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Clinical efficacy and cost effectiveness of OPAT

PRACTICAL THERAPEUTICS
Outpatient parenteral antimicrobial therapy is clinically efficacious and cost effective compared with inpatient care when assessed in a range of healthcare settings

Vicky Goodall
Chris Winnard
Department of Pharmacy
Ann LN Chapman BM BCh FRCP DTM&H PhD
Department of Infection and Tropical Medicine, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
Email: Ann.Chapman@sth.nhs.uk 
As healthcare systems across Europe strive to achieve ever-increasing levels of excellence in relation to efficacious and cost-effective treatments, patient satisfaction with services has become an increasingly important factor. Outpatient parenteral antimicrobial therapy (OPAT) is a service first piloted in the US in the 1970s, which, if delivered well, can address all of these issues. OPAT involves the administration of antimicrobials in an outpatient setting. 
This can be delivered in the patient’s own home (through self-administration or utilising the skills of district nursing or private nursing teams) or through daily attendance at a hospital or community clinic. OPAT is now practised in a number of countries across Europe, including the UK, Italy, Spain and Germany(1,2) and its use is likely to increase, given its advantages over traditional inpatient care.
An OPAT service clearly has many benefits: reduced inpatient stay results in lower costs from fewer overnight stays in hospital (bed day saving), a reduced risk of hospital-acquired infections, the more rapid return of patients to their own home, and the possibility of an earlier return to work, which will aid the wider economy and have benefits for the patient. However, such a service is not without clinical risk and it is imperative that patients using this service receive treatment of the same standard as that afforded to inpatients.(3) Different cost pressures also apply, and the need to evaluate the clinical efficacy and cost effectiveness of any such service should not be overlooked.(3–6)
Clinical efficacy
When evaluating clinical efficacy, there are a variety of parameters that might be considered, relating both to the patient and to the OPAT service itself. Some centres list a comprehensive set of criteria;(4) however, others have classified clinical outcomes more simply, for example, the UK National OPAT Patient Management System (Table 1).(3,6,7) It is hoped that this new resource will enable information regarding clinical outcomes to be shared between centres, and will provide a useful resource for others looking to establish and assess their OPAT services.(7)
Many studies have demonstrated that OPAT is indeed an effective and safe service.(2,5,6,8) Corwin and colleagues assessed the efficacy, safety and acceptability of IV antibiotic therapy delivered through OPAT in the home compared with the in-patient setting.(8) A total of 200 patients with cellulitis were randomised to homecare (101 patients) or hospital care (99 patients). The primary outcome was time to no advancement of cellulitis, and the two treatment groups were shown to be not significantly different (1.5 days versus 1.49 days). Other outcome measures included time on intravenous and oral antibiotics, and again there was no statistically significant difference between the two groups.
Hitchcock et al report on a case series of 303 episodes of OPAT care.(5) Of these, 37% of episodes involved treatment of cellulitis; other patients had a range of infections including bone and joint infection (30%), deep abscesses, endocarditis, and urinary tract infection, demonstrating that, with the correct expertise and careful monitoring, OPAT need not be limited to skin and soft tissue infections. Readmission to hospital was required in 23 episodes (7.6%), and two patients lost vascular access, resulting in the early termination of OPAT. Of the remaining 273 episodes of care, over 95% of cases were resolved with a single course of antibiotics and few adverse events were reported. 
A series of 334 episode of OPAT care was reported by Chapman et al.6 Skin and soft tissue infections accounted for 59% of all episodes, with the remaining 41% comprising a variety of other infections. Clinical outcomes were recorded as improved/cured, readmitted, no change and change of plan. A total of 87% of patients across all diagnoses were classified as improved or cured (92% when including skin and soft tissue infections only). Twenty-one patients (6.3%) were readmitted, although 12 of these were for reasons unrelated to OPAT. The group also looked to address the issue of patient satisfaction. Of 449 patients surveyed, 276 responded (61%). 272 (98.6%) rated the service as very good or excellent, and 275 (99.6%) stated that they would choose the OPAT service again.
A report looking specifically at OPAT treatment of endocarditis included patients with risk factors deemed by some to preclude OPAT therapy, for example, infections caused by Staphylococcus aureus (S. aureus).(9) In this series, 34 of 36 episodes were treated successfully. Further case series have also demonstrated the clinical efficacy of OPAT for endocarditis when delivered through a formal service model, and OPAT is now included in European, UK and US guidelines on the management of endocarditis.(10,11) 
Matthews et al(12) reported on 2059 OPAT episodes over a period of 13 years. 
This report specifically addressed whether self-administration of antibiotics in the home (administration by either the patient themselves or a non-professional carer) was a safe practice, compared with healthcare professional administration. Of 2009 cases where detailed information was available, 473 patients self-administered their treatment. Of these, 84% of patients were diagnosed with musculoskeletal (including skin and soft tissue) infections, compared with 78% in the healthcare professional group. Complications and readmission to hospital were two of the main outcomes recorded. A total of 476 of 2009 patients had any complication recorded, of which 31% were unrelated to OPAT. Complications occurred equally across both groups, with 353 (23.2%) in the healthcare professional-administered group affected versus 112 (23.6%) in the self-administered group. Complications with the IV line were more prevalent in the self-administering group; however, the difference was not statistically significant.
Cost effectiveness
Costs associated with OPAT
The costs associated with running an OPAT service can be divided into two main groups: staffing costs and non-staffing costs. Chapman et al(6) estimated that it cost approximately £300,000 per year to run an OPAT service that treated 334 infections over a two-year period between 2006 and 2008. The staffing costs accounted for 42% of this expenditure. The majority of this cost was due to the employment of a team of specialist nurses to work specifically for the OPAT service. The non-staffing costs accounted for 56% of expenditure. This included payment for equipment and consumables and funding for the transport of patients. It also included payment of support services within the health organisation (for example, laboratory medicine, pharmacy, physiotherapy) and overhead costs (for example, domestic services, capital costs and charges). The other 2% of costs were related to two readmissions of patients due to complications that it was felt would not have occurred if the patients had been treated as inpatients.
Antimicrobials with a long half-life that can be administered once daily are the preferred option when prescribing for patients in OPAT services. This may require the use of more expensive antibiotics such as ertapenem or daptomycin. These agents were used infrequently in the study detailed above, and only 7% of the costs were due to expenditure on drugs. In addition, there was no expenditure on the use of ambulatory pumps, which are commonly used in other areas of the world, but are rarely used in the UK for parenteral antimicrobial administration. Ambulatory pumps have many benefits, which include increasing the number of drugs that can be used in the OPAT setting. In the UK, they are relatively expensive compared with standard intravenous administration.
OPAT versus inpatient care
Many studies have shown that antimicrobial treatment in an outpatient setting is cheaper than treating the same patients in hospital for the full antimicrobial course. Chapman et al6 also compared the cost of treating 334 patient episodes by the OPAT service with the equivalent theoretical cost of treating the same patients as inpatients. The cost of treatment using the OPAT service was £601,042. If the same patients had been treated as inpatients on an infectious disease ward, the cost would have been £1,502,769, which is more than double the OPAT cost. If the patients were treated on non-specialist wards (which are likely to have lower associated costs), then treatment as an inpatient would still cost £1,312,537 (using national average costs of inpatient treatment). Similar results have been shown in Canada, where the average cost per treatment course of OPAT was calculated to be CAN$1910 compared with an average cost of $14,271 per treatment course if the patient completed the full course of antimicrobial treatment in hospital.(13)
Other studies have examined the cost-effectiveness of OPAT for specific infections. Patients with bone and joint infections often need prolonged courses of intravenous antibiotics. Nathwani et al compared the cost of treating bone and joint infections with intravenous teicoplanin by OPAT with the theoretical cost of treating the same people as inpatients.(14) They quoted a cost of £1749 per case using OPAT services, compared with £11,400 per case if the patient had been treated in hospital. The authors also calculated the likely cost of treating the same patients with oral linezolid as an outpatient. In this scenario, the cost per case would be approximately £2546, which is nearly £800 more than teicoplanin administered through OPAT. The cost of linezolid tablets would have to reduce by 32% for the treatment costs to be similar.
A study in France also investigated the potential cost saving that could be made by treating 39 patients with osteomyelitis in the OPAT setting rather than as inpatients in hospital.(15) Some patients had very protracted parenteral therapy, and the patient group overall had a total of 2147 treatment days. The actual cost of OPAT, which included medication, staff and supply costs, was $129 per day, whereas the comparative daily inpatient cost was quoted as $710. The latter figure was based on the average daily direct variable cost for care in an infectious diseases or orthopaedic unit, although no information was given as to how this figure was derived. Using these cost figures, the authors calculated that using OPAT led to a saving of $1,873,885 compared with the theoretical cost of treating these infections as inpatients.
Bed day savings
Another advantage of OPAT services is the inpatient bed days that are saved if patients are discharged earlier. Matthews et al(12) showed that in one calendar year 6200 bed days were saved through discharge of patients into an OPAT service. These extra bed days may be used for new admissions, or may increase capacity for additional operations, which will increase income for the health organisation. It may also allow for the closing of some beds again with associated cost savings. There are some countries where payment for services is based on activity. If services delivered as an outpatient or at home are not included in this payment system, then OPAT could actually lead to the organisation losing revenue.
Associated costs
One of the perceived benefits of OPAT is the reduced risk of healthcare-associated infections. These have health implications for the patient but also cost implications for the health organisation. It has been estimated that an avoidable case of methicillin-resistant S. aureus bacteraemia costs £4300 per case to treat in hospital. Hospital-acquired infections are thought to cost the National Health Service in the UK over £1 billion a year to treat. Patients treated through OPAT services are at lower risk due to not having a long period of inpatient hospital stay. A study detailing the experience of a hospital-based OPAT service saved over 39,000 inpatient bed days over a ten-year period.(16) The authors found a very low rate of healthcare-associated infections. They reported a rate of 0.4 line infections and 0.05 cases of Clostridium difficile-associated diarrhoea per 1000 OPAT patients. There were also no reported cases of S. aureus bacteraemia in this period. 
Conclusions
All the above studies address OPAT delivery in specific settings, but what about the overall picture? A good view of this is provided by the European Surveillance of Antimicrobial Consumption,(1) which conducted a review of OPAT use across 20 European countries in 2006. The study looked at the proportion of outpatient antibiotics that were delivered via the parenteral route, expressed in defined daily dosage per 1000 inhabitants. The average across the 20 countries was 2.04%. However, a great variation in OPAT use was demonstrated, with Russia showing 6.75% compared with <0.02% in Finland, the Czech Republic and Iceland. Italy reported the second highest OPAT use, with almost 10% of all outpatient antibiotic scripts written in 1996 being for an injectable cephalosporin.(2) The variations seen can be attributed to many factors, including cost, infrastructure and basic prescribing practices.
What is clear is that since the idea of OPAT was raised in the 1970s, a wealth of experience from across Europe, Canada and the US has been gained. Numerous guidelines and supporting documents are available to help with the development and monitoring of an OPAT service.(3,4,7) The use of OPAT is likely to continue to increase, not only in secondary care but also with the development of entirely primary care-led services. Good antimicrobial stewardship must be a key principle, and this will ensure cost-effective use of antibiotics and an efficient switch to cheaper, oral agents when appropriate.(17) Pharmacists play a vital role in providing high quality pharmaceutical care in differing settings, and a clinical pharmacist should be an integral part of any OPAT team. 
Key points
  • Outpatient parenteral antimicrobial therapy (OPAT) is used throughout many parts of Europe and is likely to expand further.
  • OPAT is clinically effective when delivered through a formal programme.
  • OPAT is cost effective compared with inpatient care when assessed in a range of healthcare settings.
  • In addition to direct comparative cost effectiveness, there are further indirect cost–benefits through improved efficiency of inpatient bed use and reduced rates of healthcare‑associated infection.
  • Pharmacists play a key role in the OPAT team, in ensuring high-quality antimicrobial prescribing and stewardship.
References
  1. Coenen S et al. European Surveillance of antimicrobial consumption (ESAC): outpatient parenteral antibiotic treatment in Europe. J Antimicrob Chemother 2009;64:200–5.
  2. Esposito S. Outpatient parenteral treatment of bacterial infections: the Italian model as an international trend? J Antimicrob Chemother 2000;45:724–7.
  3. Chapman ALN et al. Good practice recommendations for outpatient parenteral antimicrobial therapy (OPAT) in adults in the UK: a consensus statement. J Antimicrob Chemother January 2012. [Epub ahead of print].
  4. Tice AD, Rehm SJ et al. Practice guidelines for outpatient parenteral antimicrobial therapy. IDSA guidelines. Clin Infect Dis 2004;38:1651–72.
  5. Hitchcock J et al. Establishment of an outpatient and home parenteral antimicrobial therapy service at a London teaching hospital: a case series. J Antimicrob Chemother 2009;64:630–4.
  6. Chapman ALN et al. Clinical efficacy and cost effectiveness of outpatient parenteral antibiotic therapy (OPAT): a UK perspective. J Antimicrob Chemother 2009;64:1316–24.
  7. British Society for Antimicrobial Chemotherapy OPAT UK Project. [Online]. http://e-opat.com/ (accessed 17 January 2013).
  8. Corwin P et al. Randomised controlled trial of intravenous antibiotic treatment for cellulitis at home compared with hospital. BMJ 2005;330:129–32.
  9. Partridge DG et al. Outpatient parenteral antibiotic therapy for infective endocarditis: a review of 4 years’ experience at a UK centre. Postgrad Med J 2012;88:3. 
  10. Gould FK et al. Guidelines for the diagnosis and antibiotic treatment of endocarditis in adults: a report of the Working Party of the British Society. J Antimicrob Chemother 2012;67:269–89.
  11. The Task Force on the Prevention, Diagnosis, and Treatment of Infective Endocarditis of the European Society of Cardiology (ESC). Guidelines on the prevention, diagnosis, and treatment of infective endocarditis. Eur Heart J 2009;30:2369–413.
  12. Matthews PC et al. Outpatient parenteral antimicrobial therapy (OPAT): is it safe for selected patients to self-administer at home? A retrospective analysis of a large cohort over 13 years. J Antimicrob Chemother 2007;60:356–62.
  13. Wai AO et al. Cost analysis of an adult outpatient parenteral antibiotic therapy (OPAT) programme. A Canadian teaching hospital and Ministry of Health perspective. Pharmacoeconomics 2000;18:451–7.
  14. Nathwani D, Barlow GD et al. Cost-minimization analysis and audit of antibiotic management of bone and joint infections with ambulatory teicoplanin, in-patient care or outpatient oral linezolid therapy. J Antimicrob Chemother 2003;51:391–6.
  15. Bernard L et al. Outpatient parenteral antimicrobial therapy (OPAT) for the treatment of osteomyelitis: evaluation of efficacy, tolerance and cost. J Clin Pharm Ther 2001;26:445–51.
  16. Barr DA, Semple L, Seaton RA. Outpatient parenteral antimicrobial therapy (OPAT) in a teaching hospital-based practice: a retrospective cohort study describing experience and evolution over 10 years. Int J Antimicrob Agents 2012;39:407–13.
  17. Department of Health. Antimicrobial Stewardship: Start Smart – Then Focus. London: Department of Health 2011. [Online]. http://e-opat.com/wp-content/uploads/2012/07/DH-guidance-on-Antimicrobia... (accessed 17 January 2013).

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