- Email: [email protected]
Acceptable Success Rate in Patients With Periprosthetic Knee Joint Infection Treated With Debridement, Antibiotics, and Implant Retention
Accepted Manuscript Acceptable success rate in patients with periprosthetic knee joint infection treated with debridement, antibiotics and implant retention Casper Ottesen, MD, Anders Troelsen, MD, DMSc, PhD, Håkon Sandholdt, Steffen Jacobsen, MD, DMSc, PhD, Henrik Husted, MD, DMSc, PhD, Kirill Gromov, MD, PhD PII:
S0883-5403(18)30871-4
DOI:
10.1016/j.arth.2018.09.088
Reference:
YARTH 56855
To appear in:
The Journal of Arthroplasty
Received Date: 23 May 2018 Revised Date:
25 September 2018
Accepted Date: 26 September 2018
Please cite this article as: Ottesen C, Troelsen A, Sandholdt H, Jacobsen S, Husted H, Gromov K, Acceptable success rate in patients with periprosthetic knee joint infection treated with debridement, antibiotics and implant retention, The Journal of Arthroplasty (2018), doi: https://doi.org/10.1016/ j.arth.2018.09.088. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Acceptable success rate in patients with periprosthetic knee joint infection treated
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with debridement, antibiotics and implant retention.
Casper Ottesen, MD
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Griffenfeldsgade 4B, 4.tv, 2200 Copenhagen, Denmark Phone: +45 20932792 Department of Orthopedic Surgery, Copenhagen University Hospital, Hvidovre. [email protected]
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Anders Troelsen, MD, DMSc, PhD Department of Orthopedic Surgery, Copenhagen University Hospital, Hvidovre. Håkon Sandholdt Department of Orthopedic Surgery, Copenhagen University Hospital, Hvidovre.
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Steffen Jacobsen, MD, DMSc, PhD Department of Orthopedic Surgery, Copenhagen University Hospital, Hvidovre.
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Henrik Husted, MD, DMSc, PhD Department of Orthopedic Surgery, Copenhagen University Hospital, Hvidovre.
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Kirill Gromov, MD, PhD Department of Orthopedic Surgery, Copenhagen University Hospital, Hvidovre.
ACCEPTED MANUSCRIPT 1
Acceptable success rate in patients with periprosthetic knee joint infection
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treated with debridement, antibiotics and implant retention.
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Methods and patients: Sixty-seven patients with PJI following primary TKA surgery treated with DAIR were identified. Patients with insufficient data and patients that did not fulfill MSIS PJI criteria were excluded, leaving 58 patients for analysis. Minimum follow-up was 2 years. A DAIR was considered a success if the patient was infection-free after 2 years. Results: The overall success rate of PJI treated with DAIR was 84%. Median time until DAIR was 21 days (7-1092). Thirty-four patients (59%) were revised within 28 days, 42 patients (72%) within 42 days, while 10 patients (17%) were revised more than 90 days after primary TKA surgery. The success rates were 85%, 88% and 60% respectively. In the patients revised within 90 days our success rate was 90%(43/48) regardless of the involved microorganism.
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Conclusion: We find DAIR to be a viable and safe treatment option for PJI following primary TKA surgery, when performed early after primary surgery and with the addition of a relevant post revision antibiotic regime. Keywords: Acute periprosthetic joint infection; revision knee arthroplasty; timing; prosthesis retention; Debridement.
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Abstract: Background: Acute periprosthetic joint infection (PJI) following primary TKA surgery can be treated with debridement, antibiotics and implant retention (DAIR). However, varying results have been reported in the literature and optimal timing of the procedure is still debated. In this retrospective cohort study we investigate a) success rate of DAIR for treating PJI following primary TKA surgery and b) whether time after primary surgery until DAIR and c) type of isolated microorganism influences outcome.
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ACCEPTED MANUSCRIPT Background.
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Although aseptic loosening of the prosthesis still accounts for the overall most frequent cause of the
45
revision surgery following primary TKA, PJI is the leading cause of early revision [1, 2]. PJI is a rare
46
event, but costly and with major consequences for the patient [3]. Consequently identifying risk
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factors for the development of PJI is of particular interest. Age, ASA score, diabetes mellitus, reumatoid
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arthritis and steroid therapy have all previously been suspected to be isolated risk factors, while the
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presence of malignancy has also been suspected to increase the risk of PJI [4-8]. Because of very
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different outcomes in success rates following TKA revision surgery, a number of peroperative factors
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have been subjected to investigation: the involved microorganism, whether or not to exchange the
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polyliner, the postoperative antibiotic regime, time interval from primary surgery to revision (joint
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age), as well as time from debut of symptoms until revision surgery [1, 9-14].
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Acute PJI following primary TKA can be treated with debridement, antibiotics and implant retention
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(DAIR), with various success rates reported, varying from 9% to 80% [7, 10]. Recently published
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studies continue to show these discrepancies in successful outcome (44%-75%) and the role of
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optimal timing of DAIR, antibiotic regime, the involved microorganism and whether or not to exhange
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the polyliner is still unclear [9, 12].
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Different guidelines suggest DAIR as a treatment option only in patients with joint age under 30 days
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and duration of symptoms under 3 weeks [15]. However 84% of the delegates at a consensus meeting
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in 2014 agreed to a 90 days joint age cut-off with ongoing symptoms of joint infection under 3 weeks
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for DAIR with retention of the prosthesis [16].
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The involved microorganism and the chosen post revision antibiotic regime is believed to have major
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influence on a successful long term outcome, primarily in cases where Staphyloccocus aureus is found
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to be the culprit [17]. Thus optimal timing and the role of the infecting pathogene remains unclear.
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The aim of this study was to investigate the success rate of DAIR for treating PJI following primary
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ACCEPTED MANUSCRIPT 69
TKA surgery. And secondly whether joint age and type of isolated microorganism influences outcome.
70 Methods and patients.
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All patients that underwent primary TKA at our institution and were subsequently treated with DAIR,
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from January 2008 until June 2013, due to infection were included in the study. Complete dataset
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was available in 62 patients and 4 patients were excluded as they did not meet the MSIS infection
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diagnostic criteria [18], leaving 58 patients for analysis, n=58. Patient related and surgery related
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parameters were registered, including: Age, ASA score, BMI, joint age, and type of microorganism
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involved.
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Primary outcome was infection eradication at 2 years following DAIR. Time from primary
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TKA surgery until revision surgery with DAIR was registered in days.
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A DAIR was considered a success if the patient did not receive antibiotic treatment and had not
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undergone further revision surgery 2 years following DAIR according to their medical records.
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Primary surgery as well as DAIR was performed using a standard operating setup at our institution.
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Preoperatively, the surgical site was disinfected twice with 83% ethyl-alcohol with 0.5%
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chlorhexidine-digluconate coloured with curcumine allowing drying up in between applications.
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Primary surgery as well as revision surgery was performed in operating theaters that uses positive
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pressure ventilation with shifting of the air 20 times/hour. During revision surgery, joint fluid was
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retreived, as well as tissue samples ad modum Kamme were collected for investigation of involved
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microorganism. Neither torniquet, nor drains were used during primary as well as DAIR surgery.
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Polyethylene was exchanged if possible, depending on the implant design (polyethylene liner was
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changed in modular tibial components, while this was not possible in molded monoblock tibial
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components). Previous medial parapatella incision was used and the wound was debrided. After tissue
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samling and removal of the polyethylene liner, systematic debridement was perfomed with
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debridement of all infected synovium. The joint was irrigated with 3L saline mixed with 0,24 g/L
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ACCEPTED MANUSCRIPT gentamicin. Two gentamicin-loaded collagen fleeces (Gentafleece) were placed intraarticularly prior
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to standard 3 layer closure.
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In line with regional guidelines patients were administered antibiotics intravenously for two weeks
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after surgery, followed by at least four weeks of additional peroral antibiotics until clinical and
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paraclinical infection eradication. Antibiotics were chosen based on the identified pathogen.
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Cefuroxime was used as postoperative intravenously antiobiotic if the pathogen was not known prior
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to DAIR surgery.
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102 Statistics.
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Chi square test was applied for contingency tables, if the number of observations was lower than 5 for
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a cell, then Fisher´s exact test was applied to compute p-values. In case of larger contengency tabels
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monte carlo method was applied to simulate p-values. For numeric outcomes mean or median was
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used when apporiate, t-test was used to compute p-values.
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108 Results.
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Median time until DAIR was 21 days (7-1092). Overall succes rate of DAIR after two years was 84%
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(Table 1). Successes and failures did not differ with respect to ASA-score, Diabetes mellitus, gender or
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BMI (Table 1). The polyethylene component was exchanged in 31% (18/58) of the patients.
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There was no difference in succes rates when performing DAIR within 28 (85%) and 42 days (88%)
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(Table 1, p =1, p=0.24). The success rate was significantly lower when performing DAIR later than 90
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days (60%)(p=0.0387).
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Duration of antibiotic treatment mean was 81.4 days (7-137). We are not able to explain the 7 day
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outlier.
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The relationship between success rate and the diagnosed microorganism is presented in Table 2.
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None of seven patients with a sinus tract present at the time of revision surgery had undergone re-
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revision within the two years follow-up period.
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ACCEPTED MANUSCRIPT Staphylococcus aureus was the most common microorganism found ((29/58), 50%). No cases of
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methicillin-resistant Staphylococcus aureus (MRSA) were found (Table 2).
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Postoperatively rifampicin was added in 38% (11/29) of the cases where Staphylococcus aureus was
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isolated. Out of the 29 patients with Staphylococcus aureus, 76% (22/29) received dicloxacillin
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postoperatively either as monotherapy or in combination with other antibiotics. Our overall success
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rate in PJIs where Staphylococcus aureus was isolated as causing agent was 89% (26/29)(table 2). The
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success rate in patients with coagulase-negative staphylococcus was 87% (7/8).
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Discussion.
In this retrospective single center cohort study we present an overall success rate of 84% (49/58) on
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128 129 130 131
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DAIR in patients with PJI, with infection eradication at 2 year follow up as primary outcome. We found
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no difference in success rates when performing DAIR within 28 (85%)(P=1) and 42 days
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(88%)(P=0.2428), while the success rate was significantly lower when performing DAIR later then 90
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days (60%)(p=0.0387). These results represent a much better outcome and chance of prosthetic
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retention compared to a study at our institution two decades ago, which may be attributable to
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different bacteriology, different antibiotic treatment, different surgical technique or a combination
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hereof [10]. The nature of this and the earlier study does not allow for determination as to why the
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outcome differs, but may represent a shift from always recommending the two-stage solution to a
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more balanced differentiated approach allowing DAIR, one stage or two stage solutions depending on
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the specific situation.
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Recent studies by Holmberg et al and Peel et al have found similar results, with success rates, at the
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two year follow up, of 75% and 77% respectively [9, 19]. Holmberg et als data is based upon
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nationwide data on patients undergoing DAIR, where the tibial insert was exchanged. As in our study,
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Holmberg et al isolated no strains of MRSA.
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Peel et al investigated solely patients in which MRSA was isolated in two or more intraoperative
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specimens and subjected them to a treatment regime of repeated arthrotomies with pulsatile lavage.
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ACCEPTED MANUSCRIPT The success rates presented by Holmberg et al and Peel et al, as well as the success rate found in our
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study, differ from another recent study that reported a success rate of 44% [12], as well as when
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comparing them to a multiple series of earlier studies sumarised by Rand in 1993, who reported an
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overall success rate of 29% [11].
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Azzam et al looked at PJI and subsequent DAIR in both hip and knee replacement patients. They did
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not comment on their postoperative antibiotic regime, but noted that their results tended towards a
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lower success rate, in patients where MRSA was the isolated microorganism.
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Timing of surgery is being debated and two parameters are suspected to be of importance: joint age
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and duration of symptoms. Different guidelines suggest DAIR as a treatment option only in patients
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with joint age under 30 days and duration of symptoms under 3 weeks [15]. Duration of symptoms
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was not available for evaluation in our case.
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Although no difference in success rate could be found when comparing PJIs revised within 28 days
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(85%)(p=1) and PJIs revised within 42 days (88%)(p=0.2428), we found that revision after 90 days
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was associated with a significantly higher failure rate (60%)(p=0.0387). This supports sustaining a 30
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day cut-off after primary surgery for this procedure suggested by Osmon et al, though our results
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suggests a cut-off possible up to 42 days after primary TKA surgery would be within a safe margin
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[15].
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In our study the polyliner was exchanged when possible due to the design of the implant. Exchange of
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the polyliner was possible in 31% (18/58) of the cases. We could not find any relationship between
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success rate and exchanging the polyliner (Table 1)(p=0.4380). This differs from findings by Choi et al
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who suggested possible correlation between retention of the polyliner and increased failure rates [13].
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Choi et als findings were, as in our case, based on retrospectively collected data. They were not able to
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identify and comment on in which cases and why, or why not, the liner had been exchanged
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peroperatively.
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ACCEPTED MANUSCRIPT Our microbiological findings, with Staphyloccocus aureus being the most frequent microorganism, is
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similar to most other studies [8, 9, 20]. It is important to note that we did not isolate any methicillin-
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resistant Staphylococcus aureus in any of our cases.
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Although MRSA is on the rise in our country, discovering MRSA as the culprit in a periprostetic
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infection, is still rare compared with other countries. Some of the major differences in a successful
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outcome, when treating PJI with DAIR in patients infected with Staphyloccocus aureus, might be due to
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these regional differences in the presence of these higher virulence methicillin-resistant strains. A
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future rise in PJIs as a result of MRSA national or at our institution would most possibly lead us to
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reinvestigate DAIR in relation to this change in microbiological findings.
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Choi et al as well as Brandt et al found identification of Staphylococcus aureus as involved
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microorganism to correlate with increased failure rates [5,13]. Deirminigan showed a 65% success
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rate with DAIR, with an only 8% success rate, when looking only at Staphylococcus aureus. At least
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some of the difference in outcome might be related to the fact that four out of the twelve failures were
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with MRSA as the microbiological finding [7].
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Although Staphylococcus aureus, as noted, has been associated with poorer outcome of DAIR, no such
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relation could be found in our study [5,12,13,21].
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Meehan et al found a 89.5% success rate when looking at penicillin-susceptible streptococcal
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prosthetic joint infections treated with debridement and retention of the prosthesis in 29 patients
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revised within 30 days of primary surgery [22]. We found a 75% (12/16) success rate when looking at
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streptococcal species alone (Table 2).
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The importance of the antibiotic regime is also under evaluation. Holmberg et al found favorable
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outcomes of DAIR (75%) and suggested, among other factors, individualised antibiotic regime post
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revision to be a possible factor in successful outcome [9]. Our findings support an individualised
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antibiotic regime but we also suggest regional differences in microbiological findings, and bacteria
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with different susceptibility to the postoperative antibiotic regime, to be part of the explanation for the
198
big differences in the presented success rates in the literature.
199 There are several limitiations to our study: First, this is a retrospective study with associated
201
inaccuracies in reporting. Second, whilst we recorded ASA score, BMI and DM, we did not record other
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factors potentially affecting the outcome such as cancer, RA and use of steroids.
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Unfortunately it was not possible for us to retreive information as to when the patients first reported
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symptoms of PJI. This would have been interesting in comparing our findings with findings from other
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earlier studies. Duration of symptoms is often used as a factor in deciding whether or not to perform
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DAIR.
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Our results are susceptible to selection bias, and the low success rate of DAIR performed after 90 days
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following primary surgery can be due to patient selection: i.e: sicker patients who are not suitable for
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two stage revision could receive DAIR >90 days.
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In terms of evaluating the success of DAIR in patients with PJI, the diagnosis criteria for identifying
211
patients with DAIR and criteria for a successful outcome must be comparable between performed
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studies. In our study we decided to follow the diagnosis criteria of the MSIS. Even though these criteria
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are associated with a high specificity, infections due to microorganisms like coagulasis-negative
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staphylococcus might be under-diagnosed in this study because of its low virulence [17].
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Further long-term follow-up would be of interest in order to possibly identify slow low-virulence
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infections, that might present itself later than our two years follow-up.
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200
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We present an overall success rate of 84% in the included 58 patients in this study, with a minimum
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follow-up of two years. In the patients revised within 90 days our success rate was 90% regardless of
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the involved microorganism. Therefore we find DAIR to be a viable and safe treatment option, when
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timed correctly and with the addition of a relevant post revision antibiotic regime [14, 20].
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ACCEPTED MANUSCRIPT References: [1] Portillo ME, Salvadó M, Alier A, Sorli L, Martínez S, Horcajada JP, Puig L. Prosthesis failure within 2 years of implantation is highly predictive of infection. Clin Orthop Relat Res 2013; 471(11): 3672–8. [2] Dalury D F, Pomeroy D L, Gorab R S, Adams M J. Why are total knee arthroplasties being revised? J Arthroplasty 2013; 28(8 Suppl): 120–1.
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[3] Zimmerli et al. Prosthetic joint infections, N Engl J Med 2004;351:1645-54. [4] Berbari EF, Hanssen AD, Duffy MC, Steckelberg JM, Ilstrup DM, Harmsen WS, Osmon DR. Risk factors for prosthetic joint infection: Case-control study. Clin Infect Dis 1998; 1247-1254. [5] Brandt CM, Sistrunk WW, Duffy MC, et al. Staphyloccocus aureus prostetic joint infection treated with debridement and prosthesis retention. Clin Infect Dis 1997;24:914-9
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[6] Silva M, Tharani R, Schmalzried TP. Results of direct exchange or debridement of the infected total knee arthroplasty. Clin Orthop relat Res 2002; 125.
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[7] Deirminigan C. Limited success with open debridement and retention of components in the treatment of acute Staphylococcus Aureus infections after total knee arthroplasty. The Journal of Arthroplasty Vol 18 No 7 Suppl 1 2003. [8] Tattevin P, Cremieux AC, Pottier P et al. Prosthetic joint infection: when can prothesis salvage be considered? Clin Infect Dis 1999; 29: 292. [9] Holmberg, A, Thórhallsdóttir VG, Robertsson O, W-Dahl A , Stefánsdóttir A. 75% success rate after open debridement, exchange of tibial insert, and antibiotics in knee prosthetic joint infections, Report on 145 cases from the Swedish Knee Arthroplasty Register, Acta Orthopaedica 2015; 86 (4): 457–462
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[10] Husted H, Toftgaard Jensen T. Clinical outcome after treatment of infected primary total knee arthroplasty. Acta Orthop Belg. 2002 Dec;68(5):500-7. [11] Rand JA. Alternatives to reimplantation for salvage of the total knee arthroplasty complicated by infection. J Bone Joint Surg Am 1993; 75(2): 282–9.
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[12] Azzam KA. Irrigation and debridement in the Management of Prosthetic Joint Infection. Traditional Indications revisited. The Journal of Arthroplasty Vol 25 No 7 October 2010 [13] Choi H-R, von Knoch F, Zurakowski D, Nelson S B, Malchau H. Can implant retention be recommended for treatment of infected TKA? Clin Orthop Relat Res 2011; 469(4): 961–9.
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223 224 225 226 227 228 229 230 231 232 233 234 235 236 237 238 239 240 241 242 243 244 245 246 247 248 249 250 251 252 253 254 255 256 257 258 259 260 261 262 263 264 265 266 267 268 269 270 271 272 273 274 275 276 277 278 279
[14] Mont MA. Multiple Irrigation, Debridement, and Retention of Components in Infected Total Knee Arthroplasty, The Journal of Arthroplasty Vol. 12 No. 4 1997 [15] Osmon DR, Berbari E F, Berendt A R, et al. Diagnosis and management of prosthetic joint infection: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis 2013; 56(1): 1–25. [16] Haasper C et al. Irrigation and debridement. Inc. J Orthop Res 32:S130–S135, 2014. [17] Zimmerli W, Widmer A, Blatter M, Frei R, Ochsner PE. Role of rifampin for treatment of orthopedic implant related staphylococcal infections. JAMA 1998; 279:1537–41. [18] Parvizi J, Zmistowski B, Berbari EF, Bauer TW, Springer BD, Della Valle CJ, Garvin KL, Mont MA, Wongworawat MD, Zalavras CG. New Definition for Periprosthetic Joint Infection: From the Workgroup of the Musculoskeletal Infection Society. Clin Orthop Relat Res. 2011 Nov; 469(11): 2992–2994.
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ACCEPTED MANUSCRIPT [19] Peel T N, Buising KL, Dowsey M, Aboltins CA, Daffy JR, Stanley PA, Choong PFM. Outcome of debridement and retention in prosthetic joint infections by methicillin-resistant staphylococci, with special reference to rifampin and fusidic acid combination therapy. Antimicrob Agents Chemother 2013; 57(1): 350–5. [20] Geurts JAP, Janssen DMC, Kessels AGH, Walenkamp GHIM. Good results in postoperative and hematogenous deep infections of 89 stable hip and knee replacements with retention of prosthesis and local antibiotics. Acta Orthopaedica 2013; 84(6):509-516.
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[21] Schoifet SD and Morrey BF. Treatment of infection after total knee arthroplasty by debridement with retention of the components. J Bone Joint Surg AM 1990; 72: pp.1383.
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[22] Meehan AM, Osmon DR, Duffy MC, Hanssen AD, Keating M. Outcome of penicillin-susceptible streptococcal prosthetic joint infection treated with debridement and retention of the prosthesis. Clin Infect Dis 2003; 36:8459
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280 281 282 283 284 285 286 287 288 289 290 291 292 293 294 295 296
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ACCEPTED MANUSCRIPT Table 1 (n=58).
<25 25-30 >30 1 2 3 Yes No Yes
Success (%) 23 (76%) 26 (92%) 66.7 8 (72%) 22 (91%) 19 (83%) 9 (82%) 30 (83%) 10 (90%) 8 (89%) 41 (84%) 29 (85%)
Failure (%) 7 (24%) 2 (8%) 64.3 3 (28%) 2 (9%) 4 (17%) 2 (18%) 6 (17%) 1 (10%) 1 (11%) 8 (16%) 5 (15%)
No Yes
20 (82%) 37 (88%)
4 (18%) 5 (12%)
0.2428
No Yes
12 (75%) 6 (60%)
4 (25%) 4 (40%)
0.0387
No Yes No Yes
43 (90%) 14 (78%) 35 (90%) 47 (85%)
5 (10%) 4 (22%) 5 (10%) 8 (15%)
No
2 (67%) 49 (84%)
1 (33%) 9 (16%)
ASA score
DM Revised within 28 days Revised within 42 days Revised after 90 days Poly exchange Post op AB effective
0.3240 0.3541
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Age (mean) BMI
p-value 0.1468
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Male Female
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Total
0.8919
1.000
1.000
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Gender
0.4380 0.4029
ACCEPTED MANUSCRIPT
Table 2 (n=58).
•
Success 89 % (26/29) 87 % (7/8) 75 % (12/16) No re-revision No re-revision No re-revision Re- Revised No re-revision No re-revision No re-revision No re-revision No re-revision
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No 29 8 16 3 1 1 1 1 1 1 1 1
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Microorganism Staph. aureus Con staph. Streptococcus Enterococcus Enterobacter cloacae Parvomonas micra Klebsiella pneumoniae Pseudomonas E.coli Corynebacterium spp Citrobacter freundii Staph capitis
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Two patients had positive cultures from preoperative wound-cultures with Staph. aureus and streptococcus and were given antibiotic treatment prior to surgery. These showed no microbiological findings from cultures and are therefore not part of the table above. ** In one patient both Streptococcus and Staph. aureus were found. Rifampicin was added post-revision. No re-revision was performed. *** One patient was re-revised without any data of the initially involved microorgamism although 5 positiv cultures were found.
S0883-5403(18)30871-4
DOI:
10.1016/j.arth.2018.09.088
Reference:
YARTH 56855
To appear in:
The Journal of Arthroplasty
Received Date: 23 May 2018 Revised Date:
25 September 2018
Accepted Date: 26 September 2018
Please cite this article as: Ottesen C, Troelsen A, Sandholdt H, Jacobsen S, Husted H, Gromov K, Acceptable success rate in patients with periprosthetic knee joint infection treated with debridement, antibiotics and implant retention, The Journal of Arthroplasty (2018), doi: https://doi.org/10.1016/ j.arth.2018.09.088. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Acceptable success rate in patients with periprosthetic knee joint infection treated
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with debridement, antibiotics and implant retention.
Casper Ottesen, MD
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Griffenfeldsgade 4B, 4.tv, 2200 Copenhagen, Denmark Phone: +45 20932792 Department of Orthopedic Surgery, Copenhagen University Hospital, Hvidovre. [email protected]
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Anders Troelsen, MD, DMSc, PhD Department of Orthopedic Surgery, Copenhagen University Hospital, Hvidovre. Håkon Sandholdt Department of Orthopedic Surgery, Copenhagen University Hospital, Hvidovre.
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Steffen Jacobsen, MD, DMSc, PhD Department of Orthopedic Surgery, Copenhagen University Hospital, Hvidovre.
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Henrik Husted, MD, DMSc, PhD Department of Orthopedic Surgery, Copenhagen University Hospital, Hvidovre.
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Kirill Gromov, MD, PhD Department of Orthopedic Surgery, Copenhagen University Hospital, Hvidovre.
ACCEPTED MANUSCRIPT 1
Acceptable success rate in patients with periprosthetic knee joint infection
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treated with debridement, antibiotics and implant retention.
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Methods and patients: Sixty-seven patients with PJI following primary TKA surgery treated with DAIR were identified. Patients with insufficient data and patients that did not fulfill MSIS PJI criteria were excluded, leaving 58 patients for analysis. Minimum follow-up was 2 years. A DAIR was considered a success if the patient was infection-free after 2 years. Results: The overall success rate of PJI treated with DAIR was 84%. Median time until DAIR was 21 days (7-1092). Thirty-four patients (59%) were revised within 28 days, 42 patients (72%) within 42 days, while 10 patients (17%) were revised more than 90 days after primary TKA surgery. The success rates were 85%, 88% and 60% respectively. In the patients revised within 90 days our success rate was 90%(43/48) regardless of the involved microorganism.
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Conclusion: We find DAIR to be a viable and safe treatment option for PJI following primary TKA surgery, when performed early after primary surgery and with the addition of a relevant post revision antibiotic regime. Keywords: Acute periprosthetic joint infection; revision knee arthroplasty; timing; prosthesis retention; Debridement.
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Abstract: Background: Acute periprosthetic joint infection (PJI) following primary TKA surgery can be treated with debridement, antibiotics and implant retention (DAIR). However, varying results have been reported in the literature and optimal timing of the procedure is still debated. In this retrospective cohort study we investigate a) success rate of DAIR for treating PJI following primary TKA surgery and b) whether time after primary surgery until DAIR and c) type of isolated microorganism influences outcome.
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ACCEPTED MANUSCRIPT Background.
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Although aseptic loosening of the prosthesis still accounts for the overall most frequent cause of the
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revision surgery following primary TKA, PJI is the leading cause of early revision [1, 2]. PJI is a rare
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event, but costly and with major consequences for the patient [3]. Consequently identifying risk
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factors for the development of PJI is of particular interest. Age, ASA score, diabetes mellitus, reumatoid
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arthritis and steroid therapy have all previously been suspected to be isolated risk factors, while the
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presence of malignancy has also been suspected to increase the risk of PJI [4-8]. Because of very
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different outcomes in success rates following TKA revision surgery, a number of peroperative factors
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have been subjected to investigation: the involved microorganism, whether or not to exchange the
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polyliner, the postoperative antibiotic regime, time interval from primary surgery to revision (joint
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age), as well as time from debut of symptoms until revision surgery [1, 9-14].
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Acute PJI following primary TKA can be treated with debridement, antibiotics and implant retention
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(DAIR), with various success rates reported, varying from 9% to 80% [7, 10]. Recently published
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studies continue to show these discrepancies in successful outcome (44%-75%) and the role of
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optimal timing of DAIR, antibiotic regime, the involved microorganism and whether or not to exhange
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the polyliner is still unclear [9, 12].
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Different guidelines suggest DAIR as a treatment option only in patients with joint age under 30 days
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and duration of symptoms under 3 weeks [15]. However 84% of the delegates at a consensus meeting
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in 2014 agreed to a 90 days joint age cut-off with ongoing symptoms of joint infection under 3 weeks
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for DAIR with retention of the prosthesis [16].
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The involved microorganism and the chosen post revision antibiotic regime is believed to have major
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influence on a successful long term outcome, primarily in cases where Staphyloccocus aureus is found
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to be the culprit [17]. Thus optimal timing and the role of the infecting pathogene remains unclear.
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The aim of this study was to investigate the success rate of DAIR for treating PJI following primary
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TKA surgery. And secondly whether joint age and type of isolated microorganism influences outcome.
70 Methods and patients.
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All patients that underwent primary TKA at our institution and were subsequently treated with DAIR,
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from January 2008 until June 2013, due to infection were included in the study. Complete dataset
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was available in 62 patients and 4 patients were excluded as they did not meet the MSIS infection
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diagnostic criteria [18], leaving 58 patients for analysis, n=58. Patient related and surgery related
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parameters were registered, including: Age, ASA score, BMI, joint age, and type of microorganism
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involved.
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Primary outcome was infection eradication at 2 years following DAIR. Time from primary
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TKA surgery until revision surgery with DAIR was registered in days.
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A DAIR was considered a success if the patient did not receive antibiotic treatment and had not
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undergone further revision surgery 2 years following DAIR according to their medical records.
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Primary surgery as well as DAIR was performed using a standard operating setup at our institution.
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Preoperatively, the surgical site was disinfected twice with 83% ethyl-alcohol with 0.5%
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chlorhexidine-digluconate coloured with curcumine allowing drying up in between applications.
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Primary surgery as well as revision surgery was performed in operating theaters that uses positive
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pressure ventilation with shifting of the air 20 times/hour. During revision surgery, joint fluid was
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retreived, as well as tissue samples ad modum Kamme were collected for investigation of involved
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microorganism. Neither torniquet, nor drains were used during primary as well as DAIR surgery.
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Polyethylene was exchanged if possible, depending on the implant design (polyethylene liner was
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changed in modular tibial components, while this was not possible in molded monoblock tibial
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components). Previous medial parapatella incision was used and the wound was debrided. After tissue
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samling and removal of the polyethylene liner, systematic debridement was perfomed with
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debridement of all infected synovium. The joint was irrigated with 3L saline mixed with 0,24 g/L
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ACCEPTED MANUSCRIPT gentamicin. Two gentamicin-loaded collagen fleeces (Gentafleece) were placed intraarticularly prior
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to standard 3 layer closure.
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In line with regional guidelines patients were administered antibiotics intravenously for two weeks
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after surgery, followed by at least four weeks of additional peroral antibiotics until clinical and
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paraclinical infection eradication. Antibiotics were chosen based on the identified pathogen.
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Cefuroxime was used as postoperative intravenously antiobiotic if the pathogen was not known prior
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to DAIR surgery.
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102 Statistics.
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Chi square test was applied for contingency tables, if the number of observations was lower than 5 for
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a cell, then Fisher´s exact test was applied to compute p-values. In case of larger contengency tabels
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monte carlo method was applied to simulate p-values. For numeric outcomes mean or median was
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used when apporiate, t-test was used to compute p-values.
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Median time until DAIR was 21 days (7-1092). Overall succes rate of DAIR after two years was 84%
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(Table 1). Successes and failures did not differ with respect to ASA-score, Diabetes mellitus, gender or
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BMI (Table 1). The polyethylene component was exchanged in 31% (18/58) of the patients.
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There was no difference in succes rates when performing DAIR within 28 (85%) and 42 days (88%)
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(Table 1, p =1, p=0.24). The success rate was significantly lower when performing DAIR later than 90
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days (60%)(p=0.0387).
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Duration of antibiotic treatment mean was 81.4 days (7-137). We are not able to explain the 7 day
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outlier.
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The relationship between success rate and the diagnosed microorganism is presented in Table 2.
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None of seven patients with a sinus tract present at the time of revision surgery had undergone re-
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revision within the two years follow-up period.
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ACCEPTED MANUSCRIPT Staphylococcus aureus was the most common microorganism found ((29/58), 50%). No cases of
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methicillin-resistant Staphylococcus aureus (MRSA) were found (Table 2).
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Postoperatively rifampicin was added in 38% (11/29) of the cases where Staphylococcus aureus was
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isolated. Out of the 29 patients with Staphylococcus aureus, 76% (22/29) received dicloxacillin
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postoperatively either as monotherapy or in combination with other antibiotics. Our overall success
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rate in PJIs where Staphylococcus aureus was isolated as causing agent was 89% (26/29)(table 2). The
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success rate in patients with coagulase-negative staphylococcus was 87% (7/8).
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Discussion.
In this retrospective single center cohort study we present an overall success rate of 84% (49/58) on
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DAIR in patients with PJI, with infection eradication at 2 year follow up as primary outcome. We found
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no difference in success rates when performing DAIR within 28 (85%)(P=1) and 42 days
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(88%)(P=0.2428), while the success rate was significantly lower when performing DAIR later then 90
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days (60%)(p=0.0387). These results represent a much better outcome and chance of prosthetic
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retention compared to a study at our institution two decades ago, which may be attributable to
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different bacteriology, different antibiotic treatment, different surgical technique or a combination
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hereof [10]. The nature of this and the earlier study does not allow for determination as to why the
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outcome differs, but may represent a shift from always recommending the two-stage solution to a
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more balanced differentiated approach allowing DAIR, one stage or two stage solutions depending on
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the specific situation.
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Recent studies by Holmberg et al and Peel et al have found similar results, with success rates, at the
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two year follow up, of 75% and 77% respectively [9, 19]. Holmberg et als data is based upon
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nationwide data on patients undergoing DAIR, where the tibial insert was exchanged. As in our study,
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Holmberg et al isolated no strains of MRSA.
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Peel et al investigated solely patients in which MRSA was isolated in two or more intraoperative
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specimens and subjected them to a treatment regime of repeated arthrotomies with pulsatile lavage.
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ACCEPTED MANUSCRIPT The success rates presented by Holmberg et al and Peel et al, as well as the success rate found in our
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study, differ from another recent study that reported a success rate of 44% [12], as well as when
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comparing them to a multiple series of earlier studies sumarised by Rand in 1993, who reported an
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overall success rate of 29% [11].
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Azzam et al looked at PJI and subsequent DAIR in both hip and knee replacement patients. They did
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not comment on their postoperative antibiotic regime, but noted that their results tended towards a
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lower success rate, in patients where MRSA was the isolated microorganism.
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Timing of surgery is being debated and two parameters are suspected to be of importance: joint age
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and duration of symptoms. Different guidelines suggest DAIR as a treatment option only in patients
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with joint age under 30 days and duration of symptoms under 3 weeks [15]. Duration of symptoms
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was not available for evaluation in our case.
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Although no difference in success rate could be found when comparing PJIs revised within 28 days
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(85%)(p=1) and PJIs revised within 42 days (88%)(p=0.2428), we found that revision after 90 days
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was associated with a significantly higher failure rate (60%)(p=0.0387). This supports sustaining a 30
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day cut-off after primary surgery for this procedure suggested by Osmon et al, though our results
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suggests a cut-off possible up to 42 days after primary TKA surgery would be within a safe margin
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[15].
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In our study the polyliner was exchanged when possible due to the design of the implant. Exchange of
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the polyliner was possible in 31% (18/58) of the cases. We could not find any relationship between
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success rate and exchanging the polyliner (Table 1)(p=0.4380). This differs from findings by Choi et al
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who suggested possible correlation between retention of the polyliner and increased failure rates [13].
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Choi et als findings were, as in our case, based on retrospectively collected data. They were not able to
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identify and comment on in which cases and why, or why not, the liner had been exchanged
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peroperatively.
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ACCEPTED MANUSCRIPT Our microbiological findings, with Staphyloccocus aureus being the most frequent microorganism, is
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similar to most other studies [8, 9, 20]. It is important to note that we did not isolate any methicillin-
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resistant Staphylococcus aureus in any of our cases.
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Although MRSA is on the rise in our country, discovering MRSA as the culprit in a periprostetic
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infection, is still rare compared with other countries. Some of the major differences in a successful
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outcome, when treating PJI with DAIR in patients infected with Staphyloccocus aureus, might be due to
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these regional differences in the presence of these higher virulence methicillin-resistant strains. A
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future rise in PJIs as a result of MRSA national or at our institution would most possibly lead us to
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reinvestigate DAIR in relation to this change in microbiological findings.
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Choi et al as well as Brandt et al found identification of Staphylococcus aureus as involved
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microorganism to correlate with increased failure rates [5,13]. Deirminigan showed a 65% success
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rate with DAIR, with an only 8% success rate, when looking only at Staphylococcus aureus. At least
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some of the difference in outcome might be related to the fact that four out of the twelve failures were
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with MRSA as the microbiological finding [7].
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Although Staphylococcus aureus, as noted, has been associated with poorer outcome of DAIR, no such
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relation could be found in our study [5,12,13,21].
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Meehan et al found a 89.5% success rate when looking at penicillin-susceptible streptococcal
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prosthetic joint infections treated with debridement and retention of the prosthesis in 29 patients
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revised within 30 days of primary surgery [22]. We found a 75% (12/16) success rate when looking at
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streptococcal species alone (Table 2).
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The importance of the antibiotic regime is also under evaluation. Holmberg et al found favorable
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outcomes of DAIR (75%) and suggested, among other factors, individualised antibiotic regime post
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revision to be a possible factor in successful outcome [9]. Our findings support an individualised
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antibiotic regime but we also suggest regional differences in microbiological findings, and bacteria
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with different susceptibility to the postoperative antibiotic regime, to be part of the explanation for the
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big differences in the presented success rates in the literature.
199 There are several limitiations to our study: First, this is a retrospective study with associated
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inaccuracies in reporting. Second, whilst we recorded ASA score, BMI and DM, we did not record other
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factors potentially affecting the outcome such as cancer, RA and use of steroids.
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Unfortunately it was not possible for us to retreive information as to when the patients first reported
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symptoms of PJI. This would have been interesting in comparing our findings with findings from other
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earlier studies. Duration of symptoms is often used as a factor in deciding whether or not to perform
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DAIR.
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Our results are susceptible to selection bias, and the low success rate of DAIR performed after 90 days
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following primary surgery can be due to patient selection: i.e: sicker patients who are not suitable for
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two stage revision could receive DAIR >90 days.
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In terms of evaluating the success of DAIR in patients with PJI, the diagnosis criteria for identifying
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patients with DAIR and criteria for a successful outcome must be comparable between performed
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studies. In our study we decided to follow the diagnosis criteria of the MSIS. Even though these criteria
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are associated with a high specificity, infections due to microorganisms like coagulasis-negative
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staphylococcus might be under-diagnosed in this study because of its low virulence [17].
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Further long-term follow-up would be of interest in order to possibly identify slow low-virulence
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infections, that might present itself later than our two years follow-up.
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We present an overall success rate of 84% in the included 58 patients in this study, with a minimum
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follow-up of two years. In the patients revised within 90 days our success rate was 90% regardless of
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the involved microorganism. Therefore we find DAIR to be a viable and safe treatment option, when
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timed correctly and with the addition of a relevant post revision antibiotic regime [14, 20].
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ACCEPTED MANUSCRIPT References: [1] Portillo ME, Salvadó M, Alier A, Sorli L, Martínez S, Horcajada JP, Puig L. Prosthesis failure within 2 years of implantation is highly predictive of infection. Clin Orthop Relat Res 2013; 471(11): 3672–8. [2] Dalury D F, Pomeroy D L, Gorab R S, Adams M J. Why are total knee arthroplasties being revised? J Arthroplasty 2013; 28(8 Suppl): 120–1.
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[3] Zimmerli et al. Prosthetic joint infections, N Engl J Med 2004;351:1645-54. [4] Berbari EF, Hanssen AD, Duffy MC, Steckelberg JM, Ilstrup DM, Harmsen WS, Osmon DR. Risk factors for prosthetic joint infection: Case-control study. Clin Infect Dis 1998; 1247-1254. [5] Brandt CM, Sistrunk WW, Duffy MC, et al. Staphyloccocus aureus prostetic joint infection treated with debridement and prosthesis retention. Clin Infect Dis 1997;24:914-9
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[6] Silva M, Tharani R, Schmalzried TP. Results of direct exchange or debridement of the infected total knee arthroplasty. Clin Orthop relat Res 2002; 125.
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[7] Deirminigan C. Limited success with open debridement and retention of components in the treatment of acute Staphylococcus Aureus infections after total knee arthroplasty. The Journal of Arthroplasty Vol 18 No 7 Suppl 1 2003. [8] Tattevin P, Cremieux AC, Pottier P et al. Prosthetic joint infection: when can prothesis salvage be considered? Clin Infect Dis 1999; 29: 292. [9] Holmberg, A, Thórhallsdóttir VG, Robertsson O, W-Dahl A , Stefánsdóttir A. 75% success rate after open debridement, exchange of tibial insert, and antibiotics in knee prosthetic joint infections, Report on 145 cases from the Swedish Knee Arthroplasty Register, Acta Orthopaedica 2015; 86 (4): 457–462
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[10] Husted H, Toftgaard Jensen T. Clinical outcome after treatment of infected primary total knee arthroplasty. Acta Orthop Belg. 2002 Dec;68(5):500-7. [11] Rand JA. Alternatives to reimplantation for salvage of the total knee arthroplasty complicated by infection. J Bone Joint Surg Am 1993; 75(2): 282–9.
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[12] Azzam KA. Irrigation and debridement in the Management of Prosthetic Joint Infection. Traditional Indications revisited. The Journal of Arthroplasty Vol 25 No 7 October 2010 [13] Choi H-R, von Knoch F, Zurakowski D, Nelson S B, Malchau H. Can implant retention be recommended for treatment of infected TKA? Clin Orthop Relat Res 2011; 469(4): 961–9.
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[14] Mont MA. Multiple Irrigation, Debridement, and Retention of Components in Infected Total Knee Arthroplasty, The Journal of Arthroplasty Vol. 12 No. 4 1997 [15] Osmon DR, Berbari E F, Berendt A R, et al. Diagnosis and management of prosthetic joint infection: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis 2013; 56(1): 1–25. [16] Haasper C et al. Irrigation and debridement. Inc. J Orthop Res 32:S130–S135, 2014. [17] Zimmerli W, Widmer A, Blatter M, Frei R, Ochsner PE. Role of rifampin for treatment of orthopedic implant related staphylococcal infections. JAMA 1998; 279:1537–41. [18] Parvizi J, Zmistowski B, Berbari EF, Bauer TW, Springer BD, Della Valle CJ, Garvin KL, Mont MA, Wongworawat MD, Zalavras CG. New Definition for Periprosthetic Joint Infection: From the Workgroup of the Musculoskeletal Infection Society. Clin Orthop Relat Res. 2011 Nov; 469(11): 2992–2994.
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ACCEPTED MANUSCRIPT [19] Peel T N, Buising KL, Dowsey M, Aboltins CA, Daffy JR, Stanley PA, Choong PFM. Outcome of debridement and retention in prosthetic joint infections by methicillin-resistant staphylococci, with special reference to rifampin and fusidic acid combination therapy. Antimicrob Agents Chemother 2013; 57(1): 350–5. [20] Geurts JAP, Janssen DMC, Kessels AGH, Walenkamp GHIM. Good results in postoperative and hematogenous deep infections of 89 stable hip and knee replacements with retention of prosthesis and local antibiotics. Acta Orthopaedica 2013; 84(6):509-516.
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[21] Schoifet SD and Morrey BF. Treatment of infection after total knee arthroplasty by debridement with retention of the components. J Bone Joint Surg AM 1990; 72: pp.1383.
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[22] Meehan AM, Osmon DR, Duffy MC, Hanssen AD, Keating M. Outcome of penicillin-susceptible streptococcal prosthetic joint infection treated with debridement and retention of the prosthesis. Clin Infect Dis 2003; 36:8459
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ACCEPTED MANUSCRIPT Table 1 (n=58).
<25 25-30 >30 1 2 3 Yes No Yes
Success (%) 23 (76%) 26 (92%) 66.7 8 (72%) 22 (91%) 19 (83%) 9 (82%) 30 (83%) 10 (90%) 8 (89%) 41 (84%) 29 (85%)
Failure (%) 7 (24%) 2 (8%) 64.3 3 (28%) 2 (9%) 4 (17%) 2 (18%) 6 (17%) 1 (10%) 1 (11%) 8 (16%) 5 (15%)
No Yes
20 (82%) 37 (88%)
4 (18%) 5 (12%)
0.2428
No Yes
12 (75%) 6 (60%)
4 (25%) 4 (40%)
0.0387
No Yes No Yes
43 (90%) 14 (78%) 35 (90%) 47 (85%)
5 (10%) 4 (22%) 5 (10%) 8 (15%)
No
2 (67%) 49 (84%)
1 (33%) 9 (16%)
ASA score
DM Revised within 28 days Revised within 42 days Revised after 90 days Poly exchange Post op AB effective
0.3240 0.3541
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Age (mean) BMI
p-value 0.1468
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Table 2 (n=58).
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Success 89 % (26/29) 87 % (7/8) 75 % (12/16) No re-revision No re-revision No re-revision Re- Revised No re-revision No re-revision No re-revision No re-revision No re-revision
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No 29 8 16 3 1 1 1 1 1 1 1 1
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Microorganism Staph. aureus Con staph. Streptococcus Enterococcus Enterobacter cloacae Parvomonas micra Klebsiella pneumoniae Pseudomonas E.coli Corynebacterium spp Citrobacter freundii Staph capitis
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Two patients had positive cultures from preoperative wound-cultures with Staph. aureus and streptococcus and were given antibiotic treatment prior to surgery. These showed no microbiological findings from cultures and are therefore not part of the table above. ** In one patient both Streptococcus and Staph. aureus were found. Rifampicin was added post-revision. No re-revision was performed. *** One patient was re-revised without any data of the initially involved microorgamism although 5 positiv cultures were found.