Guideline fail?

What if adherence to a guideline was associated with worse outcomes? How much independent validation of guideline recommendations should occur? Is it realistic to expect guidelines to be subjected to “real-world” testing prior to adoption?

If these questions intrigue you, you’ll be interested in a Pfizer-pfunded four-center performance improvement initiative that included education around the ATS-IDSA pneumonia guidelines and a prospective assessment of outcomes. As the authors report in Lancet Infectious Diseases this week, patients who received “guideline compliant” empiric therapy were more likely to be dead at 28 days than were those who received “guideline non-compliant” therapy.

Before you submit your resignations to IDSA and ATS, you should know that there were plenty of problems with this observational study—most of them are well-summarized in an accompanying editorial. The failure of the authors to consider appropriate de-escalation of therapy in their determination of guideline compliance is an especially big problem, given that antibiotic overuse has been linked to increased mortality in the ICU.

Despite the limitations, I think this study raises important questions about guideline-driven approaches to complex infections. It is interesting, for example, that guideline non-compliant empiric therapy was equally or even more likely to cover the eventually-isolated pathogen than was compliant therapy (85% vs. 81% of the time, respectively).

What to do with a vancomycin MIC?

In response to a spate of papers suggesting that elevated vancomycin MICs within the susceptible range are associated with poor clinical outcome, many clinicians now reflexively change to alternative therapy (daptomycin or linezolid) for treatment of any MRSA isolate with a vancomycin MIC of 2 mcg/mL. The most recent such paper can be found here.

As a result of this evolving standard of practice, one particular section of the new IDSA MRSA treatment guideline is generating discussion on our clinical microbiology listserv:

How should results of vancomycin susceptibility testing be used to guide therapy?

For isolates with a vancomycin minimum inhibitory concentration (MIC) ≤2 μg/mL (eg, susceptible according to Clinical and Laboratory Standards Institute [CLSI] breakpoints), the patient's clinical response should determine the continued use of vancomycin, independent of the MIC (A-III).

--If the patient has had a clinical and microbiologic response to vancomycin, then it may be continued with close follow-up

--If the patient has not had a clinical or microbiologic response to vancomycin despite adequate debridement and removal of other foci of infection, an alternative to vancomycin is recommended regardless of MIC.

For isolates with a vancomycin MIC >2 μg/mL (eg, vancomycin-intermediate S. aureus [VISA] or vancomycin-resistant S. aureus [VRSA]), an alternative to vancomycin should be used (A-III).

The bottom line? S is S, I is I, R is R. Treat the patient, not the MIC. If the patient is responding, good. If not, then you ought to be seeking alternatives, regardless of the exact MIC.

I agree with this approach for several reasons, not the least of which is that exact vancomycin MICs are method and laboratory dependent. In addition, +/- 1 dilution step in MIC is within the usual variability of our clinical laboratory MIC testing (MIC quality control ranges usually encompass 3 or 4 dilution steps). Even if every clinical microbiology laboratory did population analysis profiling of each MRSA strain, other treatment and host factors would likely have overriding impact on the clinical outcome.

Despite the fact that vancomycin is a bad (and mysterious) drug, we still lack alternatives that have been convincingly shown to be better for most MRSA infections….

IDSA Releases MRSA Treatment Guidelines

Perhaps to celebrate the 50th anniversary of MRSA's discovery in 1961, IDSA just released their first MRSA treatment guidelines. The guidelines don't discuss infection prevention strategies but rather focus on specific clinical questions such as "What is the management of skin and soft-tissue infections (SSTIs) in the era of community-associated MRSA (CA-MRSA)?"

A recommendation getting a lot of attention in the press is that you don't always have to treat MRSA with antibiotics. What! We treat viruses and pseudo-infectious syndromes with antibiotics, we should at least give antibiotics to patients with pathogenic bacteria even if they aren't needed. It's only fair! (sarcasm alert) The press attention focuses on the first recommendation in the document that says "For a cutaneous abscess, incision and drainage is the primary treatment (A-II). For simple abscesses or boils, incision and drainage alone is likely to be adequate, but additional data are needed to further define the role of antibiotics, if any, in this setting."

My favorite section deals with "Research Gaps" such as whether vancomycin should be the first drug of choice for empirical therapy or should the patient also receive a β-lactam antibiotic to cover for MSSA? The guidelines also have a "Performance Measures" section that includes weight-based dosing of vancomycin combined with trough-monitoring.

Overall, for an almost 30-page guideline (not counting references), I found it very well written and organized. Nine of 15 authors (if I counted correctly) report COI. The guidelines were endorsed by the Pediatric Infectious Diseases Society, the American College of Emergency Physicians, and the American Academy of Pediatrics.

-Eli

Liu C. et al CID Feb 1, 2011 (full text of Guidelines)
IDSA Press release 1/5/2011