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Review: Oral Step Down Therapy Effective for Infective Endocarditis

Use of prolonged IV antibiotics to treat infective endocarditis is outdated, and oral step-down therapy has been shown to be at least as effective.

Oral step-down antibiotic therapy is at least as effective as intravenous (IV)-only therapy for treating infective endocarditis (IE), according to a recent review.

The review, published in JAMA Internal Medicine, examined research that evaluated oral step-down therapy. Multiple studies found improved clinical cure and mortality rates, and none found the treatment to be inferior to IV-only treatment.

“There are extensive data to support the use of oral step-down antibiotic therapy for infective endocarditis, and no data to the contrary. It is time to incorporate routine use of oral antibiotic step-down therapy for selected patients,” Brad Spellberg, MD, FIDSA, FACP, chief medical officer at LAC+USC Medical Center, told Contagion®.

“The criteria for selecting those patients include: 1) Clinical stability; 2) Cleared bacteremia; 3) Absorb oral medications; 4) No psychosocial reasons to specifically prefer IV therapy; 5) A published oral regimen is available that has been shown to result in favorable outcomes and that is active against the causative bacteria.”

The review included 21 observational or quasi-experimental studies and 3 randomized clinical trials that examined the effectiveness of oral antibiotic treatment for IE.

Among the findings, 12 of the publications revealed cure rates of 77% to 100% for IE patients who received oral β-lactams, oral ciprofloxacin plus rifampin, or oral linezolid monotherapy regimens to treat traditional IE pathogens like streptococci, staphylococci, and enterococci.

“The biggest surprise was the total absence of contrary data,” Spellberg told Contagion®. “The incredibly deep dogma that therapy must be IV for endocarditis derives from poor outcomes of sulfanilamide, erythromycin, and tetracycline from 75-80 years ago. There are no contrary data with modern oral antibiotics. The dogma is entirely based on the eminence of old-school clinicians from the 1950s-1960s who reflected the failure of old antibiotics that are poorly absorbed and achieve poor drug levels in blood.”

The review didn’t conclude whether an initial IV course was needed, but said that it is reasonable to step down to oral treatment after a patient is stable and without bacteremia. The studies that were reviewed included an initial course of intravenous with durations ranging from only that given in emergency departments prior to admission, to 7 days, to 18-24 days.

“Medicine needs to adapt as new data come along,” Spellberg told Contagion®. “Prolonged IV therapy is dangerous. It causes harm—10-60% rate of DVT, line sepsis, catheter fracture and migration, and central venous stenosis. We should be routinely using safer oral therapy now that we know that it is as least as effective as prolonged IV therapy.”

Authors of the review are affiliated with Los Angeles County + University of Southern California Medical Center; University of California, San Francisco; Baylor College of Medicine; Allegheny General Hospital; Lundquist Institute for Biomedical Innovation; and The Geffen School of Medicine, University of California, Los Angeles.

Spellberg said next steps include continuing conversations about oral therapy, ensuring that it is put into societal guidelines and ensuring that health care payers are on board.

IE is a concern amid the opioid crisis, as people with substance use disorder are at substantial risk for such infections, according to a retrospective cohort study published in Clinical Infectious Diseases, which found that the proportion of hospitalizations for IE accompanied by a diagnosis of substance use disorder increased from 19.9% to 39.4% between 2012 and 2017.