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The role of implant sonication in the diagnosis of periprosthetic shoulder infection
J Shoulder Elbow Surg (2019) -, 1–7
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The role of implant sonication in the diagnosis of periprosthetic shoulder infection €n, MDa,b,*, Nina Maziak, MDa,b, Fabian Plachel, MD, PhDa,b, Doruk Akgu Paul Siegert, MDa,b, Marvin Minkus, MDa,b, Kathi Thiele, MDa,b, Philipp Moroder, MDa,b a b
Charite-Universit€ atsmedizin Berlin, Corporate Member of Freie Universit€at Berlin, Humboldt-Universit€at zu Berlin Berlin Institute of Health, Center for Musculoskeletal Surgery, Berlin, Germany Background: The aim of this study was to investigate the validity of implant sonication fluid cultures in the diagnosis of shoulder periprosthetic joint infection (PJI) compared with tissue culture. Methods: This was a retrospective case-control study analyzing all patients who underwent a revision surgery for any kind of suspected septic or aseptic event due to failed shoulder arthroplasty at our institution between July 2014 and December 2018. The diagnostic validity of implant sonication was analyzed on the basis of the last proposed definition criteria of the International Consensus Meeting and compared with standard tissue cultures. Results: Of the 72 patients, a total of 28 (38.9%) were classified as infected. Of the 28 infected patients, 20 (71.4%) had an identified organism by tissue cultures, and Cutibacterium acnes was the most commonly isolated pathogen. The sensitivities of sonicate fluid (50 CFU/mL) and periprosthetic tissue culture for the diagnosis of periprosthetic shoulder infection were 36% and 61% (P ¼ .016), and the specificities were 97.7% and 100% (P > .99), respectively. If no cutoff value was used in sonication culture, the sensitivity increased to 75% whereas the specificity dropped to 82%. Although there was no significant difference in sensitivity between tissue culture and the no-cutoff sonication fluid culture (61% vs. 75%, P ¼ .125), the specificity of tissue culture was significantly higher (100% vs. 82%, P ¼ .01). Conclusion: Tissue culture showed a higher sensitivity and specificity than implant sonication in the diagnosis of shoulder PJI and should remain the gold standard for microbiological diagnosis of shoulder PJI. Level of evidence: Level IV; Case-Control Design; Diagnostic Study Ó 2019 Journal of Shoulder and Elbow Surgery Board of Trustees. All rights reserved. Keywords: Periprosthetic shoulder infection; sonication; diagnostic; tissue culture
This study protocol was reviewed and approved by the Institutional Review Board of Charite Universit€atsmedizin (application no. EA4/040/14). *Reprint requests: Doruk Akg€un, MD, Center for Musculoskeletal Surgery, Charite-Universit€atsmedizin Berlin, Augustenburger Platz 1, Berlin 13353, Germany. E-mail address: [email protected] (D. Akg€un).
Periprosthetic joint infection (PJI) is a highly problematic and devastating complication after routine joint arthroplasty and has been a notable research topic in the last decades.1 Although great steps forward have been made regarding diagnosis of periprosthetic infections in the last decade, shoulder arthroplasty–related infections remain a diagnostic challenge because of the often stealth-type
1058-2746/$ - see front matter Ó 2019 Journal of Shoulder and Elbow Surgery Board of Trustees. All rights reserved. https://doi.org/10.1016/j.jse.2019.10.011
D. Akg€un et al.
2 clinical appearance mimicking an aseptic failure due to the predominance of microorganisms with low virulence, such as Cutibacterium acnes.8,12 Furthermore, the strong ability of these low-virulence microorganisms to adhere to the implant surface and their change from the planktonic to the mature biofilm phenotype impair the effectiveness of conventional tissue culture methods and leads to hard-to-detect biofilm aggregates.5,20 Recent studies showed significantly higher bacterial identification rates by dislodging the sessile microorganisms with the use of sonication compared with current conventional methods using a periprosthetic tissue or synovial fluid culture for the diagnosis of PJI involving the hip, knee, and spine.3,10,21,23,26 Thus, the committee from the second International Consensus Meeting (ICM) on musculoskeletal infection concluded that sonication is a viable method and has a beneficial role in the diagnosis of hip and knee PJI.2 However, because of conflicting results of the only 2 existing studies in the literature about the use of sonication for the diagnosis of shoulder PJI, including the diagnostic criteria and length of culture,7,14 the committee from the same meeting was not able to give any recommendation.5 Therefore, the aim of this study was to investigate the validity of implant sonication fluid cultures in the diagnosis of shoulder PJI based on the definition criteria from the last ICM compared with tissue culture. Our hypothesis was that sonication would represent a reliable test for the diagnosis of shoulder PJI with a greater sensitivity and specificity than conventional periprosthetic tissue cultures.
Materials and methods Study design and population This was a retrospective case-control study analyzing all patients who had undergone a revision surgery for any kind of suspected septic or aseptic reason due to failed shoulder arthroplasty in our institution between July 2014 and December 2018. A total of 80 patients were identified from the institutional shoulder database. Patients with fewer than 2 tissue specimens for culture or absence of sonication fluid culture results were excluded from further analysis.
Study cohort After applying the exclusion criteria, 72 patients were available for further analysis. None of the patients had received antibiotics within 2 weeks before revision surgery. The mean age of the patients at the time of revision surgery was 69.6 years (standard deviation 9 years) and 39 patients were female (54%). The mean interval and standard deviation between the primary arthroplasty and revision surgery was 4.1 3 years. The type of arthroplasty at the time of revision surgery was hemiarthroplasty in 26 patients, total shoulder arthroplasty in 19, and reverse shoulder arthroplasty in 27.
Data collection Patient-specific information such as age and gender, clinical manifestation, surgical history of the involved joint, type of arthroplasty, time interval between the index arthroplasty and revision surgery, laboratory values including C-reactive protein and serum leucocyte count as well as microbiologic, histopathologic, and sonication fluid results of revision surgery were recorded for all patients. Furthermore, component loosening was evaluated radiologically and intraoperatively and documented in our database for every patient, as well as intraoperative findings such as cloudy fluid or gross intra-articular purulence.
Definition of shoulder PJI Shoulder PJI was diagnosed according to the last proposed definition criteria of the lCM.6 According to these criteria, patients were classified into 4 infection subgroups: (1) definitive infection, (2) probable infection, (3) possible infection, and (4) infection unlikely. Meeting one of the following criteria was diagnostic of definitive periprosthetic shoulder infection: (1) a sinus tract communicating with the prosthesis; (2) gross intra-articular pus; and (3) 2 positive cultures with phenotypically identical virulent organisms (Table I). In the lack of these defining signs, weighted minor criteria (Table II) are summed and used to distinguish between probable, possible, and unlikely infection. The 3 categories in these less distinct scenarios are defined as follows: -
Six or greater with identified organism: probable infection Six or greater without identified organism: possible infection Fewer than 6 Single positive culture for virulent organism: possible infection Two positive cultures for low-virulence organism: possible infection - Negative cultures or only single positive culture for low-virulence organism: infection unlikely
Specimen collection Preoperative aspiration was only performed in cases with high suspicion of infection and not routinely. At least 3 periprosthetic tissue cultures were obtained during revision surgery from various surgical sites with suspicious appearance with a new sterile instrument each time, were placed directly into sterile containers without touching by hand, sent to the microbiology laboratory within 1 hour, and processed immediately. They were plated onto aerobic and anaerobic sheep blood agar plates and incubated for 14 days. Perioperative antibiotics were not given until all samples were obtained for culture analysis. Sonication was performed for 1 minute at 40 kHz (BactoSonic; Bandelin Electronic, Berlin, Germany) as previously described.19 The retrieved implants were also collected by a no-touch technique, placed directly into sterile containers and transferred immediately to microbiology laboratory; the resulting sonication fluid was plated onto aerobic and anaerobic sheep blood agar plates and incubated also for 14 days. Furthermore, at least 1 tissue culture was obtained for histopathologic analysis.
Implant sonication of periprosthetic shoulder infection Table I
significant. SPSS, version 20 (IBM, Armonk, NY, USA), was used for the statistical analyses.
Criteria for definitive infection
Presence of a sinus tract from the skin surface to the prosthesis Gross intra-articular pus Two positive cultures with phenotypically identical virulent organisms
Statistical analysis Sensitivity, specificity, positive predictive value, and negative predictive value for diagnosis of infection were determined for sonication fluid cultures and tissue cultures with 2-by-2 contingency tables. For analysis of the diagnostic utility of sonicate fluid cultures, patients in the definitive, probable, and possible infection groups were combined and defined as infection group and patients in the infection-unlikely group were defined as noninfection group. Sonication fluid cultures were not incorporated into the infection criteria, so the microbiologic results used for the infection definition were only based on tissue cultures. Tissue culture positivity was defined as isolation of the same organism from 2 or more tissue specimens. A cutoff value of 50 colony-forming units per milliliter (CFU/mL) was applied for sonication fluid culture according to the literature.16,19,20 Sonication fluid culture validity was analyzed both with a cutoff of 50 CFU/mL and without a cutoff value. The sensitivities and specificities of both methods were compared by using the McNemar test. Chi-squared and Fisher exact tests were used to find significant differences between categorical variables. The 2-sample t test (for parametric distribution) or Mann-Whitney U test (for nonparametric distribution) was used to compare continuous variables between groups. The results were expressed as mean and standard deviation or as number and percentage. A P value <.05 was considered
Table II
Minor criteria Weight
Unexpected wound drainage Single positive tissue culturedvirulent organism Single positive tissue culturedlow-virulence organism Second positive tissue culturedidentical low-virulence organism Humeral loosening Positive frozen section (5 PMN in at least 5 high-power fields) Positive preoperative aspirate culture (low or high virulence) Elevated synovial neutrophil percentage (>80%) Elevated synovial WBC (>3000 cells/mL) Elevated ESR (>30 mm/h) Elevated CRP (>10 mg/L) Cloudy fluid
3
4 3 1 3 3 3 3 2 2 2 2 2
PMN, polymorphonuclear neutrophils; WBC, white blood cells; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein.
Results A total of 28 patients (38.9%) were classified as infected: 6 meeting the criteria for definitive infection, 11 for probable infection, and 11 for possible infection. In 44 patients (61.1%), the infection was considered unlikely. Of all infected patients, 71.4% (20/28 patients) had an identified organism by tissue cultures, and C acnes was the most commonly isolated pathogen, in 13/28 patients (46%), followed by coagulase-negative staphylococci (5/28, 17.9%), Staphylococcus aureus (2/28, 7%), Finegoldia magna (1/28, 3.6%), Streptococcus agalactiae (1/28, 3.6%), Enterococcus faecalis (1/28, 3.6%), and Peptoniphilus asaccharolyticus (1/28, 3.6%). In the remaining all but one culture-negative patients, the infection was classified as possible according to the definition criteria. Polymicrobial infection was evident in 4 of 28 infected patients (14.3%), all but one with C acnes with a concomitant growth of coagulase-negative staphylococci. The remaining patient had a polymicrobial infection with Staphylococcus aureus and P asaccharolyticus. A detailed demographic and clinical comparison between patients with and without PJI is shown in Table III. In 21 of 28 patients with shoulder PJI (75%) an organism could have been isolated by sonication fluid culture. Sonication and tissue sample cultures in the infection group were discordant in 9 of 28 patients (32%). In 4 polymicrobial infections detected by tissue cultures, sonicate fluid culture was only able to find a single organism. In 1 definitive and 1 possibly infected patient, no organism growth was detected by tissue cultures but by sonication fluid culture, albeit with a growth of <50 CFU/mL. One probably infected patient had a positive organism growth detected by tissue, but not by sonicate fluid, culture. In the 2 remaining patients, different organisms were found by tissue and sonication fluid culture. The detailed microbiological profile of the infected patients is summarized in Table IV. The sensitivities of sonicate fluid (50 CFU/mL) and periprosthetic tissue culture (2) for the diagnosis of periprosthetic shoulder infection were 36% and 61% (P ¼ .016) and the specificities were 97.7% and 100% (P > .99), respectively. If no cutoff value was used in sonication culture, the sensitivity increased to 75% whereas the specificity dropped to 82%. Although there was no significant difference in sensitivity between tissue culture and the no-cutoff sonication fluid culture (61% vs. 75%, P ¼ .125), the specificity of tissue culture was significantly higher (100% vs. 82%, P ¼ .01). Furthermore, the tissue cultures had a better accuracy than the sonication fluid culture with and without a cutoff (85% vs. 74% and 79%, respectively). The calculated sensitivity, specificity, positive predictive
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4 Table III
Patient demographic and clinical characteristics
Variable
Infection group (n¼28)
Noninfection group (n¼44)
All patients (n¼72)
P value
Age at revision surgery, yr* Sexy Male Female Type of arthroplastyy Hemiarthroplasty TSA RSA Interval between index and revision arthroplasty, yr* CRP at admission, mg/L* No. of patients with previous septic revisionsy
69.6 8
69.9 9
69.6 9
>.99
17 (61) 11 (39)
16 (36) 28 (64)
33 (46) 39 (54)
8 (29) 4 (14) 16 (57) 3.7 3 25.9 36 11 (39)
18 (41) 15 (34) 11 (25) 4.5 3 5.9 11.5 8 (18)
26 (36) 19 (26) 27 (38) 4.1 3 13.7 25.8 19 (26)
.05
.3 <.001 .06
TSA, total shoulder arthroplasty; RSA, reverse shoulder arthroplasty; CRP, C-reactive protein. * Values are given as mean and standard deviation. y Values are given as number (percentage of the group).
value, negative predictive value, and accuracy of the sonication culture (<50 CFU/mL and 50 CFU/mL) as well as tissue culture results (1 and 2 positive cultures) are summarized in Table V. Sonication fluid cultures were positive in 8 patients from the noninfection group, with only 1 having an organism growth 50 CFU/mL. Of these 8 patients, 5 had negative tissue culture results and the remaining 3 had 1 positive tissue culture; in 2 patients, it was concordant with the sonication fluid culture results.
Discussion Despite several studies revealing a superiority of the sonication fluid culture over conventional tissue culture in the diagnosis of hip and knee PJI, there is currently not enough evidence to support routine sonication of the retrieved implants in the diagnosis of shoulder PJI due to limited and conflicting data in literature. In the current study, sonication fluid culture did not show any additional benefit compared with conventional tissue culture in the diagnosis of shoulder PJI. Furthermore, implant sonication was not able to detect the concomitant organisms in patients with polymicrobial shoulder PJI. Our hypothesis that sonication would represent a reliable test for the diagnosis of shoulder PJI with a greater sensitivity and specificity than conventional periprosthetic tissue cultures was not supported by the results of this study. Piper et al14 compared sonication fluid and tissue culture in 136 patients undergoing revision shoulder arthroplasty and have found a significantly higher sensitivity of sonication fluid culture compared with tissue culture using a cutoff of 20 CFU per plate to exclude contaminants (66.7% vs. 54.5%, respectively, P ¼ .046), whereas the specificities of both diagnostic methods were not significantly different.
Thus, the authors stated that sonication is useful for the diagnosis of shoulder PJI with an improvement of diagnostic accuracy. Contrary to these findings, Grosso et al7 recently showed in their study analyzing 53 cases that tissue culture had a significantly higher sensitivity than the >20 CFU/mL cutoff sonication results (96% vs. 56%, respectively, P < .001) and no significant difference in specificities. Moreover, there was no significant difference in sensitivity and specificity if no cutoff was used for sonication. Given these findings, the authors did not recommend the routine use of sonication in revision shoulder arthroplasty. Differences in the methodology might contradict these contrary results. First, the criteria used for the definition of shoulder PJI has differed in both studies, as there remains controversy and uncertainty about the definition of shoulder PJI. Piper et al14 required at least 2 positive cultures, whereas Grosso et al allowed 1 positive culture, if there was another sign of infection. Second, tissue cultures were held only for 7 days, whereas sonication cultures were held for a period of 14 days to optimize detection in the study of Piper et al14 compared with an incubation time of 12-14 days for tissue and sonication cultures in the study of Grosso et al.7 Based on several studies in the literature, the majority recommends a minimum incubation period of 14 days in order to optimize detection of all organisms, but especially C acnes, because of its late recovery.4,13,22,28 The significantly lower sensitivity of tissue culture in the study of Piper et al14 may be related to the shorter incubation time of tissue cultures compared with sonication fluid cultures. Although both studies have used a cutoff value of 20 CFU per plate or 20 CFU/mL to exclude contaminants, the cutoff value of 50 CFU/mL in our study has been advised by Trampuz et al26 and is consistent with the literature.15,17,20,24,27 The chosen CFU value is an important criterion in the methodology of the study and directly
Implant sonication of periprosthetic shoulder infection Table IV
5
Microbiologic results of tissue and sonication fluid culture
Case no. (n¼28)
Category of infection (sum of minor criteria)
Tissue cultures Microorganism
No. of positive cultures
Sonication fluid cultures
1 2 3 4 5 6 7 8 9
Probable (9) Probable (8) Definitive Probable (9) Probable (12) Probable (14) Definitive Possible (7) Probable (7)
10 11 12
Definitive Possible (5) Definitive
13 14 15 16 17 18 19
Definitive Possible (7) Definitive Possible (5) Probable (10) Probable (11) Probable (10)
20 21 22 23 24 25 26 27 28
Possible (5) Possible (8) Possible (8) Probable (14) Possible (8) Possible (10) Possible (8) Possible (5) Probable (7)
Staphylococcus epidermidis Staphylococcus aureus Neg S epidermidis C acnes C acnes C acnes Neg C acnes Staphylococcus capitis Streptococcus agalactiae C acnes S aureus Peptoniphilus asaccharolyticus Finegoldia magna Neg Enterococcus faecalis C acnes C acnes C acnes S epidermidis C acnes C acnes Neg Neg C acnes Neg Neg Neg C acnes C acnes S capitis
5/7 1/5 0/3 1/4 5/5 3/5 4/4 0/7 2/4 1/4 4/5 3/3 6/6 3/6 2/5 0/6 3/5 2/3 3/3 1/3 5/7 2/7 3/3 0/6 0/5 5/5 0/6 0/8 0/5 3/3 1/7 4/7
S epidermidis >50 CFU/mL Neg Cutibacterium acnes <50 CFU/mL C acnes <50 CFU/mL C acnes >50 CFU/mL C acnes <50 CFU/mL C acnes >50 CFU/mL Neg S capitis <50 CFU/mL Str agalactiae >50 CFU/mL C acnes >50 CFU/mL S aureus >50 CFU/mL F magna <50 CFU/mL Neg E faecalis >50 CFU/mL C acnes <50 CFU/mL C acnes >50 CFU/mL S epidermidis <50 CFU/mL S epidermidis <50 CFU/mL C acnes <50 CFU/mL Neg Neg C acnes >50 CFU/mL Neg S epidermidis <50 CFU/mL Neg C acnes >50 CFU/mL C acnes <50 CFU/mL
Neg, negative; CFU, colony-forming unit.
influences the calculated sensitivity and specificity. It seems logical that the presence of greater numbers of organism would be associated with the presence and severity of a PJI. However, the paucity of available information, knowledge,
Table V
and understanding of the role of quantitative culture in the evaluation and management of shoulder PJI should be pointed out.5 The applied cutoff value of 50 CFU/mL has led to an unacceptably low sensitivity of implant
Performance of tissue culture and sonication fluid culture
Tissue culture 1 positive culture 2 positive cultures Sonication fluid culture <50 CFU/mL 50 CFU/mL
Sensitivity, %
Specificity, %
PPV, %
NPV, %
Accuracy, %
71.4 60.7
77.3 100
66.7 100
81 80
75 84.7
75 35.7
81.8 97.7
72.4 90.9
83.72 70.5
79.2 73.6
CFU, colony-forming unit; PPV, positive predictive value; NPV, negative predictive value.
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6 sonication, which was significantly lower than the tissue culture sensitivity. Although the sensitivity of sonication without cutoff reached the level of the sensitivity of tissue culture, the specificity of sonication decreased to 82%, which was significantly lower than the specificity of tissue culture. Furthermore, the previously mentioned improved identification of polymicrobial infections through sonication could not be confirmed by the current study.9,11 In 4 polymicrobial infections detected by tissue cultures, only a single organism was identified by sonication. Interestingly, in 2 of these cases, sonication cultures identified the organism, which grew only in 1 tissue culture. Although organism growth in only 1 tissue culture is highly suspicious for a possible contamination, the complementary results of sonication in both cases support a true polymicrobial infection. On the other hand, in 1 definitive and 1 possibly infected case, no organism growth was detected by tissue cultures but by sonication fluid culture, albeit with a growth of <50 CFU/mL. Despite the results of this study, sonication could be helpful in some selected cases, such as patients who received preoperative antimicrobial treatment up to the time point of surgery. Trampuz et al26 were able to show a significantly higher sensitivity of sonication compared to tissue culture in this patient population. Furthermore, it may give additional information in cases with only 1 positive culture and support a possible infection if the same organism can be isolated by sonication. In the current study, 2 patients had 1 positive tissue culture concordant with the sonication fluid culture result, but were defined as not infected, as sonication fluid cultures were not incorporated into the infection criteria. To our knowledge, this is the first study in the literature using the shoulder PJI definition criteria from the last ICM. An internationally accepted PJI definition for shoulder should be applied to discuss and compare studies adequately. Acceptance of a uniform definition for the hip and knee PJI led to improved comparability of the literature evaluating prevention, diagnosis, and treatment of PJI. This is even more crucial in the field of shoulder arthroplasty, where unexpected positive cultures are reported to be as high as 50% in patients undergoing shoulder revision arthroplasty because of the unique microbiologic profile and stealth type of clinical appearance.18,25 This study has several limitations. The retrospective study design limits the reliability and completeness of our results. Although the used cutoff of 50 CFU/mL for sonication was in accordance with the literature, it seems to be very high in the diagnosis of shoulder PJI, most likely because of the high prevalence of low-virulence organisms. New studies analyzing sonication should report standardized quantitative results of sonication to identify the best threshold for diagnosis of shoulder PJI. Use of a lower cutoff for sonication may have led to increased accuracy. However, we do not believe this change would
have had a significant impact on our conclusions, as the sensitivity of sonication without cutoff was not significantly higher than sensitivity of tissue cultures, and additionally it may be prone to misdiagnose patients who are aseptic as having a shoulder PJI (false positive), leading to unnecessary surgical and antimicrobial treatment.
Conclusion Tissue culture showed a higher sensitivity and specificity than implant sonication in the diagnosis of shoulder PJI, and tissue culture should remain the gold standard for microbiological diagnosis of shoulder PJI. However, sonication may have a complementary role in further optimizing microbiological yield in selected cases. Upcoming studies analyzing sonication should report standardized quantitative results of sonication to identify the best threshold for diagnosis of shoulder PJI.
Disclaimer The authors, their immediate families, and any research foundations with which they are affiliated have not received any financial payments or other benefits from any commercial entity related to the subject of this article.
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7 18. Pottinger P, Butler-Wu S, Neradilek MB, Merritt A, Bertelsen A, Jette JL, et al. Prognostic factors for bacterial cultures positive for Propionibacterium acnes and other organisms in a large series of revision shoulder arthroplasties performed for stiffness, pain, or loosening. J Bone Joint Surg Am 2012;94:2075-83. https://doi.org/10. 2106/JBJS.K.00861 19. Renz N, Feihl S, Cabric S, Trampuz A. Performance of automated multiplex PCR using sonication fluid for diagnosis of periprosthetic joint infection: a prospective cohort. Infection 2017;45:877-84. https:// doi.org/10.1007/s15010-017-1073-5 20. Renz N, Mudrovcic S, Perka C, Trampuz A. Orthopedic implantassociated infections caused by Cutibacterium spp.da remaining diagnostic challenge. PLoS One 2018;13:e0202639. https://doi.org/10. 1371/journal.pone.0202639 21. Rothenberg AC, Wilson AE, Hayes JP, O’Malley MJ, Klatt BA. Sonication of arthroplasty implants improves accuracy of periprosthetic joint infection cultures. Clin Orthop Relat Res 2017;475: 1827-36. https://doi.org/10.1007/s11999-017-5315-8 22. Schafer P, Fink B, Sandow D, Margull A, Berger I, Frommelt L. Prolonged bacterial culture to identify late periprosthetic joint infection: a promising strategy. Clin Infect Dis 2008;47:1403-9. https://doi. org/10.1086/592973 23. Shen H, Tang J, Wang Q, Jiang Y, Zhang X. Sonication of explanted prosthesis combined with incubation in BD Bactec bottles for pathogen-based diagnosis of prosthetic joint infection. J Clin Microbiol 2015;53:777-81. https://doi.org/10.1128/JCM.02863-14 24. Tani S, Lepetsos P, Stylianakis A, Vlamis J, Birbas K, Kaklamanos I. Superiority of the sonication method against conventional periprosthetic tissue cultures for diagnosis of prosthetic joint infections. Eur J Orthop Surg Traumatol 2018;28:51-7. https://doi.org/10.1007/ s00590-017-2012-y 25. Topolski MS, Chin PY, Sperling JW, Cofield RH. Revision shoulder arthroplasty with positive intraoperative cultures: the value of preoperative studies and intraoperative histology. J Shoulder Elbow Surg 2006;15:402-6. https://doi.org/10.1016/j.jse.2005.10.001 26. Trampuz A, Piper KE, Jacobson MJ, Hanssen AD, Unni KK, Osmon DR, et al. Sonication of removed hip and knee prostheses for diagnosis of infection. N Engl J Med 2007;357:654-63. https://doi.org/ 10.1056/NEJMoa061588 27. Van Diek FM, Albers CGM, Van Hooff ML, Meis JF, Goosen JHM. Low sensitivity of implant sonication when screening for infection in revision surgery. Acta Orthop 2017;88:294-9. https://doi.org/10.1080/ 17453674.2017.1300021 28. Zappe B, Graf S, Ochsner PE, Zimmerli W, Sendi P. Propionibacterium spp. in prosthetic joint infections: a diagnostic challenge. Arch Orthop Trauma Surg 2008;128:1039-46. https://doi.org/10.1007/ s00402-007-0454-0
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The role of implant sonication in the diagnosis of periprosthetic shoulder infection €n, MDa,b,*, Nina Maziak, MDa,b, Fabian Plachel, MD, PhDa,b, Doruk Akgu Paul Siegert, MDa,b, Marvin Minkus, MDa,b, Kathi Thiele, MDa,b, Philipp Moroder, MDa,b a b
Charite-Universit€ atsmedizin Berlin, Corporate Member of Freie Universit€at Berlin, Humboldt-Universit€at zu Berlin Berlin Institute of Health, Center for Musculoskeletal Surgery, Berlin, Germany Background: The aim of this study was to investigate the validity of implant sonication fluid cultures in the diagnosis of shoulder periprosthetic joint infection (PJI) compared with tissue culture. Methods: This was a retrospective case-control study analyzing all patients who underwent a revision surgery for any kind of suspected septic or aseptic event due to failed shoulder arthroplasty at our institution between July 2014 and December 2018. The diagnostic validity of implant sonication was analyzed on the basis of the last proposed definition criteria of the International Consensus Meeting and compared with standard tissue cultures. Results: Of the 72 patients, a total of 28 (38.9%) were classified as infected. Of the 28 infected patients, 20 (71.4%) had an identified organism by tissue cultures, and Cutibacterium acnes was the most commonly isolated pathogen. The sensitivities of sonicate fluid (50 CFU/mL) and periprosthetic tissue culture for the diagnosis of periprosthetic shoulder infection were 36% and 61% (P ¼ .016), and the specificities were 97.7% and 100% (P > .99), respectively. If no cutoff value was used in sonication culture, the sensitivity increased to 75% whereas the specificity dropped to 82%. Although there was no significant difference in sensitivity between tissue culture and the no-cutoff sonication fluid culture (61% vs. 75%, P ¼ .125), the specificity of tissue culture was significantly higher (100% vs. 82%, P ¼ .01). Conclusion: Tissue culture showed a higher sensitivity and specificity than implant sonication in the diagnosis of shoulder PJI and should remain the gold standard for microbiological diagnosis of shoulder PJI. Level of evidence: Level IV; Case-Control Design; Diagnostic Study Ó 2019 Journal of Shoulder and Elbow Surgery Board of Trustees. All rights reserved. Keywords: Periprosthetic shoulder infection; sonication; diagnostic; tissue culture
This study protocol was reviewed and approved by the Institutional Review Board of Charite Universit€atsmedizin (application no. EA4/040/14). *Reprint requests: Doruk Akg€un, MD, Center for Musculoskeletal Surgery, Charite-Universit€atsmedizin Berlin, Augustenburger Platz 1, Berlin 13353, Germany. E-mail address: [email protected] (D. Akg€un).
Periprosthetic joint infection (PJI) is a highly problematic and devastating complication after routine joint arthroplasty and has been a notable research topic in the last decades.1 Although great steps forward have been made regarding diagnosis of periprosthetic infections in the last decade, shoulder arthroplasty–related infections remain a diagnostic challenge because of the often stealth-type
1058-2746/$ - see front matter Ó 2019 Journal of Shoulder and Elbow Surgery Board of Trustees. All rights reserved. https://doi.org/10.1016/j.jse.2019.10.011
D. Akg€un et al.
2 clinical appearance mimicking an aseptic failure due to the predominance of microorganisms with low virulence, such as Cutibacterium acnes.8,12 Furthermore, the strong ability of these low-virulence microorganisms to adhere to the implant surface and their change from the planktonic to the mature biofilm phenotype impair the effectiveness of conventional tissue culture methods and leads to hard-to-detect biofilm aggregates.5,20 Recent studies showed significantly higher bacterial identification rates by dislodging the sessile microorganisms with the use of sonication compared with current conventional methods using a periprosthetic tissue or synovial fluid culture for the diagnosis of PJI involving the hip, knee, and spine.3,10,21,23,26 Thus, the committee from the second International Consensus Meeting (ICM) on musculoskeletal infection concluded that sonication is a viable method and has a beneficial role in the diagnosis of hip and knee PJI.2 However, because of conflicting results of the only 2 existing studies in the literature about the use of sonication for the diagnosis of shoulder PJI, including the diagnostic criteria and length of culture,7,14 the committee from the same meeting was not able to give any recommendation.5 Therefore, the aim of this study was to investigate the validity of implant sonication fluid cultures in the diagnosis of shoulder PJI based on the definition criteria from the last ICM compared with tissue culture. Our hypothesis was that sonication would represent a reliable test for the diagnosis of shoulder PJI with a greater sensitivity and specificity than conventional periprosthetic tissue cultures.
Materials and methods Study design and population This was a retrospective case-control study analyzing all patients who had undergone a revision surgery for any kind of suspected septic or aseptic reason due to failed shoulder arthroplasty in our institution between July 2014 and December 2018. A total of 80 patients were identified from the institutional shoulder database. Patients with fewer than 2 tissue specimens for culture or absence of sonication fluid culture results were excluded from further analysis.
Study cohort After applying the exclusion criteria, 72 patients were available for further analysis. None of the patients had received antibiotics within 2 weeks before revision surgery. The mean age of the patients at the time of revision surgery was 69.6 years (standard deviation 9 years) and 39 patients were female (54%). The mean interval and standard deviation between the primary arthroplasty and revision surgery was 4.1 3 years. The type of arthroplasty at the time of revision surgery was hemiarthroplasty in 26 patients, total shoulder arthroplasty in 19, and reverse shoulder arthroplasty in 27.
Data collection Patient-specific information such as age and gender, clinical manifestation, surgical history of the involved joint, type of arthroplasty, time interval between the index arthroplasty and revision surgery, laboratory values including C-reactive protein and serum leucocyte count as well as microbiologic, histopathologic, and sonication fluid results of revision surgery were recorded for all patients. Furthermore, component loosening was evaluated radiologically and intraoperatively and documented in our database for every patient, as well as intraoperative findings such as cloudy fluid or gross intra-articular purulence.
Definition of shoulder PJI Shoulder PJI was diagnosed according to the last proposed definition criteria of the lCM.6 According to these criteria, patients were classified into 4 infection subgroups: (1) definitive infection, (2) probable infection, (3) possible infection, and (4) infection unlikely. Meeting one of the following criteria was diagnostic of definitive periprosthetic shoulder infection: (1) a sinus tract communicating with the prosthesis; (2) gross intra-articular pus; and (3) 2 positive cultures with phenotypically identical virulent organisms (Table I). In the lack of these defining signs, weighted minor criteria (Table II) are summed and used to distinguish between probable, possible, and unlikely infection. The 3 categories in these less distinct scenarios are defined as follows: -
Six or greater with identified organism: probable infection Six or greater without identified organism: possible infection Fewer than 6 Single positive culture for virulent organism: possible infection Two positive cultures for low-virulence organism: possible infection - Negative cultures or only single positive culture for low-virulence organism: infection unlikely
Specimen collection Preoperative aspiration was only performed in cases with high suspicion of infection and not routinely. At least 3 periprosthetic tissue cultures were obtained during revision surgery from various surgical sites with suspicious appearance with a new sterile instrument each time, were placed directly into sterile containers without touching by hand, sent to the microbiology laboratory within 1 hour, and processed immediately. They were plated onto aerobic and anaerobic sheep blood agar plates and incubated for 14 days. Perioperative antibiotics were not given until all samples were obtained for culture analysis. Sonication was performed for 1 minute at 40 kHz (BactoSonic; Bandelin Electronic, Berlin, Germany) as previously described.19 The retrieved implants were also collected by a no-touch technique, placed directly into sterile containers and transferred immediately to microbiology laboratory; the resulting sonication fluid was plated onto aerobic and anaerobic sheep blood agar plates and incubated also for 14 days. Furthermore, at least 1 tissue culture was obtained for histopathologic analysis.
Implant sonication of periprosthetic shoulder infection Table I
significant. SPSS, version 20 (IBM, Armonk, NY, USA), was used for the statistical analyses.
Criteria for definitive infection
Presence of a sinus tract from the skin surface to the prosthesis Gross intra-articular pus Two positive cultures with phenotypically identical virulent organisms
Statistical analysis Sensitivity, specificity, positive predictive value, and negative predictive value for diagnosis of infection were determined for sonication fluid cultures and tissue cultures with 2-by-2 contingency tables. For analysis of the diagnostic utility of sonicate fluid cultures, patients in the definitive, probable, and possible infection groups were combined and defined as infection group and patients in the infection-unlikely group were defined as noninfection group. Sonication fluid cultures were not incorporated into the infection criteria, so the microbiologic results used for the infection definition were only based on tissue cultures. Tissue culture positivity was defined as isolation of the same organism from 2 or more tissue specimens. A cutoff value of 50 colony-forming units per milliliter (CFU/mL) was applied for sonication fluid culture according to the literature.16,19,20 Sonication fluid culture validity was analyzed both with a cutoff of 50 CFU/mL and without a cutoff value. The sensitivities and specificities of both methods were compared by using the McNemar test. Chi-squared and Fisher exact tests were used to find significant differences between categorical variables. The 2-sample t test (for parametric distribution) or Mann-Whitney U test (for nonparametric distribution) was used to compare continuous variables between groups. The results were expressed as mean and standard deviation or as number and percentage. A P value <.05 was considered
Table II
Minor criteria Weight
Unexpected wound drainage Single positive tissue culturedvirulent organism Single positive tissue culturedlow-virulence organism Second positive tissue culturedidentical low-virulence organism Humeral loosening Positive frozen section (5 PMN in at least 5 high-power fields) Positive preoperative aspirate culture (low or high virulence) Elevated synovial neutrophil percentage (>80%) Elevated synovial WBC (>3000 cells/mL) Elevated ESR (>30 mm/h) Elevated CRP (>10 mg/L) Cloudy fluid
3
4 3 1 3 3 3 3 2 2 2 2 2
PMN, polymorphonuclear neutrophils; WBC, white blood cells; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein.
Results A total of 28 patients (38.9%) were classified as infected: 6 meeting the criteria for definitive infection, 11 for probable infection, and 11 for possible infection. In 44 patients (61.1%), the infection was considered unlikely. Of all infected patients, 71.4% (20/28 patients) had an identified organism by tissue cultures, and C acnes was the most commonly isolated pathogen, in 13/28 patients (46%), followed by coagulase-negative staphylococci (5/28, 17.9%), Staphylococcus aureus (2/28, 7%), Finegoldia magna (1/28, 3.6%), Streptococcus agalactiae (1/28, 3.6%), Enterococcus faecalis (1/28, 3.6%), and Peptoniphilus asaccharolyticus (1/28, 3.6%). In the remaining all but one culture-negative patients, the infection was classified as possible according to the definition criteria. Polymicrobial infection was evident in 4 of 28 infected patients (14.3%), all but one with C acnes with a concomitant growth of coagulase-negative staphylococci. The remaining patient had a polymicrobial infection with Staphylococcus aureus and P asaccharolyticus. A detailed demographic and clinical comparison between patients with and without PJI is shown in Table III. In 21 of 28 patients with shoulder PJI (75%) an organism could have been isolated by sonication fluid culture. Sonication and tissue sample cultures in the infection group were discordant in 9 of 28 patients (32%). In 4 polymicrobial infections detected by tissue cultures, sonicate fluid culture was only able to find a single organism. In 1 definitive and 1 possibly infected patient, no organism growth was detected by tissue cultures but by sonication fluid culture, albeit with a growth of <50 CFU/mL. One probably infected patient had a positive organism growth detected by tissue, but not by sonicate fluid, culture. In the 2 remaining patients, different organisms were found by tissue and sonication fluid culture. The detailed microbiological profile of the infected patients is summarized in Table IV. The sensitivities of sonicate fluid (50 CFU/mL) and periprosthetic tissue culture (2) for the diagnosis of periprosthetic shoulder infection were 36% and 61% (P ¼ .016) and the specificities were 97.7% and 100% (P > .99), respectively. If no cutoff value was used in sonication culture, the sensitivity increased to 75% whereas the specificity dropped to 82%. Although there was no significant difference in sensitivity between tissue culture and the no-cutoff sonication fluid culture (61% vs. 75%, P ¼ .125), the specificity of tissue culture was significantly higher (100% vs. 82%, P ¼ .01). Furthermore, the tissue cultures had a better accuracy than the sonication fluid culture with and without a cutoff (85% vs. 74% and 79%, respectively). The calculated sensitivity, specificity, positive predictive
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4 Table III
Patient demographic and clinical characteristics
Variable
Infection group (n¼28)
Noninfection group (n¼44)
All patients (n¼72)
P value
Age at revision surgery, yr* Sexy Male Female Type of arthroplastyy Hemiarthroplasty TSA RSA Interval between index and revision arthroplasty, yr* CRP at admission, mg/L* No. of patients with previous septic revisionsy
69.6 8
69.9 9
69.6 9
>.99
17 (61) 11 (39)
16 (36) 28 (64)
33 (46) 39 (54)
8 (29) 4 (14) 16 (57) 3.7 3 25.9 36 11 (39)
18 (41) 15 (34) 11 (25) 4.5 3 5.9 11.5 8 (18)
26 (36) 19 (26) 27 (38) 4.1 3 13.7 25.8 19 (26)
.05
.3 <.001 .06
TSA, total shoulder arthroplasty; RSA, reverse shoulder arthroplasty; CRP, C-reactive protein. * Values are given as mean and standard deviation. y Values are given as number (percentage of the group).
value, negative predictive value, and accuracy of the sonication culture (<50 CFU/mL and 50 CFU/mL) as well as tissue culture results (1 and 2 positive cultures) are summarized in Table V. Sonication fluid cultures were positive in 8 patients from the noninfection group, with only 1 having an organism growth 50 CFU/mL. Of these 8 patients, 5 had negative tissue culture results and the remaining 3 had 1 positive tissue culture; in 2 patients, it was concordant with the sonication fluid culture results.
Discussion Despite several studies revealing a superiority of the sonication fluid culture over conventional tissue culture in the diagnosis of hip and knee PJI, there is currently not enough evidence to support routine sonication of the retrieved implants in the diagnosis of shoulder PJI due to limited and conflicting data in literature. In the current study, sonication fluid culture did not show any additional benefit compared with conventional tissue culture in the diagnosis of shoulder PJI. Furthermore, implant sonication was not able to detect the concomitant organisms in patients with polymicrobial shoulder PJI. Our hypothesis that sonication would represent a reliable test for the diagnosis of shoulder PJI with a greater sensitivity and specificity than conventional periprosthetic tissue cultures was not supported by the results of this study. Piper et al14 compared sonication fluid and tissue culture in 136 patients undergoing revision shoulder arthroplasty and have found a significantly higher sensitivity of sonication fluid culture compared with tissue culture using a cutoff of 20 CFU per plate to exclude contaminants (66.7% vs. 54.5%, respectively, P ¼ .046), whereas the specificities of both diagnostic methods were not significantly different.
Thus, the authors stated that sonication is useful for the diagnosis of shoulder PJI with an improvement of diagnostic accuracy. Contrary to these findings, Grosso et al7 recently showed in their study analyzing 53 cases that tissue culture had a significantly higher sensitivity than the >20 CFU/mL cutoff sonication results (96% vs. 56%, respectively, P < .001) and no significant difference in specificities. Moreover, there was no significant difference in sensitivity and specificity if no cutoff was used for sonication. Given these findings, the authors did not recommend the routine use of sonication in revision shoulder arthroplasty. Differences in the methodology might contradict these contrary results. First, the criteria used for the definition of shoulder PJI has differed in both studies, as there remains controversy and uncertainty about the definition of shoulder PJI. Piper et al14 required at least 2 positive cultures, whereas Grosso et al allowed 1 positive culture, if there was another sign of infection. Second, tissue cultures were held only for 7 days, whereas sonication cultures were held for a period of 14 days to optimize detection in the study of Piper et al14 compared with an incubation time of 12-14 days for tissue and sonication cultures in the study of Grosso et al.7 Based on several studies in the literature, the majority recommends a minimum incubation period of 14 days in order to optimize detection of all organisms, but especially C acnes, because of its late recovery.4,13,22,28 The significantly lower sensitivity of tissue culture in the study of Piper et al14 may be related to the shorter incubation time of tissue cultures compared with sonication fluid cultures. Although both studies have used a cutoff value of 20 CFU per plate or 20 CFU/mL to exclude contaminants, the cutoff value of 50 CFU/mL in our study has been advised by Trampuz et al26 and is consistent with the literature.15,17,20,24,27 The chosen CFU value is an important criterion in the methodology of the study and directly
Implant sonication of periprosthetic shoulder infection Table IV
5
Microbiologic results of tissue and sonication fluid culture
Case no. (n¼28)
Category of infection (sum of minor criteria)
Tissue cultures Microorganism
No. of positive cultures
Sonication fluid cultures
1 2 3 4 5 6 7 8 9
Probable (9) Probable (8) Definitive Probable (9) Probable (12) Probable (14) Definitive Possible (7) Probable (7)
10 11 12
Definitive Possible (5) Definitive
13 14 15 16 17 18 19
Definitive Possible (7) Definitive Possible (5) Probable (10) Probable (11) Probable (10)
20 21 22 23 24 25 26 27 28
Possible (5) Possible (8) Possible (8) Probable (14) Possible (8) Possible (10) Possible (8) Possible (5) Probable (7)
Staphylococcus epidermidis Staphylococcus aureus Neg S epidermidis C acnes C acnes C acnes Neg C acnes Staphylococcus capitis Streptococcus agalactiae C acnes S aureus Peptoniphilus asaccharolyticus Finegoldia magna Neg Enterococcus faecalis C acnes C acnes C acnes S epidermidis C acnes C acnes Neg Neg C acnes Neg Neg Neg C acnes C acnes S capitis
5/7 1/5 0/3 1/4 5/5 3/5 4/4 0/7 2/4 1/4 4/5 3/3 6/6 3/6 2/5 0/6 3/5 2/3 3/3 1/3 5/7 2/7 3/3 0/6 0/5 5/5 0/6 0/8 0/5 3/3 1/7 4/7
S epidermidis >50 CFU/mL Neg Cutibacterium acnes <50 CFU/mL C acnes <50 CFU/mL C acnes >50 CFU/mL C acnes <50 CFU/mL C acnes >50 CFU/mL Neg S capitis <50 CFU/mL Str agalactiae >50 CFU/mL C acnes >50 CFU/mL S aureus >50 CFU/mL F magna <50 CFU/mL Neg E faecalis >50 CFU/mL C acnes <50 CFU/mL C acnes >50 CFU/mL S epidermidis <50 CFU/mL S epidermidis <50 CFU/mL C acnes <50 CFU/mL Neg Neg C acnes >50 CFU/mL Neg S epidermidis <50 CFU/mL Neg C acnes >50 CFU/mL C acnes <50 CFU/mL
Neg, negative; CFU, colony-forming unit.
influences the calculated sensitivity and specificity. It seems logical that the presence of greater numbers of organism would be associated with the presence and severity of a PJI. However, the paucity of available information, knowledge,
Table V
and understanding of the role of quantitative culture in the evaluation and management of shoulder PJI should be pointed out.5 The applied cutoff value of 50 CFU/mL has led to an unacceptably low sensitivity of implant
Performance of tissue culture and sonication fluid culture
Tissue culture 1 positive culture 2 positive cultures Sonication fluid culture <50 CFU/mL 50 CFU/mL
Sensitivity, %
Specificity, %
PPV, %
NPV, %
Accuracy, %
71.4 60.7
77.3 100
66.7 100
81 80
75 84.7
75 35.7
81.8 97.7
72.4 90.9
83.72 70.5
79.2 73.6
CFU, colony-forming unit; PPV, positive predictive value; NPV, negative predictive value.
D. Akg€un et al.
6 sonication, which was significantly lower than the tissue culture sensitivity. Although the sensitivity of sonication without cutoff reached the level of the sensitivity of tissue culture, the specificity of sonication decreased to 82%, which was significantly lower than the specificity of tissue culture. Furthermore, the previously mentioned improved identification of polymicrobial infections through sonication could not be confirmed by the current study.9,11 In 4 polymicrobial infections detected by tissue cultures, only a single organism was identified by sonication. Interestingly, in 2 of these cases, sonication cultures identified the organism, which grew only in 1 tissue culture. Although organism growth in only 1 tissue culture is highly suspicious for a possible contamination, the complementary results of sonication in both cases support a true polymicrobial infection. On the other hand, in 1 definitive and 1 possibly infected case, no organism growth was detected by tissue cultures but by sonication fluid culture, albeit with a growth of <50 CFU/mL. Despite the results of this study, sonication could be helpful in some selected cases, such as patients who received preoperative antimicrobial treatment up to the time point of surgery. Trampuz et al26 were able to show a significantly higher sensitivity of sonication compared to tissue culture in this patient population. Furthermore, it may give additional information in cases with only 1 positive culture and support a possible infection if the same organism can be isolated by sonication. In the current study, 2 patients had 1 positive tissue culture concordant with the sonication fluid culture result, but were defined as not infected, as sonication fluid cultures were not incorporated into the infection criteria. To our knowledge, this is the first study in the literature using the shoulder PJI definition criteria from the last ICM. An internationally accepted PJI definition for shoulder should be applied to discuss and compare studies adequately. Acceptance of a uniform definition for the hip and knee PJI led to improved comparability of the literature evaluating prevention, diagnosis, and treatment of PJI. This is even more crucial in the field of shoulder arthroplasty, where unexpected positive cultures are reported to be as high as 50% in patients undergoing shoulder revision arthroplasty because of the unique microbiologic profile and stealth type of clinical appearance.18,25 This study has several limitations. The retrospective study design limits the reliability and completeness of our results. Although the used cutoff of 50 CFU/mL for sonication was in accordance with the literature, it seems to be very high in the diagnosis of shoulder PJI, most likely because of the high prevalence of low-virulence organisms. New studies analyzing sonication should report standardized quantitative results of sonication to identify the best threshold for diagnosis of shoulder PJI. Use of a lower cutoff for sonication may have led to increased accuracy. However, we do not believe this change would
have had a significant impact on our conclusions, as the sensitivity of sonication without cutoff was not significantly higher than sensitivity of tissue cultures, and additionally it may be prone to misdiagnose patients who are aseptic as having a shoulder PJI (false positive), leading to unnecessary surgical and antimicrobial treatment.
Conclusion Tissue culture showed a higher sensitivity and specificity than implant sonication in the diagnosis of shoulder PJI, and tissue culture should remain the gold standard for microbiological diagnosis of shoulder PJI. However, sonication may have a complementary role in further optimizing microbiological yield in selected cases. Upcoming studies analyzing sonication should report standardized quantitative results of sonication to identify the best threshold for diagnosis of shoulder PJI.
Disclaimer The authors, their immediate families, and any research foundations with which they are affiliated have not received any financial payments or other benefits from any commercial entity related to the subject of this article.
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