As an Infectious Disease physician, I see many patients with osteomyelitis, or infection of the bone. It’s a common infection especially in patients with diabetes, poor circulation, and following joint replacement.
It’s not often I am struck by what appears to be a game-changing study. The OVIVA study should be practice changing for patients with bone infections. This Oral Versus Intravenous Antibiotics for Bone and Joint Infection trial just found that oral antibiotics are as efficacious as IV (intravenous) antibiotics, so should greatly improve the quality of life for patients, as well as reducing hospitalization costs. OVIVA is better than earlier studies as it was randomized and more representative of clinical practice.
Osteomyelitis can occur by several routes—spread by a bloodstream infection, following trauma, especially if there is an open wound (like with diabetes or poor circulation), from spread of an adjacent infection, or postoperatively.
In the US, there were 332,000 total hip and 719,000 total knee replacement surgeries in 2010—and the numbers are expected to increase to 572,000 and 3.48 million by 2030, given the aging population. The incidence of postoperative joint infection is 1-2%, with most occurring in the first two years following surgery. Risk factors for infection include age, obesity, diabetes, and other immunosuppression.
Consequences of infection are significant—infections of bones and joints often require surgical as well as medical treatment. Prosthetic joint infections are often treated with removal of the implant followed by at least six weeks IV and localized antibiotics before a prosthesis can be reimplanted, or replaced. Sometimes, an immediate reimplantation of a prosthesis was done after an infected one was removed. This “one-stage revision” occurred in ~8% of study patients and 23% were able to only have the one surgery to replace the infected joint. This is higher than what I have seen in consultation, where a 2-stage revision is more common.
Complications of osteomyelitis treatment include infections from IV lines, blood clots, and problems from prolonged inpatient stays, as many of these patients have to stay in a nursing home because of Medicare’s arcane rules, which don’t cover home IV antibiotic therapy, although it is safer and cheaper than institutionalization.
Dr. Paul Sax, of Harvard’s Brigham and Women’s Hospital explains the OVIVA study findings in a quite humorous and creative fashion, reporting results as an “interview,” where he is playing both roles. At one year’s follow-up, treatment failures occurred in 15% of those receiving IV antibiotics vs. 13% in the oral group.
In this British study, 1054 patients were randomized to oral or IV antibiotic therapy after initiating treatment with IV drugs. Specific drugs were at the discretion of the treating physician—a real world scenario.
Patients received a median of 10 weeks of antibiotic treatment. Serious adverse events occurred in about a quarter of participants in each group, but antibiotic related events such as severe allergy were more common in the IV group (13.6 vs. 6.7%). Kidney injury was 4x more common in the oral group. I don’t understand why this would occur, given the antibiotic choices, unless patients became dehydrated.
For IV treatment, about 40% of patients were intended to receive antibiotics to cover MRSA infections, another ~40% cephalosporins, both of which are standard choices.
For oral treatment, quionolones (e.g., Levaquin, Cipro) were given to 36%, clindamycin (Cleocin) in 13%. Other antibiotic classes were used less often than they might be in the US, and no definitive recommendation could be made about optimal therapy.
Most unexpectedly and inexplicably, C. difficile colitis only occurred in a small number of study patients (1.7 vs. 1%).
C. difficile colitis is 7-10x more likely in patients on antibiotics than others and is estimated to occur in 13 per 1000 hospitalized patients in the US. It has also been increasing in the community in recent years. Age is another risk factor for C. diff and deaths from this infection. Cumulative antibiotic exposure—especially to clindamycin and quinolones—are additional risks. Thus, the incidence of C. diff complications in this British study is remarkably low.
Unsurprisingly, there were fewer complications from IVs in those who only received them short periods before being changed to oral meds, than those who had IVs for more than 4 weeks.
In sum, oral treatment of bone infections reduced hospital length of stay and associated costs and complications of therapy.
Will this be adopted in the US? It may take a while, as guidelines will be debated and rewritten. Some of us have been treating some patients with oral antibiotics for years, having weighed the risks and benefits for our particular patients, but this practice has raised eyebrows, especially from surgeons.
It’s unclear what the best antibiotic choices would be in the US as a whole or in specific regions—clindamycin would likely be riskier here, as C. diff is more common in the US than Britain. Also the heavy use of quinolones is a concern to me, because they are a risk both for C. difficile colitis and for increasing MRSA infection.
Every antibiotic has side effects—especially allergic reactions from penicillins and sulfa, but hospitalization rates following Emergency Room visits were higher (14.5%) for quinolones than all other classes of antibiotics.
I particularly hesitate to use quinolones in my elderly patients. I worry about their neurologic effects, which include insomnia, hallucinations, and dizziness—serious problems especially in elderly patients. Quinolones can also cause hypoglycemia, tendon rupture and, most recently, reports of aortic aneurysms (tears of the aorta, the main artery from the heart) and deaths.
Nonetheless, oral antibiotic treatment has significant advantages—reducing costs by thousands of dollars per day, risk of bloodstream infections from prolonged IV catheterization, and has a lower risk of superinfections. It’s an example of “pick your poison,” but it is great to be more confident in treating our patients with oral antibiotics—or IV, if that appears safer for that individual.