Prosthetic Joint Infection

Javier Cobo; Jose Luis Del Pozo

Expert Rev Anti Infect Ther. 2011;9(9):787-802.

Expert Commentary & Five-year View

The projected increase of PJI will impact the workload and resources of the orthopedic services in the coming years. Multidisciplinary specialized teams will be essential in order to optimize these patients' care.

Prosthetic joint infections represent an extraordinary challenge for the investigators and physicians who treat these diseases. All the aspects related to its management raise questions not yet resolved. Regarding diagnosis, we need to know if it is feasible to diagnose 'late chronic' infections earlier. These infections are acquired (almost certainly) during surgery. If we were able to detect them earlier, we could possibly avoid implant removal. A closer follow-up of patients based on serum markers or, even on a scheduled analysis of synovial fluid in selected patients, could help us to attain this goal. In the coming years, we should also be able to determine the true role of new molecular microbiological tools and the usefulness of implant sonication. These techniques could also improve our knowledge of the microbiology of these infections. Confirmation of a polyclonal or polimicrobial etiology in chronic infections would have an impact on the antimicrobial therapy.

During the coming years, it will be crucial to establish a wide consensus on classification, terminology and PJI stage in order to contrast series and algorithms of management.

Regarding therapy, the actual challenge lies in the design and validation of algorithms for the management of patients diagnosed with PJIs. We should analyze not only microbiological cure, but also functional results and quality of life, using different strategies for different scenarios. Large multicenter databases are, clearly, necessary for this purpose. Details regarding the optimal antimicrobial therapy remain fully open. By selecting specific scenarios with homogeneous surgical approaches, it would be possible to design clinical trials focusing on concrete aspects (i.e., the duration of therapy, the role of new antibacterials or the appropriateness of one-stage prosthesis exchange). Nevertheless, hundred of patients should be recruited and it only could be achieved in large multicenter studies. Meanwhile, large databases containing qualified data should help us to deal with these questions.

On a more long-term scale, the exploration of novel antibiofilm therapies would impact both prevention and treatment of PJI.

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Financial & competing interests disclosure
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.

Box 1. Unusual organisms associated with prosthetic joint infection.
Actinomyces israelii, Arcanobacterium bernardie, Aspergillus fumigatus, Brucellaspp., Campylobacterspp., Candidaspp.,Capnocytophaga canimorsus, Chlamydia pneumoniae, Chryseobacterium meningosepticum, Clostridiumspp., Corynebacteriumspp., Cryptococcus neoformans, Echinococcusspp. Erysipelothrix rhusiopathiae, Francisella tularensis, Granulicatella adiacens, Haemophilus parainfluenzae, Histoplasma capsulatum, Klebsiella pneumoniae, Listeria monocytogenes, Moraxella catarrhalis, Mycobacterium abscessus, Mycobacterium avium complex, Mycobacterium chelonae, Mycobacterium farcinogenes, Mycobacterium fortuitum, Mycoplasma hominis, Mycobacterium kansasii, Mycobacterium smegmatis, Mycobacterium tuberculosiscomplex, Mycobacterium wolinskyi, Oerskovia xanthineolytica, Pasteurella multocida, Peptostreptococcusspp., Rhodotorula minuta, Rhodotorula mucilaginosa Rothia dentocariosa, Rothia mucilaginosa, Salmonellaspp., Serratia marcescens, Sporothrix schenkii, Tropheryma whipplei, Veillonellaspp., Yersinia enterocolitica

Box 2. Classification of infection.
*Zimmerli et al.* [47,48] According to the route of infection: Perioperative (inoculation of microorganisms into the surgical wound during surgery or immediately thereafter) Hematogenous (from blood or lymph spread from a distant site of infection) Contiguous (spread from an adjacent focus of infection) According to the onset of symptoms after implantation: Early (<3 months) Delayed or low-grade infections (3–24 months) Late (>24 months) Tsukayama et al. [25]** I. Positive intraoperative culture II. Early postoperative infection (<1 month after implantation): A. Superficial; B. Deep III. Acute hematogenous (whenever after implantation) IV. Late chronic (>1 month after implantation)

Box 3. Prosthetic joint infection diagnostic tests.
We recommend peripheral blood leukocytes, erythrocyte sedimentation rate and C-reactive protein testing for all patients assessed for periprosthetic joint infection Tsukayama's II and III Microbiologic studies: Blood cultures. Preoperative joint aspiration, with differential cell counts and culture of the synovial fluid Intraoperative histopathological studies Tsukayama's IV Microbiologic studies: Preoperative joint aspiration, with differential cell counts and culture of the synovial fluid. Culture after prosthesis sonication. Molecular tools Intraoperative histopathological studies Imaging studies: Radionuclide imaging: Bone scintigraphy. Gallium imaging. Indium¹¹¹–labeled autologous leukocyte imaging. ¹⁸F-fluoro-2-deoxyglucose PET

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Key Issues

Prosthetic joint infection (PJI) is the most feared complication of arthroplasties. A significant increase is expected in the number of these infections observed during the coming decades. Treatment of PJI is multifaceted, prolonged and expensive. Orthopedic surgeons, infectious disease specialists and microbiologists should work together in order to improve diagnosis and provide an adequate therapeutic approach.
In our point of view, Tsukayama's classification (i.e., positive intraoperative culture, early postoperative infection, acute hematogenous and late-chronic) is useful to facilitate diagnosis and treatment.
Distinguishing late-chronic infection from aseptic loosening is extremely important because treatment is completely different. No single clinical or laboratory test has been shown to achieve ideal sensitivity, specificity and accuracy for the diagnosis of prosthetic joint infection. We recommend preoperative joint aspiration, with differential cell counts and culture of the synovial fluid of patients, who have abnormal erythrocyte sedimentation rate and/or C-reactive protein results, being assessed for periprosthetic knee infections.
Although bone scintigraphy may be useful for screening purposes, combined leukocyte/marrow scintigraphy remains the imaging procedure of choice for diagnosing late-chronic PJI.
With the use of new microbiological techniques (i.e., implant sonication and culture, molecular techniques), the rate of culture-negative implant-associated infections may decrease in the future.
The goal of treatment of a PJI is to cure the infection, to prevent recurrence and to achieve a pain-free and functional joint; however, the three objectives cannot be always achieved. Future studies should address not only the microbiological eradication but functional outcomes of different treatment strategies.
PJI management must be individualized. Several options, including debridement and retention of the implant, exchange of the prosthesis or resection arthroplasty, should be considered depending on PJI type and other variables such us implant stability, number of previous procedures, bone stock, soft-tissue condition, etiology and patient circumstances and preferences. Clinical randomized trials to compare these different surgical approaches are difficult to perform in this setting and most recommendations are – and will continue to be – based on case-series reports and database analysis.
Antimicrobial treatment of PJIs is becoming more challenging because of the increasing prevalence of antimicrobial resistance among Gram-positive microorganisms. Therapeutic options for the treatment of methicillin-resistant staphylococcal infections are limited, and new antimicrobial agents are needed.
Antimicrobial therapy should be selected in agreement with the surgical strategy and treatment goals. Most early and hematogenous (acute) PJI can be managed successfully without removal of the implant, provided that an aggressive and prompt debridement has been performed.
Participation of an infectious diseases specialist must be provided for the care of patients with PJI because treatment is usually prolonged, rifampin (an agent with a high number of medical interactions) is frequently prescribed, and new antimicrobials are often required owing to resistance.

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Prosthetic Joint Infection

Expert Commentary & Five-year View

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