Oral Treatment for Infective Endocarditis

Do I need to be hospitalized?

The principles of drug therapy for infective endocarditis (IE) emerged at least 50 years ago, based on clinical experience and through trial and error in the course of treatment.

The current practice, established in the guidelines, with the administration of bactericidal parenteral therapy, 4 to 6 weeks, has grown after unsuccessful treatment attempts with less aggressive therapies. Historically, patients who remained hospitalized for most of their treatment received inpatient parenteral antibiotic therapy, bed rest, daily evaluation for signs of cardiac infection continuously, signs of heart failure, heart block or arrhythmia, embolic complications of IE and side effects of antibiotics. Approximately 25% of these patients needed valve replacement surgery as part of the IE therapy during the hospital stay, due to the disease’s aggressiveness.

There are publications dated from two decades on home treatment of IE with parenteral antibiotic therapy, although with limited series of studies and often with poor outcomes. They also lack robust studies to support the indication. Over the years, therapy has been established with strict criteria that were defined by Infectious Diseases Society of America (IDSA) in 2001, criteria that are still used in the series of studies today.

Recently, January 2019, a retrospective analysis of data from a multicenter cohort study of 2000 consecutive IE patients was published in 25 Spanish hospitals from 2008 to 2012. They compared outpatient parenteral antibiotic treatment (OPAT) with hospital-based antibiotic treatment (HBAT). In this study, it was observed that outpatient treatment achieved good results, despite applying broader inclusion criteria than those used by IDSA, which demonstrated the current criteria should be expanded.

Another major publication, in the New England Journal of Medicine (NEJM), August 2018, suggested the change from intravenous to oral antibiotics, once the patient is in a stable condition, which would result in efficacy and safety, similar to those with continuous intravenous treatment. In this randomized, multicenter, non-inferiority study, 400 patients with IE, 199 were selected to continue intravenous treatment and 201 to switch to oral treatment. After at least 10 days of intravenous treatment in patients with endocarditis in the left chambers who were in a stable condition, the switch to treatment with oral antibiotics was not inferior to treatment with continuous intravenous antibiotics. However, the study had many limitations, for instance, patients with IE on the right side, presence of intracavitary devices and infections by certain bacteria were not included, which excluded at least 25% of infections by unusual germs or with negative culture, among others. These limitations, perhaps, hamper the extrapolation of results.

Notes:

  • Although there are studies demonstrating both the use of parenteral therapy and partial oral therapy, in general, it is clear that there is still no consensus on which patients would benefit, perhaps the least serious, but the risk of complication still brings concerns.
  • When it comes to infection, we know that the environment and hospital flora change from region to region and from hospital to hospital. Therefore, before establishing which best treatment, it is necessary to know the infection and the bacteria, as well as antibiotic sensitivity for each germ found.
  • Once partial oral treatment is indicated, it is important to know that it will be done by a combination of two or more classes of antibiotics, a concerning component, as the result depends on patient compliance, associated with the non-occurrence of side effects that lead to treatment interruption, possibly impacting on results.
  • In regards to this context, the risk of complications of the disease, due to many restrictions and pitfalls, is not the best time to start partial oral therapy. Let us continue with residential parenteral therapy (home-care) and after further studies we may transition to partial oral. (Editorial team opinion).

Suggested literature:

  1. Iversen, K, Ihlemann, N, Gill, Su, et al. Partial Oral versus Intravenous Antibiotic Treatment of Endocarditis. New England Journal of Medicine. doi:10.1056/nejmoa1808312.
  2. Andrews, M, von Reyn, CF. Critérios de Seleção de Pacientes e Diretrizes de Manejo para Terapia Antibiótica Parenteral de Ambulatório para Endocardite Infecciosa de Válvula Nativa. Clinical Infectious Diseases, 33 (2), 203–209.
  3. Pericàs, JM, Llopis, J, González-Ramallo, et al. Outpatient Parenteral Antibiotic Treatment (OPAT) for Infective Endocarditis: a Prospective Cohort Study From the GAMES Cohort. Clinical Infectious Diseases. doi:10.1093/cid/ciz030.

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