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Diagnosis of periprosthetic infection following total hip arthroplasty – evaluation of the diagnostic values of pre- and intraoperative parameters and the associated strategy to preoperatively select patients with a high probability of joint infection

Diagnosis of periprosthetic infection following total hip arthroplasty – evaluation of the... Background: The correct diagnosis of a prosthetic joint infection (PJI) is crucial for adequate surgical treatment. The detection may be a challenge since presentation and preoperative tests are not always obvious and precise. This prospective study was performed to evaluate a variety of pre- and intraoperative investigations. Furthermore a detailed evaluation of concordance of each preoperative diagnosis was performed, together with a final diagnosis to assess the accuracy of the pre-operative assumption of PJI. Methods: Between 01/2005 and 02/2007, a prospective analysis was performed in 50 patients, who had a two stage revision because of assumed PJI. Based on clinical presentation, radiography, haematological screening, or early failure, infection was assumed and a joint aspiration was performed. Depending upon these findings, a two stage revision was performed, with intra-operative samples for culture and histological evaluation obtained. Final diagnosis of infection was based upon the interpretation of the clinical presentation and the pre- and intraoperative findings. Results: In 37 patients a positive diagnosis of PJI could be made definitely. The histopathology yielded the highest accuracy (0.94) in identification of PJI and identified 35 of 37 infections (sensitivity 0.94, specificity 0.94, positive-/negative predictive value 0.97/0.86). Intra-operative cultures revealed sensitivities, specificities, positive-/negative predictive values and accuracy of 0.78, 0.92, 0.96, 0.63 and 0.82. These values for blood screening tests were 0.95, 0.62, 0.88, 0.80, and 0.86 respectively for the level of C-reactive protein, and 0.14, 0.92, 0.83, 0.29 and, 0.34 respectively for the white blood-cell count. The results of aspiration were 0.57, 0.5, 0.78, 0.29, and 0.54. Conclusion: The detection of PJI is still a challenge in clinical practice. The histopathological evaluation emerges as a highly practical diagnostic tool in detection of PJI. Furthermore, we found a discrepancy between the pre-operative suspicion of PJI and the final post-operative diagnosis, resulting in a slight uncertainty in whether loosening is due to bacterial infection or not. The variation in accuracy of the single tests may influence the detection of PJI. Level of Evidence: Diagnostic Level I. Page 1 of 8 (page number not for citation purposes) Journal of Orthopaedic Surgery and Research 2008, 3:31 http://www.josr-online.com/content/3/1/31 Based on the following preoperative parameters, infection Background The diagnosis of periprosthetic joint infection (PJI) can of the hip prosthesis was supposed [5,6]: present a challenge due to the fact that both clinical pres- entation and preoperative tests are not always obvious ▪ clinical presentation of infection (Pain, fever, fistula) and precise. The clinical assessment depends strongly on the symptoms of fever, pain, and fistula. Frequently, per- ▪ plain radiography sistent pain is the only symptom which is present [1]. Numerous preoperative tests for determination and diag- ▪ haematological screening tests (level of c-reactive pro- nosis of a failed total hip replacement are available. These tein (>0,5 mg/dl), white blood-cell count (> 12/nl)) tests include haematological screening tests (measure- ment of the erythrocyte sedimentation rate, and the level ▪ early failure within the first five years in connection with of C-reactive protein, white blood-cell count,), aspiration clinical or haematological suspicion of the hip joint, plain radiography, and radionuclide imaging studies. None of these tests is 100 percent reliable When at least one of these parameters was observed, a and are subject to a variable spectrum of false negative or joint aspiration was performed. Joint aspiration was done false positive results [2]. A misdiagnosis has crucial conse- according to the standards described in the Guidelines of quences for the treatment and for the patient. In case of a Hospital Hygiene and Infectious Disease Prevention [7] misdiagnosed periprosthetic infection, revision of the (Robert-Koch Institut; Berlin), under sterile conditions in prosthesis without appropriate débridement and antibio- an operation theatre, after preparation and draping, using sis would keep a failed total hip replacement and risk an a sterile technique without local anaesthetics and con- early failure. On the other hand a wrong assumption firming intraarticular placement by radiograph. If no fluid about periprosthetic infection caused by a false positive was aspirated, 10 ml of normal saline was injected and test, the patient has to undergo surgery which would be reaspirated. If there was a sample of less than 5 ml, only highly inadequate as a girdlestone operation (two stage an aerobic bottle was inoculated. revision) or a cemented revision (one stage revision). In case of positive aspiration and/or clear clinical or radi- Principal intraoperative tests include the histological eval- ographic findings and/or persistence of elevated haemato- uation and microbiological cultures of the periprosthetic logical parameters which could not explained by other tissue which have a high validity [3,4]. However the conditions, periprosthetic joint infection was diagnosed appropriateness of these tests in determining surgical and a two stage revision has been performed. treatment is limited due to the time required to allow for histological preparation and bacteria growth. Hence, final Microbacterial Cultures and Intraoperative diagnosis of periprosthetic infection can not be made Histopathological Evaluation until a couple of days after surgery, when histological and Intraoperative samples for culture and histological evalu- microbiological results are available. Therefore, there is an ation were obtained from the cup and stem region. Six occasional slight uncertainty whether the right treatment samples were incubated for 10 days to analyse bacterial was accomplished. growth. The aim of this study was to compare pre- and intraoper- This time period is based on an actual literature review [8- ative diagnostic tests including haematological screening, 10]. It could be shown that some microorganisms require aspiration, histological evaluation, and microbacterial a minimum incubation time of 8 days, since these micro- cultures and to investigate the diagnostic pathway for the organisms grow slowly [9,10]. Specimens were inoculated detection of periprosthetic joint infection. Additionally, in various culture media (standard eg, blood and choco- the accuracy of preoperative diagnosis of periprosthetic late agar, as well as Brain-heart bouillon, Wilkins Chal- joint infection was evaluated by comparing preoperative gren agar, McConkey agar, Sabouraud agar and selection with the final diagnosis. thioglycolate broth). A result was considered positive if a minimum of 1 speci- Methods Patients and study design men showed growth associated with purulence for viru- Between January 2005 and February 2007 a prospective lent organism, such as Staphylococcus aureus, analysis was performed in 50 patients (23 male, 27 Streptococci species, or a Gram-negative bacterium. For female) in the mean age of 69 years (range, 46 – 84) who pathogens with low virulence, such as coagulase negative had a two stage revision because of the suspicion of Staphylococci or Propionibacterium species, at least three periprosthetic total hip-joint infection. specimens were required positive (with identical pheno- type bacteria profile) for a positive result [11]. Page 2 of 8 (page number not for citation purposes) Journal of Orthopaedic Surgery and Research 2008, 3:31 http://www.josr-online.com/content/3/1/31 Table 2: Pre- and intraoperative tests. The tissue samples for histopathological evaluation were immediately fixed in buffered formalin (4%). Paraffin ▪ Preoperative Tests block sections were obtained (5 μm slice-thickness, slide - Plain radiography area 30 × 25 mm) and were stained with haematoxylin - Haematological screening tests (level of c-reactive protein (>0,5 mg/ and eosin. The slides were postoperatively studied under dl), white blood-cell count (> 12/nl)) - Aspiration normal and polarised light microscopy. Evaluation was done using the histopathological classification of the ▪ Intraoperative Tests periprosthetic interface membrane according to Krenn - Histopathological Evaluation and Morawietz [3] (Table 1). - Intraoperative Cultures Diagnosis of Infection At least three of these tests had to be positive whereas either positive The final diagnosis of infection was based on the interpre- histopathological evaluation or positive intraoperative cultures had to tation of the clinical presentation and the preoperative be included. and intraoperative findings rather than on a single test. The final diagnosis of infection was made when the and infection was also measured. In 18 of 37 patients patient met at least one of three criteria: an open wound (48.6%) periprosthetic joint infection was diagnosed or sinus in communication with the joint, a systemic within the first year after primary implantation, in 6 cases infection with pain in the hip and purulent fluid within (16,2%) infection occurs between the first and third year the joint, or a positive result on at least three tests (Table and in 13 of 37 patients (35.2%) implant failure was diag- 2) whereas either histological evaluation or intraoperative nosed after three years. The minimum survival of the pros- cultures had to be positive [4]. thesis was one month and the maximum survival was 17 years. In total 31 (62%) of the 50 patients had at least one Patients who had neither suspected preoperative signs (as revision before caused by aseptic/septic loosening, dislo- open wound, sinus in communication with the joint, sys- cation or wound healing deficits. All hip prostheses were temic infection with pain in the hip, purulent fluid within total hip arthroplasties. An analysis of the type and fre- the joint) nor had positive results on intraoperative his- quency of infecting organisms was conducted and coagu- topathological evaluation or cultures were not held for an lase-negative Staphylococcus (CNS) was found to be the infected joint prosthesis. most common (Table 3). For the evaluation, the results of every single infection Sensitivity, specificity, positive (PPV) and negative (NPV) parameter were related to the final diagnosis. On the basis predictive values, and accuracy for aspiration, intraopera- of this relation, sensitivity, specifity, positive and negative tive cultures, histopathology, C-reactive protein and white predictive values, and accuracy were calculated for each of blood-cell count are shown in table 4. The histopathology the tests. yielded the highest accuracy (0.94) in identification of periprosthetic joint infection and correctly identified 35 of 37 infected joint prostheses (Sensitivity 0.94, specificity Results A two stage revision was performed in 50 patients due to 0.94). preoperative conspicuousness of clinical presentation and preoperative findings in terms of periprosthetic joint In 13 patients (26%) an infected joint prosthesis could infection. After consideration of the intraoperative test not be confirmed postoperatively (table 5). All 13 patients results, final diagnose was made. In 37 patients (74 per- had clear preoperative findings as pain, early failure, cent) a diagnosis of periprosthetic joint infection could be recurrent dislocations or previous revisions caused by made definitely. The time between primary implantation Table 1: Definition of the histological types of periprosthetic membranes (Krenn and Morawietz et al.) Type Characteristics Type I – Periprosthetic membrane of the wear particle induced type Infiltration of predominantly macrophages and multinuclear giant cells containing PE particles Type II – Periprosthetic membrane of the infectious type Activated fibroblasts, proliferation of small blood vessels, oedema, and inflammatory infiltrate of neutrophilic granulocytes Type III – Periprosthetic membrane of the combined type Combination of the histomorphological changes described for types I and II Type IV – Periprosthetic membrane of the indeterminate type Connective tissue low in cells and rich in collagen fibres (non infected, non wear particle induced) Page 3 of 8 (page number not for citation purposes) Journal of Orthopaedic Surgery and Research 2008, 3:31 http://www.josr-online.com/content/3/1/31 Table 3: Type and frequency of infecting organism thetic hip joint infection. Additionally a strategy of preop- erative selection of patients with high suspicion of PJI was Organism Frequency Multiple existence evaluated and compared with the final postoperative diagnosis. CNS 13 6 Staph. epidermidis 10 4 A limitation of this study is that the study has no control Staph. capitis 2 1 Staph. haemolyticus 1 1 group. This limitation is caused by the fact that there is a Staphphylococcus aureus 10 3 lack of a gold-standard definition of periprosthetic joint Enterococcus faecalis 4 1 infection in the current literature. Periprosthetic joint Propionibacteria 3 infection is a multimodal process based on different B streptococcus 2 2 causes and occurs in a variety of clinical presentations. E. coli 2 1 Different diagnostic parameters are published with a Pseudomonas aeruginosa 2 broad range of sensitivity and specifity. The Diagnosis of MRSA 1 1 PJI depends on several tests rather than on a single test. An additional problem is that some tests are only postopera- aseptic or septic loosening. None of them had an open tively available such a microbiological cultures or his- wound, a fistula or purulent aspiration. topathological evaluation. Therefore the preselection of patients with a high suspicion of periprosthetic joint Six of these patients had a positive joint aspiration infection is a vast challenge. whereby 4 showed a growth of CNS, one Propionibacteria and one had E. coli. No pathogen was detected in six cases In this study the histopathological investigation turns out neither in joint aspiration nor in intraoperative culture. as a very practical and valid diagnostic tool for intraoper- One patient had an intraoperative growth of CNS but ative detection of periprosthetic joint infection with a showed neither elevated C-reactive protein nor a positive high sensitivity (0.95) and specificity (0.92). Because of histopathological finding. C-reactive protein was elevated detailed histopathological and polarised characterisation in 5 patients, 3 of them showed a growth in aspiration. In of the periprosthetic interface membrane the clarification 9 of 13 cases histopathological metal or polyethylene whether loosening is due to bacterial infection or not is wear particles could be found (type I) and in 3 cases an very precise. A harvesting of tissue samples was possible in indifference type (type IV). One patient showed micro- all cases. Caused by the study design, tissue samples were scopically type III that is containing areas dominated by only taken in patients with clinical or anamnestic suspi- wear induced antibody reaction and areas with inflamma- cion of infection. A recently published study by Morawi- tory reaction caused by granulocytes (lowgrade) but no etz et al, in which 370 periprosthetic membranes from other suspicious tests were present at this patient. One revision surgery were analyzed, could be shown, that most patient had a positive intraoperative culture and another of the samples (94.9%) were suitable for histological clas- positive histopathological result, but no other findings. sification [3]. A differentiation of infected and non- Only three patients had neither elevated C-reactive pro- infected loosening was well possible. A discrepancy tein, positive joint aspiration nor positive cultures and between microbiological and histological findings was positive histological results but at these three patients, an found in only 10.7% of the cases. early failure of the joint, persistent pain, previous revi- sions, recurrent dislocations, were preoperatively noticea- In 28 of the 37 septic prostheses (75%) the histological ble. and microbiological results were concordant. Similar investigations found a concordance of 89 percent (155/ Discussion 174) [3]. This fact raises the question as to whether micro- The aim of this study was to investigate the accuracy of biological culture or histological examinations are more pre- and intraoperative diagnostic parameters of peripros- valid with respect to sensitivity and specificity. Both tests Table 4: Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values, and accuracy for each of the tests are shown. Aspiration Intraoperative Histopathology C-reactive White blood-cell Cultures protein count Sensitivity 0.57 0.78 0.95 0.95 0.14 Specificity 0.5 0.92 0.92 0.62 0.92 PPV 0.78 0.96 0.97 0.88 0.83 NPV 0.29 0.63 0.86 0.80 0.29 Accuracy 0.54 0.82 0.94 0.86 0.34 Page 4 of 8 (page number not for citation purposes) Journal of Orthopaedic Surgery and Research 2008, 3:31 http://www.josr-online.com/content/3/1/31 Table 5: Pre- and Intraoperative Parameter of patients PJI could not be confirmed postoperatively CNS: Patient Preoperative Aspiration Intraop. Histo- C-reactive Prev. Interpretation Findings Cultures pathology protein mg/dl Revision (Type) 1 pain, radiogr. loosening E. coli - IV 0.95 2 lowgrade 2 Pain Metal/metal CNS - I 0.6 - metalosis wear (ME) lowegrade 3 Pain, Radiogr. loosening, chronic CNS - I 8.5 1 wear (PE+ME) lowgrade bronchitis 4 Early failure with in 2 years Propioni - IV - - lowgrade persistent pain since surgery 5 persistent pain CNS - I - - wear (PE) lowgrade 6 pain CNS - I - 2 wear (PE) lowgrade 7 stem breakage prev. sept. revision n.a. CNS I - 1 metallosis lowgrade 8 Persistent pain Previous septic - - III - 1 lowgrade revision 9 Early failure after stem revision by - - IV - 1 Pseudarthrose periprosthetic fracture 10 Pain Recurrent dislocations -- I - 6 wear (PE) Previous septic revision 11 Pain recurrent dislocations Metal/ -- I - 1 metallosis wear (ME) metal Failure within 5 years 12 Pain Recurrent dislocation Early -- I 2.9 4 wear (PE) failure within 5 years 13 Pain, radiogr. loosening - - I 1.1 1 wear (PE+ME) Coagulase negative Staphylococcus; PE: Polyethylen; E. coli: Escherichia coli; ME: metal (PE: polyethylene, ME: metal, CNS: Coagulase-negative Staphylococcus species, Propioni: Propionibacteria, n.a.: no aspiration) have there individual pitfalls as inappropriate incubation ous and adequate antibiotic treatment may not be time, previous antimicrobial therapy given to the patient, realized. However, in literature intraoperative cultures contamination in terms of cultures or e.g. insufficient have a broad range of sensitivity (range 0.65 to 0.94 (0.78 preparation of the tissue samples. in this study)) and specificity (range 0.71 to 1.0) (0.92 in this study)) depending on the definition of infection and To improve the results of histological diagnosis, the surgi- they are subjected to a variable rate of false positive and cal pathologist should be provided with additional clini- negative results [4]. In this study tissue cultures yielded a cal data, such as the lifetime of the prosthesis, type of false result in 8 (16%) of 50 patients (seven false-negative fixation, relevant records on clinical pathology, and results (14%) and 1 false-positive result (2%)) what is microbiological findings by the orthopaedic surgeon. This similar to results reported in the literature [12,15,16]. information would help the pathologist interpret results Inadequate incubation time, inappropriate choice of of histopathological samples. Caused by the necessity of media and antimicrobial therapy, as well as sample con- tissue sample preparation, an intraoperative statement of tamination from human skin flora are responsible for the pathologist was not possible in this study. It should be false-negative or false-positive results. Such problems proofed whether the classification system of peripros- reduce the level of significance of microbiological culture thetic interface membrane is applicable to frozen section methods, and have been pointed out in several studies or preoperative biopsy of the neocapsule because a pre- or [12,15-18]. It has been reported that, due to the small direct intraoperative test result would be a worthwhile numbers and low metabolism of bacteria involved in effort. Despite the fact, that the neocapsule is not respon- periprosthetic infections generally increase the time sible for loosening, it is generally accepted that the needed to resuscitate them [17,18]. Therefore, the growth changes in histological appearance are very similar in period should be extended to increase the detection rate these different tissue specimens in the same patient of infectious bacteria in excised tissue samples. It could be caused by interaction of the new joint space with the shown that some microorganisms require a minimum periprosthetic space [12-14]. incubation time of 8 days, since these microorganisms grow slowly [10]. Intraoperative cultures are a crucial parameter in diagno- sis of PJI and therefore cultures are frequently used as the Furthermore, it has been emphasized, to improve the hos- gold standard to which every other diagnostic parameter pital culturing of tissue samples, at least eight tissue sam- is correlated [2,4]. Without correct detection and identifi- ples should be taken from different sites in the operative cation of microorganisms the final diagnosis is ambigu- field [19]. Recent studies criticise that traditionally stand- Page 5 of 8 (page number not for citation purposes) Journal of Orthopaedic Surgery and Research 2008, 3:31 http://www.josr-online.com/content/3/1/31 ard diagnostic tests are designed for examining planktonic Another recommended blood parameter in detection of bacteria and those that are adequate for detecting of sep- periprosthetic hip joint infection is the erythrocyte sedi- sis-related pathogens without involvement of foreign mentation rate. In this study we focused our investigation material; therefore a significant number of infections of only on the C-reactive protein. Our decision to concen- orthopaedic devices may remain undetected [9,17]. The trate on C-reactive protein was reinforced by the fact that nutrient media and isolation procedures do not provide the C-reactive protein level increases from normal values the requisite conditions for recovering such bacteria in to reach maximum values within 24 hours after surgery culture. and then returns to trace amounts in approximately two to three weeks [25,26]. The erythrocyte sedimentation rate In this study, preoperative hip aspiration had a low sensi- may remain elevated for months after an uncomplicated tivity (0.57) and specificity (0.5), indicating that indolent total hip replacement [24]. Therefore, the ability of the C- joint infection cannot be diagnosed on the basis of aspira- reactive protein level to return to normal much faster than tion alone. However, it may be the most suitable preoper- the erythrocyte sedimentation rate enables it to be a more ative tool to provide preoperative information, such as the sensitive indicator of infection, particularly in the early identity of the infecting organism and it sensitivity to anti- postoperative period. biotics [20]. In the literature, preoperative joint aspiration for detecting PJI has a broad range of values of sensitivity Definitely postoperative infection could not be confirmed varying between 0.11 and 1.00 and specificity varying in 13 patients, although there were clear preoperative from 0.78 to 1.00 [2,6,21] certainly depending on the dif- findings which highly indicated PJI. None of them had an ferent technique or definition of infection. open wound, a fistula or purulent aspiration. Most critical issue in hip aspiration is a high false-positive In 6 of these 13 patients the preoperative suspicion of PJI 6/50 12% and false-negative 14/50 28% rate due to con- was reinforced by a positive preoperative hip aspiration. tamination at the time of aspiration or in the microbiol- But intraoperative microbiological cultures and his- ogy laboratory or false-negative rate due to low topathological results could not confirm the positive concentrations of organisms, delay in transport or inocu- results of preoperative aspiration at these patients. It has lating the sample. The inability to aspirate fluid and sub- to assume that aspiration results were false positive. sequent washout with saline may contribute to samples with low concentration. Also a two stage revision was performed in the remaining 7 patients even though preoperative aspiration was nega- Microorganisms involved in infections of orthopaedic tive. Conspicuous clinical signs like previous septical revi- devices are highly adapted on the implant or in the bone- sion (3 cases), early failure within 5 years (n = 3), and cement interphase, adhering to the environment of the in unclear elevated C-reactive protein in connection with vivo biofilm, but not planktonic in the synovia and there- persistent hip pain (n = 1) led to septical revision proce- fore join aspiration may be insufficient [9,17,22]. dure as a precaution not to overlook a creeping infection. Our results demonstrate that hip aspiration is only of Obviously, there is a difference between the preoperative assistance if there is any conspicuous preoperative sign suspicion of PJI (depending on the clinical presentation such as an open wound or sinus in communication with and the evaluation of the consultant) and the final post- the joint or in case of elevated C-reactive protein which operative diagnosis that could be made by consideration could not be explained by other conditions what is corre- of all pre- and intraoperative test results. This raises the sponding to the experience of other authors [2]. question of whether the consultant is too prudent in diag- nosing PJI or the final definition of PJI is not precise An elevated C-reactive protein which could not be enough or the diagnosis parameters are too insensitive. In explained by other conditions highly indicates a PJI espe- consideration of the fact that a miss diagnosed peripros- cially if there is evidence from clinical or radiographic thetic joint infection may have serious consequences for examination. the patient, a minimum of over diagnosed and over treat- ment is tolerable. Moreover, in case of negative intraoper- In the literature, values of sensitivity and specificity range ative test results and absence of fistula, open wound or from 0.61 to 1.0 and from 0.81 to 1.0 [2,4,23,24]. In gen- purulent aspiration, reimplantation would be performed eral, C-reactive protein is a relevant parameter in diagnos- earlier (as soon as test results come up) than it is usual in ing PJI and the elevation of C-reactive protein is a the standard two stage revision procedure. Negative effects prerequisite to joint aspiration. of a two stage revision like muscles atrophy, immobilisa- tion, contractures and leg length differences will be lim- ited to minimum. On the other hand, the relative high Page 6 of 8 (page number not for citation purposes) Journal of Orthopaedic Surgery and Research 2008, 3:31 http://www.josr-online.com/content/3/1/31 review. Scandinavian journal of infectious diseases 2004, 36(6- number of patients drop out of the diagnosis pattern, 7):410-416. could be explained through the definition of PJI. For def- 3. Morawietz L, Classen RA, Schroder JH, Dynybil C, Perka C, Skwara inition of PJI we tried to include both, clinical presenta- A, Neidel J, Gehrke T, Frommelt L, Hansen T, Otto M, Barden B, Aigner T, Stiehl P, Schubert T, Meyer-Scholten C, Konig A, Strobel P, tion and pre/intraoperative test results, similar to the Rader CP, Kirschner S, Lintner F, Ruther W, Bos I, Hendrich C, definition of Spangehl et al and Giulieri et al, to obtain a Kriegsmann J, Krenn V: Proposal for a histopathological consen- sus classification of the periprosthetic interface membrane. diversified diagnostic pattern [4,27]. But nevertheless, all Journal of clinical pathology 2006, 59(6):591-597. tests are subjected to a certain rate of false positive and 4. Spangehl MJ, Masri BA, O'Connell JX, Duncan CP: Prospective false negative test results, as this and other studies have analysis of preoperative and intraoperative investigations for the diagnosis of infection at the sites of two hundred and two shown. To obtain highest accuracy in diagnosis of PJI and revision total hip arthroplasties. TJ Bone Joint Surg Am 1999, to improve the detection rate, an exact implementation 81(5):672-683. and interpretation of each single diagnostic test is crucial. 5. Fehring TK, Cohen B: Aspiration as a guide to sepsis in revision total hip arthroplasty. The Journal of arthroplasty 1996, Improvements in the technique of joint aspiration, 11(5):543-547. reported by Ali et al, appropriate incubation time of the 6. Ali F, Wilkinson JM, Cooper JR, Kerry RM, Hamer AJ, Norman P, Stockley I: Accuracy of joint aspiration for the preoperative cultures, the correct choice of media, and stopping previ- diagnosis of infection in total hip arthroplasty. The Journal of ous antimicrobial therapy in advance, are all important arthroplasty 2006, 21(2):221-226. points [6]. However, it is recommended that joint aspira- 7. Anlage 5.1. In Richtlinie für Krankenhaushygiene und Infektionsprävent- ion Edited by: Berlin RKI. Munich , Urban und Fischer Verlag; tion should not be performed, if there is no elevation of C 2003:7–8. – reactive protein, or clear clinical or radiological signs. 8. Lutz MF, Berthelot P, Fresard A, Cazorla C, Carricajo A, Vautrin AC, Fessy MH, Lucht F: Arthroplastic and osteosynthetic infections Other reasons for elevation of C – reactive protein should due to Propionibacterium acnes: a retrospective study of 52 be excluded. cases, 1995-2002. Eur J Clin Microbiol Infect Dis 2005, 24(11):739-744. 9. Zimmerli W, Trampuz A, Ochsner PE: Prosthetic-joint infections. Recent investigations have pioneered new techniques for The New England journal of medicine 2004, 351(16):1645-1654. detection of PJI. A notable success in detection of pros- 10. Gunthard H, Hany A, Turina M, Wust J: Propionibacterium acnes thetic hip infection at revision arthroplasty could be as a cause of aggressive aortic valve endocarditis and impor- tance of tissue grinding: case report and review. Journal of clin- achieved by Immunofluorescence Microscopy, Polymer- ical microbiology 1994, 32(12):3043-3045. ase Chain Reaction (PCR), by analysis of explanted pros- 11. Widmer AF: New developments in diagnosis and treatment of infection in orthopedic implants. Clin Infect Dis 2001, 33 Suppl theses surfaces and by confocal laser scanning microscopy 2:S94-106. [18,28,29]. However, it remains to be seen if these new 12. Pandey R, Drakoulakis E, Athanasou NA: An assessment of the techniques can be established in clinical practice. histological criteria used to diagnose infection in hip revision arthroplasty tissues. Journal of clinical pathology 1999, 52(2):118-123. Conclusion 13. Bos I: [Tissue reactions around loosened hip joint endopros- Although periprosthetic joint infection is a well known theses. A histological study of secondary capsules and inter- face membranes]. Der Orthopade 2001, 30(11):881-889. complication in orthopedics, this study indicates that the 14. Urban RM, Jacobs JJ, Gilbert JL, Galante JO: Migration of corrosion detection of PJI is still a challenge in clinical practice. Pre- products from modular hip prostheses. Particle microanaly- sis and histopathological findings. J Bone Joint Surg Am 1994, and intraoperative parameters are subjected to a variety 76(9):1345-1359. rate of false negative and false positive test results which 15. Peersman G, Laskin R, Davis J, Peterson M: Infection in total knee influences the accuracy of the final diagnosis. In this replacement: a retrospective review of 6489 total knee replacements. Clin Orthop Relat Res 2001:15-23. investigation a discrepancy between the preoperative sus- 16. von Eiff C, Bettin D, Proctor RA, Rolauffs B, Lindner N, Winkelmann picion of PJI and the final postoperative diagnosis was W, Peters G: Recovery of small colony variants of Staphyloco- found that implies in some cases a slight uncertainty in ccus aureus following gentamicin bead placement for osteo- myelitis. Clin Infect Dis 1997, 25(5):1250-1251. whether loosening is due to bacterial infection or not. 17. Ince A, Rupp J, Frommelt L, Katzer A, Gille J, Lohr JF: Is "aseptic" loosening of the prosthetic cup after total hip replacement due to nonculturable bacterial pathogens in patients with Additionally, one of the most essential facts of this exam- low-grade infection? Clin Infect Dis 2004, 39(11):1599-1603. ination is the evidence of the high accuracy of the his- 18. Neut D, van Horn JR, van Kooten TG, van der Mei HC, Busscher HJ: topathological classification of the periprosthetic Detection of biomaterial-associated infections in orthopae- dic joint implants. Clin Orthop Relat Res 2003:261-268. interface membrane in detection of PJI. This classification 19. Atkins BL, Bowler IC: The diagnosis of large joint sepsis. The system proves as a very practical diagnostic tool in detec- Journal of hospital infection 1998, 40(4):263-274. 20. Hughes SP, Dash CH, Benson MK, Field CA: Infection following tion of periprosthetic joint infection, with both a high total hip replacement and the possible prophylactic role of sensitivity and specificity. cephaloridine. Journal of the Royal College of Surgeons of Edinburgh 1978, 23(1):9-12. 21. Patel D, Karchmer A, Harris HW: Role of preoperative aspira- References tion of the hip prior to total hip replacement. The Hip 1. Bozic KJ, Rubash HE: The painful total hip replacement. Clinical 1976:219-223. orthopaedics and related research 2004:18-25. 22. Costerton JW, Stewart PS, Greenberg EP: Bacterial biofilms: a 2. Bernard L, Lubbeke A, Stern R, Bru JP, Feron JM, Peyramond D, common cause of persistent infections. Science (New York, NY Denormandie P, Arvieux C, Chirouze C, Perronne C, Hoffmeyer P: 1999, 284(5418):1318-1322. Value of preoperative investigations in diagnosing prosthetic joint infection: retrospective cohort study and literature Page 7 of 8 (page number not for citation purposes) Journal of Orthopaedic Surgery and Research 2008, 3:31 http://www.josr-online.com/content/3/1/31 23. Sanzen L, Carlsson AS: The diagnostic value of C-reactive pro- tein in infected total hip arthroplasties. J Bone Joint Surg Br 1989, 71(4):638-641. 24. Shih LY, Wu JJ, Yang DJ: Erythrocyte sedimentation rate and C- reactive protein values in patients with total hip arthro- plasty. Clin Orthop Relat Res 1987:238-246. 25. Aalto K, Osterman K, Peltola H, Rasanen J: Changes in erythro- cyte sedimentation rate and C-reactive protein after total hip arthroplasty. Clin Orthop Relat Res 1984:118-120. 26. Niskanen RO, Korkala O, Pammo H: Serum C-reactive protein levels after total hip and knee arthroplasty. J Bone Joint Surg Br 1996, 78(3):431-433. 27. Giulieri SG, Graber P, Ochsner PE, Zimmerli W: Management of infection associated with total hip arthroplasty according to a treatment algorithm. Infection 2004, 32(4):222-228. 28. Tunney MM, Patrick S, Curran MD, Ramage G, Hanna D, Nixon JR, Gorman SP, Davis RI, Anderson N: Detection of prosthetic hip infection at revision arthroplasty by immunofluorescence microscopy and PCR amplification of the bacterial 16S rRNA gene. Journal of clinical microbiology 1999, 37(10):3281-3290. 29. Tunney MM, Patrick S, Curran MD, Ramage G, Anderson N, Davis RI, Gorman SP, Nixon JR: Detection of prosthetic joint biofilm infection using immunological and molecular techniques. Methods in enzymology 1999, 310:566-576. Publish with Bio Med Central and every scientist can read your work free of charge "BioMed Central will be the most significant development for disseminating the results of biomedical researc h in our lifetime." Sir Paul Nurse, Cancer Research UK Your research papers will be: available free of charge to the entire biomedical community peer reviewed and published immediately upon acceptance cited in PubMed and archived on PubMed Central yours — you keep the copyright BioMedcentral Submit your manuscript here: http://www.biomedcentral.com/info/publishing_adv.asp Page 8 of 8 (page number not for citation purposes) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Orthopaedic Surgery and Research Springer Journals

Diagnosis of periprosthetic infection following total hip arthroplasty – evaluation of the diagnostic values of pre- and intraoperative parameters and the associated strategy to preoperatively select patients with a high probability of joint infection

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Springer Journals
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Copyright © 2008 by Müller et al; licensee BioMed Central Ltd.
Subject
Medicine & Public Health; Orthopedics; Surgical Orthopedics
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1749-799X
DOI
10.1186/1749-799X-3-31
pmid
18644107
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Abstract

Background: The correct diagnosis of a prosthetic joint infection (PJI) is crucial for adequate surgical treatment. The detection may be a challenge since presentation and preoperative tests are not always obvious and precise. This prospective study was performed to evaluate a variety of pre- and intraoperative investigations. Furthermore a detailed evaluation of concordance of each preoperative diagnosis was performed, together with a final diagnosis to assess the accuracy of the pre-operative assumption of PJI. Methods: Between 01/2005 and 02/2007, a prospective analysis was performed in 50 patients, who had a two stage revision because of assumed PJI. Based on clinical presentation, radiography, haematological screening, or early failure, infection was assumed and a joint aspiration was performed. Depending upon these findings, a two stage revision was performed, with intra-operative samples for culture and histological evaluation obtained. Final diagnosis of infection was based upon the interpretation of the clinical presentation and the pre- and intraoperative findings. Results: In 37 patients a positive diagnosis of PJI could be made definitely. The histopathology yielded the highest accuracy (0.94) in identification of PJI and identified 35 of 37 infections (sensitivity 0.94, specificity 0.94, positive-/negative predictive value 0.97/0.86). Intra-operative cultures revealed sensitivities, specificities, positive-/negative predictive values and accuracy of 0.78, 0.92, 0.96, 0.63 and 0.82. These values for blood screening tests were 0.95, 0.62, 0.88, 0.80, and 0.86 respectively for the level of C-reactive protein, and 0.14, 0.92, 0.83, 0.29 and, 0.34 respectively for the white blood-cell count. The results of aspiration were 0.57, 0.5, 0.78, 0.29, and 0.54. Conclusion: The detection of PJI is still a challenge in clinical practice. The histopathological evaluation emerges as a highly practical diagnostic tool in detection of PJI. Furthermore, we found a discrepancy between the pre-operative suspicion of PJI and the final post-operative diagnosis, resulting in a slight uncertainty in whether loosening is due to bacterial infection or not. The variation in accuracy of the single tests may influence the detection of PJI. Level of Evidence: Diagnostic Level I. Page 1 of 8 (page number not for citation purposes) Journal of Orthopaedic Surgery and Research 2008, 3:31 http://www.josr-online.com/content/3/1/31 Based on the following preoperative parameters, infection Background The diagnosis of periprosthetic joint infection (PJI) can of the hip prosthesis was supposed [5,6]: present a challenge due to the fact that both clinical pres- entation and preoperative tests are not always obvious ▪ clinical presentation of infection (Pain, fever, fistula) and precise. The clinical assessment depends strongly on the symptoms of fever, pain, and fistula. Frequently, per- ▪ plain radiography sistent pain is the only symptom which is present [1]. Numerous preoperative tests for determination and diag- ▪ haematological screening tests (level of c-reactive pro- nosis of a failed total hip replacement are available. These tein (>0,5 mg/dl), white blood-cell count (> 12/nl)) tests include haematological screening tests (measure- ment of the erythrocyte sedimentation rate, and the level ▪ early failure within the first five years in connection with of C-reactive protein, white blood-cell count,), aspiration clinical or haematological suspicion of the hip joint, plain radiography, and radionuclide imaging studies. None of these tests is 100 percent reliable When at least one of these parameters was observed, a and are subject to a variable spectrum of false negative or joint aspiration was performed. Joint aspiration was done false positive results [2]. A misdiagnosis has crucial conse- according to the standards described in the Guidelines of quences for the treatment and for the patient. In case of a Hospital Hygiene and Infectious Disease Prevention [7] misdiagnosed periprosthetic infection, revision of the (Robert-Koch Institut; Berlin), under sterile conditions in prosthesis without appropriate débridement and antibio- an operation theatre, after preparation and draping, using sis would keep a failed total hip replacement and risk an a sterile technique without local anaesthetics and con- early failure. On the other hand a wrong assumption firming intraarticular placement by radiograph. If no fluid about periprosthetic infection caused by a false positive was aspirated, 10 ml of normal saline was injected and test, the patient has to undergo surgery which would be reaspirated. If there was a sample of less than 5 ml, only highly inadequate as a girdlestone operation (two stage an aerobic bottle was inoculated. revision) or a cemented revision (one stage revision). In case of positive aspiration and/or clear clinical or radi- Principal intraoperative tests include the histological eval- ographic findings and/or persistence of elevated haemato- uation and microbiological cultures of the periprosthetic logical parameters which could not explained by other tissue which have a high validity [3,4]. However the conditions, periprosthetic joint infection was diagnosed appropriateness of these tests in determining surgical and a two stage revision has been performed. treatment is limited due to the time required to allow for histological preparation and bacteria growth. Hence, final Microbacterial Cultures and Intraoperative diagnosis of periprosthetic infection can not be made Histopathological Evaluation until a couple of days after surgery, when histological and Intraoperative samples for culture and histological evalu- microbiological results are available. Therefore, there is an ation were obtained from the cup and stem region. Six occasional slight uncertainty whether the right treatment samples were incubated for 10 days to analyse bacterial was accomplished. growth. The aim of this study was to compare pre- and intraoper- This time period is based on an actual literature review [8- ative diagnostic tests including haematological screening, 10]. It could be shown that some microorganisms require aspiration, histological evaluation, and microbacterial a minimum incubation time of 8 days, since these micro- cultures and to investigate the diagnostic pathway for the organisms grow slowly [9,10]. Specimens were inoculated detection of periprosthetic joint infection. Additionally, in various culture media (standard eg, blood and choco- the accuracy of preoperative diagnosis of periprosthetic late agar, as well as Brain-heart bouillon, Wilkins Chal- joint infection was evaluated by comparing preoperative gren agar, McConkey agar, Sabouraud agar and selection with the final diagnosis. thioglycolate broth). A result was considered positive if a minimum of 1 speci- Methods Patients and study design men showed growth associated with purulence for viru- Between January 2005 and February 2007 a prospective lent organism, such as Staphylococcus aureus, analysis was performed in 50 patients (23 male, 27 Streptococci species, or a Gram-negative bacterium. For female) in the mean age of 69 years (range, 46 – 84) who pathogens with low virulence, such as coagulase negative had a two stage revision because of the suspicion of Staphylococci or Propionibacterium species, at least three periprosthetic total hip-joint infection. specimens were required positive (with identical pheno- type bacteria profile) for a positive result [11]. Page 2 of 8 (page number not for citation purposes) Journal of Orthopaedic Surgery and Research 2008, 3:31 http://www.josr-online.com/content/3/1/31 Table 2: Pre- and intraoperative tests. The tissue samples for histopathological evaluation were immediately fixed in buffered formalin (4%). Paraffin ▪ Preoperative Tests block sections were obtained (5 μm slice-thickness, slide - Plain radiography area 30 × 25 mm) and were stained with haematoxylin - Haematological screening tests (level of c-reactive protein (>0,5 mg/ and eosin. The slides were postoperatively studied under dl), white blood-cell count (> 12/nl)) - Aspiration normal and polarised light microscopy. Evaluation was done using the histopathological classification of the ▪ Intraoperative Tests periprosthetic interface membrane according to Krenn - Histopathological Evaluation and Morawietz [3] (Table 1). - Intraoperative Cultures Diagnosis of Infection At least three of these tests had to be positive whereas either positive The final diagnosis of infection was based on the interpre- histopathological evaluation or positive intraoperative cultures had to tation of the clinical presentation and the preoperative be included. and intraoperative findings rather than on a single test. The final diagnosis of infection was made when the and infection was also measured. In 18 of 37 patients patient met at least one of three criteria: an open wound (48.6%) periprosthetic joint infection was diagnosed or sinus in communication with the joint, a systemic within the first year after primary implantation, in 6 cases infection with pain in the hip and purulent fluid within (16,2%) infection occurs between the first and third year the joint, or a positive result on at least three tests (Table and in 13 of 37 patients (35.2%) implant failure was diag- 2) whereas either histological evaluation or intraoperative nosed after three years. The minimum survival of the pros- cultures had to be positive [4]. thesis was one month and the maximum survival was 17 years. In total 31 (62%) of the 50 patients had at least one Patients who had neither suspected preoperative signs (as revision before caused by aseptic/septic loosening, dislo- open wound, sinus in communication with the joint, sys- cation or wound healing deficits. All hip prostheses were temic infection with pain in the hip, purulent fluid within total hip arthroplasties. An analysis of the type and fre- the joint) nor had positive results on intraoperative his- quency of infecting organisms was conducted and coagu- topathological evaluation or cultures were not held for an lase-negative Staphylococcus (CNS) was found to be the infected joint prosthesis. most common (Table 3). For the evaluation, the results of every single infection Sensitivity, specificity, positive (PPV) and negative (NPV) parameter were related to the final diagnosis. On the basis predictive values, and accuracy for aspiration, intraopera- of this relation, sensitivity, specifity, positive and negative tive cultures, histopathology, C-reactive protein and white predictive values, and accuracy were calculated for each of blood-cell count are shown in table 4. The histopathology the tests. yielded the highest accuracy (0.94) in identification of periprosthetic joint infection and correctly identified 35 of 37 infected joint prostheses (Sensitivity 0.94, specificity Results A two stage revision was performed in 50 patients due to 0.94). preoperative conspicuousness of clinical presentation and preoperative findings in terms of periprosthetic joint In 13 patients (26%) an infected joint prosthesis could infection. After consideration of the intraoperative test not be confirmed postoperatively (table 5). All 13 patients results, final diagnose was made. In 37 patients (74 per- had clear preoperative findings as pain, early failure, cent) a diagnosis of periprosthetic joint infection could be recurrent dislocations or previous revisions caused by made definitely. The time between primary implantation Table 1: Definition of the histological types of periprosthetic membranes (Krenn and Morawietz et al.) Type Characteristics Type I – Periprosthetic membrane of the wear particle induced type Infiltration of predominantly macrophages and multinuclear giant cells containing PE particles Type II – Periprosthetic membrane of the infectious type Activated fibroblasts, proliferation of small blood vessels, oedema, and inflammatory infiltrate of neutrophilic granulocytes Type III – Periprosthetic membrane of the combined type Combination of the histomorphological changes described for types I and II Type IV – Periprosthetic membrane of the indeterminate type Connective tissue low in cells and rich in collagen fibres (non infected, non wear particle induced) Page 3 of 8 (page number not for citation purposes) Journal of Orthopaedic Surgery and Research 2008, 3:31 http://www.josr-online.com/content/3/1/31 Table 3: Type and frequency of infecting organism thetic hip joint infection. Additionally a strategy of preop- erative selection of patients with high suspicion of PJI was Organism Frequency Multiple existence evaluated and compared with the final postoperative diagnosis. CNS 13 6 Staph. epidermidis 10 4 A limitation of this study is that the study has no control Staph. capitis 2 1 Staph. haemolyticus 1 1 group. This limitation is caused by the fact that there is a Staphphylococcus aureus 10 3 lack of a gold-standard definition of periprosthetic joint Enterococcus faecalis 4 1 infection in the current literature. Periprosthetic joint Propionibacteria 3 infection is a multimodal process based on different B streptococcus 2 2 causes and occurs in a variety of clinical presentations. E. coli 2 1 Different diagnostic parameters are published with a Pseudomonas aeruginosa 2 broad range of sensitivity and specifity. The Diagnosis of MRSA 1 1 PJI depends on several tests rather than on a single test. An additional problem is that some tests are only postopera- aseptic or septic loosening. None of them had an open tively available such a microbiological cultures or his- wound, a fistula or purulent aspiration. topathological evaluation. Therefore the preselection of patients with a high suspicion of periprosthetic joint Six of these patients had a positive joint aspiration infection is a vast challenge. whereby 4 showed a growth of CNS, one Propionibacteria and one had E. coli. No pathogen was detected in six cases In this study the histopathological investigation turns out neither in joint aspiration nor in intraoperative culture. as a very practical and valid diagnostic tool for intraoper- One patient had an intraoperative growth of CNS but ative detection of periprosthetic joint infection with a showed neither elevated C-reactive protein nor a positive high sensitivity (0.95) and specificity (0.92). Because of histopathological finding. C-reactive protein was elevated detailed histopathological and polarised characterisation in 5 patients, 3 of them showed a growth in aspiration. In of the periprosthetic interface membrane the clarification 9 of 13 cases histopathological metal or polyethylene whether loosening is due to bacterial infection or not is wear particles could be found (type I) and in 3 cases an very precise. A harvesting of tissue samples was possible in indifference type (type IV). One patient showed micro- all cases. Caused by the study design, tissue samples were scopically type III that is containing areas dominated by only taken in patients with clinical or anamnestic suspi- wear induced antibody reaction and areas with inflamma- cion of infection. A recently published study by Morawi- tory reaction caused by granulocytes (lowgrade) but no etz et al, in which 370 periprosthetic membranes from other suspicious tests were present at this patient. One revision surgery were analyzed, could be shown, that most patient had a positive intraoperative culture and another of the samples (94.9%) were suitable for histological clas- positive histopathological result, but no other findings. sification [3]. A differentiation of infected and non- Only three patients had neither elevated C-reactive pro- infected loosening was well possible. A discrepancy tein, positive joint aspiration nor positive cultures and between microbiological and histological findings was positive histological results but at these three patients, an found in only 10.7% of the cases. early failure of the joint, persistent pain, previous revi- sions, recurrent dislocations, were preoperatively noticea- In 28 of the 37 septic prostheses (75%) the histological ble. and microbiological results were concordant. Similar investigations found a concordance of 89 percent (155/ Discussion 174) [3]. This fact raises the question as to whether micro- The aim of this study was to investigate the accuracy of biological culture or histological examinations are more pre- and intraoperative diagnostic parameters of peripros- valid with respect to sensitivity and specificity. Both tests Table 4: Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values, and accuracy for each of the tests are shown. Aspiration Intraoperative Histopathology C-reactive White blood-cell Cultures protein count Sensitivity 0.57 0.78 0.95 0.95 0.14 Specificity 0.5 0.92 0.92 0.62 0.92 PPV 0.78 0.96 0.97 0.88 0.83 NPV 0.29 0.63 0.86 0.80 0.29 Accuracy 0.54 0.82 0.94 0.86 0.34 Page 4 of 8 (page number not for citation purposes) Journal of Orthopaedic Surgery and Research 2008, 3:31 http://www.josr-online.com/content/3/1/31 Table 5: Pre- and Intraoperative Parameter of patients PJI could not be confirmed postoperatively CNS: Patient Preoperative Aspiration Intraop. Histo- C-reactive Prev. Interpretation Findings Cultures pathology protein mg/dl Revision (Type) 1 pain, radiogr. loosening E. coli - IV 0.95 2 lowgrade 2 Pain Metal/metal CNS - I 0.6 - metalosis wear (ME) lowegrade 3 Pain, Radiogr. loosening, chronic CNS - I 8.5 1 wear (PE+ME) lowgrade bronchitis 4 Early failure with in 2 years Propioni - IV - - lowgrade persistent pain since surgery 5 persistent pain CNS - I - - wear (PE) lowgrade 6 pain CNS - I - 2 wear (PE) lowgrade 7 stem breakage prev. sept. revision n.a. CNS I - 1 metallosis lowgrade 8 Persistent pain Previous septic - - III - 1 lowgrade revision 9 Early failure after stem revision by - - IV - 1 Pseudarthrose periprosthetic fracture 10 Pain Recurrent dislocations -- I - 6 wear (PE) Previous septic revision 11 Pain recurrent dislocations Metal/ -- I - 1 metallosis wear (ME) metal Failure within 5 years 12 Pain Recurrent dislocation Early -- I 2.9 4 wear (PE) failure within 5 years 13 Pain, radiogr. loosening - - I 1.1 1 wear (PE+ME) Coagulase negative Staphylococcus; PE: Polyethylen; E. coli: Escherichia coli; ME: metal (PE: polyethylene, ME: metal, CNS: Coagulase-negative Staphylococcus species, Propioni: Propionibacteria, n.a.: no aspiration) have there individual pitfalls as inappropriate incubation ous and adequate antibiotic treatment may not be time, previous antimicrobial therapy given to the patient, realized. However, in literature intraoperative cultures contamination in terms of cultures or e.g. insufficient have a broad range of sensitivity (range 0.65 to 0.94 (0.78 preparation of the tissue samples. in this study)) and specificity (range 0.71 to 1.0) (0.92 in this study)) depending on the definition of infection and To improve the results of histological diagnosis, the surgi- they are subjected to a variable rate of false positive and cal pathologist should be provided with additional clini- negative results [4]. In this study tissue cultures yielded a cal data, such as the lifetime of the prosthesis, type of false result in 8 (16%) of 50 patients (seven false-negative fixation, relevant records on clinical pathology, and results (14%) and 1 false-positive result (2%)) what is microbiological findings by the orthopaedic surgeon. This similar to results reported in the literature [12,15,16]. information would help the pathologist interpret results Inadequate incubation time, inappropriate choice of of histopathological samples. Caused by the necessity of media and antimicrobial therapy, as well as sample con- tissue sample preparation, an intraoperative statement of tamination from human skin flora are responsible for the pathologist was not possible in this study. It should be false-negative or false-positive results. Such problems proofed whether the classification system of peripros- reduce the level of significance of microbiological culture thetic interface membrane is applicable to frozen section methods, and have been pointed out in several studies or preoperative biopsy of the neocapsule because a pre- or [12,15-18]. It has been reported that, due to the small direct intraoperative test result would be a worthwhile numbers and low metabolism of bacteria involved in effort. Despite the fact, that the neocapsule is not respon- periprosthetic infections generally increase the time sible for loosening, it is generally accepted that the needed to resuscitate them [17,18]. Therefore, the growth changes in histological appearance are very similar in period should be extended to increase the detection rate these different tissue specimens in the same patient of infectious bacteria in excised tissue samples. It could be caused by interaction of the new joint space with the shown that some microorganisms require a minimum periprosthetic space [12-14]. incubation time of 8 days, since these microorganisms grow slowly [10]. Intraoperative cultures are a crucial parameter in diagno- sis of PJI and therefore cultures are frequently used as the Furthermore, it has been emphasized, to improve the hos- gold standard to which every other diagnostic parameter pital culturing of tissue samples, at least eight tissue sam- is correlated [2,4]. Without correct detection and identifi- ples should be taken from different sites in the operative cation of microorganisms the final diagnosis is ambigu- field [19]. Recent studies criticise that traditionally stand- Page 5 of 8 (page number not for citation purposes) Journal of Orthopaedic Surgery and Research 2008, 3:31 http://www.josr-online.com/content/3/1/31 ard diagnostic tests are designed for examining planktonic Another recommended blood parameter in detection of bacteria and those that are adequate for detecting of sep- periprosthetic hip joint infection is the erythrocyte sedi- sis-related pathogens without involvement of foreign mentation rate. In this study we focused our investigation material; therefore a significant number of infections of only on the C-reactive protein. Our decision to concen- orthopaedic devices may remain undetected [9,17]. The trate on C-reactive protein was reinforced by the fact that nutrient media and isolation procedures do not provide the C-reactive protein level increases from normal values the requisite conditions for recovering such bacteria in to reach maximum values within 24 hours after surgery culture. and then returns to trace amounts in approximately two to three weeks [25,26]. The erythrocyte sedimentation rate In this study, preoperative hip aspiration had a low sensi- may remain elevated for months after an uncomplicated tivity (0.57) and specificity (0.5), indicating that indolent total hip replacement [24]. Therefore, the ability of the C- joint infection cannot be diagnosed on the basis of aspira- reactive protein level to return to normal much faster than tion alone. However, it may be the most suitable preoper- the erythrocyte sedimentation rate enables it to be a more ative tool to provide preoperative information, such as the sensitive indicator of infection, particularly in the early identity of the infecting organism and it sensitivity to anti- postoperative period. biotics [20]. In the literature, preoperative joint aspiration for detecting PJI has a broad range of values of sensitivity Definitely postoperative infection could not be confirmed varying between 0.11 and 1.00 and specificity varying in 13 patients, although there were clear preoperative from 0.78 to 1.00 [2,6,21] certainly depending on the dif- findings which highly indicated PJI. None of them had an ferent technique or definition of infection. open wound, a fistula or purulent aspiration. Most critical issue in hip aspiration is a high false-positive In 6 of these 13 patients the preoperative suspicion of PJI 6/50 12% and false-negative 14/50 28% rate due to con- was reinforced by a positive preoperative hip aspiration. tamination at the time of aspiration or in the microbiol- But intraoperative microbiological cultures and his- ogy laboratory or false-negative rate due to low topathological results could not confirm the positive concentrations of organisms, delay in transport or inocu- results of preoperative aspiration at these patients. It has lating the sample. The inability to aspirate fluid and sub- to assume that aspiration results were false positive. sequent washout with saline may contribute to samples with low concentration. Also a two stage revision was performed in the remaining 7 patients even though preoperative aspiration was nega- Microorganisms involved in infections of orthopaedic tive. Conspicuous clinical signs like previous septical revi- devices are highly adapted on the implant or in the bone- sion (3 cases), early failure within 5 years (n = 3), and cement interphase, adhering to the environment of the in unclear elevated C-reactive protein in connection with vivo biofilm, but not planktonic in the synovia and there- persistent hip pain (n = 1) led to septical revision proce- fore join aspiration may be insufficient [9,17,22]. dure as a precaution not to overlook a creeping infection. Our results demonstrate that hip aspiration is only of Obviously, there is a difference between the preoperative assistance if there is any conspicuous preoperative sign suspicion of PJI (depending on the clinical presentation such as an open wound or sinus in communication with and the evaluation of the consultant) and the final post- the joint or in case of elevated C-reactive protein which operative diagnosis that could be made by consideration could not be explained by other conditions what is corre- of all pre- and intraoperative test results. This raises the sponding to the experience of other authors [2]. question of whether the consultant is too prudent in diag- nosing PJI or the final definition of PJI is not precise An elevated C-reactive protein which could not be enough or the diagnosis parameters are too insensitive. In explained by other conditions highly indicates a PJI espe- consideration of the fact that a miss diagnosed peripros- cially if there is evidence from clinical or radiographic thetic joint infection may have serious consequences for examination. the patient, a minimum of over diagnosed and over treat- ment is tolerable. Moreover, in case of negative intraoper- In the literature, values of sensitivity and specificity range ative test results and absence of fistula, open wound or from 0.61 to 1.0 and from 0.81 to 1.0 [2,4,23,24]. In gen- purulent aspiration, reimplantation would be performed eral, C-reactive protein is a relevant parameter in diagnos- earlier (as soon as test results come up) than it is usual in ing PJI and the elevation of C-reactive protein is a the standard two stage revision procedure. Negative effects prerequisite to joint aspiration. of a two stage revision like muscles atrophy, immobilisa- tion, contractures and leg length differences will be lim- ited to minimum. On the other hand, the relative high Page 6 of 8 (page number not for citation purposes) Journal of Orthopaedic Surgery and Research 2008, 3:31 http://www.josr-online.com/content/3/1/31 review. Scandinavian journal of infectious diseases 2004, 36(6- number of patients drop out of the diagnosis pattern, 7):410-416. could be explained through the definition of PJI. For def- 3. Morawietz L, Classen RA, Schroder JH, Dynybil C, Perka C, Skwara inition of PJI we tried to include both, clinical presenta- A, Neidel J, Gehrke T, Frommelt L, Hansen T, Otto M, Barden B, Aigner T, Stiehl P, Schubert T, Meyer-Scholten C, Konig A, Strobel P, tion and pre/intraoperative test results, similar to the Rader CP, Kirschner S, Lintner F, Ruther W, Bos I, Hendrich C, definition of Spangehl et al and Giulieri et al, to obtain a Kriegsmann J, Krenn V: Proposal for a histopathological consen- sus classification of the periprosthetic interface membrane. diversified diagnostic pattern [4,27]. But nevertheless, all Journal of clinical pathology 2006, 59(6):591-597. tests are subjected to a certain rate of false positive and 4. Spangehl MJ, Masri BA, O'Connell JX, Duncan CP: Prospective false negative test results, as this and other studies have analysis of preoperative and intraoperative investigations for the diagnosis of infection at the sites of two hundred and two shown. To obtain highest accuracy in diagnosis of PJI and revision total hip arthroplasties. TJ Bone Joint Surg Am 1999, to improve the detection rate, an exact implementation 81(5):672-683. and interpretation of each single diagnostic test is crucial. 5. Fehring TK, Cohen B: Aspiration as a guide to sepsis in revision total hip arthroplasty. The Journal of arthroplasty 1996, Improvements in the technique of joint aspiration, 11(5):543-547. reported by Ali et al, appropriate incubation time of the 6. Ali F, Wilkinson JM, Cooper JR, Kerry RM, Hamer AJ, Norman P, Stockley I: Accuracy of joint aspiration for the preoperative cultures, the correct choice of media, and stopping previ- diagnosis of infection in total hip arthroplasty. The Journal of ous antimicrobial therapy in advance, are all important arthroplasty 2006, 21(2):221-226. points [6]. However, it is recommended that joint aspira- 7. Anlage 5.1. In Richtlinie für Krankenhaushygiene und Infektionsprävent- ion Edited by: Berlin RKI. Munich , Urban und Fischer Verlag; tion should not be performed, if there is no elevation of C 2003:7–8. – reactive protein, or clear clinical or radiological signs. 8. Lutz MF, Berthelot P, Fresard A, Cazorla C, Carricajo A, Vautrin AC, Fessy MH, Lucht F: Arthroplastic and osteosynthetic infections Other reasons for elevation of C – reactive protein should due to Propionibacterium acnes: a retrospective study of 52 be excluded. cases, 1995-2002. Eur J Clin Microbiol Infect Dis 2005, 24(11):739-744. 9. Zimmerli W, Trampuz A, Ochsner PE: Prosthetic-joint infections. Recent investigations have pioneered new techniques for The New England journal of medicine 2004, 351(16):1645-1654. detection of PJI. A notable success in detection of pros- 10. Gunthard H, Hany A, Turina M, Wust J: Propionibacterium acnes thetic hip infection at revision arthroplasty could be as a cause of aggressive aortic valve endocarditis and impor- tance of tissue grinding: case report and review. Journal of clin- achieved by Immunofluorescence Microscopy, Polymer- ical microbiology 1994, 32(12):3043-3045. ase Chain Reaction (PCR), by analysis of explanted pros- 11. Widmer AF: New developments in diagnosis and treatment of infection in orthopedic implants. Clin Infect Dis 2001, 33 Suppl theses surfaces and by confocal laser scanning microscopy 2:S94-106. [18,28,29]. However, it remains to be seen if these new 12. Pandey R, Drakoulakis E, Athanasou NA: An assessment of the techniques can be established in clinical practice. histological criteria used to diagnose infection in hip revision arthroplasty tissues. Journal of clinical pathology 1999, 52(2):118-123. Conclusion 13. Bos I: [Tissue reactions around loosened hip joint endopros- Although periprosthetic joint infection is a well known theses. A histological study of secondary capsules and inter- face membranes]. Der Orthopade 2001, 30(11):881-889. complication in orthopedics, this study indicates that the 14. Urban RM, Jacobs JJ, Gilbert JL, Galante JO: Migration of corrosion detection of PJI is still a challenge in clinical practice. Pre- products from modular hip prostheses. Particle microanaly- sis and histopathological findings. J Bone Joint Surg Am 1994, and intraoperative parameters are subjected to a variety 76(9):1345-1359. rate of false negative and false positive test results which 15. Peersman G, Laskin R, Davis J, Peterson M: Infection in total knee influences the accuracy of the final diagnosis. In this replacement: a retrospective review of 6489 total knee replacements. Clin Orthop Relat Res 2001:15-23. investigation a discrepancy between the preoperative sus- 16. von Eiff C, Bettin D, Proctor RA, Rolauffs B, Lindner N, Winkelmann picion of PJI and the final postoperative diagnosis was W, Peters G: Recovery of small colony variants of Staphyloco- found that implies in some cases a slight uncertainty in ccus aureus following gentamicin bead placement for osteo- myelitis. Clin Infect Dis 1997, 25(5):1250-1251. whether loosening is due to bacterial infection or not. 17. Ince A, Rupp J, Frommelt L, Katzer A, Gille J, Lohr JF: Is "aseptic" loosening of the prosthetic cup after total hip replacement due to nonculturable bacterial pathogens in patients with Additionally, one of the most essential facts of this exam- low-grade infection? Clin Infect Dis 2004, 39(11):1599-1603. ination is the evidence of the high accuracy of the his- 18. Neut D, van Horn JR, van Kooten TG, van der Mei HC, Busscher HJ: topathological classification of the periprosthetic Detection of biomaterial-associated infections in orthopae- dic joint implants. Clin Orthop Relat Res 2003:261-268. interface membrane in detection of PJI. This classification 19. Atkins BL, Bowler IC: The diagnosis of large joint sepsis. The system proves as a very practical diagnostic tool in detec- Journal of hospital infection 1998, 40(4):263-274. 20. Hughes SP, Dash CH, Benson MK, Field CA: Infection following tion of periprosthetic joint infection, with both a high total hip replacement and the possible prophylactic role of sensitivity and specificity. cephaloridine. Journal of the Royal College of Surgeons of Edinburgh 1978, 23(1):9-12. 21. Patel D, Karchmer A, Harris HW: Role of preoperative aspira- References tion of the hip prior to total hip replacement. The Hip 1. Bozic KJ, Rubash HE: The painful total hip replacement. Clinical 1976:219-223. orthopaedics and related research 2004:18-25. 22. Costerton JW, Stewart PS, Greenberg EP: Bacterial biofilms: a 2. Bernard L, Lubbeke A, Stern R, Bru JP, Feron JM, Peyramond D, common cause of persistent infections. Science (New York, NY Denormandie P, Arvieux C, Chirouze C, Perronne C, Hoffmeyer P: 1999, 284(5418):1318-1322. Value of preoperative investigations in diagnosing prosthetic joint infection: retrospective cohort study and literature Page 7 of 8 (page number not for citation purposes) Journal of Orthopaedic Surgery and Research 2008, 3:31 http://www.josr-online.com/content/3/1/31 23. Sanzen L, Carlsson AS: The diagnostic value of C-reactive pro- tein in infected total hip arthroplasties. J Bone Joint Surg Br 1989, 71(4):638-641. 24. Shih LY, Wu JJ, Yang DJ: Erythrocyte sedimentation rate and C- reactive protein values in patients with total hip arthro- plasty. Clin Orthop Relat Res 1987:238-246. 25. Aalto K, Osterman K, Peltola H, Rasanen J: Changes in erythro- cyte sedimentation rate and C-reactive protein after total hip arthroplasty. Clin Orthop Relat Res 1984:118-120. 26. Niskanen RO, Korkala O, Pammo H: Serum C-reactive protein levels after total hip and knee arthroplasty. J Bone Joint Surg Br 1996, 78(3):431-433. 27. Giulieri SG, Graber P, Ochsner PE, Zimmerli W: Management of infection associated with total hip arthroplasty according to a treatment algorithm. Infection 2004, 32(4):222-228. 28. Tunney MM, Patrick S, Curran MD, Ramage G, Hanna D, Nixon JR, Gorman SP, Davis RI, Anderson N: Detection of prosthetic hip infection at revision arthroplasty by immunofluorescence microscopy and PCR amplification of the bacterial 16S rRNA gene. Journal of clinical microbiology 1999, 37(10):3281-3290. 29. Tunney MM, Patrick S, Curran MD, Ramage G, Anderson N, Davis RI, Gorman SP, Nixon JR: Detection of prosthetic joint biofilm infection using immunological and molecular techniques. Methods in enzymology 1999, 310:566-576. Publish with Bio Med Central and every scientist can read your work free of charge "BioMed Central will be the most significant development for disseminating the results of biomedical researc h in our lifetime." Sir Paul Nurse, Cancer Research UK Your research papers will be: available free of charge to the entire biomedical community peer reviewed and published immediately upon acceptance cited in PubMed and archived on PubMed Central yours — you keep the copyright BioMedcentral Submit your manuscript here: http://www.biomedcentral.com/info/publishing_adv.asp Page 8 of 8 (page number not for citation purposes)

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Journal of Orthopaedic Surgery and ResearchSpringer Journals

Published: Jul 21, 2008

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