU settings.

This brings me to: Defense exhibit three: A character witness. My organization’s strategy for the past 9 years has been a strategy most akin to Group 2 (screening, isolation and decolonization). Though we started in the ICU, we failed to see the kind of reduction we wanted (see defense exhibit 2) until we later expanded to universal screening. We used this experience to develop a robust multi-variable prediction model that was built as decision support system into our electronic medical record. This tool automatically calculates a MRSA risk score as patient data is entered and evolves within the record during the patient’s admission. When the risk score reaches a threshold the user is instructed to screen the patient. We used this to transition from universal screening to targeted screening in January 2012.

Ok. I am by no means an expert on MRSA. I am good with numbers though.

In the NEJM article, the best intervention for reducing MRSA clinical isolates is a rate of infection of 2.1 per 1,000 patient days. At NorthShore (and for comparison purposes, these measures are in our ICUs only) in the past 38 months, our unadjusted rate of MRSA infection is 0.3 per 1,000 patient days. Their best intervention netted an infection rate ratio versus my own ICUs of 7.0 (95%CI: 4.3-11.5, p=5.9 * 10-23).

Similarly, the NEJM article reported an overall, unadjusted rate of bloodstream infection from any pathogen of 3.6 per 1,000 patient days in the universal decolonization intervention arm. At NorthShore (and for comparison purposes, this is in our ICUs only) in the past 38 months, our unadjusted rate of bloodstream infection is 1.08 per 1,000 patient days. Their best intervention netted an infection rate ratio versus my own ICUs of 3.33 (95%CI: 2.54 -4.38, p=1.3 * 10-22).

I’m afraid I’ve only had 1 BSI due to MRSA in the past 38 months. My crude rate comes out as 0.018 per 1,000 patient days. If I understand Table 3 of the NEJM article correctly, the universal decolonization group experienced 48 BSIs with MRSA during the intervention and attributable ICU patient days of 101.603 for a rate of 0.47 per 1,000 patient days. This yields an infection rate ratio versus my own ICUs of 26.11 (95%CI: 4.53-150.45, p=3.1 * 10-8).

I am all too happy when a group of dedicated and brilliant people in hospital epidemiology find a new and improved way to prevent infection. And for this group, they did discover a new strategy for reducing their MRSA and bloodstream infections. I was not surprised to see that they have decided to implement the universal decolonization strategy across all HCA hospitals. But as long as their best rates are between 3 and 26 times higher than mine, I’ll be sticking with my own plan.

Defense exhibit four: If the antibiotic doesn’t fit you must acquit. Arguably, the single greatest concerning factor of this study that wasn’t addressed is the rise of mupirocin resistance. This exhibit, like the preceding, is rooted in personal experience. Until this year, our organization decolonized all MRSA-screen positive patients. During that 8 year endeavor our proportion of mupirocin resistant MRSA increased from about 3% to almost 12%. Nasal decolonization has been most convincingly demonstrated to reduce infection risk in the pre-surgical patient population and arguably only with select procedures. Our rise in resistant strains and the overwhelming desire to reserve this ammunition for the people that really need it (pre-surgical patients) gave rise to our decision to suspend mupirocin decolonization starting in 2013. We hope to see our resistance pattern return to baseline, though such a decline will likely be slow.

Justice may be blind, but we shouldn’t be to known potential adverse outcomes like antibiotic resistance.

Closing argument:  If none of the above convinced you that this case is far from closed at least consider this final argument. Living in Illinois, I am frightened awake at night with the sounds of what I imagine to be fingers typing on keyboards. The well-intentioned hands of a well-meaning lawmaker in our state or federal capital pounding out some new legislation in light of the latest and greatest publication on preventing some iteration of our nation’s bacterial scourges. Convinced that if they don’t do something those conniving hospital epidemiologists and infection preventionists won’t do anything to protect our nation’s sickest and frailest citizens. That all we’re here for is the big money check we get every week. By heaven, we must mandate! *shudder*

This paper, like all well designed and well-conducted studies deserves critical attention and consideration. Consider the methods they used and those they didn’t, the intervention processes they measured (CHG/mupirocin supply) and those they did not (isolation compliance), the settings in which the study was conducted (ICUs) and where it was not (everywhere else) and the outcomes they measured (MRSA and BSIs) and those they did not (antibiotic resistance). You must also compare their outcomes to your own performance. With such a wide variety of organizations the results may be generalizable despite HCA’s additional vertical strategies for MRSA that may have overlapped the study periods. How do your rates in your methods group compare those published here (1, 2, or 3?) versus the alternatives? Use this evidence as a tool for your ongoing risk assessment and make an educated decision before someone makes an uneducated one for you.

The defense rests.

S. aureus decolonization: Review of the benefits

In the December 2011 Lancet ID, Andrew Simor from the University of Toronto reviewed articles listed in PubMed from 1989-2010 assessing the benefits of S. aureus decolonization. There were no surprising results. In fact, most of the conclusions were hedged.  For example he says that "some data support the use of decolonisation in surgical patients colonised with S aureus, particularly in those undergoing cardiothoracic procedures" and  "patients undergoing chronic haemodialysis or peritoneal dialysis might benefit from decolonisation, although repeated courses of treatment are needed, and the effects are modest." The hedging is not a criticism of the author, but rather due to the lack of funding for proper infection prevention studies.  What is surprising is that this is a single-author paper.  Any systematic review should be completed by more than one author, in my opinion. Another limitation is the lack of summary odds ratios. However, this is a very good literature review and a wonderful resource.

Source:  Simor AE, Lancet ID December 2011

Papers you should read, September 2011

We know. Postings have been light these past few weeks. Hey, we are getting ready for ICAAC and IDSA. So cut us some slack, already...(joking)

OK, in a matter of full disclosure, I have conflicts of interest with both of these papers, so following our standard practice of not critiquing papers where we have conflicts, I will leave the interpretation of each paper to you, our dear readers.

Click to enlarge: Frequency of non-prescription use of antimicrobials in the general population

Dan Morgan, who was our invited contributor on Veterans Day, has published a review of world-wide, non-prescription antimicrobial use in this months Lancet ID.  The review included 117 articles including 35 community surveys published between 1970 and 2009. I've pasted a summary figure above.

Co-blogger Dan has a paper coming out in ICHE (ahead of print) surveying IDSA's EIN Network of ID clinicians on their pre-op screening and decolonization practices for S. aureus. The survey included 488 respondents, who had knowledge of their hospital's pre-op screening. Overall, 60% screened for S. aureus with 47% screening for MRSA only and 13% for all S. aureus. Less than 20% screened extranasally. Screening method was led by PCR (36%) followed by standard culture (30%) and chromogenic agar (27%). Additionally, 52% decolonized with 31% decolonizing MRSA carriers, 8% decolonizing S. aureus carriers and 15% decolonized irrespective of colonization status. To find out more, you need to read the paper!

To screen or not to screen? That's AHRQ's question.

AHRQ has just opened for public comment a potential research topic titled "Comparative Effectiveness of Screening for MRSA Carriage." It's open for comment until October 5. Hey! Now's your chance to influence the national research agenda! or at least answer 6 questions.

AHRQ Research Comment Page