Recognizing the Value of Infection Control in Addressing the AMR Crisis

One of the challenges that all infection control and QI programs face is obtaining the necessary funding to complete all their required activities such as surveillance, reporting and prevention. Anthony Harris from the University of Maryland spent a great deal of time (e.g. SHEA White Paper on Necessary Infrastructure) as SHEA President pushing for increased resources for hospital epi activities. In a recent BMJ Quality and Safety editorial, Anthony offered suggestions for advancing the recognition and resources for infection control and QI activities, including societies (i.e. SHEA, APIC, ESCMID) partnering with governments to create comprehensive recommendations for infection control programs and funding.

Specifically, he recommends:

(a) guidelines by major organisations outlining the optimal reimbursement and full time employee (FTE) of hospital epidemiologists and infection preventionists for healthcare facilities in various settings. Currently, agencies such as CMS list certain conditions of participation for institutions relative to infection control and soon to be antibiotic stewardship; however, details of these requirements are vague and should be expanded

(b) as reimbursement moves away from fee per service and more towards quality outcomes driving reimbursement and penalties, we need more effective and novel methods of directing resources for day-to-day infection prevention. For example, an infection prevention fee could be imposed on all procedures that require significant infection prevention resources such as surgery or central line insertion and maintenance

(c) funding for state health departments to assist individual hospitals in establishing effective infection prevention programmes

(d) novel reimbursement models such as a fixed fee per surveillance culture reviewed, a fee for each chart reviewed to assess the appropriateness of antibiotic selection or an hourly fee for performing outbreak investigation may be warranted

(e) certification requirements for hospital epidemiology and QI experts that will help recruit and establish more experts to the field.

The full editorial (free full text access) is well worth reading. (COI alert: I'm a co-author)

Hand Hygiene Interventions: A Network Meta-Analysis

Summer is in full blaze (especially for those in Rome, France and the western US), so we don't have much time for long posts. However, I had to point you to an excellent study in the BMJ (open access) by Luangasanatip et al. that utilized a systematic review and network meta-analysis to determine the comparative effectiveness of the WHO 2005 hand hygiene campaign and other interventions. The WHO-5 Campaign (not to be confused with the WHO 5 Moments) recommended a multimodal strategy consisting of five components: system change, training and education, observation and feedback, reminders in the hospital and a hospital safety climate.

The authors completed a systematic review of interventions from 2009-2014 and used prior reviews to identify other studies. A strength of the analysis was that they looked beyond randomized trials and included high quality quasi-experimental studies including non-randomised trials, controlled before-after trials, and interrupted time series studies. They then completed a network meta-analysis which suggested that the WHO-2005 campaign was effective and compliance could be improved if other interventions were added including goal setting, reward incentives and accountability.

For those interested in reading more about network meta-analysis, I suggest you read John Cornell's editorial and the PRISMA Extension Statement in this past June's Annals. Briefly, it allows direct and indirect comparisons of interventions. For example, if two interventions are not directly compared they can still be compared if they were both directly compared to a third intervention (see Figure 1 above - Treatment D vs Treatment B or C through their direct comparison to Treatment A). Additionally if there is a closed-loop of studied interventions, additional information can be gained from indirect comparisons even if direct comparisons also exist. For example, in Figure 1 above, we can learn about Treatment A vs Treatment B from their direct comparison but also indirectly through Treatment C.

I encourage you to read the full study and the editorial by Matthew Muller. Very nice to see that the BMJ published this important study. And for those in the southern hemisphere, enjoy your cool weather...these summers seem to be getting worse and worse.

Sometimes, what we suffer from is bigger than we think

There was a time when the makers of Tamiflu (oseltamivir) ran ads with the tagline "sometimes, what we suffer from is bigger than we think" urging folks to see their doctor for viral URIs and get treatment for the influenza.  Now, however, I think the tagline is perfect for describing the predicament clinicians, public health officials and governments are in when trying to decide what to do with neuraminidase inhibitors (oseltamivir and zanamivir) for influenza prevention and treatment. You see, what they all suffered from when trying to decide what to recommend was a missing data problem, specifically unpublished clinical trial data held back by the pharmaceutical companies (Roche and GlaxoSmithKline). This "missing data" problem was bigger, much bigger, than initially appreciated.

Today, the Cochrane Review updated the "Neuraminidase inhibitors for preventing and treating influenza in healthy adultsand children" based on full internal reports of 46 clinical trails. The key findings are that neuraminidase inhibitors reduced the duration of symptoms by 1/2-day in adults, with data uncertain in children and that there was no evidence of a reduction in hospitalisations or serious influenza complications including pneumonia in adults or children. Side-effects, such as nausea, vomiting, psychiatric events etc, were significantly more common in the oseltamivir treated groups. In prophylaxis trials, both agents reduced the risk of symptomatic influenza in individuals and in households.

Some quotes from key individuals involved with the release of this report:

Dr. David Tovey, Editor-in-Chief, Cochrane: “Initially thought to reduce hospitalisations and serious complications from influenza, the review highlights that Tamiflu is not proven to do this, and it also seems to lead to harmful effects that were not fully reported in the original publications."

Dr. Tom Jefferson and co-authors of the review: “We urge people not to trust in published trials alone or on comment from conflicted health decision makers, but to view the information for themselves.”

Dr. Fiona Godlee, BMJ Editor: “We need the commitment of organisations and drug companies to make all data available, even if it means going back 20 years. Otherwise we risk another knee-jerk reaction to a potential pandemic. And can we really afford it?”

Dr. Harlan Krumholz, Yale Professor, wrote an accompanying editorial in the BMJ. In addition to describing the surprising need for more studies 15 years after the drugs were approved and listing the current and outdated public health guidelines he emphasized that "from a health system perspective, the enormous expenditures do not appear to have commensurate benefit."

UPDATE: CDC Says Stay the Course; Main reason appears to be that observational data were not included in Cochrane analysis. Of course, it is unethical to do an RCT in a pandemic, so much of the data required for decision making around pandemic preparedness wouldn't be from RCTs.

Additional References:
1) Heneghan et al. Zanamivir for influenza in adults and children: systematic review of clinical study reports and summary of regulatory comments BMJ 2014

2) Jefferson et al. Oseltamivir for influenza in adults and children: systematic review of clinical study reports and summary of regulatory comments. BMJ 2014

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!

Save your mupirocin for SSI prevention in cardiac and orthopedic surgery

As our guest blogger, Marc-Oliver Wright, posted last week, widespread use of mupirocin was associated with 400% increase in mupirocin resistance at his hospital. Many are very concerned about widespread and non-selective use of mupirocin as a result of the REDUCE MRSA trial, particularly since the incremental benefit of mupirocin added to CHG is not known. Based on prior studies, it is possible that many of the benefits seen were due to CHG and not necessarily mupirocin.

With that in mind, why should we care about mupirocin resistance? Well, there are instances were mupirocin has more established benefits in the literature and one is in surgical site infection prevention. The issue with most infection prevention intervention studies is that most outcomes like SSIs are rare (fortunately) and research budgets are small, which leads to numerous underpowered quasi-experimental studies. The problem with this type of literature base is that it can lead to unnecessary controversy with clinicians cherry-picking study results to support their specific hypothesis.

To make use of such a literature base and scientifically determine the benefits of nasal decolonization (and other interventions), Marin Schweizer and Loreen Herwaldt at the University of Iowa completed a meta-analysis of SSI prevention intervention studies in cardiac and orthopedic surgery, which was published today in the BMJ (free open access). (COI note: I'm a co-author on the paper and was an independent reviewer/data abstracter) After screening 1423 articles published between 1995 and 2012, they identified 39 studies of moderate to high quality. 17 studies assessed the benefits of nasal decolonization (16 mupirocin and 1 nasal CHG), 15 studied glycopeptide prophylaxis and seven examined the bundle: screening+nasal decolonization+vancomycin). The pooled effects were quite impressive.

Nasal decolonization was associated with a 61% reduction in S. aureus SSIs, a 70% reduction in MRSA SSIs and a 50% reduction in MSSA SSIs. Glycopeptide prophylaxis was associated with a 60% reduction in MRSA SSIs while the full bundle was associated with a significant reduction in S. aureus, MRSA, MSSA and Gram-positive SSIs. I have pasted the table below (click to magnify), but since the full article is open access, you can also read the full article at BMJ.

This meta-analysis guided the implementation of an ongoing trial funded by AHRQ, so more data are coming soon. But what to make of this paper in the context of the recent REDUCE MRSA trial?  I myself am concerned that widespread mupirocin use in all ICU patients will select for resistant S. aureus isolates and render this highly-effective SSI bundle ineffective in short order. It will be sad to watch this example of the 'tragedy of the commons' play out in real time, as I suspect we will. And we will only have ourselves to blame. The data is right before our eyes.