Some conditions, such as bone and joint infections and endocarditis, are managed with prolonged courses of intravenous antibiotics. There is little evidence to guide the duration of intravenous therapy and whether oral antibiotics can be used.
Bone and joint infections
The Oral versus Intravenous Antibiotics for Bone and Joint Infection (OVIVA) trial was conducted at multiple centres across the UK.16 It compared early switching (within one week) from intravenous to oral therapy to continuing intravenous antibiotics for at least six weeks. It included all adults with suspected bone and joint infections, irrespective of surgical intervention or antibiotic choice, who were planned to receive at least six weeks of antibiotic therapy. Comparing the outcomes at one year suggested that appropriately selected oral therapy is non-inferior to intravenous therapy. However, there are several important caveats:
- the trial was not powered to evaluate the outcome between different types of infection
- Gram-negative infections were under-represented
- most patients had surgical management of the infection
- rifampicin was used as a treatment option in approximately one-third of the cohort
- the clinicians managing the patients were specialist-led teams.
Although the events were not necessarily related to the antibiotics, one in four patients experienced a serious adverse event. This shows that ongoing monitoring is still required even with an oral antibiotic regimen.16,17 Further studies are required to look more closely at the different types of infection and the varying antibiotic regimens. Ideally these trials should be performed in the Australian healthcare system.
Endocarditis
The Partial Oral Treatment of Endocarditis (POET) trial was a study of left-sided endocarditis caused by streptococci, Enterococcus faecalis, Staphylococcus aureus or coagulase-negative staphylococci. The patients were randomised to either receive intravenous drugs for the full course of therapy, or for a minimum of 10 days followed by oral therapy. Patients were clinically stable before the switch and required transoesophageal echocardiography to confirm the response to treatment. Oral antibiotic regimens were designed to include at least two drugs with different mechanisms of action and were based on pharmacokinetic–pharmacodynamic analyses to enhance synergy and decrease the risk of resistance.18
There was no difference in a composite end point of all-cause mortality, unplanned cardiac surgery, embolic events or relapse of bacteraemia from the primary pathogen. A subsequent analysis at 3.5 years showed similar results.18,19
Important caveats on these results included the heterogeneity in the bacterial pathogens being treated and the antibiotic combinations used and the lack of infections with multiresistant organisms. Few patients had cardiac devices or were injecting drug users. The study was also led by physicians in specialist centres.20