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Oral or intravenous antibiotics for bone and heart valve infections?

Antibiotics are a miracle, killing the bacteria that might otherwise kill us. They are also dangerous, with side effects that can be fatal as well as merely annoying. They kill good bacteria as well as bad ones, disturbing the delicate balance of the bacterial communities with which we share our bodies.

Intravenous antibiotics can work quickly to forestall life threatening blood stream infections and can reach high levels in the blood and penetrate structures such as bone, eventually eradicating infections that might hide out and cause chronic infection. Oral antibiotics, however, are also very powerful and are sometimes absorbed so well that they are just as effective as intravenous (IV) ones.

Whether to use oral or IV antibiotics is based on several considerations, but we usually believe that infections on the heart valves or in the bone or joint or artificial joints require IV antibiotics. Long term treatment with IV antibiotics can be logistically difficult. Consider these two pretty common scenarios:

1. A 35 year old man, recently diagnosed with diabetes, but probably an untreated diabetic for years, comes into the clinic with a sore and smelly wound on his foot. When it is cleaned up, it is deep and you can feel bone through the hole. A diagnosis of osteomyelitis is made, since the exposed bone means there is infection there. A central intravenous catheter is placed, a procedure that costs nearly $2000.00 and he is told he will need to be on IV antibiotics for 8 weeks. His insurance won't pay for a home health nurse to administer the antibiotics so he remains in the hospital. He loses his job and his portion of the hospital bill after insurance pays their part bankrupts him and his family.

2. A young woman is hospitalized with a high fever. She has various lab abnormalities and eventually her blood cultures grow Staphylococcus aureus. She admits to using intravenous drugs sometimes. She is started on IV antibiotics which she will need to be on for 6 weeks. A central venous catheter is inserted because it is difficult to maintain an IV in her scarred veins. She can't be discharged with the central venous catheter because she will probably use it to inject her recreational drugs, thus creating a new infection. She stays in the hospital for the duration of her treatment, getting progressively bored and being emotionally explosive, straining caregivers' capacity. She develops a blood clot in her central catheter, requiring a course of anticoagulant. The final bill for her hospitalization, picked up by Medicaid, is over $100,000.

We have treated bone, joint, prosthetic joint and heart valve infections with prolonged courses of IV antibiotics for many years because the consequences of these infections not being cleared up is potentially devastating. But do we really need to continue the IV route for the whole course of treatment?

Today in the New England Journal of Medicine (NEJM) I read reports of two studies evaluating shorter courses of IV antibiotics followed by oral antibiotics.

Dr. H.-K. Li and colleagues at Oxford conducted the OVIVO trial (oral vs IV antibiotics for bone and joint infections.) Participants in the treatment group got IV antibiotics for at least 7 days (or 7 days from operation) and were then switched to an oral antibiotic which was appropriate to their infection, per cultures or clinical judgment. The control group received IV antibiotics for the whole time. They recruited over 1000 patients and found that the longer duration of intravenous antibiotics was no better, in fact might have been worse, than going to oral antibiotics after a week. The relapse rate in the oral antibiotic arm was 13.2% and for the long term IV antibiotic arm, was 14.6%. Patients received very long antibiotic courses, an average of 78 days in the IV group and 71 days in the oral antibiotic group.

Dr. Kasper Iverson from University of Copenhagen Hospital and colleagues for the POET (partial oral endocarditis treatment) study showed no superiority of prolonged antibiotics for heart valve infections.  Patients with infections involving the aortic or mitral valve, even those involving artificial valves, were no more likely to have recurrences of their valve infections or complications such as cardiac surgery, emboli or death in the 6 months after treatment.

The practice of using prolonged courses of IV antibiotics for these serious infections is strongly ingrained in us. We feel that we can be more sure of success with IV therapy. We should probably question this practice. There are too many sacrifices for our patients who are subjected to long courses of IV therapy. With an epidemic of intravenous drug abuse, obesity and diabetes, the incremental suffering and costs of extra weeks of IV therapy will continue to have increasingly negative impacts.

We should be wary of changing our practice precipitously. These studies aren't entirely representative of our situations, since the antibiotics available in Denmark are different than those available to us in the US and the populations in England and Denmark may be different in how well they take their antibiotics after discharge. It will be important to do similar studies in US hospitals. In the mean time, this does suggest that we should consider switching to oral antibiotics earlier than we have done when long term IV antibiotics may be harmful or impossible.





Comments

dfactual.com said…
i think price control will help alot
Janice Boughton said…
Long term followup shows that the patients treated with oral antibiotics did not have more relapses. In fact, it looks like they do somewhat better!

https://www.nejm.org/doi/full/10.1056/NEJMc1902096?query=TOC

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