COMMENTARY

Oral Antibiotics for Infective Endocarditis: Time to Switch?

Paul G. Auwaerter, MD

Disclosures

October 31, 2018

This is Paul Auwaerter with Medscape Infectious Diseases, speaking from the Johns Hopkins School of Medicine.

I've taken care of patients for more than 30 years in this area at Johns Hopkins Hospital, where endocarditis is a fairly common request for consultation. Trainees and faculty are often faced with difficult decisions in patients who may not be great candidates for the traditional 4-6 weeks of intravenous (IV) antibiotic therapy, whether it's because they are threatening to leave against medical advice, they don't have the financial wherewithal for home-based therapy, or they have substance abuse issues that would affect the likelihood of success if they were to have an IV line in place. Ethical issues aside, I've always been amazed at the number of patients who did not receive full courses of therapy, yet they don't seem to come back with repeat bouts of endocarditis.

A more structured approach in terms of what can be accomplished has been investigated. In fact, here at Johns Hopkins over 20 years ago, the hospital funded a study[1] in 85 patients that looked at whether oral antibiotic therapy (OAT) would be equivalent to standard IV therapy. The IV therapy was established years ago in the 1940s when lower-dose penicillin did not seem to cure endocarditis, but high-dose IV penicillin did.[2] Penicillin combined with streptomycin seemed to be much more effective against enterococcus, so IV antibiotics have been the standard of care for decades, based on clinical and animal model data.[2]

The OAT study was the first randomized clinical trial that looked at the use of oral therapy (ciprofloxacin and rifampin) compared with IV oxacillin and vancomycin (plus gentamicin for 5 days). They found similar outcomes, with markedly fewer adverse outcomes in the oral treatment arm. The study, unfortunately, didn't change behavior dramatically in terms of adoption, although oral antibiotics are often listed as an option for infective endocarditis. Some of the hesitation to adopt oral antibiotic therapy was due to fear of resistance with the use of fluoroquinolones for staphylococci, even when combined with rifampin. Others pointed to methodological and blinding issues with the study, which were felt to make the study less robust, so the findings weren't widely adopted.

Studies have looked at other strategies for treating endocarditis in patients who might not be well suited to the traditional 4-6 weeks of therapy. These have included such innovative approaches as home-based self-administered outpatient parenteral antimicrobial therapy, without nursing help, in patients with limited financial resources.[3] Also, long-acting IV antibiotics such as dalbavancin have been examined for partial treatment, including a recent study[4] from Austria where, after initial traditional therapy, patients successfully completed therapy with a long-acting antibiotic such as dalbavancin. Oral antibiotic therapy has also been examined in small case series and subjected to a systematic review,[5] which at least seemed to have some favorable aspects.

From a biological perspective, a well-absorbed oral antibiotic should be equivalent to an IV antibiotic, but we all know that there are issues on either side which can be argued. So I think it's with some interest that one of the most robust studies examining whether oral therapy may be helpful was the POET (Partial Oral vs Intravenous Antibiotic Treatment) study,[6] which didn't really look at stem-to-stern oral therapy, but rather at partial oral antibiotic therapy of endocarditis.

This study was performed in 400 patients randomized to IV or oral therapy after an initial 10 days of IV therapy. The primary endpoint was a composite of all-cause mortality, relapse of bacteremia after 6 months, embolic events, and other complications. The composite outcome occurred in 12.5% of the IV group versus 9% of the oral therapy group. This was a noninferiority study, suggesting that oral antibiotic switch is an option for the management of endocarditis.

The infections in this study were caused by Enterococcus faecalis, Streptococcus, and coagulase-negative Staphylococcus, but not methicillin-resistant Staphylococcus, and few patients were using IV drugs; so the findings may not reflect the experience and needs here in the United States. However, I think it gives some indication that further studies of oral antibiotic therapy certainly should be entertained. Although oral therapy may pose logistical issues, some safety improvements might be achieved.

I don't think that with the severity of endocarditis, people are likely to switch from the IV route. I have an open mind and will be looking to use oral antibiotics a bit more rather than forcing patients who may not be predisposed to completing 4-6 weeks of antibiotic therapy to do so. This is an area that we will continue to look at, I believe, much like the advances on the diagnostic side. Our therapeutic interventions for endocarditis have not advanced dramatically over the years, mainly because such studies are very difficult and costly to do. I hope this stimulates renewed interest, and if there are similar confirmatory studies, there will be a change in a wider sense for practices.

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