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Review
. 2020 May 1;180(5):769-777.
doi: 10.1001/jamainternmed.2020.0555.

Evaluation of a Paradigm Shift From Intravenous Antibiotics to Oral Step-Down Therapy for the Treatment of Infective Endocarditis: A Narrative Review

Brad Spellberg  1 , Henry F Chambers  2 , Daniel M Musher  3 , Thomas L Walsh  4 , Arnold S Bayer  5   6
Affiliations
Review

Evaluation of a Paradigm Shift From Intravenous Antibiotics to Oral Step-Down Therapy for the Treatment of Infective Endocarditis: A Narrative Review

Brad Spellberg et al. JAMA Intern Med. .

Abstract

Importance: The requirement of prolonged intravenous antibiotic courses to treat infective endocarditis (IE) is a time-honored dogma of medicine. However, numerous antibiotics are now available that achieve adequate levels in the blood after oral administration to kill bacteria. Moreover, prolonged intravenous antibiotic regimens are associated with high rates of adverse events. Accordingly, recent studies of oral step-down antibiotic treatment have stimulated a reevaluation of the need for intravenous-only therapy for IE.

Observations: PubMed was reviewed in October 2019, with an update in February 2020, to determine whether evidence supports the notion that oral step-down antibiotic therapy for IE is associated with inferior outcomes compared with intravenous-only therapy. The search identified 21 observational studies evaluating the effectiveness of oral antibiotics for treating IE, typically after an initial course of intravenous therapy; none found such oral step-down therapy to be inferior to intravenous-only therapy. Multiple studies described an improved clinical cure rate and an improved mortality rate among patients treated with oral step-down vs intravenous-only antibiotic therapy. Three randomized clinical trials also demonstrated that oral step-down antibiotic therapy is at least as effective as intravenous-only therapy in right-sided, left-sided, or prosthetic valve IE. In the largest trial, at 3.5 years of follow-up, patients randomized to receive oral step-down antibiotic therapy had a significantly improved cure rate and mortality rate compared with those who received intravenous-only therapy.

Conclusions and relevance: This review found ample data demonstrating the therapeutic effectiveness of oral step-down vs intravenous-only antibiotic therapy for IE, and no contrary data were identified. The use of highly orally bioavailable antibiotics as step-down therapy for IE, after clearing bacteremia and achieving clinical stability with intravenous regimens, should be incorporated into clinical practice.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Spellberg reported receiving consulting fees from Alexion, Paratek, Acurx, Shionogi, Klaris, Merck; and owning equity in Motif, BioAIM, Synthetic Biologics, Mycomed, and ExBaq. Dr Walsh reported receiving consulting fees from Accelerate Diagnostics. Dr Bayer reported grants from ContraFect Corporation and grants from Roivant Pharmaceuticals outside the submitted work. No other disclosures were reported.

Figures

Figure.
Figure.. Considerations for Oral Step-Down Antibiotic Therapy for Infective Endocarditis
Q indicates question.
See this image and copyright information in PMC

References

    1. Northey EH. The Sulfonamides and Allied Compounds. Reinhold Publishing, Inc; 1948.
    1. Lichtman SS. Treatment of subacute bacterial endocarditis: current results. Ann Intern Med. 1943; 19:787–704. doi:10.7326/0003-4819-19-5-787 - DOI
    1. Finland M Treatment of bacterial endocarditis. N Engl J Med. 1954;250(10):419–428. doi:10.1056/NEJM195403112501005 - DOI - PubMed
    1. Finland M Treatment of bacterial endocarditis. N Engl J Med. 1954;250(9):372–383. doi:10.1056/NEJM195403042500906 - DOI - PubMed
    1. Marshall EK, Emerson K Jr, Cutting WC. Para-aminobenzenesulfonamide: absorption and excretion: method of determination in urine and blood. JAMA. 1937;108:953–957. doi:10.1001/jama.1937.02780120023005 - DOI

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