Setting the Scene

Evidence has emerged from trials (POET & OVIVA) that an earlier switch to oral antimicrobials in bone and joint infections and endocarditis is as clinically effective as prolonged IV therapy, in selected patient groups.

In future, an increasing proportion of patients with serious infections are likely to be switched from IV to oral antimicrobials earlier in their clinical pathways. Or treated from the start using high dose, complex oral regimes that require a systematic approach to monitoring of both the antimicrobial regimen and clinical progress.

This shift has already begun with an increase in the use of intravenous (IV) antimicrobials and complex oral antimicrobial regimens within various outpatient or community-based clinical environments.

Infections managed by OPAT services are diverse, but include bloodstream, brain, bone & joint, cardiac, and renal tract infections, and many others. A fuller list can be seen here.

This has occurred within the context of:

• a rise in serious and/or resistant infections

• increasing recognition of the importance of discharging patients from hospital as soon as possible after clinical stability has occurred

• avoiding admission to hospital

In a UK-based study by Dryden et al, 1 in 8 hospitalised patients prescribed systemic antibiotics were considered suitable for discharge with ongoing outpatient oral therapy; the authors considered that some form of non-general practitioner, outpatient-based enhanced monitoring was necessary for all of these patients.

Oral antimicrobial regimens commonly prescribed and monitored by the Hull OPAT Service

Adverse effects

Oral antibiotics are common causes of drug-related adverse effects. In the USA, for example, sulfonamides, penicillins and quinolones are the most commonly implicated antibiotic classes in drug-related adverse effect presentations to emergency departments. Therefore, enhanced monitoring is required.

Perhaps the best example of an oral antibiotic that requires enhanced monitoring in the outpatient setting is Linezolid, which is 100% bioavailable via the oral route (if intact) resulting in therapeutic concentrations in many body tissues. It has activity against a wide-range of Gram-positive bacteria including those resistant to first-line antibiotics. It is therefore an attractive option when switching from IV to oral antibiotics, or for oral therapy from the start, when treating serious Gram-positive infections requiring an antibiotic with such characteristics.

Linezolid has potentially serious adverse effects (AEs), however, in particular, bone marrow suppression and, less frequently, neuropathy: mandating weekly enhanced monitoring for prolonged therapy.

Likewise, some oral Gram-negative agents, such as Chloramphenicol and Co-trimoxazole, also require monitoring – the exact requirements of which are sometimes dependent upon the nature of the patient being treated (i.e. comorbidity and medications) and the antimicrobial regimen prescribed.

This course considers two aspects of practice in the outpatient environment:

1) Switching from IV to oral antibiotics at the end of a course of OPAT.

2) Monitoring complex oral antibiotic regimens within an OPAT service (increasingly referred to as complex oral and parenteral antibiotic therapy or COPAT).

Andrew Seaton and Mark Gilchrist consider the basic, fundamentals of OPAT within their complementary FutureLearn course OPAT.

You may also find some chapters in the free BSAC e-book Antimicrobial Stewardship – From Principles to Practice useful too.