*Sudhahar TA, Ashcroft GP, Duthie RA, Mackenzie AR, Laing RBS, Douglas JG, Corrigan H

*Trauma and Orthopaedic department,
Infectious diseases department,
Grampian university hospitals NHS trust, Aberdeen, Scotland, UK.

Address for Correspondence
Mr.Sudhahar.T.A,
No 3, St Marks view, Longwood, Huddersfield, HD34TF, UK.
Phone:01484 460 337, 0783525 8719
tas_dr@hotmail.comtas_dr@hotmail.com

We have retrospectively analysed our first year’s experience with outpatient parenteral antimicrobial therapy (OPAT) for two-stage hip and knee revisions and compared this with previous in-patient antibiotic treatment using Hickman lines.  Significant differences  (p value < 0.01) are seen in length of stay, 14 days with OPAT versus 54 days with Hickmann line. Easy and safe self-administration is possible with OPAT using peripherally inserted central venous catheter (PICC) line. This represents an average cost saving per patient of £7000. No patient has had a significant complication from OPAT and at present there have been no re-infections. We conclude therefore that early mobilisation and OPAT can be safely considered for suitable patients under going a two-stage revision of an infected joint prosthesis as an alternative to prolonged hospital stay.

J.Orthopaedics 2005;2(5)e3

Introduction:

With increasing numbers of patients undergoing hip and knee arthroplasty, the number of infected arthroplasties requiring treatment is also increasing.1-3 Management of such cases usually involves two-stage surgical intervention.4 The first stage is removal of the infected prosthesis and all potentially infected material.  The debrided space may then be filled with an antibiotic-loaded cement spacer in some patients and following closure, prolonged intravenous antimicrobial therapy is administrated. Traditional treatment is carried out as an in-patient with intravenous antimicrobial therapy continuing up to 6 weeks, or longer if inflammatory markers (C-reactive protein, white cell count) remain elevated.5,6  More recently, patients in our hospital have been treated using a regimen of early mobilisation and discharge, receiving their intravenous antibiotic as an outpatient i.e. Outpatient parenteral anti-microbial therapy (OPAT).  OPAT can be provided in several settings including the patient’s home, Infectious Diseases Outpatient Department, or specialised District Nurse facilities.  It is not restricted to use in infected arthroplasties but can also be used in acute and chronic osteomyelitis, septic arthritis, epidural abscess, soft tissue infections, and diabetes mellitus foot with osteomyelitis.7-9 This study reviews our early experience with OPAT treatment of infected arthroplasties and compares it to our previous policy of prolonged hospital stay with intravenous antibiotics administered via central lines.

Patients and Methods:

The notes of all patients undergoing two-stage revision for infected arthroplasty over one year period were reviewed.   Patients requiring prolonged intravenous antibiotic therapy were identified and separated into two groups

1. Those undergoing outpatient antibiotic therapy using a peripherally inserted central catheter (PICC) line
2. Those receiving inpatient therapy via Hickman line.

Note was taken of joint involved, surgical technique, organism grown, antibiotic therapy and length of stay (including second admission in early discharge group).

A Mann-Whitney non-parametric Test was used to study the statistical significance.

Results:

The details of the 9 patients (5 hip replacements, and 4 knee replacements) treated with OPAT are seen in Table I and the 5 Infected hip replacements treated with inpatient therapy are seen in Table II. The median age of the OPAT group was 70 years (range 51-81) and the inpatient group was 66 years (range 40-78). The organisms isolated were Staphylococcus Aureus (6), Coagulase- negative Staphylococcus (1), Enterobacter cloacae (1), Neisseria gonococcus (1), and in five cases no growth was obtained despite the fact there was clinical and biochemical evidence of infection. Only one patient in this group had a cement spacer inserted.  All patients underwent early mobilisation. The median inpatient stay (including second admission for infected arthroplasty) with OPAT was significantly shorter (14 days) than that for those patients treated with Hickmann line (54 days) (p< 0.01). This represents a cost saving is £ 7,000 pp (175£ cost savings per bed days). There were 2 PICC line blockages requiring line replacement.  One patient experienced deranged liver enzymes level while receiving flucloxacillin and required antibiotic change. One patient required change of the Hickmann line because of the infection, which ultimately had to be removed.

Table I- Patients treated with PICC line and OPAT.

  *flucloxacillin – liver enzymes elevated. **teicoplanin – pyrexia.

Table II – Patients treated with Hickman line and IV line

 * Febrile episodes – infected Hickman line – changed at 3 weeks.  Hickman line abandoned at 6 weeks due to infection of Hickman line.

Table III - Criteria for patient selection for OPAT and PICC line

1. Patients requiring intravenous anti-microbial therapy for > 1 week.
2. No equally safe and effective oral anti-microbial regime.
3. Anti-microbial therapy suitable for once or twice daily injection.
4. Active infectious disease requiring continued treatment beyond the anticipated period of hospitalisation.
5. No further need for hospitalisation other than treatment of infectious disease.
6. Patients and/or relatives mentally and physically stable (iv drug abusers and alcoholics excluded).
7. Home support or neighbourhood support available.
8. Ready access to transport available.
9. Telephone access.
10. Running water at home.
11. Minimum age 15.

Discussion:

With our ageing population an increasing number of arthroplasties are being performed each      year.10,11 The incidence of infected arthroplasty varies between 0.1% and 2.1% 1,12 and so this is becoming an increasingly frequent clinical problem.

The management of such cases is costly (Hospital acquired infection in general costs around 170milliom £ per year in England alone) 12 and involves extensive use of resources.12 The traditional treatment of such patients involved in-patient administration of intravenous antimicrobial therapy given for a period of 6 weeks or longer.  The use of intravenous cannula is often problematic in such situations because of constant need for resiting. Many types of intravenous access devices are available and theoretically, any of these can be used to administer OPAT including short peripheral intravenous catheters, midline catheters, PICC, and implanted ports.13 The use of a Hickman line requires a sterile theatre environment for adequate insertion and removal.  The proximal portion of the catheter is tunnelled through the skin requiring surgical placement.  If a Hickman line becomes blocked, reinsertion cannot be done in the Outpatient Department.

An ideal situation for such a patient is to have self-administration of the antibiotic on an outpatient basis, using a longer lasting intravenous line. All these criteria are met with a PICC line. Single, as opposed to multi-lumen, catheters are used for OPAT and the risk of infection is less as compared to multilumen catheter. 14

Our three specialist revision Orthopaedic consultants now routinely utilise OPAT with PICC lines following the first stage of revision of infected arthroplasty. After identification of infection, the patient is referred to the Infectious Disease team for assessment of suitability for OPAT and antimicrobial selection. The inclusion criteria for OPAT treatment are detailed in table III. Prior to starting therapy, counselling and demonstration of safe PICC line use are given.  When a patient is deemed unsuitable for OPAT a PICC line is also used but the patient remain in hospital for their therapy.

 A once daily dose antibiotic e.g. teicoplanin is preferred for convenience of administration. Recent work suggests that thrice-weekly Teicoplanin is also effective.15 The infectious disease OPAT nurse trains the patient and/or a relative in the technique of PICC line care and administration of intravenous antibiotics. A median of three days is spent in teaching the patient. Once the acute medical and surgical care of the patients has been completed, and the patient or relative is proficient in the technique, they are discharged home.  Subsequently, the patients are given combined follow-up in the Infectious Disease Outpatient Clinic and Orthopaedics Outpatient Departments.

The OPAT specialist nurse and the staff in the Infectious Disease unit provide an emergency 24-hour telephone contact.

Advantages of PICC line – A PICC line can be inserted and removed safely in the ward, in the outpatient department, or the patient’s home with no need for a theatre environment or IV sedation.  PICC line insertion does not have some of the potential lethal complications of Hickman line (such as pneumothroax.) and both bolus and infusion drugs can be safely administered making self-medication and home administration possible.  With the use of a PICC line, patients with an infected arthroplasty can be cared for in the community rather than in hospital. This reduces the number of bed days in the hospital and the costs for the treatment.

The median length of stay for an OPAT patient was 14 days. Usually 3-5 days was sufficient to set up OPAT.  Initial delays in discharge because of limited availability of staff for OPAT have been overcome by having a full complement of OPAT staff (1 sister and 2 staff nurse). Occasionally discharge was delayed due to reasons other than medical needs. Average cost saving is £ 7,000 pp (175£ cost savings per bed days), which is comparable with the cost savings shown by Nathwani D et al in 2003 of £ 9695.85 pp.16

Complications with PICC line

Two of the 9 PICC line become blocked but this is an infrequent complication according to the literature. Catheter removal or exchange is required in these situations.17 The other complications described in the literature are sterile phlebitis, catheter induced thrombosis in one of the large veins, air embolism, migration of catheter tip if it severed during insertion, and migration of the catheter. 18,19 The other potential problem in the management of these patients is toxicity of antimicrobial therapy, particularly important in the treatment of patients with musculoskeletal infections who require 4 to 6 weeks or more of outpatient intravenous antimicrobial therapy. The incidence of adverse effects with OPAT is low.10

There are no studies in which patients with infectious disease were randomly assigned to receive inpatient or outpatient parenteral antibiotic therapy. OPAT has become a standard of care for many conditions including Orthopaedic infections in the U.K and Europe.20 With the current emphasis on shorter hospital stays, it is unlikely that any such studies will be undertaken. In most of the centres the use of PICC line is replacing Hickmann lines.21 The available literature contains only case series of patients who were treated with OPAT utilising a variety of intravenous catheters and infusion devices. Our report shows similar rates of success and complications compared to other series in the literature.18 UK guidelines for OPAT have been published. Where possible experience with OPAT should be contributed to the International OPAT Outcomes Registry to facilitate further evaluation of this approach to therapy.20 In the future if new generation oral antibiotics (such as Linazolid) are available, the need for parenteral therapy may become obsolete. But at present we do not have any proven equally effective oral therapy.

Conclusions: 

From our experience, we can recommend OPAT using PICC lines for most of the musculoskeletal infections as it is clearly effective and it shortens the in-patient time for these patients.  Even though there is no controlled, randomised trial comparing the various IV devices for OPAT, the PICC line proved to be low risk, easy to use and less expensive. There are huge savings both financially16 and in terms of bed days16 saved.

References:

1, Phillips CB, Barrett JA, Losina E, et al. Incidence rates of dislocation, pulmonary embolism, and deep infection during the first six months after elective total hip replacement. J Bone Joint Surg Am 2003 Jan; 85-A(1):20-6
2, Hoffman-Terry ML, Fraimow HS, Fox TR, Swift BG, Wolf JE. Adverse effects of outpatient parenteral antibiotic therapy. Am J Med 1999 Jan; 106(1): 44-9  
3, Wilde AH.  Management of infected knee and hip prostheses. Curr Opin Rheumatol 1994 Mar; 6(2): 172-6.
4, Bengston S, Knutson K, Lidgren L.  Treatment of infected knee arthroplasty.  Clin Orthop 1989; 245;  173-178.  
5, Houshian S, Zawadski AS, Riegels-Neilsen P. Duration of post-operative antibiotic therapy following revision for infected knee and hip arthroplasties.  Scand J Infect Dis 2000; 32(6);  685-688. 
6, Mader JT, Shirtliff ME, Bergquist SC, Calhoun J: Antimicrobial treatment of chronic osteomyelitis.  Clin Orthop 1999; 360:47–65,  
7, Tice AD.  Outpatient parenteral anti-microbial therapy for osteomyelitis.  Infect Dis Clin North Am 1998; 2; 903-919. 
8, Tice AD.  Outpatient intravenous anti-microbial therapy.  In:  Mandell GL, Bennett JE, Dolin R (eds).  Principals and Practice of Infectious Diseases.  5th edition.  Philadephia, Churchill Livingstone; 2000; 546-550. 
9, Williams DN, Rehm SJ, Tice AD, et al.  Practice guidelines for community-based parenteral anti-infective therapy.  Clin Infect Dis 1997; 25; 787-801. 
10, Sir John Bourn. Hip replacements: Getting it right first time. UK National Audit Office Press Notice. HC 417 1999/2000; 19 April 2000, ISBN: 0105567493
11, Professor Trevor Sheldon, Alison Eastwood, Dr Amanda Sowden, Frances Sharp. Total Hip Replacement. Effective Health Care. UK Churchill Livingstone.  Oct 1996; 2(7): 1-12. ISSN 0965-0288
12, AM Glenny, F Song. Antimicrobial prophylaxis in total hip replacement : a systemic review. Health technology assessment 1999, (3)21.
13, Mortlock NJ, Schleis T. Outpatient parenteral anti-microbial therapy technology. Infect Dis Clin North Am 1998; 12; 861-878.  
14, Pearson ML. Guideline for prevention of intravascular device-related infections. Hospital Infection Control Practices Advisory Committee. Infect Control Hosp Epidemiol 1996; 17; 438-473.
15, Lazzarini L, Tramarin A, Bragagnolo L, Tositti G, Manfrin V, de LF. Three–times weekly teicoplanin in the outpatient treatment of acute methicillin- resistant staphylococcal osteomyelitis: a pilot study. J Chemother 2002 Feb;14 (1); 71-5. 
16, Nathwani D, Barlow GD, Ajdukiewicz K, 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 Antimicob Chemother 2003 Feb; 51 (2): 391-6. 
17, Hoffman-Terry ML, Fraeimow HS, Fox TR, Swift BG, Wolf JE. Adverse effects of outpatient parenteral antibiotic therapy. Am J Med 1999; 106; 44-49.
18, Osmon D R, Berbari E F. Outpatient intravenous anti-microbial therapy for the practicing orthopaedic surgeon. Clin Orth Rel Res 2002; 403 (1); 80-86.  
19, Gilbert DN, Dworking RJ, Raber SR, Leggett JE. Outpatient parenteral anti-microbial drug therapy. N Engl J Med 1997; 337; 829-838   
20, Dilip Nathwani and Alan Tice. Ambulatory antimicrobial use: the value of an outcomes registry. Jour of Antimicrobial Chemotherapy 2002; 49, 149-154.
21, Bernard L, El- Hajj, Pron B, Lotthe A, et al. Outpatient parenteral antimicrobial therapy (OPAT) for the treatment of osteomyelitis: evaluation of efficacy, tolerence and cost. J Clin Pharm Ther. Dec 2001;26(6):445-51.

 This is a peer reviewed paper 

Please cite as :Sudhahar TA: Early experience of outpatient parenteral antibiotic therapy for infected joint replacements

J.Orthopaedics 2005;2(5)e3

URL: http://www.jortho.org/2005/2/5/e3

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