Pérez-Prieto et al. BMC Musculoskeletal Disorders (2021) 22:653 https://doi.org/10.1186/s12891-021-04431-1 RESEARCH ARTICLE Open Access Adherence to a reliable PJI diagnostic protocol minimizes unsuspected positive cultures rate Daniel Pérez-Prieto1,2*, Pedro Hinarejos1, Albert Alier1, Lluïsa Sorlí3, Santos Martínez1, Lluís Puig1 and Juan C. Monllau1,2 Abstract Background: The aim of the present study was to evaluate the incidence of unsuspected PJI when prosthetic revisions are thoroughly evaluated by PJI dedicated orthopedic surgeon before surgery. The hypothesis is that the incidence of unsuspected PJI is reduced by applying this protocol. Methods: This is a historical cohort study carried out in one university hospital. The prosthetic revision assessment was carried out in January 2019. From that date on, all patients that were programmed for hip or knee revision (either by an orthopedic surgeon specialized or not in septic revisions) were scheduled for a preoperative visit with the same orthopedic surgeon specialized in septic revisions. The diagnostic algorithm applied was based on the Pro-Implant Foundation diagnostic criteria. Prior to the revision assessment, the indication for joint aspiration was done at the surgeons’ discretion (non-specialized in septic revisions) and the preoperative identification of PJI was also done by a hip or knee surgeon (not specialized in septic surgery). Results: Based on the PIF criteria, there were 15 infections among the revisions in group 1 and 18 PJI in group 2 (p > 0.05). The most interesting finding was that there were 7 patients with unsuspected positive cultures in group 1. That represents 11% of all revisions. No patient in group 2 was found with unsuspected positive cultures (p < 0.001). Conclusion: A thorough PJI diagnostic algorithm should be implemented before prosthetic revision to avoid unsuspected positive cultures. Keywords: PJI diagnosis, Culture-negative-PJI, Unsuspected positive cultures * Correspondence: dperezprieto@parcdesalutmar.cat 1 Department of Traumatology and Orthopaedic Surgery, Hospital del Mar – Universitat Autònoma de Barcelona (UAB), Barcelona, Spain 2 Catalan Institute for Traumatology and Sports Medicine (ICATME), Hospital Universitari Dexeus. – Universitat Autònoma de Barcelona (UAB), Barcelona, Spain Full list of author information is available at the end of the article © The Author(s). 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Pérez-Prieto et al. BMC Musculoskeletal Disorders (2021) 22:653 Page 2 of 7 Background that were thoroughly evaluated before surgery represents According to the reports published in the last decades, Group2. The diagnostic algorithm applied is the one rec- prosthetic joint infection (PJI) is one of the most dreaded ommended by the Pro-Implant Foundation (PIF) and complications among orthopedic surgeons [1–3]. The can be seen in Fig. 1 [1, 23]. This diagnostic protocol reason for this fear is multifactorial. The burden of PJI in was based on the Zimmerli criteria [16, 24]. Recently the developing countries is rising and the costs are among the European Bone and Joint Infection Society (EBJIS) and highest in orthopedic procedures [4–7]. Another cause is the Musculoskeletal Infection Society (MSIS) and the the poor results published in some studies in which the European Society for of Clinical Microbiology and Infec- success rate is lower than 50% [8]. Moreover, undertreated tious Diseases (ESCMID) have published the EBJIS def- or untreated PJI usually correlates with bad functional inition of PJI, which is based on the aforementioned PIF outcomes and even depressed and despondent patients criteria [25, 26]. [9]. For all of this, some orthopedic surgeons just A virtual visit was scheduled to revise all medical look the other way and do not look pro-actively to records. Those records included time of implantation find and diagnose this complication. and onset of pain, septic signs at any time (redness, Acute PJI often comes with clear signs and symptoms, wound healing problems, the presence of sinuses), making the diagnosis of acute PJI uncomplicated [10]. previous surgeries and the indication for them, loos- Moreover, most diagnostic tests demonstrate high ening on radiographs (time when loosening started sensitivity. Conversely, chronic low-grade infections and and type of loosening), blood test (C-reactive protein aseptic prosthetic failures are often quite similar in -CRP-, erythrocyte sedimentation rate -ESR-) and terms of the clinical presentation. Therefore, a thorough joint aspiration. When there was any doubt or when algorithmic approach that combines both the preopera- the joint aspiration had not yet been performed, the tive and intraoperative results is required to reliably patient was then scheduled for an in person visit. diagnose or rule out PJI [1]. Prior to this revision assessment, the indication for The reality is that some patients with PJI (especially joint aspiration was done at the surgeons’ discretion and low-grade and chronic PJI) are not diagnosed [11, 12]. the preoperative identification of PJI was also done by a Therefore, they go untreated while suffering from hip or knee surgeon (not specialized in septic surgery). chronic pain. Indeed, Jacobs et al. reported an approxi- This group of patients represents Group 1. mately 10% rate “unsuspected” PJI among prosthetic ex- The diagnosis of PJI was always done according to change procedures [13]. Some of them were not adequately the PIF criteria for PJI (which are based on previously screened for PJI. published Zimmerli’s criteria) [1, 16, 23, 24, 27]. PJI Contrariwise, up to a 90% PJI success rate has been re- was considered present when at least one of the ported in the literature with similar functional outcomes following items was fulfilled: (i) the presence of to uninfected prosthesis [1, 14–16]. The reported suc- purulence or a sinus tract; (ii) >2000 leucocyte per ml cess rate slightly varies depending on the procedure in the synovial fluid or >65% of PMN; (iii) positive [17–19]. All those studies follow a thorough work-up, hytopathology; (iv) at least 2 positive tissue cultures diagnostic criteria and treatment for PJI with better (or one in case of virulent microorganisms) or a posi- outcomes when the patients are treated by specialists tive sonication culture. in PJI [20–22]. Once the revision assessment protocol was put in The aim of the present study was to evaluate the inci- place in those cases in which infection had been dence of unsuspected PJI when prosthetic revisions are completely ruled out, a knee or hip surgeon performed thoroughly evaluated before surgery by PJI dedicated the revision. In these cases, 5 periprosthetic tissue orthopedic surgeon. The hypothesis is that the incidence cultures, sonication and histopathology samples were of unsuspected PJI is reduced by applying this protocol. collected. Intravenous antibiotic prophylaxis was ad- ministered prior to surgery as it does not impact on Methods intraoperative cultures, but no antibiotic treatment This is a historical cohort study carried out in one uni- was maintained after surgery [27–29]. In doubtful versity hospital. The study was performed following the cases (e.g. early loosening, unaccountable pain and Helsinki and Fortaleza protocols. The prosthetic revision punctio sicca, etc.), a similar protocol was followed assessment was implemented in January 2019. From that with some recommendations from the septic surgery date on, all patients that were programmed for hip or team. They involved maintaining postoperative anti- knee revision (either by an orthopedic surgeon special- biotic therapy until cultures and histopathology were ized or not in septic revisions) were scheduled for a available, carrying out a thorough debridement (like a preoperative visit with the same orthopedic surgeon spe- one-stage exchange) and using antibiotic loaded cialized in septic surgery (DPP). The group of patients cement in the case of a cemented prosthesis. Pérez-Prieto et al. BMC Musculoskeletal Disorders (2021) 22:653 Page 3 of 7 Fig. 1 Diagnostic algorithm for PJI. Reproduced with permission from the Pocket Guide to Diagnosis & Treatment of PJI, PROIMPLANT Foundation (version 9, October 2019) When the diagnosis of PJI was confirmed, surgery cases, a p value of less than 0.05 was considered sta- was carried out by the septic surgery team and tistically significant. The statistical analysis was done treated accordingly. The debridement performed here using the SPSS 18.0 (SPSS Inc., Chicago, IL) statistical was a tumor-like debridement. software package. Statistical analysis Results Variables are expressed as raw numbers or percentages There were 64 prosthesis revisions in group 1 (38 depending on the case. When 2 related items of data knees and 26 hips) and 69 revised prostheses in were analyzed, the Student’s t-Test was used. In all group 2 (39 knees and 30 hips). Pérez-Prieto et al. BMC Musculoskeletal Disorders (2021) 22:653 Page 4 of 7 Based on the PIJ criteria, there were 15 infections among When it comes to adherence to the diagnostic the revisions in group 1 and 18 PJI in group 2 (p > 0.05). algorithm, 42 patients in group 1 (65.5%) followed The details of all infections can be seen in Table 1. the diagnostic protocol to completion. The most fre- The most interesting finding was that there were 7 quent test missing was the preoperative joint punc- patients with unsuspected positive cultures in group ture (14 patients). There was only one patient in 1. That represents 11% of all revisions. No patient in group 2 that did not follow the diagnostic protocol group 2 was found with unsuspected positive cultures to end (1.4%) (p < 0.001). It was due to the surgery (p < 0.001). All these 7 patients required a 2-stage being brought forward because of a worsening revision within a period of 2–46 weeks. clinical state. Table 1 Additional data from patients of both groups Type of prosthesis Microorganism Protocol fulfillment Unsuspected positive culture Group 1 1 THR CNS No: sinus tract present. Joint aspiration missing Yes 2 THR Staphylococcus aureus No: joint aspiration missing No 3 TKR CNS Yes No 4 THR Cutibacterium acnes No: joint aspiration missing Yes 5 THR Escherichia coli No: sinus tract present. Joint aspiration missing Yes 6 THR CNS No: joint aspiration missing Yes 7 TKR Escherichia coli Yes No 8 TKR Enterococcus faecalis + CNS Yes No 9 THR Cutibacterium acnes No: joint aspiration missing Yes 10 TKR Pseudomonas aeruginosa Yes No 11 THR Culture negative No: joint aspiration missing No 12 TKR Streptococcus viridans Yes No 13 TKR Cutibacterium acnes No: joint aspiration missing Yes 14 TKR CNS No: joint aspiration missing Yes 15 THR Escherichia coli Yes No Group 2 1 TKA Pseudomonas aeruginosa Yes No 2 TKA CNS Yes No 3 THA Candida glabrata Yes No 4 TKA Staphylococcus aureus Yes No 5 THA Staphylococcus aureus Yes No 6 THA Enterococcus faecium Yes No 7 THA Enterobacter cloacae Yes No 8 TKA CNS Yes No 9 THA Cutibacterium acnes Yes No 10 THA CNS Yes No 11 THA CNS Yes No 12 TKA Cutibacterium acnes Yes No 13 THA Escherichia coli + CNS No: aspiration missing No 14 THA Pseudomonas aeruginosa Yes No 15 TKA Culture negative Yes No 16 THA Cutibacterium acnes + CNS Yes No 17 TKA Streptococcus agalactiae Yes No 18 TKA Culture negative Yes No Pérez-Prieto et al. BMC Musculoskeletal Disorders (2021) 22:653 Page 5 of 7 Discussion of PJI. For instance, in temporary sinus tract, this may The most important finding of the present study was occur when the patient is not asked if he or she had a that by assessing prosthetic revisions using a strict diag- sinus tract at any time. nostic algorithm, the number of unsuspected positive The risk of unsuspected positive cultures has not been cultures can be reduced. This is an important finding widely studied. A recent study by Jabobs et al. showed since patients are evaluated prior to surgery and there- that 7.9% of TKA and 12.1% of THA of the supposed fore, they are properly treated if the reason for revision aseptic revisions were really PJI [13]. Moojen et al. found is PJI. Otherwise, undiagnosed patients do not receive that between 4 and 13% of patients with the preoperative proper debridement. They may even be discharged with- diagnosis of aseptic loosening were infected [35]. Similar out antibiotic treatment. results have been found in the present study as 11% of Any painful prosthetic joint could be a sign of infec- “non-controlled” revisions obtained unsuspected positive tion and should be thoroughly assessed to rule out PJI. cultures. The initial steps to be taken include a clinical examin- Another important result of the present study is the ation of the patient and analyses of CRP and ERS as well improvement in PJI management when a dedicated sep- as plain radiographs. The aforementioned systemic in- tic surgery team is involved. It is well known how im- flammatory parameters are neither sensitive enough or portant a multidisciplinary approach to PJI is. Such a specific to the diagnosis of PJI [11]. Nevertheless, they team would include orthopedic surgeons, infectious dis- are easy to acquire and give important information on eases specialists, plastic surgeons and microbiologists the systemic repercussion of the infection (in case it ex- [36]. Borens et al. proved that the surgical outcome im- ists). They are also important in the PJI follow-up. proved if an orthopedic surgeon specialized in septic Therefore, it is important to have them preoperatively to surgery performed the PJI revisions. They found a PJI know its evolution. success rate of 83% vs. 61% taking this particular ap- There are several diagnostic algorithms for PJI. One of proach to the surgical procedure. Moreover, the eco- the most widely used is the one proposed by the Ameri- nomic impact is also relevant. In osteomyelitis cases, can Association of Orthopedic Surgeons (AAOS) in Ferguson et al. found that treating infections in dedi- which they suggest that if a normal CRP and normal cated specialist multidisciplinary centers requires a lot of ESR are both normal, PJI is discounted [30–32]. How- resources and costs are elevated [37]. However, treating ever, there are several studies that have proven that CRP infections outside that environment seems to cost more and ESR are very non-specific PJI markers and can mis- and results in longer patient stays and higher associated diagnose some 20% of PJI [11]. The most common PJI costs. that those markers do not identify are low-grade infec- Ideally, PJI should be diagnosed or excluded by per- tions due to coagulase-negative staphylococci (CNS) and forming joint aspiration before revision. Doing so makes Cutibacterium spp. [13, 23, 33–35]. Moreover, the diag- for sure planning of the most appropriate treatment nostic criteria proposed by the Musculoskeletal Infection strategy. Preoperatively, purulent wound secretion and/ Society (MSIS) has been found to be less reliable than or sinus tract communication with the prosthetic joint the European criteria proposed by the PIF in recent are confirmative signs of a PJI. In that case, no further studies [23]. For this reason, new diagnostic algorithms diagnostic steps need be taken since it confirms PJI. At have arrived on the scene. One of the most used is the this juncture, revision surgery should be scheduled. one applied in the present study. It has been employed However, joint aspiration is recommended to try to de- in several studies for PJI diagnosis in recent years [6, 22, termine the causative microorganism and its antibiotic 36]. With the results presented here, it has been shown susceptibility before revision. This is important to tailor- to be effective at reducing the risk of unsuspected posi- ing the antibiotics to the bone cement and/or planning tive cultures in prosthetic revision surgery. revision in one or two stages. With no confirmatory Interestingly enough, the present study has demon- signs, the most important and sensitive diagnostic meas- strated that even though both groups were diagnosed ure in the preoperative setting is the leukocyte count of applying the same diagnostic criteria, there were 2 pa- the synovial fluid and the granulocyte differential. Join tients in Group1 with clear diagnoses of PJI (presence of aspiration must be performed in line with the standard sinus tract) that were not correctly identified. This is im- aseptic technique. Culturing of synovial fluid shows low portant because an orthopedic surgeon who is not spe- sensitivity as only planktonic bacteria are detected. Most cialized in PJI may misdiagnose infection even though of the bacterial load is embedded in the biofilm on the there is a clear sign of it. Moreover, a preoperative joint implant surface and will not be recognized in standard aspiration was not performed in 9 patients (60%). One synovial fluid cultures [38]. Synovial fluid leukocyte reason could be the fact that orthopedic surgeons that count analysis is more sensitive. It reflects the host’s re- are not acquainted with PJI may underestimate the signs action to the microorganisms [39]. However, specificity Pérez-Prieto et al. BMC Musculoskeletal Disorders (2021) 22:653 Page 6 of 7 is compromised in situations associated with aseptic in- related to one specific diagnostic algorithm approach, flammatory changes of the joint. Those circumstances which prevents us knowing whether other algorithms include the healing process in the first 4–6 weeks after are equally effective or not. surgery, inflammatory changes after trauma, recurrent dislocations and in underlying inflammatory arthropa- Conclusions thies [39]. Additionally, the optimal cutoff for PJI diag- The incidence of unsuspected positive cultures may be nosis is still subject to controversy. In general, a test reduced when a thorough PJI diagnostic algorithm is with a high sensitivity is preferred at this stage of the implemented before prosthetic revision. diagnostic algorithm. Therefore, a lower leukocyte count Abbreviations (e.g. 2000/μl) is preferred even though it carries the PJI: Prosthetic joint infection; PIF: Pro-Implant Foundation; CRP: C-reactive protein; risk of over diagnosis but it avoids missing an infec- ESR: Erythrocyte sedimentation rate; PMN: Polymorphonuclear granulocytes; tion [1, 25]. The performance of novel biomarkers AAOS: American Association of Orthopedic Surgeons; CNS: Coagulase-negative staphylococci; TKA: Total knee arthroplasty; THA: Total hip arthroplasty such as synovial fluid alpha defensin have been assessed in several studies by applying different defin- Acknowledgements ition criteria. The results of these studies showed that We are grateful to Mr. Eric L. Goode for the help with English editing and style. the leukocyte count is equal to or better than alpha Authors’ contributions defensin tests and indeed much cheaper [23, 34]. Conceptualization and methodology DPP and AA; Formal analysis and In the case of a dry joint tap, the instillation of saline investigation DPP; Resources and data curation LS, SM and LP; Writing—original draft preparation DPP; Writing—review and editing PH and JCM; Supervision, may lead to a leukocyte count analysis no longer being JCM and PH. The author(s) read and approved the final manuscript representative as it dilutes the synovial fluid [39, 40]. If the synovial fluid analysis rules out infection, differential Funding There is no funding source. diagnoses should be considered and further investigated (malpositioning of the implant, muscle weakness, tendi- Availability of data and materials nopathy, wear, etc.). If the pain remains unexplained, PJI Data and materials are available upon request to the corresponding author. should be still considered. In the case of severe pain with Declarations significant compromising of quality-of-life or a loosened prosthesis, revision surgery with meticulous intraopera- Ethics approval and consent to participate This article does not contain any studies with human participants or animals tive diagnostics are advised. A one-stage revision along performed by any of the authors. This historical cohort study was based on with a thorough debridement is recommended. Postop- approved recommended guidelines without any intervention. Moreover, erative empiric antibiotic therapy is also recommended ethical approval was not necessary because data was collected, using a format protecting their identity, as a standard practice on all patients. Verbal until intraoperative microbiology and pathology is consent to participate in the study was obtained. available in these cases. In cases when the reason for pain is not clear and the prosthesis is stable and well Consent for publication fixed, biopsy through arthroscopy or mini-open arthrot- The authors confirm they consent for publication. omy is an alternative. However, the diagnostic yield is Competing interests rarely significant as the representative area (i.e., the The authors declare that they have no conflict of interest. interface between implant and bone) may be difficult to Author details reach. Arthroscopy should be the first option to obtain 1 Department of Traumatology and Orthopaedic Surgery, Hospital del Mar – these biopsies since it is less aggressive. Of course, that Universitat Autònoma de Barcelona (UAB), Barcelona, Spain. 2Catalan Institute depends on the affected joint and the expertise of the for Traumatology and Sports Medicine (ICATME), Hospital Universitari Dexeus. – Universitat Autònoma de Barcelona (UAB), Barcelona, Spain. 3Department treating orthopedic surgeon. Nevertheless, every inter- of Infectious Diseases, Hospital del Mar – Universitat Autònoma de Barcelona vention presents a risk of superinfection. Therefore, they (UAB), Barcelona, Spain. should be avoided as much as possible and reserved for Received: 13 January 2021 Accepted: 6 June 2021 very selected cases, as previously stated. If the pain is satisfactorily managed with analgesics, and the patient does not request immediate intervention, another joint References 1. Izakovicova P, Borens O, Trampuz A. Periprosthetic joint infection: current aspiration should be repeated after 1–3 months in order concepts and outlook. 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