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Am Fam Physician. 2022;106(4):362-363

Original Article: Diabetes-Related Foot Infections: Diagnosis and Treatment

Issue Date: October 2021

To the Editor: The authors provide an excellent primer on how to diagnose and manage diabetes mellitus-related foot infections. However, one of their key recommendations for practice is problematic. The authors recommend that antibiotic methicillin-resistant Staphylococcus aureus (MRSA) coverage may be discontinued in a patient with a diabetes-related foot infection if they have a negative MRSA nares culture due to its high negative predictive value. Although antibiotic stewardship is important, the consequences of untreated MRSA infections can be significant.

Negative MRSA nares cultures have been used to de-escalate MRSA antibiotic therapy in patients with respiratory tract infections; studies validating nares culture use found a relatively low prevalence of MRSA pneumonia (4% to 9%).1 It is important to remember the role of disease prevalence in calculating negative predictive value. The performance of MRSA nasal screening in predicting clinical MRSA infections correlates with the prevalence of MRSA in that specific infection source. MRSA nares screening has a lower negative predictive value in skin and soft tissue infections than in infectious sources with lower MRSA prevalence because these infections have a high prevalence of MRSA.2

Even among skin and soft tissue infections, one study found significant variance in MRSA prevalence, with nonextremity cultures having a prevalence of MRSA at 8.7% compared with ulcers and extremity infections with a prevalence of 27.8%. This study also found that nearly one-third of patients with MRSA skin and soft tissue infections were not nasally colonized, suggesting that colonization may not precede disease and that this negative test would not rule out MRSA when prevalence is moderate to high.3

All available research assessing the utility of MRSA nares screening to predict MRSA in skin and soft tissue infections is based on retrospective data. One study found a negative predictive value of 73% using MRSA nares screening, which performed better than using MRSA clinical risk factors.4 Although this may be the case, a negative predictive value of 73% would still miss a significant number of actual MRSA infections.

Prospective trials are needed to establish the safety and effectiveness of MRSA nares screening to guide antibiotic therapy, especially in diabetes-related foot infections. Evidence is not strong enough to recommend discontinuing MRSA antibiotic coverage in diabetes-related foot infections based solely on a negative MRSA nares test.

The views expressed in this article are those of the author and do not necessarily reflect the official policy or position of the U.S. Air Force, the U.S. Department of Defense, or the U.S. government.

In Reply: We appreciate the caution raised by Dr. Gaillardetz in response to one of our key practice recommendations. We agree that a negative MRSA nares test should not be the only factor in deciding to discontinue MRSA antibiotic coverage for a diabetes-related foot infection, and prospective studies to validate the clinical utility of a MRSA nares culture to guide empiric antibiotic coverage would be valuable. Many factors, such as a patient's history of foot infections, severity of illness, risk of worsening infection, and community MRSA prevalence, should play a role in de-escalating antibiotic therapy. The key practice recommendation from our article should have stated that stopping MRSA coverage in response to a negative nares swab could be considered rather than universally recommended.

MRSA nares testing to guide antibiotic de-escalation is a promising antimicrobial stewardship strategy.1,2 Antimicrobial resistance and multidrug-resistant organisms are a growing threat to global public health.3 Overprescribing antibiotics is a common driver of antimicrobial resistance. New tools are needed to minimize the use of broad antimicrobials, shorten antibiotic courses, and allow for earlier de-escalation of treatment without worsening clinical outcomes.3

Thankfully, multiple retrospective studies report high negative predictive values of negative MRSA nares cultures in patients with diabetes-related foot infections.1,2 An analysis of more than 8,000 patients (7.5% of whom had MRSA foot infections) found an 89.6% negative predictive value.1 In another study, the negative predictive value was 94% in a population of 200 patients with diabetes-related foot infections.2

Mounting evidence supports the value of a negative MRSA nares test to reduce inappropriate antibiotic use and the development of bacterial resistance. We think our original B rating is appropriate based on limited-quality patient-oriented evidence but would note the importance of not relying on a negative MRSA nares culture as the only factor when de-escalating antibiotic coverage in patients with diabetes-related foot infections.

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This series is coordinated by Kenny Lin, MD, MPH, deputy editor.

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