By Dean L. Winslow, MD, FACP, FIDSA

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: Investigators evaluated 135 patients with Staphylococcus aureus bacteremia (SAB) in a prospective cohort study comparing early switch to oral linezolid to continued treatment with standard parenteral therapy (SPT). Patients with complicated SAB and osteoarticular infection were excluded. Early switch to oral therapy yielded similar outcomes to continued SPT and allowed earlier hospital discharge.

SOURCE: Willekens R, Puig-Asensio M, Ruiz-Camps I, et al. Early oral switch to linezolid for low-risk patients with Staphylococcus aureus bloodstream infections: A propensity-matched cohort study. Clin Infect Dis 2018; doi:10.1093/cid/ciy916. [Epub ahead of print].

The authors conducted a prospective cohort study of Staphylococcus aureus bacteremia (SAB) in adult patients at a university hospital in Spain over four years. Investigators compared the efficacy, safety, and hospital length of stay for patients who received standard parenteral therapy (SPT) for the duration of their treatment course and for patients who switched from SPT to oral linezolid between days 3-9 of treatment. The researchers excluded patients with complicated SAB and osteoarticular infections from the study.

The researchers analyzed 45 patients in the linezolid group and 90 patients in the SPT group. Sources of SAB included IV catheter-related (50%), unknown origin (20%), and skin and soft tissue (17%). Patients in the groups were comparable, although less chronic renal disease was seen in the linezolid-treated patients. There were no differences in 90-day relapse rate (2.2% in the linezolid group and 4.4% in the SPT group) or the 30-day mortality rate (2.2% for linezolid and 13.3% for SPT; P = 0.08). The median hospital length of stay was significantly shorter in the group that received linezolid than in the group that received SPT (eight days vs. 19 days; P < 0.01).

COMMENTARY

In selected patients with SAB, an early switch from IV antibiotics to oral linezolid until treatment completion results in similar clinical outcomes and allows for earlier discharge from the hospital. The outcomes should be convincing to physicians that the strategy of switching early from IV to oral treatment of SAB is appropriate, with the caveat that patients in this study were highly selected.

Exclusions for “high risk” SAB included patients with persistent positive blood cultures after three days or more of appropriate SPT, septic thrombophlebitis, endocarditis, vascular graft or other endovascular infection, metastatic foci of infection, device-related infection, and osteoarticular infection. The exclusion of osteoarticular infection from this study was a bit surprising since pediatricians have been comfortable for years with early switch from IV vancomycin or IV beta-lactam to oral antibiotics (often clindamycin) in bacteremic bone and joint infections due to S. aureus. The safety and efficacy of this has been demonstrated in large studies.1 (In one study cited below, researchers studied 265 children with acute bone or joint infections proven by cultures. All of the patients received two to four days of IV antibiotic treatment followed by oral antibiotics. Whether the patients had positive blood cultures on admission or not, researchers found that the clinical outcomes and inflammatory biomarker resolution were the same.)

Antibiotics such as linezolid and clindamycin are particularly attractive in bone and joint infections since they have nearly 100% oral bioavailability. Both drugs also are lipophilic, so they achieve good tissue levels in bones, joints, and other tissues. Linezolid can be problematic when used for > 2-3 weeks because it displays mitochondrial toxicity. Thrombocytopenia, peripheral neuropathy, and lactic acidosis can be seen with prolonged use.

I also found it interesting that in this trial from Europe, median antibiotic treatment duration was 15 days in both arms of the study. Relapse rates also were incredibly low in both arms (4.4% and 2.2%). Treatment of low-risk SAB for just 14-15 days was a common practice when I trained in the late 1970s. However, I have noticed progressive “duration creep” of IV antibiotic courses for SAB over my career, with SAB patients commonly receiving four to six weeks IV antibiotics even when endocarditis and other high-risk conditions have been excluded. This study should reassure clinicians that short-course oral therapy of low-risk SAB often is appropriate. I also hope that the IDSA practice guideline currently under development will help provide clinicians with better guidance in selecting duration of treatment regimens and early conversion of SPT to oral antibiotics.

REFERENCE

  1. Paakkonen M, Kallio PE, Kallio MJ, Peltola H. Does bacteremia associated with bone and joint infections necessitate prolonged parenteral antimicrobial therapy? J Pediatric Infect Dis Soc 2015;4:174-177.