- Email: [email protected]
Positive Blood Cultures Decrease the Treatment Success in Acute Hematogenous Periprosthetic Joint Infection Treated With Debridement, Antibiotics, and Implant Retention
The Journal of Arthroplasty xxx (2019) 1e5
Contents lists available at ScienceDirect
The Journal of Arthroplasty journal homepage: www.arthroplastyjournal.org
Positive Blood Cultures Decrease the Treatment Success in Acute Hematogenous Periprosthetic Joint Infection Treated With Debridement, Antibiotics, and Implant Retention Feng-Chih Kuo, MD a, b, Karan Goswami, MD a, Mitchell R. Klement, MD a, Noam Shohat, MD a, c, Javad Parvizi, MD, FRCS a, * a b c
Rothman Orthopaedic Institute, Philadelphia, PA Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel
a r t i c l e i n f o
a b s t r a c t
Article history: Received 25 April 2019 Received in revised form 13 June 2019 Accepted 25 June 2019 Available online xxx
Background: The influence of positive blood cultures on surgical outcome of acute hematogenous periprosthetic joint infection (PJI) treated by debridement, antibiotics, and implant retention (DAIR) remains unknown. This study evaluated the influence of positive blood cultures on the treatment success of DAIR in patients with acute hematogenous PJI. Methods: A retrospective chart review on 49 patients with blood culture data for acute hematogenous PJI was performed from 2005 to 2016 at a single institution. All patients were treated by DAIR and had a minimum follow-up of 1 year. Treatment success was defined by the Delphi criteria. Multivariate logistic regression analysis was performed to identify variables associated with positive blood culture and treatment success. Kaplan-Meier survivorship curves and log-rank tests were used for analysis. Results: Overall, 44.9% (22/49) of blood cultures obtained yielded positive growth. Elevated Elixhauser comorbidity index was a significant risk factor associated with positive blood (adjusted odds ratio [OR], 1.65; 95% confidence interval [CI], 1.13-2.40; P ¼ .049). A positive blood culture was the only significant factor predicting treatment failure in acute hematogenous PJI (OR, 3.94; 95% CI, 1.18-13.1; P ¼ .026) after adjusting for confounding variables. Kaplan-Meier survivorship for infection-free implant survivorship was 53.1% (95% CI, 38.3%-65.8%) at 1 year for all patients, 66.7% (95% CI, 45.7%-81.1%) for patients with negative blood cultures, and 36.4% (95% CI, 17.2%-55.7%) for patients with positive blood cultures (P ¼ .037). Conclusion: The presence of positive blood cultures is associated with decreased treatment success of DAIR for acute hematogenous PJI. Patients with more comorbidities may need to be treated more aggressively for a favorable outcome. © 2019 Published by Elsevier Inc.
Keywords: blood culture acute hematogenous periprosthetic joint infection treatment arthroplasty
Periprosthetic joint infection (PJI) is an uncommon but devastating complication after total knee and hip arthroplasty. The overall incidence of PJI has been reported to be approximately 1%2% [1]. Acute hematogenous PJI may be introduced through hematogenous seeding and accounts for 5.6%-43% of all PJI [2e5].
One or more of the authors of this paper have disclosed potential or pertinent conflicts of interest, which may include receipt of payment, either direct or indirect, institutional support, or association with an entity in the biomedical field which may be perceived to have potential conflict of interest with this work. For full disclosure statements refer to https://doi.org/10.1016/j.arth.2019.06.053. * Reprint requests: Javad Parvizi, MD, FRCS, Rothman Orthopaedic Institute, 125 S 9th St. Ste 1000, Philadelphia, PA 19107. https://doi.org/10.1016/j.arth.2019.06.053 0883-5403/© 2019 Published by Elsevier Inc.
A debridement, antibiotics, and implant retention (DAIR) procedure remains the first-line treatment choice for patients presenting with acute hematogenous PJI [6]. However, the success rate of DAIR for acute hematogenous PJI remains poor, ranging from 31% to 82% [7e11]. Bacteremia is an etiology of acute hematogenous PJI and patients with suspicion for acute hematogenous PJI should have blood cultures obtained as per the current diagnostic guidelines [12,13]. The estimated incidence of positive blood cultures among PJI ranges from 4.3% to 7.3% [14,15] to as high as 25.2% to 32%[8,16]. A recent study reported that positive blood cultures decrease the rate of treatment success [16]. However, previous studies included all PJI patients, used various surgical options, and did not obtain blood
2
F.-C. Kuo et al. / The Journal of Arthroplasty xxx (2019) 1e5
culture samples from all acute hematogenous PJI cases [8,16]. Meanwhile, blood cultures are rarely obtained in chronic PJI in clinical practice. To date, there has been no study to predict the risk factors associated with yielding a positive blood culture. Furthermore, the association between a positive blood culture result and treatment outcome in patients with acute hematogenous PJI remains unknown. The purpose of this study is to (1) investigate the risk factors associated with yielding a positive blood culture and (2) investigate the influence of positive blood cultures upon surgical treatment outcome in patients with acute hematogenous PJI treated with DAIR. We hypothesized that patients with positive blood cultures are more likely to experience treatment failure. Materials and Methods Following approval by our institutional review board, a retrospective study was conducted for patients undergoing DAIR after a total knee arthroplasty (TKA) or total hip arthroplasty (THA) at a single academic institution from 2005 to 2017. These patients were identified from a prospectively maintained institutional PJI database. All patients who underwent DAIR for acute hematogenous PJI were included. Acute hematogenous PJI was defined as having an infection occurring more than 3 months from the index surgery, with abrupt symptoms lasting less than 3 weeks in a well-fixed and functioning THA or TKA. Patients with a history of perioperative infection or wound healing problems were excluded to avoid the inclusion of acute postoperative or chronic infections. We also excluded cases where radiologic loosening suggestive of chronic PJI was evident. Patients who did not meet Musculoskeletal Infection
Society criteria for infection were excluded. In total, 52 patients who underwent DAIR for acute hematogenous PJIs were included. Among them, 3 patients did not have blood culture data. The final cohort consisted of 49 patients with blood culture data who had undergone surgical management for 42 infected TKAs and 7 infected THAs. Patients were followed up for a minimum of 1 year or until treatment failure. Irrigation and debridement (I&D) were performed using a medial parapatellar approach for the knee, while the same approach as the index procedure (direct anterior, direct lateral, or posterolateral) was used for hips. A well-fixed component was also confirmed intraoperatively. Any devitalized or infective bony and soft tissue structures were removed in all cases. Modular components, consisting of the polyethylene component for knees and femoral head and polyethylene liner in hips, were exchanged with new components. A total of 3 to 5 samples were collected for microbiologic culture and sent for routine aerobic and anaerobic bacterial, fungal, and acid-fast bacillus testing. Following surgery, parenteral antibiotic therapy was initiated and guided by culture results. If cultures were negative, patients were treated empirically with intravenous vancomycin. Antibiotic therapy was then continued for 6 weeks with serial monitoring of inflammatory markers including erythrocyte sedimentation rate (ESR) and Creactive protein (CRP). A manual chart review was performed for all patients who met inclusion criteria. Patient characteristics (age, gender, body mass index, Elixhauser comorbidity index [ECI; Appendix 1], infected joint [knee or hip], and index surgery [primary/revision]) were recorded. Laboratory results (serum CRP, ESR, serum and synovial white blood cells [WBC, sWBC], the result of blood cultures),
Table 1 Demographic Data of Acute Hematogenous PJI. Variable Age, median (IQR), y Male, n (%) BMI, median (IQR), kg/m2 Elixhauser comorbidity index, median (IQR) Procedure, n (%) Primary Revision Joints, n (%) Hip Knee Blood culture timing, n (%) Preoperative Positive (%) Postoperative Positive (%) Time to having blood culture, median (IQR), h Preoperative Postoperative Fever >38 C, n (%) Laboratory values, median (IQR) Serum WBC Serum ESR, mm/h Serum CRP, mg/dL Synovial WBC, mL Synovial PMNs, n (%) PJI organism profile, n (%) MSSA Staphylococcus epidermidis MRSA All staphylococcal species, subtotal Streptococcus Gram negative Polymicrobial Treatment success at 1 y, n (%)
Positive Blood Culture (N ¼ 22) 68.9 10 30.9 4.5
(63.9-77.4) (45.5) (25.0-35.4) (2.0-5.5)
Negative Blood Culture (N ¼ 27) 67.5 16 30.9 2
(58.9-79.5) (59.3) (27.4-39.6) (1-3)
19 (86.4) 3 (13.6)
24 (88.9) 3 (11.1)
3 (13.6) 19 (86.4)
4 (14.8) 23 (85.2)
19 (86.4)
26 (96.3)
P Value .520 .397 .228 .004 1.000
1.000
.312 38.8
n/a 3 (13.6)
6.1
1 (3.7) n/a
16.8 (11.2-45.4) 24.9 (15.7-39.3) 12 (54.5) 15,255 91.5 24.9 35,663 89 11 1 4 16 5 0 1 8
(10,535-19,640) (64-104) (13.9-35.2) (13,437-52,695) (85.8-92.0) (50.0) (4.5) (18.2) (72.7) (22.7) (0) (4.5) (36.4)
19.7 (11.1-37.1) 31.75 7 (25.9) 11,490 90.0 17.8 49,386 88 7 1 2 10 10 3 4 18
(9300-14,700) (45-107) (10.2-25.6) (20,700-196000) (85.5-94.0) (25.9) (3.7) (7.4) (37.0) (37.0) (11.1) (14.8) (66.7)
.982 d .076 .049 .619 .061 .113 .689 .136 1.000 .388 .021 .358 .242 .362 .047
IQR, interquartile range; BMI, body mass index; WBC, white blood cell; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; PMNs, polymorphonuclear neutrophils; PJI, periprosthetic joint infection; MSSA, methicillin-sensitive Staphylococcus aureus; MRSA, methicillin-resistant Staphylococcus aureus.
F.-C. Kuo et al. / The Journal of Arthroplasty xxx (2019) 1e5
3
Table 2 Demographic Result of Treatment Success and Treatment Failure in Patients Having Blood Cultures. Variable Age, median (IQR), y Male, n (%) BMI, median (IQR), kg/m2 Elixhauser comorbidity index, median (IQR) Procedure, n (%) Primary Revision Joints n (%) Hip Knee Positive blood culture Fever > 38 C, n (%) Laboratory values, median (IQR) Serum WBC Serum ESR, mm/h Serum CRP, mg/dL Synovial WBC, mL Synovial PMNs, n (%) Organism profile, n (%) MSSA Staphylococcus epidermidis MRSA All staphylococcal species, subtotal Streptococcus Gram negative Polymicrobial
Success (N ¼ 26) 67.3 15 32.2 2
Failure (N ¼ 23)
(59.8-79.4) (57.7) (26.9-37.7) (1-3)
68.8 11 29.5 4
(63.4-77.2) (47.8) (24.8-36.5) (3-5)
23 (88.5) 3 (11.5)
20 (87.0) 3 (13.0)
3 23 8 9
4 19 14 10
P Value .718 .572 .298 .026 1.000
.692
11,770 94 18.6 49,943 88 10 1 2 13 11 2 0
(11.5) (88.5) (30.8) (34.6) (8825-16,225) (70-109) (10.2-29.1) (26,489-217,405) (82.5-93.0) (38.5) (3.8) (7.7) (50.0) (42.3) (7.7) (0)
13,070 76.5 18.7 34,024 89 8 1 4 13 4 1 5
(17.4) (82.6) (60.9) (43.5)
.047 .569
(10,450-17,788) (52-99) (13.7-28.8) (14,909-48,830) (86.5-93.8)
.513 .166 .764 .086 .414
(34.8) (4.3) (17.4) (56.5) (17.4) (4.3) (21.7)
1.000 1.000 .400 .776 .071 1.000 .018
IQR, interquartile range; BMI, body mass index; WBC, white blood cell; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; PMNs, polymorphonuclear neutrophils; MSSA, methicillin-sensitive Staphylococcus aureus; MRSA, methicillin-resistant Staphylococcus aureus.
fever > 38 C before surgery, and the PJI organism cultured from synovial fluid and/or tissue culture from the operating room were also recorded. The timing of collecting blood culture before or after operation was also documented. In general, there were no uniform criteria for ordering blood cultures. Blood cultures were ordered at the discretion of the attending surgeon, and the emergency department, internal medicine, or infectious disease teams. Blood cultures were obtained within 48 hours before or after the time of the index I&D procedure. A standard set of 2 blood culture bottles were routinely obtained per patient. Similar to previous studies [16], at least 8-10 mL per bottle was recommended to achieve optimum culture yield. The organisms cultured from blood culture and intraoperative samples were compared. Treatment failure was assessed in keeping with the Delphi International Consensus criteria [17], which is defined as: (1) infection eradication, characterized by a healed wound without fistula, drainage, or pain, and no infection recurrence caused by the same organism strain; (2) no subsequent surgical intervention for infection after reimplantation surgery; and (3) no occurrence of PJI- related mortality (by causes such as sepsis, necrotizing fasciitis), within 1-year follow-up.
test. A P value < .05 is considered statistically significant for all tests. Statistical analysis was calculated by using MedCalc software (version 17.9.7; Ostend, Belgium). Results Blood cultures were obtained from 94.2% of acute hematogenous PJI patients (49/52) at the time of diagnosis. Twenty-two patients had positive results for blood culture, and 27 patients had negative growth on blood cultures. Overall, 44.9% of blood cultures obtained yielded positive growth, with 38.8% of positive growth occurring in preoperative blood cultures and 6.1% in postoperative blood cultures. Patients with acute hematogenous PJIs and positive blood cultures seemed to have higher ECI (P ¼ .004) and serum WBC level (P ¼ .049) compared with the negative blood culture group.
Statistical Analysis Categorical variables were expressed as count and percentage, while continuous data were presented as medians and interquartile ranges. Because a preliminary Kolmogorov-Smirnov test did not demonstrate normal distribution for our small sample size, we decided to use the nonparametric Mann-Whitney U test to compare the continuous variables. Categorical variables were compared using the Fisher exact test. The covariates with P value < .2 were integrated in the stepwise multivariate logistic regression model. Certain variables were extracted from the model due to multicollinearity (r 0.7). Odd ratios (OR) are presented with 95% confidence intervals (CIs). A Kaplan-Meier survivorship curve for infection-free implant survival was generated for follow-up at 1 year. Differences in survivorship were assessed using the log-rank
Fig. 1. A Kaplan-Meier survivorship for implant free of infection between patients with a positive blood culture as opposed to a negative blood culture.
4
F.-C. Kuo et al. / The Journal of Arthroplasty xxx (2019) 1e5
Table 3 Blood Culture Result vs PJI Organism. Results
Blood Culture
PJI Organism.
Positive in both methods, concordance on species level (n ¼ 19)
Methicillin-sensitive Staphylococcus aureus (11) Methicillin-resistant Staphylococcus aureus (4) Beta-hemolytic Streptococcus, group B (3) Streptococcus mitis (1) Methicillin-resistant coagulase-negative Staphylococcus Clostridium ramosum Methicillin-sensitive Staphylococcus aureus
Beta-hemolytic Streptococcus, group B Staphylococcus epidermidis Polymicrobial
Positive in both methods but discordant (n ¼ 3)
PJI, periprosthetic joint infection.
Staphylococcal species were the most common organism identified in the acute hematogenous PJI cohort to cause positive blood cultures (P ¼ .021; Table 1). In the multivariate logistic regression, the ECI was the only significant factor to predict positive blood cultures in acute hematogenous PJI (adjusted OR, 1.65; 95% CI, 1.13-2.40; P ¼ .049) after adjusting for serum WBC level, serum CRP, synovial WBC, and staphylococcal species infection. The overall rate of treatment success was 53.1%. Patients with a positive blood culture in acute hematogenous PJI also had a significantly decreased rate of treatment success (36.3%) compared with patients with negative blood cultures (66.7%; P ¼ .047). Higher ECI (P ¼ .026), positive blood culture (P ¼ .047), and polymicrobial PJI (P ¼ .018) were significant risk factors for treatment failure in the univariate analysis. The rate of blood culture positivity was 2 times higher in the failure vs the success cohort (14 vs 8; P ¼ .047). Similarly, the ECI of patients in the failure group was double the success group (4 vs 2; P ¼ .026). Five patients with polymicrobial acute hematogenous PJI all failed after DAIR (Table 2). In the multivariate logistic regression, positive blood culture was the only significant factor to predict treatment failure in acute hematogenous PJI (OR, 3.94; 95% CI, 1.18-13.1; P ¼ .026) after adjusting for ECI, serum ESR, synovial WBC, and streptococcal and polymicrobial organisms. The Kaplan-Meier survivorship for infection-free implant survival was 53.1% (95% CI, 38.3%-65.8%) at 1 year for all patients, 66.7% (95% CI, 45.7%-81.1%) for patients with negative blood cultures, and 36.4% (95% CI, 17.2%-55.7%) for patients with a positive blood culture. The log-rank test indicated that the difference in survivorship between these 2 groups was significant (P ¼ .037; Fig. 1). The organisms to cause acute hematogenous PJI were listed in Table 1 and Table 2. Of the organisms isolated in blood cultures, 12 (54.5%) were Staphylococcus aureus, 4 (18.2%) were methicillinresistant S aureus, 3 (13.6%) were beta-hemolytic Streptococcus, Group B, 1 (4.5%) was Streptococcus mitis, 1 (4.5%) was methicillinresistant coagulase-negative Staphylococcus, and 1 (4.5%) was Clostridium ramosum (Table 3). When compared with the organism cultured from synovial fluid and/or tissue culture, the same organism was identified in 86.4% (19/22) of positive blood cultures. Of the positive blood cultures taken before surgery, 77.3% (17/19) matched the tissue and/or fluid culture. For positive blood cultures taken after surgery, the concordance rate dropped to 66.7% (2/3). There was no difference seen with regard to blood culture yield between samples taken before or after surgery (P ¼.371). Discussion The influence of positive blood cultures on surgical outcome in the setting of acute hematogenous PJI remains unknown. The purpose of this study was to evaluate the influence of positive blood cultures on the surgical management of patients with acute hematogenous PJI and investigate the risk factors for blood culture positivity in these patients. Our study is the first to demonstrate that patients with a higher ECI have higher risk of developing
positive blood cultures in the setting of acute hematogenous PJI. We found that of the blood cultures obtained from the 94.2% of patients worked-up for acute hematogenous PJI, 44.9% had positive blood cultures. Overall, 86.4% of these blood culture results matched the organism identified upon joint aspiration or surgery. Klement et al [16] showed blood cultures were obtained from 53.1% of all PJI patients and only 25.2% of blood cultures obtained yielded positive growth. Similar to the present study, 86% of these blood cultures matched the operative culture. Konigsberg et al [8] found 62.5% of patients had blood cultures obtained at the time of PJI diagnosis with a 32% rate of positive growth. In this study, 100% of blood culture organisms matched the operative culture. However, neither of these 2 studies further investigated risk factors for development of positive blood culture in acute hematogenous PJI. Patients with a higher ECI are sicker, with more comorbidities, and it follows that these patients are more prone to developing bacteremia and having positive blood cultures when they encounter infection [18]. This study further elucidated that patients who develop positive blood culture had a higher failure rate (63.6%)for acute hematogenous PJI. The results of the present study showed a worse outcome in this subgroup of PJI patients than the previous studies. Klement et al [16] reported a failure rate of 35% in the setting of primary PJI with a positive blood culture, although the results were not reported separately for acute postoperative as opposed to acute hematogenous infections or chronic infection. A study regarding blood cultures in acute hematogenous PJI showed a better outcome of treatment success (76%) [8]. However, no further analysis was executed to detect the association between positive blood culture and treatment outcome. In most PJI studies, the outcome of I&D for acute postoperative and acute hematogenous PJI has a lower treatment success than 2-stage exchange arthroplasty for chronic PJI [19,20]. Therefore, our study demonstrates the association between a positive blood culture and a worse treatment outcome in the setting of acute hematogenous PJI, potentially identifying a group of patients who would benefit from an initial 2-stage treatment procedure. The reason for treatment failure for acute hematogenous PJI varies in the literature [21e25]. In our study, we found that higher ECI, positive blood cultures, and polymicrobial infection were risk factors for treatment failure in the univariate analysis. However, only positive blood cultures remained significant after a stepwise multivariate logistic regression. Our study also showed 42.2%of blood cultures were done during the preoperative period and 75%of blood cultures done postoperatively yielded positive results. According to these results from our study, we suggest that patients with acute hematogenous PJI should obtain blood culture test before or after operation. The present study is not without limitations. First, this was a retrospective study prone to the inherent limitations of such a design. Second, our sample size was relatively limited. However, given the low incidence of acute hematogenous PJI, we feel our data still significantly contribute to the literature. Third, the criteria for obtaining a blood culture were not standardized, and we did not
F.-C. Kuo et al. / The Journal of Arthroplasty xxx (2019) 1e5
collect information regarding remove site infections. Furthermore, while a strict definition for acute hematogenous PJI was set at 3 months after index surgery with acute symptom onset, this definition remains a point of debate and controversy within the literature, and it is possible that certain patients had chronic periprosthetic infection. Furthermore, blood cultures were drawn before or after the index I&D surgery at the discretion of the treatment team, but this timing was not standardized. Although no significant difference in the results of blood cultures drawn at the preoperative vs postoperative setting was noted, most blood cultures in our study were drawn in the preoperative period (91.8%). Pragmatically, we recommend that blood cultures should be drawn preoperatively at the earliest convenience of the clinical team, either in the emergency room or the ward, before commencing antibiotic treatment. Finally, the type of systemic antibiotics was not recorded, which have may influenced the treatment outcome. In conclusion, patients with higher ECI are more likely to develop positive blood culture when encountering acute hematogenous PJI and those with positive blood cultures are more likely to experience treatment failure. We recommend drawing blood cultures in patients with acute hematogenous PJI treated with DAIR to further determine their treatment outcome. References [1] Kurtz SM, Lau E, Watson H, Schmier JK, Parvizi J. Economic burden of periprosthetic joint infection in the United States. J Arthroplasty 2012;27: 61e65.e1. https://doi.org/10.1016/j.arth.2012.02.022. [2] Schmalzried TP, Amstutz HC, Au MK, Dorey FJ. Etiology of deep sepsis in total hip arthroplasty. The significance of hematogenous and recurrent infections. Clin Orthop 1992:200e7. [3] Segawa H, Tsukayama DT, Kyle RF, Becker DA, Gustilo RB. Infection after total knee arthroplasty. A retrospective study of the treatment of eighty-one infections. J Bone Joint Surg Am 1999;81:1434e45. [4] Tsukayama DT, Estrada R, Gustilo RB. Infection after total hip arthroplasty. A study of the treatment of one hundred and six infections. J Bone Joint Surg Am 1996;78:512e23. [5] Giulieri SG, Graber P, Ochsner PE, Zimmerli W. Management of infection associated with total hip arthroplasty according to a treatment algorithm. Infection 2004;32:222e8. https://doi.org/10.1007/s15010-004-4020-1. bridement and [6] Van Kleunen JP, Knox D, Garino JP, Lee G-C. Irrigation and de prosthesis retention for treating acute periprosthetic infections. Clin Orthop 2010;468:2024e8. https://doi.org/10.1007/s11999-010-1291-y. [7] Byren I, Bejon P, Atkins BL, Angus B, Masters S, McLardy-Smith P, et al. One hundred and twelve infected arthroplasties treated with “DAIR” (debridement, antibiotics and implant retention): antibiotic duration and outcome. J Antimicrob Chemother 2009;63:1264e71. https://doi.org/10.1093/jac/dkp107. [8] Konigsberg BS, Della Valle CJ, Ting NT, Qiu F, Sporer SM. Acute hematogenous infection following total hip and knee arthroplasty. J Arthroplasty 2014;29: 469e72. https://doi.org/10.1016/j.arth.2013.07.021. [9] Odum SM, Fehring TK, Lombardi AV, Zmistowski BM, Brown NM, Luna JT, et al. Irrigation and debridement for periprosthetic infections: does the organism matter? J Arthroplasty 2011;26:114e8. https://doi.org/10.1016/j.arth.2011.03.031.
5
[10] Koh IJ, Han S-B, In Y, Oh K-J, Lee D-H, Kim TK, et al. Open debridement and prosthesis retention is a viable treatment option for acute periprosthetic joint infection after total knee arthroplasty. Arch Orthop Trauma Surg 2015;135: 847e55. https://doi.org/10.1007/s00402-015-2237-3. [11] Flierl MA, Culp BM, Okroj KT, Springer BD, Levine BR, Della Valle CJ. Poor outcomes of irrigation and debridement in acute periprosthetic joint infection with antibiotic-impregnated calcium sulfate beads. J Arthroplasty 2017;32: 2505e7. https://doi.org/10.1016/j.arth.2017.03.051. [12] Parvizi J, Della Valle CJ. AAOS Clinical Practice Guideline: diagnosis and treatment of periprosthetic joint infections of the hip and knee. J Am Acad Orthop Surg 2010;18:771e2. [13] Parvizi J, Gehrke T, Chen AF. Proceedings of the International Consensus on periprosthetic joint infection. Bone Joint J 2013;95-B:1450e2. https://doi.org/ 10.1302/0301-620X.95B11.33135. [14] Coburn B, Morris AM, Tomlinson G, Detsky AS. Does this adult patient with suspected bacteremia require blood cultures? JAMA 2012;308:502e11. https://doi.org/10.1001/jama.2012.8262. [15] Shapiro NI, Wolfe RE, Wright SB, Moore R, Bates DW. Who needs a blood culture? A prospectively derived and validated prediction rule. J Emerg Med 2008;35:255e64. https://doi.org/10.1016/j.jemermed.2008.04.001. [16] Klement MR, Siddiqi A, Rock JM, Chen AF, Bolognesi MP, Seyler TM. Positive blood cultures in periprosthetic joint infection decrease rate of treatment success. J Arthroplasty 2018;33:200e204.e1. https://doi.org/10.1016/ j.arth.2017.08.034. [17] Diaz-Ledezma C, Higuera CA, Parvizi J. Success after treatment of periprosthetic joint infection: a Delphi-based international multidisciplinary consensus. Clin Orthop 2013;471:2374e82. https://doi.org/10.1007/s11999013-2866-1. [18] van Daalen FV, Kallen MC, van den Bosch CMA, Hulscher MEJL, Geerlings SE, Prins JM. Clinical condition and comorbidity as determinants for blood culture positivity in patients with skin and soft-tissue infections. Eur J Clin Microbiol Infect Dis 2017;36:1853e8. https://doi.org/10.1007/s10096-017-3001-0. [19] Kuzyk PRT, Dhotar HS, Sternheim A, Gross AE, Safir O, Backstein D. Two-stage revision arthroplasty for management of chronic periprosthetic hip and knee infection: techniques, controversies, and outcomes. J Am Acad Orthop Surg 2014;22:153e64. https://doi.org/10.5435/JAAOS-22-03-153. [20] Triantafyllopoulos GK, Soranoglou V, Memtsoudis SG, Poultsides LA. Implant retention after acute and hematogenous periprosthetic hip and knee infections: whom, when and how? World J Orthop 2016;7:546e52. https:// doi.org/10.5312/wjo.v7.i9.546. [21] Choong PFM, Dowsey MM, Carr D, Daffy J, Stanley P. Risk factors associated with acute hip prosthetic joint infections and outcome of treatment with a rifampin-based regimen. Acta Orthop 2007;78:755e65. https://doi.org/ 10.1080/17453670710014527. [22] Azzam KA, Seeley M, Ghanem E, Austin MS, Purtill JJ, Parvizi J. Irrigation and debridement in the management of prosthetic joint infection: traditional indications revisited. J Arthroplasty 2010;25:1022e7. https://doi.org/10.1016/ j.arth.2010.01.104. [23] Buller LT, Sabry FY, Easton RW, Klika AK, Barsoum WK. The preoperative prediction of success following irrigation and debridement with polyethylene exchange for hip and knee prosthetic joint infections. J Arthroplasty 2012;27: 857e64. https://doi.org/10.1016/j.arth.2012.01.003. e1-4. [24] Tande AJ, Palraj BR, Osmon DR, Berbari EF, Baddour LM, Lohse CM, et al. Clinical presentation, risk factors, and outcomes of hematogenous prosthetic joint infection in patients with Staphylococcus aureus bacteremia. Am J Med 2016;129:221. https://doi.org/10.1016/j.amjmed.2015.09.006. e11-20. [25] Lora-Tamayo J, Murillo O, Iribarren JA, Soriano A, S anchez-Somolinos M, Baraia-Etxaburu JM, et al. A large multicenter study of methicillin-susceptible and methicillin-resistant Staphylococcus aureus prosthetic joint infections managed with implant retention. Clin Infect Dis 2013;56:182e94. https:// doi.org/10.1093/cid/cis746.
5.e1
F.-C. Kuo et al. / The Journal of Arthroplasty xxx (2019) 1e5
Appendix Appendix 1 The Elixhauser Comorbidity Index by International Classification of Diseases Ninth Revision/Tenth Revision, Clinical Modification (ICD-9-CM, ICD-10-CM). Comorbidities
ICD-9-CM
ICD-10-CM
Congestive heart failure
398.91, 402.01, 402.11, 402.91, 404.01, 404.03, 404.11, 404.13, 404.91, 404.93, 428.x 426.10, 426.11, 426.13, 426.2-426.53, 426.6-426.8, 427.0, 427.2, 427.31, 427.60, 427.9, 785.0, V45.0, V53.3 93.2, 394.x-397.1, 397.9, 424.x, 746.3-746.6, V42.2, V43.3 416.x, 417.9 440.x, 441.x, 442.x, 443.1-443.9, 447.1, 557.1, 557.9, V43.4 401.0, 401.1, 401.9, 402.x-405.x, 642.0-642.2, 642.7, 642.9 342.x-344.x, 438.2-438.5
I09.9, I11.0, I13.0, I13.2, I25.5, I42.0, 142.5-I42.9, I43.x, I50.x, P29.0 I44.1-I44.3, I45.6, I45.9, I47.x-I49.x, ROO.O, ROO.1, ROO.8, T82.1, Z45.0, Z95.0
Cardiac arrhythmias
Valvular disease Pulmonary circulation disorders Peripheral vascular disorders Hypertension Paralysis Other neurologic disorders
330.x-331.x, 332.0, 333.4, 333.5, 334.x, 335.x, 340, 341.1-341.9, 345.x, 347.x, 780.3, 784.3
Chronic pulmonary disease
490x-492.x, 493.x, 494x-505.x, 506.4
Diabetes, uncomplicated
250.0-250.3, 648.0
Diabetes, complicated
250.4-250.7, 250.9
Hypothyroidism Renal failure
Metastatic cancer Solid tumor without metastasis
243-244.2, 244.8, 244.9 403.01, 403.11, 403.91, 404.02, 404.03, 404.12, 404.13, 404.92, 404.93, 585.x, 586.x, V42.0, V45.1, V56.x 70.22, 70.23, 70.32, 70.33, 70.44, 70.54, 456.0, 456.1, 456.20, 571.0, 571.2-571.9, 572.3, 572.8, V42.7 531.41, 531.51, 531.61, 531.7, 531.91, 532.41, 532.51, 532.61, 532.7, 532.91, 533.41, 533.51, 533.61, 533.7, 533.91, 534.41, 534.51, 534.61, 534.7, 534.91 042.x-044.x 200.x-202.3, 202.5-203.0, 203.8, 238.6, 273.3, V10.71, V10.72, V10.79 196.x-199.x 140.x-172.x, 174.x, 175.x, 179.x-195.x, V10.x
Rheumatoid arthritis/collagen vascular diseases
701.0, 710.x, 714.x, 720.x, 725.x
Coagulopathy Obesity Weight loss Fluid and electrolyte disorders Blood loss anemia Deficiency anemia Alcohol abuse
286.x, 287.1, 287.3-287.5 278.0 260.x-263.x, 783.2 276.x 280.0, 648.2 280.1-281.9, 285.2, 285.9 291.0-291.3, 291.5, 291.8, 291.9, 303.x, 305.0, V113
Drug abuse
292.0, 292.82-292.89,292.9, 304.x,305.2-305.9, 648.3 295.x-298.x, 299.1 300.4, 301.12, 309.0, 309.1, 311
Liver disease Peptic ulcer disease excluding bleeding
AIDS/HIV Lymphoma
Psychoses Depression
A52.0, I05.x-I08.x, I09.1, I09.8, I34.x-I39.x, Q23.OQ23.3, Z95.2, Z95.4 I26.x, I27.x, I28.0, I28.8, I28.9 I70.x, I71.x, I73.1, I73.8, I73.9, I77.1, I79.0, I79.2, K55.1, K55.8, K55.9, Z95.8, Z95.9 I10.x, I11.x-I13.x, I15.x G04.1, G11.4, G80.1, G80.2, G81.x, G82.x, G83.0G83.4, G83.9 G10.x-G 13.x, G20.x-G22.x, G25.4, G25.5, G31.2, G31.8, G31.9, G32.x, G35.x-G37.x, G40.x, G41.x, G93.1, G93.4, R47.0, R56.x I27.8, 127.9, J40.x-J47.x, J60.x-J67.x, J68.4, J70.1, J70.3 E10.0, E10.1, E10.9, E11.0, E11.1, E11.9, E12.0, E12.1, E12.9, E13.0, E13.1, E13.9, E14.0, E14.1, E14.9 E10.2eE10.8, E11.2eE11.8, E12.2eE12.8, E13.2 eE13.8, E14.2eE14.8 E00.x-E03.x, E89.0 I12.0, I13.1, N18.x, NI9.x, N25.0, Z49.0-Z49.2, Z94.0, Z99.2 B18.x, I85.x, I86.4, I98.2, K70.x, K71.1, K71.3eK71.5, K71.7, K72.xeK74.x, K76.0, K76.2eK76.9, Z94.4 K25.7, K25.9, K26.7, K26.9, K27.7, K27.9, K28.7, K28.9
B20.x-B22.x, B24.x C81.x-C85.x, C88.x, C96.x, C90.0, C90.2 C77.x-C80.x C00.x-C26.x, C30.x-C34.x, C37.x-C41.x, C43.x, C45.x-C58.x, C60.x-C76.x, C97.x L94.0, L94.1, L94.3, M05.x, M06.x, M08.x, M12.0, M12.3, M30.x, M31.0-M31.3, M32.x-M35.x, M45.x, M46.1, M46.8, M46.9 D65-D68.x, D69.1, D69.3-D69.6 E66.x E40.x-E46.x, R63.4, R64 E22.2, E86.x, E87.x D50.0 D50.8, D50.9, D51.x-D53.x F10, E52, G62.1, I42.6, K29.2, K70.0, K70.3, K70.9, T51.x, Z50.2, Z71.4, Z72.1 F11.x-F16.x, F18.x, F19.x, Z71.5. Z72.2 F20.x, F22.x-F25.x, F28.x, F29.x, F30.2, F31.2, F31.5 F20.4, F31.3-F31.5, F32.x, F33.x, F34.1, F41.2, F43.2
Contents lists available at ScienceDirect
The Journal of Arthroplasty journal homepage: www.arthroplastyjournal.org
Positive Blood Cultures Decrease the Treatment Success in Acute Hematogenous Periprosthetic Joint Infection Treated With Debridement, Antibiotics, and Implant Retention Feng-Chih Kuo, MD a, b, Karan Goswami, MD a, Mitchell R. Klement, MD a, Noam Shohat, MD a, c, Javad Parvizi, MD, FRCS a, * a b c
Rothman Orthopaedic Institute, Philadelphia, PA Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel
a r t i c l e i n f o
a b s t r a c t
Article history: Received 25 April 2019 Received in revised form 13 June 2019 Accepted 25 June 2019 Available online xxx
Background: The influence of positive blood cultures on surgical outcome of acute hematogenous periprosthetic joint infection (PJI) treated by debridement, antibiotics, and implant retention (DAIR) remains unknown. This study evaluated the influence of positive blood cultures on the treatment success of DAIR in patients with acute hematogenous PJI. Methods: A retrospective chart review on 49 patients with blood culture data for acute hematogenous PJI was performed from 2005 to 2016 at a single institution. All patients were treated by DAIR and had a minimum follow-up of 1 year. Treatment success was defined by the Delphi criteria. Multivariate logistic regression analysis was performed to identify variables associated with positive blood culture and treatment success. Kaplan-Meier survivorship curves and log-rank tests were used for analysis. Results: Overall, 44.9% (22/49) of blood cultures obtained yielded positive growth. Elevated Elixhauser comorbidity index was a significant risk factor associated with positive blood (adjusted odds ratio [OR], 1.65; 95% confidence interval [CI], 1.13-2.40; P ¼ .049). A positive blood culture was the only significant factor predicting treatment failure in acute hematogenous PJI (OR, 3.94; 95% CI, 1.18-13.1; P ¼ .026) after adjusting for confounding variables. Kaplan-Meier survivorship for infection-free implant survivorship was 53.1% (95% CI, 38.3%-65.8%) at 1 year for all patients, 66.7% (95% CI, 45.7%-81.1%) for patients with negative blood cultures, and 36.4% (95% CI, 17.2%-55.7%) for patients with positive blood cultures (P ¼ .037). Conclusion: The presence of positive blood cultures is associated with decreased treatment success of DAIR for acute hematogenous PJI. Patients with more comorbidities may need to be treated more aggressively for a favorable outcome. © 2019 Published by Elsevier Inc.
Keywords: blood culture acute hematogenous periprosthetic joint infection treatment arthroplasty
Periprosthetic joint infection (PJI) is an uncommon but devastating complication after total knee and hip arthroplasty. The overall incidence of PJI has been reported to be approximately 1%2% [1]. Acute hematogenous PJI may be introduced through hematogenous seeding and accounts for 5.6%-43% of all PJI [2e5].
One or more of the authors of this paper have disclosed potential or pertinent conflicts of interest, which may include receipt of payment, either direct or indirect, institutional support, or association with an entity in the biomedical field which may be perceived to have potential conflict of interest with this work. For full disclosure statements refer to https://doi.org/10.1016/j.arth.2019.06.053. * Reprint requests: Javad Parvizi, MD, FRCS, Rothman Orthopaedic Institute, 125 S 9th St. Ste 1000, Philadelphia, PA 19107. https://doi.org/10.1016/j.arth.2019.06.053 0883-5403/© 2019 Published by Elsevier Inc.
A debridement, antibiotics, and implant retention (DAIR) procedure remains the first-line treatment choice for patients presenting with acute hematogenous PJI [6]. However, the success rate of DAIR for acute hematogenous PJI remains poor, ranging from 31% to 82% [7e11]. Bacteremia is an etiology of acute hematogenous PJI and patients with suspicion for acute hematogenous PJI should have blood cultures obtained as per the current diagnostic guidelines [12,13]. The estimated incidence of positive blood cultures among PJI ranges from 4.3% to 7.3% [14,15] to as high as 25.2% to 32%[8,16]. A recent study reported that positive blood cultures decrease the rate of treatment success [16]. However, previous studies included all PJI patients, used various surgical options, and did not obtain blood
2
F.-C. Kuo et al. / The Journal of Arthroplasty xxx (2019) 1e5
culture samples from all acute hematogenous PJI cases [8,16]. Meanwhile, blood cultures are rarely obtained in chronic PJI in clinical practice. To date, there has been no study to predict the risk factors associated with yielding a positive blood culture. Furthermore, the association between a positive blood culture result and treatment outcome in patients with acute hematogenous PJI remains unknown. The purpose of this study is to (1) investigate the risk factors associated with yielding a positive blood culture and (2) investigate the influence of positive blood cultures upon surgical treatment outcome in patients with acute hematogenous PJI treated with DAIR. We hypothesized that patients with positive blood cultures are more likely to experience treatment failure. Materials and Methods Following approval by our institutional review board, a retrospective study was conducted for patients undergoing DAIR after a total knee arthroplasty (TKA) or total hip arthroplasty (THA) at a single academic institution from 2005 to 2017. These patients were identified from a prospectively maintained institutional PJI database. All patients who underwent DAIR for acute hematogenous PJI were included. Acute hematogenous PJI was defined as having an infection occurring more than 3 months from the index surgery, with abrupt symptoms lasting less than 3 weeks in a well-fixed and functioning THA or TKA. Patients with a history of perioperative infection or wound healing problems were excluded to avoid the inclusion of acute postoperative or chronic infections. We also excluded cases where radiologic loosening suggestive of chronic PJI was evident. Patients who did not meet Musculoskeletal Infection
Society criteria for infection were excluded. In total, 52 patients who underwent DAIR for acute hematogenous PJIs were included. Among them, 3 patients did not have blood culture data. The final cohort consisted of 49 patients with blood culture data who had undergone surgical management for 42 infected TKAs and 7 infected THAs. Patients were followed up for a minimum of 1 year or until treatment failure. Irrigation and debridement (I&D) were performed using a medial parapatellar approach for the knee, while the same approach as the index procedure (direct anterior, direct lateral, or posterolateral) was used for hips. A well-fixed component was also confirmed intraoperatively. Any devitalized or infective bony and soft tissue structures were removed in all cases. Modular components, consisting of the polyethylene component for knees and femoral head and polyethylene liner in hips, were exchanged with new components. A total of 3 to 5 samples were collected for microbiologic culture and sent for routine aerobic and anaerobic bacterial, fungal, and acid-fast bacillus testing. Following surgery, parenteral antibiotic therapy was initiated and guided by culture results. If cultures were negative, patients were treated empirically with intravenous vancomycin. Antibiotic therapy was then continued for 6 weeks with serial monitoring of inflammatory markers including erythrocyte sedimentation rate (ESR) and Creactive protein (CRP). A manual chart review was performed for all patients who met inclusion criteria. Patient characteristics (age, gender, body mass index, Elixhauser comorbidity index [ECI; Appendix 1], infected joint [knee or hip], and index surgery [primary/revision]) were recorded. Laboratory results (serum CRP, ESR, serum and synovial white blood cells [WBC, sWBC], the result of blood cultures),
Table 1 Demographic Data of Acute Hematogenous PJI. Variable Age, median (IQR), y Male, n (%) BMI, median (IQR), kg/m2 Elixhauser comorbidity index, median (IQR) Procedure, n (%) Primary Revision Joints, n (%) Hip Knee Blood culture timing, n (%) Preoperative Positive (%) Postoperative Positive (%) Time to having blood culture, median (IQR), h Preoperative Postoperative Fever >38 C, n (%) Laboratory values, median (IQR) Serum WBC Serum ESR, mm/h Serum CRP, mg/dL Synovial WBC, mL Synovial PMNs, n (%) PJI organism profile, n (%) MSSA Staphylococcus epidermidis MRSA All staphylococcal species, subtotal Streptococcus Gram negative Polymicrobial Treatment success at 1 y, n (%)
Positive Blood Culture (N ¼ 22) 68.9 10 30.9 4.5
(63.9-77.4) (45.5) (25.0-35.4) (2.0-5.5)
Negative Blood Culture (N ¼ 27) 67.5 16 30.9 2
(58.9-79.5) (59.3) (27.4-39.6) (1-3)
19 (86.4) 3 (13.6)
24 (88.9) 3 (11.1)
3 (13.6) 19 (86.4)
4 (14.8) 23 (85.2)
19 (86.4)
26 (96.3)
P Value .520 .397 .228 .004 1.000
1.000
.312 38.8
n/a 3 (13.6)
6.1
1 (3.7) n/a
16.8 (11.2-45.4) 24.9 (15.7-39.3) 12 (54.5) 15,255 91.5 24.9 35,663 89 11 1 4 16 5 0 1 8
(10,535-19,640) (64-104) (13.9-35.2) (13,437-52,695) (85.8-92.0) (50.0) (4.5) (18.2) (72.7) (22.7) (0) (4.5) (36.4)
19.7 (11.1-37.1) 31.75 7 (25.9) 11,490 90.0 17.8 49,386 88 7 1 2 10 10 3 4 18
(9300-14,700) (45-107) (10.2-25.6) (20,700-196000) (85.5-94.0) (25.9) (3.7) (7.4) (37.0) (37.0) (11.1) (14.8) (66.7)
.982 d .076 .049 .619 .061 .113 .689 .136 1.000 .388 .021 .358 .242 .362 .047
IQR, interquartile range; BMI, body mass index; WBC, white blood cell; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; PMNs, polymorphonuclear neutrophils; PJI, periprosthetic joint infection; MSSA, methicillin-sensitive Staphylococcus aureus; MRSA, methicillin-resistant Staphylococcus aureus.
F.-C. Kuo et al. / The Journal of Arthroplasty xxx (2019) 1e5
3
Table 2 Demographic Result of Treatment Success and Treatment Failure in Patients Having Blood Cultures. Variable Age, median (IQR), y Male, n (%) BMI, median (IQR), kg/m2 Elixhauser comorbidity index, median (IQR) Procedure, n (%) Primary Revision Joints n (%) Hip Knee Positive blood culture Fever > 38 C, n (%) Laboratory values, median (IQR) Serum WBC Serum ESR, mm/h Serum CRP, mg/dL Synovial WBC, mL Synovial PMNs, n (%) Organism profile, n (%) MSSA Staphylococcus epidermidis MRSA All staphylococcal species, subtotal Streptococcus Gram negative Polymicrobial
Success (N ¼ 26) 67.3 15 32.2 2
Failure (N ¼ 23)
(59.8-79.4) (57.7) (26.9-37.7) (1-3)
68.8 11 29.5 4
(63.4-77.2) (47.8) (24.8-36.5) (3-5)
23 (88.5) 3 (11.5)
20 (87.0) 3 (13.0)
3 23 8 9
4 19 14 10
P Value .718 .572 .298 .026 1.000
.692
11,770 94 18.6 49,943 88 10 1 2 13 11 2 0
(11.5) (88.5) (30.8) (34.6) (8825-16,225) (70-109) (10.2-29.1) (26,489-217,405) (82.5-93.0) (38.5) (3.8) (7.7) (50.0) (42.3) (7.7) (0)
13,070 76.5 18.7 34,024 89 8 1 4 13 4 1 5
(17.4) (82.6) (60.9) (43.5)
.047 .569
(10,450-17,788) (52-99) (13.7-28.8) (14,909-48,830) (86.5-93.8)
.513 .166 .764 .086 .414
(34.8) (4.3) (17.4) (56.5) (17.4) (4.3) (21.7)
1.000 1.000 .400 .776 .071 1.000 .018
IQR, interquartile range; BMI, body mass index; WBC, white blood cell; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; PMNs, polymorphonuclear neutrophils; MSSA, methicillin-sensitive Staphylococcus aureus; MRSA, methicillin-resistant Staphylococcus aureus.
fever > 38 C before surgery, and the PJI organism cultured from synovial fluid and/or tissue culture from the operating room were also recorded. The timing of collecting blood culture before or after operation was also documented. In general, there were no uniform criteria for ordering blood cultures. Blood cultures were ordered at the discretion of the attending surgeon, and the emergency department, internal medicine, or infectious disease teams. Blood cultures were obtained within 48 hours before or after the time of the index I&D procedure. A standard set of 2 blood culture bottles were routinely obtained per patient. Similar to previous studies [16], at least 8-10 mL per bottle was recommended to achieve optimum culture yield. The organisms cultured from blood culture and intraoperative samples were compared. Treatment failure was assessed in keeping with the Delphi International Consensus criteria [17], which is defined as: (1) infection eradication, characterized by a healed wound without fistula, drainage, or pain, and no infection recurrence caused by the same organism strain; (2) no subsequent surgical intervention for infection after reimplantation surgery; and (3) no occurrence of PJI- related mortality (by causes such as sepsis, necrotizing fasciitis), within 1-year follow-up.
test. A P value < .05 is considered statistically significant for all tests. Statistical analysis was calculated by using MedCalc software (version 17.9.7; Ostend, Belgium). Results Blood cultures were obtained from 94.2% of acute hematogenous PJI patients (49/52) at the time of diagnosis. Twenty-two patients had positive results for blood culture, and 27 patients had negative growth on blood cultures. Overall, 44.9% of blood cultures obtained yielded positive growth, with 38.8% of positive growth occurring in preoperative blood cultures and 6.1% in postoperative blood cultures. Patients with acute hematogenous PJIs and positive blood cultures seemed to have higher ECI (P ¼ .004) and serum WBC level (P ¼ .049) compared with the negative blood culture group.
Statistical Analysis Categorical variables were expressed as count and percentage, while continuous data were presented as medians and interquartile ranges. Because a preliminary Kolmogorov-Smirnov test did not demonstrate normal distribution for our small sample size, we decided to use the nonparametric Mann-Whitney U test to compare the continuous variables. Categorical variables were compared using the Fisher exact test. The covariates with P value < .2 were integrated in the stepwise multivariate logistic regression model. Certain variables were extracted from the model due to multicollinearity (r 0.7). Odd ratios (OR) are presented with 95% confidence intervals (CIs). A Kaplan-Meier survivorship curve for infection-free implant survival was generated for follow-up at 1 year. Differences in survivorship were assessed using the log-rank
Fig. 1. A Kaplan-Meier survivorship for implant free of infection between patients with a positive blood culture as opposed to a negative blood culture.
4
F.-C. Kuo et al. / The Journal of Arthroplasty xxx (2019) 1e5
Table 3 Blood Culture Result vs PJI Organism. Results
Blood Culture
PJI Organism.
Positive in both methods, concordance on species level (n ¼ 19)
Methicillin-sensitive Staphylococcus aureus (11) Methicillin-resistant Staphylococcus aureus (4) Beta-hemolytic Streptococcus, group B (3) Streptococcus mitis (1) Methicillin-resistant coagulase-negative Staphylococcus Clostridium ramosum Methicillin-sensitive Staphylococcus aureus
Beta-hemolytic Streptococcus, group B Staphylococcus epidermidis Polymicrobial
Positive in both methods but discordant (n ¼ 3)
PJI, periprosthetic joint infection.
Staphylococcal species were the most common organism identified in the acute hematogenous PJI cohort to cause positive blood cultures (P ¼ .021; Table 1). In the multivariate logistic regression, the ECI was the only significant factor to predict positive blood cultures in acute hematogenous PJI (adjusted OR, 1.65; 95% CI, 1.13-2.40; P ¼ .049) after adjusting for serum WBC level, serum CRP, synovial WBC, and staphylococcal species infection. The overall rate of treatment success was 53.1%. Patients with a positive blood culture in acute hematogenous PJI also had a significantly decreased rate of treatment success (36.3%) compared with patients with negative blood cultures (66.7%; P ¼ .047). Higher ECI (P ¼ .026), positive blood culture (P ¼ .047), and polymicrobial PJI (P ¼ .018) were significant risk factors for treatment failure in the univariate analysis. The rate of blood culture positivity was 2 times higher in the failure vs the success cohort (14 vs 8; P ¼ .047). Similarly, the ECI of patients in the failure group was double the success group (4 vs 2; P ¼ .026). Five patients with polymicrobial acute hematogenous PJI all failed after DAIR (Table 2). In the multivariate logistic regression, positive blood culture was the only significant factor to predict treatment failure in acute hematogenous PJI (OR, 3.94; 95% CI, 1.18-13.1; P ¼ .026) after adjusting for ECI, serum ESR, synovial WBC, and streptococcal and polymicrobial organisms. The Kaplan-Meier survivorship for infection-free implant survival was 53.1% (95% CI, 38.3%-65.8%) at 1 year for all patients, 66.7% (95% CI, 45.7%-81.1%) for patients with negative blood cultures, and 36.4% (95% CI, 17.2%-55.7%) for patients with a positive blood culture. The log-rank test indicated that the difference in survivorship between these 2 groups was significant (P ¼ .037; Fig. 1). The organisms to cause acute hematogenous PJI were listed in Table 1 and Table 2. Of the organisms isolated in blood cultures, 12 (54.5%) were Staphylococcus aureus, 4 (18.2%) were methicillinresistant S aureus, 3 (13.6%) were beta-hemolytic Streptococcus, Group B, 1 (4.5%) was Streptococcus mitis, 1 (4.5%) was methicillinresistant coagulase-negative Staphylococcus, and 1 (4.5%) was Clostridium ramosum (Table 3). When compared with the organism cultured from synovial fluid and/or tissue culture, the same organism was identified in 86.4% (19/22) of positive blood cultures. Of the positive blood cultures taken before surgery, 77.3% (17/19) matched the tissue and/or fluid culture. For positive blood cultures taken after surgery, the concordance rate dropped to 66.7% (2/3). There was no difference seen with regard to blood culture yield between samples taken before or after surgery (P ¼.371). Discussion The influence of positive blood cultures on surgical outcome in the setting of acute hematogenous PJI remains unknown. The purpose of this study was to evaluate the influence of positive blood cultures on the surgical management of patients with acute hematogenous PJI and investigate the risk factors for blood culture positivity in these patients. Our study is the first to demonstrate that patients with a higher ECI have higher risk of developing
positive blood cultures in the setting of acute hematogenous PJI. We found that of the blood cultures obtained from the 94.2% of patients worked-up for acute hematogenous PJI, 44.9% had positive blood cultures. Overall, 86.4% of these blood culture results matched the organism identified upon joint aspiration or surgery. Klement et al [16] showed blood cultures were obtained from 53.1% of all PJI patients and only 25.2% of blood cultures obtained yielded positive growth. Similar to the present study, 86% of these blood cultures matched the operative culture. Konigsberg et al [8] found 62.5% of patients had blood cultures obtained at the time of PJI diagnosis with a 32% rate of positive growth. In this study, 100% of blood culture organisms matched the operative culture. However, neither of these 2 studies further investigated risk factors for development of positive blood culture in acute hematogenous PJI. Patients with a higher ECI are sicker, with more comorbidities, and it follows that these patients are more prone to developing bacteremia and having positive blood cultures when they encounter infection [18]. This study further elucidated that patients who develop positive blood culture had a higher failure rate (63.6%)for acute hematogenous PJI. The results of the present study showed a worse outcome in this subgroup of PJI patients than the previous studies. Klement et al [16] reported a failure rate of 35% in the setting of primary PJI with a positive blood culture, although the results were not reported separately for acute postoperative as opposed to acute hematogenous infections or chronic infection. A study regarding blood cultures in acute hematogenous PJI showed a better outcome of treatment success (76%) [8]. However, no further analysis was executed to detect the association between positive blood culture and treatment outcome. In most PJI studies, the outcome of I&D for acute postoperative and acute hematogenous PJI has a lower treatment success than 2-stage exchange arthroplasty for chronic PJI [19,20]. Therefore, our study demonstrates the association between a positive blood culture and a worse treatment outcome in the setting of acute hematogenous PJI, potentially identifying a group of patients who would benefit from an initial 2-stage treatment procedure. The reason for treatment failure for acute hematogenous PJI varies in the literature [21e25]. In our study, we found that higher ECI, positive blood cultures, and polymicrobial infection were risk factors for treatment failure in the univariate analysis. However, only positive blood cultures remained significant after a stepwise multivariate logistic regression. Our study also showed 42.2%of blood cultures were done during the preoperative period and 75%of blood cultures done postoperatively yielded positive results. According to these results from our study, we suggest that patients with acute hematogenous PJI should obtain blood culture test before or after operation. The present study is not without limitations. First, this was a retrospective study prone to the inherent limitations of such a design. Second, our sample size was relatively limited. However, given the low incidence of acute hematogenous PJI, we feel our data still significantly contribute to the literature. Third, the criteria for obtaining a blood culture were not standardized, and we did not
F.-C. Kuo et al. / The Journal of Arthroplasty xxx (2019) 1e5
collect information regarding remove site infections. Furthermore, while a strict definition for acute hematogenous PJI was set at 3 months after index surgery with acute symptom onset, this definition remains a point of debate and controversy within the literature, and it is possible that certain patients had chronic periprosthetic infection. Furthermore, blood cultures were drawn before or after the index I&D surgery at the discretion of the treatment team, but this timing was not standardized. Although no significant difference in the results of blood cultures drawn at the preoperative vs postoperative setting was noted, most blood cultures in our study were drawn in the preoperative period (91.8%). Pragmatically, we recommend that blood cultures should be drawn preoperatively at the earliest convenience of the clinical team, either in the emergency room or the ward, before commencing antibiotic treatment. Finally, the type of systemic antibiotics was not recorded, which have may influenced the treatment outcome. In conclusion, patients with higher ECI are more likely to develop positive blood culture when encountering acute hematogenous PJI and those with positive blood cultures are more likely to experience treatment failure. We recommend drawing blood cultures in patients with acute hematogenous PJI treated with DAIR to further determine their treatment outcome. References [1] Kurtz SM, Lau E, Watson H, Schmier JK, Parvizi J. Economic burden of periprosthetic joint infection in the United States. J Arthroplasty 2012;27: 61e65.e1. https://doi.org/10.1016/j.arth.2012.02.022. [2] Schmalzried TP, Amstutz HC, Au MK, Dorey FJ. Etiology of deep sepsis in total hip arthroplasty. The significance of hematogenous and recurrent infections. Clin Orthop 1992:200e7. [3] Segawa H, Tsukayama DT, Kyle RF, Becker DA, Gustilo RB. Infection after total knee arthroplasty. A retrospective study of the treatment of eighty-one infections. J Bone Joint Surg Am 1999;81:1434e45. [4] Tsukayama DT, Estrada R, Gustilo RB. Infection after total hip arthroplasty. A study of the treatment of one hundred and six infections. J Bone Joint Surg Am 1996;78:512e23. [5] Giulieri SG, Graber P, Ochsner PE, Zimmerli W. Management of infection associated with total hip arthroplasty according to a treatment algorithm. Infection 2004;32:222e8. https://doi.org/10.1007/s15010-004-4020-1. bridement and [6] Van Kleunen JP, Knox D, Garino JP, Lee G-C. Irrigation and de prosthesis retention for treating acute periprosthetic infections. Clin Orthop 2010;468:2024e8. https://doi.org/10.1007/s11999-010-1291-y. [7] Byren I, Bejon P, Atkins BL, Angus B, Masters S, McLardy-Smith P, et al. One hundred and twelve infected arthroplasties treated with “DAIR” (debridement, antibiotics and implant retention): antibiotic duration and outcome. J Antimicrob Chemother 2009;63:1264e71. https://doi.org/10.1093/jac/dkp107. [8] Konigsberg BS, Della Valle CJ, Ting NT, Qiu F, Sporer SM. Acute hematogenous infection following total hip and knee arthroplasty. J Arthroplasty 2014;29: 469e72. https://doi.org/10.1016/j.arth.2013.07.021. [9] Odum SM, Fehring TK, Lombardi AV, Zmistowski BM, Brown NM, Luna JT, et al. Irrigation and debridement for periprosthetic infections: does the organism matter? J Arthroplasty 2011;26:114e8. https://doi.org/10.1016/j.arth.2011.03.031.
5
[10] Koh IJ, Han S-B, In Y, Oh K-J, Lee D-H, Kim TK, et al. Open debridement and prosthesis retention is a viable treatment option for acute periprosthetic joint infection after total knee arthroplasty. Arch Orthop Trauma Surg 2015;135: 847e55. https://doi.org/10.1007/s00402-015-2237-3. [11] Flierl MA, Culp BM, Okroj KT, Springer BD, Levine BR, Della Valle CJ. Poor outcomes of irrigation and debridement in acute periprosthetic joint infection with antibiotic-impregnated calcium sulfate beads. J Arthroplasty 2017;32: 2505e7. https://doi.org/10.1016/j.arth.2017.03.051. [12] Parvizi J, Della Valle CJ. AAOS Clinical Practice Guideline: diagnosis and treatment of periprosthetic joint infections of the hip and knee. J Am Acad Orthop Surg 2010;18:771e2. [13] Parvizi J, Gehrke T, Chen AF. Proceedings of the International Consensus on periprosthetic joint infection. Bone Joint J 2013;95-B:1450e2. https://doi.org/ 10.1302/0301-620X.95B11.33135. [14] Coburn B, Morris AM, Tomlinson G, Detsky AS. Does this adult patient with suspected bacteremia require blood cultures? JAMA 2012;308:502e11. https://doi.org/10.1001/jama.2012.8262. [15] Shapiro NI, Wolfe RE, Wright SB, Moore R, Bates DW. Who needs a blood culture? A prospectively derived and validated prediction rule. J Emerg Med 2008;35:255e64. https://doi.org/10.1016/j.jemermed.2008.04.001. [16] Klement MR, Siddiqi A, Rock JM, Chen AF, Bolognesi MP, Seyler TM. Positive blood cultures in periprosthetic joint infection decrease rate of treatment success. J Arthroplasty 2018;33:200e204.e1. https://doi.org/10.1016/ j.arth.2017.08.034. [17] Diaz-Ledezma C, Higuera CA, Parvizi J. Success after treatment of periprosthetic joint infection: a Delphi-based international multidisciplinary consensus. Clin Orthop 2013;471:2374e82. https://doi.org/10.1007/s11999013-2866-1. [18] van Daalen FV, Kallen MC, van den Bosch CMA, Hulscher MEJL, Geerlings SE, Prins JM. Clinical condition and comorbidity as determinants for blood culture positivity in patients with skin and soft-tissue infections. Eur J Clin Microbiol Infect Dis 2017;36:1853e8. https://doi.org/10.1007/s10096-017-3001-0. [19] Kuzyk PRT, Dhotar HS, Sternheim A, Gross AE, Safir O, Backstein D. Two-stage revision arthroplasty for management of chronic periprosthetic hip and knee infection: techniques, controversies, and outcomes. J Am Acad Orthop Surg 2014;22:153e64. https://doi.org/10.5435/JAAOS-22-03-153. [20] Triantafyllopoulos GK, Soranoglou V, Memtsoudis SG, Poultsides LA. Implant retention after acute and hematogenous periprosthetic hip and knee infections: whom, when and how? World J Orthop 2016;7:546e52. https:// doi.org/10.5312/wjo.v7.i9.546. [21] Choong PFM, Dowsey MM, Carr D, Daffy J, Stanley P. Risk factors associated with acute hip prosthetic joint infections and outcome of treatment with a rifampin-based regimen. Acta Orthop 2007;78:755e65. https://doi.org/ 10.1080/17453670710014527. [22] Azzam KA, Seeley M, Ghanem E, Austin MS, Purtill JJ, Parvizi J. Irrigation and debridement in the management of prosthetic joint infection: traditional indications revisited. J Arthroplasty 2010;25:1022e7. https://doi.org/10.1016/ j.arth.2010.01.104. [23] Buller LT, Sabry FY, Easton RW, Klika AK, Barsoum WK. The preoperative prediction of success following irrigation and debridement with polyethylene exchange for hip and knee prosthetic joint infections. J Arthroplasty 2012;27: 857e64. https://doi.org/10.1016/j.arth.2012.01.003. e1-4. [24] Tande AJ, Palraj BR, Osmon DR, Berbari EF, Baddour LM, Lohse CM, et al. Clinical presentation, risk factors, and outcomes of hematogenous prosthetic joint infection in patients with Staphylococcus aureus bacteremia. Am J Med 2016;129:221. https://doi.org/10.1016/j.amjmed.2015.09.006. e11-20. [25] Lora-Tamayo J, Murillo O, Iribarren JA, Soriano A, S anchez-Somolinos M, Baraia-Etxaburu JM, et al. A large multicenter study of methicillin-susceptible and methicillin-resistant Staphylococcus aureus prosthetic joint infections managed with implant retention. Clin Infect Dis 2013;56:182e94. https:// doi.org/10.1093/cid/cis746.
5.e1
F.-C. Kuo et al. / The Journal of Arthroplasty xxx (2019) 1e5
Appendix Appendix 1 The Elixhauser Comorbidity Index by International Classification of Diseases Ninth Revision/Tenth Revision, Clinical Modification (ICD-9-CM, ICD-10-CM). Comorbidities
ICD-9-CM
ICD-10-CM
Congestive heart failure
398.91, 402.01, 402.11, 402.91, 404.01, 404.03, 404.11, 404.13, 404.91, 404.93, 428.x 426.10, 426.11, 426.13, 426.2-426.53, 426.6-426.8, 427.0, 427.2, 427.31, 427.60, 427.9, 785.0, V45.0, V53.3 93.2, 394.x-397.1, 397.9, 424.x, 746.3-746.6, V42.2, V43.3 416.x, 417.9 440.x, 441.x, 442.x, 443.1-443.9, 447.1, 557.1, 557.9, V43.4 401.0, 401.1, 401.9, 402.x-405.x, 642.0-642.2, 642.7, 642.9 342.x-344.x, 438.2-438.5
I09.9, I11.0, I13.0, I13.2, I25.5, I42.0, 142.5-I42.9, I43.x, I50.x, P29.0 I44.1-I44.3, I45.6, I45.9, I47.x-I49.x, ROO.O, ROO.1, ROO.8, T82.1, Z45.0, Z95.0
Cardiac arrhythmias
Valvular disease Pulmonary circulation disorders Peripheral vascular disorders Hypertension Paralysis Other neurologic disorders
330.x-331.x, 332.0, 333.4, 333.5, 334.x, 335.x, 340, 341.1-341.9, 345.x, 347.x, 780.3, 784.3
Chronic pulmonary disease
490x-492.x, 493.x, 494x-505.x, 506.4
Diabetes, uncomplicated
250.0-250.3, 648.0
Diabetes, complicated
250.4-250.7, 250.9
Hypothyroidism Renal failure
Metastatic cancer Solid tumor without metastasis
243-244.2, 244.8, 244.9 403.01, 403.11, 403.91, 404.02, 404.03, 404.12, 404.13, 404.92, 404.93, 585.x, 586.x, V42.0, V45.1, V56.x 70.22, 70.23, 70.32, 70.33, 70.44, 70.54, 456.0, 456.1, 456.20, 571.0, 571.2-571.9, 572.3, 572.8, V42.7 531.41, 531.51, 531.61, 531.7, 531.91, 532.41, 532.51, 532.61, 532.7, 532.91, 533.41, 533.51, 533.61, 533.7, 533.91, 534.41, 534.51, 534.61, 534.7, 534.91 042.x-044.x 200.x-202.3, 202.5-203.0, 203.8, 238.6, 273.3, V10.71, V10.72, V10.79 196.x-199.x 140.x-172.x, 174.x, 175.x, 179.x-195.x, V10.x
Rheumatoid arthritis/collagen vascular diseases
701.0, 710.x, 714.x, 720.x, 725.x
Coagulopathy Obesity Weight loss Fluid and electrolyte disorders Blood loss anemia Deficiency anemia Alcohol abuse
286.x, 287.1, 287.3-287.5 278.0 260.x-263.x, 783.2 276.x 280.0, 648.2 280.1-281.9, 285.2, 285.9 291.0-291.3, 291.5, 291.8, 291.9, 303.x, 305.0, V113
Drug abuse
292.0, 292.82-292.89,292.9, 304.x,305.2-305.9, 648.3 295.x-298.x, 299.1 300.4, 301.12, 309.0, 309.1, 311
Liver disease Peptic ulcer disease excluding bleeding
AIDS/HIV Lymphoma
Psychoses Depression
A52.0, I05.x-I08.x, I09.1, I09.8, I34.x-I39.x, Q23.OQ23.3, Z95.2, Z95.4 I26.x, I27.x, I28.0, I28.8, I28.9 I70.x, I71.x, I73.1, I73.8, I73.9, I77.1, I79.0, I79.2, K55.1, K55.8, K55.9, Z95.8, Z95.9 I10.x, I11.x-I13.x, I15.x G04.1, G11.4, G80.1, G80.2, G81.x, G82.x, G83.0G83.4, G83.9 G10.x-G 13.x, G20.x-G22.x, G25.4, G25.5, G31.2, G31.8, G31.9, G32.x, G35.x-G37.x, G40.x, G41.x, G93.1, G93.4, R47.0, R56.x I27.8, 127.9, J40.x-J47.x, J60.x-J67.x, J68.4, J70.1, J70.3 E10.0, E10.1, E10.9, E11.0, E11.1, E11.9, E12.0, E12.1, E12.9, E13.0, E13.1, E13.9, E14.0, E14.1, E14.9 E10.2eE10.8, E11.2eE11.8, E12.2eE12.8, E13.2 eE13.8, E14.2eE14.8 E00.x-E03.x, E89.0 I12.0, I13.1, N18.x, NI9.x, N25.0, Z49.0-Z49.2, Z94.0, Z99.2 B18.x, I85.x, I86.4, I98.2, K70.x, K71.1, K71.3eK71.5, K71.7, K72.xeK74.x, K76.0, K76.2eK76.9, Z94.4 K25.7, K25.9, K26.7, K26.9, K27.7, K27.9, K28.7, K28.9
B20.x-B22.x, B24.x C81.x-C85.x, C88.x, C96.x, C90.0, C90.2 C77.x-C80.x C00.x-C26.x, C30.x-C34.x, C37.x-C41.x, C43.x, C45.x-C58.x, C60.x-C76.x, C97.x L94.0, L94.1, L94.3, M05.x, M06.x, M08.x, M12.0, M12.3, M30.x, M31.0-M31.3, M32.x-M35.x, M45.x, M46.1, M46.8, M46.9 D65-D68.x, D69.1, D69.3-D69.6 E66.x E40.x-E46.x, R63.4, R64 E22.2, E86.x, E87.x D50.0 D50.8, D50.9, D51.x-D53.x F10, E52, G62.1, I42.6, K29.2, K70.0, K70.3, K70.9, T51.x, Z50.2, Z71.4, Z72.1 F11.x-F16.x, F18.x, F19.x, Z71.5. Z72.2 F20.x, F22.x-F25.x, F28.x, F29.x, F30.2, F31.2, F31.5 F20.4, F31.3-F31.5, F32.x, F33.x, F34.1, F41.2, F43.2