By Dean L. Winslow, MD, FACP, FIDSA, FPIDS

Professor of Medicine, Division of General Medical Disciplines, Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine

Dr. Winslow reports no financial relationships relevant to this field of study.

SYNOPSIS: In a retrospective cohort study, empiric anti-methicillin-resistant Staphylococcus aureus treatment was not associated with a reduction in mortality in any subgroup of patients studied and appeared to cause harm in many.

SOURCE: Jones BE, Ying J, Stevens V, et al. Empirical anti-MRSA vs standard antibiotic therapy and risk of 30-day mortality in patients hospitalized for pneumonia. JAMA Intern Med 2020; Feb 17. doi: 10.1001/jamainternmed.2019.7495. [Epub ahead of print].

Investigators conducted a retrospective, multicenter cohort study of all hospitalizations in which patients received anti-methicillin-resistant Staphylococcus aureus (MRSA) or standard therapy for community-acquired pneumonia (CAP) in the Veterans Health Administration healthcare system from Jan. 1, 2008, to Dec. 31, 2013. Subgroups of patients analyzed included those with intensive care unit (ICU) admission, MRSA risk factors, positive results of a MRSA surveillance test, and positive results of a MRSA admission culture. Among 88,605 hospitalized patients (86,851 men; median age, 70 years), empirical anti-MRSA therapy was administered to 33,632; 8,929 patients (10%) died within 30 days. Compared with standard therapy alone, in a weighted propensity score analysis, empirical anti-MRSA therapy plus standard therapy was significantly associated with an increased adjusted risk of death (adjusted risk ratio [aRR], 1.4), kidney injury (aRR, 1.4), more secondary Clostridioides difficile infections (aRR, 1.6), more vancomycin-resistant Enterococcus spp. infections (aRR, 1.6), and more secondary gram-negative rod infections (aRR, 1.5). The authors found similar associations between using anti-MRSA therapy and 30-day mortality (aRR, 1.6), and among patients admitted to the ICU (aRR, 1.3), with a high risk for MRSA (aRR, 1.2), and with MRSA detected on surveillance testing (aRR, 1.6). There was no significant favorable association between empirical anti-MRSA therapy and death among patients with MRSA detected on culture (aRR, 1.1).

COMMENTARY

This was an interesting study that certainly casts doubt on the current widely accepted practice of administering empiric anti-MRSA therapy to a large percentage of patients admitted to the hospital with CAP, especially elderly patients, those recently (or remotely) hospitalized, and patients coming from skilled nursing facilities. Although this study certainly featured a robust sample size, I cannot help but think one of the reasons this retrospective study appeared to show “harm” from empiric anti-MRSA therapy is that some subtle factors influenced clinicians to preferentially prescribe empiric anti-MRSA therapy to sicker patients. The fact that even those who tested positive for MRSA and those who returned a positive MRSA surveillance screening test did not benefit from empiric anti-MRSA therapy is particularly counterintuitive. This may be related to the relatively poor positive predictive value of isolation of S. aureus from expectorated sputum and can reflect oropharyngeal colonization rather than the etiologic agent of the pneumonia.

Although there were limitations (which the authors acknowledged), the results should seriously call into question the common practice of administering empiric anti-MRSA therapy to most patients with CAP. Not only did most patients fail to benefit, but many were harmed by this practice.

Clearly, clinicians need better diagnostic tests for rapidly determining the etiology of CAP. Of course, both new and old anti-MRSA antibiotics should be studied in well-designed, prospective, randomized trials.