Infection after total joint replacement of the hip and knee: research programme including the INFORM RCT

Ashley W Blom*, Andrew D Beswick, Amanda L Burston, Fran E Carroll, Kirsty M Garfield, Rachael Gooberman-Hill, Shaun R S Harris, Setor K Kunutsor, J. Athene Lane, Erik Lenguerrand, Alasdair P MacGowan, Charlotte M Mallon, Andrew J Moore, Sian M Noble, Cecily K Palmer, Ola Rolfson, Simon O Strange, Michael R Whitehouse

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

6 Citations (Scopus)
138 Downloads (Pure)

Abstract

Background
People with severe osteoarthritis, other joint conditions or injury may have joint replacement to reduce pain and disability. In the UK in 2019, over 200,000 hip and knee replacements were performed. About 1 in 100 replacements becomes infected, and most people with infected replacements require further surgery.

Objectives
To investigate why some patients are predisposed to joint infections and how this affects patients and the NHS, and to evaluate treatments.

Design
Systematic reviews, joint registry analyses, qualitative interviews, a randomised controlled trial, health economic analyses and a discrete choice questionnaire.

Setting
Our studies are relevant to the NHS, to the Swedish health system and internationally.

Participants
People with prosthetic joint infection after hip or knee replacement and surgeons.

Interventions
Revision of hip prosthetic joint infection with a single- or two-stage procedure.

Main outcome measures
Long-term patient-reported outcomes and reinfection. Cost-effectiveness of revision strategies over 18 months from two perspectives: health-care provider and Personal Social Services, and societal.

Data sources
National Joint Registry; literature databases; published cohort studies; interviews with 67 patients and 35 surgeons; a patient discrete choice questionnaire; and the INFORM (INFection ORthopaedic Management) randomised trial.

Review methods
Systematic reviews of studies reporting risk factors, diagnosis, treatment outcomes and cost comparisons. Individual patient data meta-analysis.

Results
In registry analyses, about 0.62% and 0.75% of patients with hip and knee replacement, respectively, had joint infection requiring surgery. Rates were four times greater after aseptic revision. The costs of inpatient and day-case admissions in people with hip prosthetic joint infection were about five times higher than those in people with no infection, an additional cost of > £30,000. People described devastating effects of hip and knee prosthetic joint infection and treatment. In the treatment of hip prosthetic joint infection, a two-stage procedure with or without a cement spacer had a greater negative impact on patient well-being than a single- or two-stage procedure with a custom-made articulating spacer. Surgeons described the significant emotional impact of hip and knee prosthetic joint infection and the importance of a supportive multidisciplinary team. In systematic reviews and registry analyses, the risk factors for hip and knee prosthetic joint infection included male sex, diagnoses other than osteoarthritis, high body mass index, poor physical status, diabetes, dementia and liver disease. Evidence linking health-care setting and surgeon experience with prosthetic joint infection was inconsistent. Uncemented fixation, posterior approach and ceramic bearings were associated with lower infection risk after hip replacement. In our systematic review, synovial fluid alpha-defensin and leucocyte esterase showed high diagnostic accuracy for prosthetic joint infection. Systematic reviews and individual patient data meta-analysis showed similar reinfection outcomes in patients with hip or knee prosthetic joint infection treated with single- and two-stage revision. In registry analysis, there was a higher rate of early rerevision after single-stage revision for hip prosthetic joint infection, but, overall, 40% fewer operations are required as part of a single-stage procedure than as part of a two-stage procedure. The treatment of hip or knee prosthetic joint infection with early debridement and implant retention may be effective in > 60% of cases. In the INFORM randomised controlled trial, 140 patients with hip prosthetic joint infection were randomised to single- or two-stage revision. Eighteen months after randomisation, pain, function and stiffness were similar between the randomised groups (p = 0.98), and there were no differences in reinfection rates. Patient outcomes improved earlier in the single-stage than in the two-stage group. Participants randomised to a single-stage procedure had lower costs (mean difference –£10,055, 95% confidence interval –£19,568 to –£542) and higher quality-adjusted life-years (mean difference 0.06, 95% confidence interval –0.07 to 0.18) than those randomised to a two-stage procedure. Single-stage was the more cost-effective option, with an incremental net monetary benefit at a threshold of £20,000 per quality-adjusted life-year of £11,167 (95% confidence interval £638 to £21,696). In a discrete choice questionnaire completed by 57 patients 18 months after surgery to treat hip prosthetic joint infection, the most valued characteristics in decisions about revision were the ability to engage in valued activities and a quick return to normal activity.

Limitations
Some research was specific to people with hip prosthetic joint infection. Study populations in meta-analyses and registry analyses may have been selected for joint replacement and specific treatments. The INFORM trial was not powered to study reinfection and was limited to 18 months’ follow-up. The qualitative study subgroups were small.

Conclusions
We identified risk factors, diagnostic biomarkers, effective treatments and patient preferences for the treatment of hip and knee prosthetic joint infection. The risk factors include male sex, diagnoses other than osteoarthritis, specific comorbidities and surgical factors. Synovial fluid alpha-defensin and leucocyte esterase showed high diagnostic accuracy. Infection is devastating for patients and surgeons, both of whom describe the need for support during treatment. Debridement and implant retention is effective, particularly if performed early. For infected hip replacements, single- and two-stage revision appear equally efficacious, but single-stage has better early results, is cost-effective at 18-month follow-up and is increasingly used. Patients prefer treatments that allow full functional return within 3–9 months.

Future work
For people with infection, develop information, counselling, peer support and care pathways. Develop supportive care and information for patients and health-care professionals to enable the early recognition of infections. Compare alternative and new treatment strategies in hip and knee prosthetic joint infection. Assess diagnostic methods and establish NHS diagnostic criteria.

Study registration
The INFORM randomised controlled trial is registered as ISRCTN10956306. All systematic reviews were registered in PROSPERO (as CRD42017069526, CRD42015023485, CRD42018106503, CRD42018114592, CRD42015023704, CRD42017057513, CRD42015016559, CRD42015017327 and CRD42015016664).

Funding
This project was funded by the National Institute for Health and Care Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research; Vol. 10, No. 10. See the NIHR Journals Library website for further project information.
Original languageEnglish
Article numberHDWL9760
Number of pages226
JournalProgramme Grants for Applied Research
Volume10
Issue number10
DOIs
Publication statusPublished - 1 Nov 2022

Bibliographical note

Funding Information:
This project was funded by the National Institute for Health and Care Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research; Vol. 10, No. 10. See the NIHR Journals Library website for further project information.

Funding Information:
Declared competing interests of authors: Ashley W Blom is a co-applicant on a grant from Stryker Corporation (Kalamazoo, MI, USA) for investigating the outcome of the Triathlon total knee replacement. He is a member of the National Joint Registry lot 2 contract (statistical analysis) team and a member of the National Institute for Health and Care Research (NIHR) Bristol Biomedical Research Centre. Erik Lenguerrand is also a member of the National Joint Registry lot 2 contract (statistical analysis) team. Ola Rolfson reports grants from Stryker Corporation, Pfizer Inc. (New York, NY, USA) and LINK Sweden AB (Åkersberga, Sweden) outside the submitted work. Michael R Whitehouse undertakes teaching on basic sciences for orthopaedic trainees preparing for the Fellowship of the Royal College of Surgeons; his institution receives market-rate payment for this teaching from Heraeus (Hanau, Germany). He undertakes teaching on total hip replacement for orthopaedic consultants and trainees; his institution receives market-rate payment for this teaching from DePuy Synthes (Raynham, MA, USA). He is a co-applicant on a grant from Stryker Corporation investigating the outcome of the Triathlon total knee replacement. He is a member of the National Joint Registry lot 2 contract (statistical analysis) team. He is NIHR Clinical Research Network West of England lead for Trauma and Emergencies, a member of the NIHR Bristol Biomedical Research Centre and principal investigator on two NIHR Health Technology Assessment grants (NIHR129011 and NIHR127849).

Publisher Copyright:
© 2022 Blom et al.

Research Groups and Themes

  • INFORM
  • Prosthetic joint infection
  • Joint replacement
  • Randomised controlled trial
  • Systematic review
  • National Joint Registry
  • Qualitative research
  • Patient and public involvement

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