Treatment Failure Among Infected Periprosthetic Patients at a Highly Specialized Revision TKA Referral Practice

Schwarzkopf, Ran; Oh, Daniel J.; Wright, Elizabeth C.; Katz, Jeffrey L.

doi:10.2174/1874325001307010264

Cited by 15 publications

(7 citation statements)

References 29 publications

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“…Due to the difficulty in treating PJIs, patients are often subjected to a staged protocol requiring two surgeries, the first being removal of the infected prosthetic joint and placement of a temporary spacer impregnated with high doses of antibiotics for several weeks, followed by a second surgery for prosthetic joint re-implantation (11-13). However, patients experiencing a prior PJI are at increased risk for subsequent infections after the placement of a new prosthesis (9, 14). The significant disease burden associated with PJIs and the increasing prevalence of antibiotic-resistant strains, such as methicillin-resistant and vancomycin-intermediate S. aureus (MRSA and VISA, respectively), highlights the importance of investigating alternative treatment paradigms.…”

Section: Introductionmentioning

confidence: 99%

IL-12 Promotes Myeloid-Derived Suppressor Cell Recruitment and Bacterial Persistence during Staphylococcus aureus Orthopedic Implant Infection

Heim

Vidlak

Scherr

et al. 2015

The Journal of Immunology

129

191

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Staphylococcus aureus (S. aureus) is a leading cause of human prosthetic joint infections (PJIs) typified by biofilm formation. We recently identified a critical role for myeloid-derived suppressor cells (MDSCs) in S. aureus biofilm persistence. Pro-inflammatory signals induce MDSC recruitment and activation in tumor models; however, the mechanisms responsible for MDSC homing to sites of biofilm infection are unknown. Here we report that several cytokines (IL-12p40, IL-1β, TNF-α, and G-CSF) and chemokines (CXCL2, CCL5) were significantly elevated in a mouse model of S. aureus PJI. This coincided with significantly increased MDSC infiltrates concomitant with reduced monocyte, macrophage, and T cell influx compared with uninfected animals. Of the cytokines detected, IL-12 was of particular interest based on its ability to possess either pro- or anti-inflammatory effects mediated through p35-p40 heterodimers or p40 homodimers, respectively. MDSC recruitment was significantly reduced in both p40 and p35 KO mice, which resulted in enhanced monocyte and neutrophil influx and bacterial clearance. Adoptive transfer of wild type MDSCs into infected p40 KO animals worsened disease outcome, as evidenced by the return of S. aureus burdens to levels typical of wild type mice. Tissues obtained from patients undergoing revision surgery for PJI revealed similar patterns of immune cell influx, with increased MDSC-like cells and significantly fewer T cells compared with aseptic revisions. These findings reveal a critical role for IL-12 in shaping the anti-inflammatory biofilm milieu by promoting MDSC recruitment.

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Section: Introductionmentioning

confidence: 99%

IL-12 Promotes Myeloid-Derived Suppressor Cell Recruitment and Bacterial Persistence during Staphylococcus aureus Orthopedic Implant Infection

Heim

Vidlak

Scherr

et al. 2015

The Journal of Immunology

129

191

View full text Add to dashboard Cite

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“…These revision strategies have a re-infection rate of 8.8% and 7.6%, respectively [ 1 ]. Risk factors for the development of recurrent infection after revision surgery include isolation of difficult micro-organisms [ 3 , 4 ], comorbidities [ 3 ], and previous surgeries [ 4 ]. Once any measures to salvage a functional TKA through multiple revision procedures have been exhausted, knee arthrodesis or the above-knee amputation represent the only options to eradicate the infection.…”

Section: Introductionmentioning

confidence: 99%

Re-infection rates and clinical outcomes following arthrodesis with intramedullary nail and external fixator for infected knee prosthesis: a systematic review and meta-analysis.

Balato

Rizzo

Ascione

et al. 2018

BMC Musculoskelet Disord

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BackgroundKnee arthrodesis with intramedullary (IM) nail or external fixator (EF) is the most reliable therapeutic option to achieve definitive infection control in patients with septic failure of total knee arthroplasty (TKA). The first aim of this study was to compare re-infection rates following knee arthrodesis for periprosthetic joint infection (PJI) with IM nail or EF. The second aim was to compare rates of radiographic union, complication, and re-operation as well as clinical outcomes.MethodsA systematic search was performed in electronic databases for longitudinal studies of PJIs (minimum ten patients; minimum follow-up = 1 year) treated by knee arthrodesis with IM nail or EF. Studies were also required to report the rate of re-infection as an outcome measure. Eligible studies were meta-analyzed using random-effect models.ResultsThe rate (95% confidence intervals) of re-infection was 10.6% (95% CI 7.3 to 14.0) in IM nail arthrodesis studies. The corresponding re-infection rate for EF was 5.4% (95% CI 1.7 to 9.1). This difference was significant (p = 0.009). The use of IM nail resulted in more advantages than EF for frequency of major complications and limb shortening. Other postoperative clinical and radiographic outcomes were similar for both surgical strategies.ConclusionsThe available evidence from the aggregate published data suggests that knee arthrodesis with EF in the specific context of PJI has a reduced risk of re-infection in comparison with the IM nail strategy. The use of IM nail is more effective for the complication rate and shortening of the affected limb.

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“…Schwarzkopf et al [30] reported a similar mean time to failure of 438 days following 12 cases of two-stage revision TKA. However, neither of these studies reported the number of failed two-stage revision TKA cases which underwent a prior I&D. The mean failure time in this study was less in the I&D group (136 days) compared with the group without prior I&D (365 days), indicating that the I&D group is more likely to fail earlier.…”

Section: Discussionmentioning

confidence: 93%

“…However, previous studies have either demonstrated a median time to failure between one and 3.6 years [19,27,28] or an average time to failure of 1.2 years. [29,30] It is possible that undetected failures of the two-stage revision TKA occurred beyond four years after surgery in some patients. Lastly, the study was too underpowered to detect a small effect size.…”

Section: Discussionmentioning

confidence: 99%

Irrigation and Debridement Before a 2-Stage Revision Total Knee Arthroplasty Does Not Increase Risk of Failure

Brimmo

Ramanathan

Schiltz

et al. 2016

The Journal of Arthroplasty

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Background Studies have suggested that the success of two-stage revision total knee arthroplasty (rTKA) may be compromised by a prior failed irrigation and debridement (I&D). The purpose of this study was to use two large state inpatient databases to compare the two-stage rTKA failure rates for those patients with and without a prior I&D. Methods This retrospective, longitudinal study used inpatient discharge data from the State Inpatient Database (SID) of two states (California and New York) from 2005 to 2011. A combination of ICD-9 diagnosis and procedure codes were used to identify rTKA patients, and compare failure rates for rTKA patients with and without prior I&D. The primary outcome was failure of the staged revision, which was defined as subsequent surgery due to infection within four years of the two-stage rTKA. Results Of the 750 patients who underwent two-stage rTKA, fifty-seven had undergone a prior I&D. In all, 126 patients failed rTKA. After four years, the estimated failure rate was 8.7% (95% CI 1.9% – 16.9%) in the group with prior I&D and 17.5% (95% CI 14.7% – 20.4%) in the group without prior I&D. After adjusting for gender, race, insurance, median household income, and comorbidities, the hazard ratio for the group with a failed I&D was 0.49 (p=0.122; 95% CI 0.20 – 1.20) which indicated a lower risk of failure compared to the group without prior I&D. Conclusions These findings indicate that the failure rate of two-stage rTKA is not increased by prior failed I&D.

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Treatment Failure Among Infected Periprosthetic Patients at a Highly Specialized Revision TKA Referral Practice

Cited by 15 publications

References 29 publications

IL-12 Promotes Myeloid-Derived Suppressor Cell Recruitment and Bacterial Persistence during Staphylococcus aureus Orthopedic Implant Infection

IL-12 Promotes Myeloid-Derived Suppressor Cell Recruitment and Bacterial Persistence during Staphylococcus aureus Orthopedic Implant Infection

Re-infection rates and clinical outcomes following arthrodesis with intramedullary nail and external fixator for infected knee prosthesis: a systematic review and meta-analysis.

Irrigation and Debridement Before a 2-Stage Revision Total Knee Arthroplasty Does Not Increase Risk of Failure

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