Culture-negative Prosthetic Joint Infection Research Articles

1312. Incidence and Microbiology of Prosthetic Joint Infection According to Time Following Total Knee Arthroplasty: A Retrospective Cohort Study Among US Veterans

Abstract Background Despite the frequency of total knee arthroplasty (TKA) and clinical impact of prosthetic joint infections (PJIs), the incidence and microbiology of these infections in the United States remains unclear. Our objective was to determine the incidence of PJI occurring ≤ 3 months (early), between > 3 and ≤ 12 months (delayed), and > 12 months (late) after primary TKA and to identify the organisms isolated from microbiologic cultures during each of these periods. Methods We conducted a retrospective study of patients in the Veterans Aging Cohort Study- National Cohort who underwent elective primary TKA in the VA between October 1, 1999 to September 30, 2019. The primary outcome was incident hospitalization with PJI. We estimated incidence rates (events/10,000 person-months) with 95% confidence intervals (CIs) of early, delayed, and late PJI. Poisson regression was used to estimate the incidence rate ratio (IRR) with 95% CI of early and delayed PJI compared to late PJI. The Kaplan-Meier method was used to demonstrate the cumulative incidence of PJI at 3, 12 and 24 months. We measured the frequency of Gram-positive, Gram-negative, fungal, polymicrobial, and culture-negative PJI occurring within each of the three time periods and compared frequencies of interest using Pearson’s chi-squared tests. Results Among 82,401 VHA patients who underwent primary TKA, a total of 1,605 incident PJIs (1.9%) were identified. The incidence rate of PJI was higher in the first 12 months after primary TKA surgery, with an IRR of 20.4 (95% CI, 18.2-222.8) for early and 4.2 (95% CI, 3.7-4.8) for delayed periods when compared to late. The cumulative incidence of PJI at 3 months was 0.77% (95% CI, 0.71-0.83%), at 12 months was 1.25% (95% CI 1.17-1.33%), and at 24 months was 1.56% (95% CI 1.48-1.65%) (Figure 1). Staphylococcus aureus was the most common organism isolated (33.2%) across the periods. Gram-negative bacteria were isolated in 11.1% of all infections, and 15.1% of early PJIs (Table 1). Kaplan Meier failure curves for prosthetic joint infection for the overall study period (upper panel) as well as the first 24 months (lower panel) following primary total knee arthroplasty. Abbreviations: PJI, prosthetic joint infection; CI, confidence interval.Table 1.Organisms isolated from synovial fluid or operative tissue cultures of early, delayed and late prosthetic joint infections after primary total knee arthroplasty. aAmong the 1,605 PJIs in the Overall Cohort, the microbiology data for 103 were missing and 1,502 PJIs with available microbiology data were included in these results. bPolymicrobial defined by multiple genera of organisms identified cIncludes: Micrococcus species, diphtheroids dIncludes: Salmonella, Pasteurella, Citrobacter, Morganella, Acinetobacter, Pasteurella, Burkholderia species, and Gram-negative organisms not otherwise specified eAll fungal infections were identified as Candida species fNumbers may not sum to group totals or percentages as polymicrobial infections with more than one organism were possible Abbreviations: PJI, prosthetic joint infection. Conclusion Incidence rates of early and delayed PJI were significantly higher than late PJI following primary TKA. Gram-negative organisms were more prevalent in early compared to delayed or late PJI. Empiric Gram-negative antibiotic therapy should be considered with a suspected PJI within 3 months after elective primary TKA. Disclosures Alisa Stephens-Shields, PhD, Gilead Sciences: Advisor/Consultant Charles Nelson, MD, Stryker: Advisor/Consultant|Zimmer-Biomet: Advisor/Consultant|Zimmer-Biomet: Grant/Research Support

Clinical and Histological Features of Prosthetic Joint Infections May Differ in Patients With Inflammatory Arthritis and Osteoarthritis.

Background: Patients with inflammatory arthritis are at increased risk of prosthetic joint infections (PJIs), but diagnosis in these patients can be challenging because active inflammatory arthritis produces elevated inflammatory markers that may mimic those seen in PJI. Purpose: In this pilot study, we sought to identify the clinical, microbiologic, and histopathologic features of culture-positive and culture-negative PJI in patients with inflammatory arthritis who underwent total hip arthroplasty (THA) or total knee arthroplasty (TKA). We also sought to obtain preliminary data to support a definitive study of optimal methods for PJI diagnosis in patients with inflammatory arthritis. Methods: We performed a retrospective analysis of TKA and THA patients treated for PJI from 2009 to 2018 at a single tertiary care orthopedic institution. Data were extracted from a longitudinally maintained hospital infection database. We reviewed hematoxylin and eosin slides of osteoarthritis and inflammatory arthritis PJI cases matched 3:1, respectively, by age, sex, and culture status. Clinical characteristics were evaluated using the Fisher exact test, χ2 test, Student t test, and Mann-Whitney U test where appropriate. Results: A total of 807 PJI cases were identified (36 inflammatory arthritis and 771 osteoarthritis cases). Patients with inflammatory arthritis presented younger, had a higher Charlson Comorbidity Index, more frequently used glucocorticoids, were more likely women, and had a higher proportion of culture-negative PJI compared with osteoarthritis patients. Of the 88 inflammatory arthritis cases reviewed for histopathology, a higher proportion of culture-positive than culture-negative PJI cases had >10 polymorphonuclear leucocytes per high-power field and met Musculoskeletal Infection Society criteria but presented with less chronic inflammation. Conclusions: This retrospective prognostic study suggests that culture-negative PJI may be more frequent in patients with inflammatory arthritis than in those with osteoarthritis. Chronic infections, antibiotic use, or misdiagnosis may be contributing factors to unclear PJI diagnoses among culture-negative cases. This preliminary work supports the need for further studies to assess the differences in clinical features between culture-negative and culture-positive PJI in patients with inflammatory arthritis and the ability of biological diagnostic markers to discriminate between them in this population.

THE PROFILE OF CAUSAL PATHOGEN OF HIP/ KNEE PROSTHETIC JOINT INFECTION (PJI): A SINGLE CENTER STUDY

Introduction: One of the most challenging and serious complications associated with total joint arthroplasty is prosthetic joint infection (PJI). Advancements in prevention, diagnosis, and treatment of PJI seem promising. Accurate identification of the causal pathogen is a key factor for successful treatment and also for choosing antibiotic treatment. This study was aimed to evaluate the prevalence of PJI and distribution of causative pathogen using microbiological culture and pathological examination. Methods: A retrospective descriptive study was conducted by collecting data from our center registry from 2018 to 2020. The inclusion criteria of this study were patients diagnosed with hip or knee PJI based on the diagnostic criteria for PJI. The exclusion criteria were incomplete microbiology data which were either refusal to participate or loss of contact. The data extracted from medical records are demographic data such as age, sex, and microbiology and pathological examination data. Results: A total of 1359 total hip/ knee arthroplasty surgeries were performed during the years 2018–2020. Among them, 1031 were total knee arthroplasty (TKA) and 321 were total hip arthroplasties (THA). During the same period, a total of 52 patients with PJI were treated at our center. There were 31 knee PJI cases (59.61%) and 21 were hip PJI cases (40.38%). Microbiology culture and pathologic anatomy results showed gram positive Staphylococcus sp bacteria, which was the common causal pathogen of PJI. Negative culture results were found in 10/52 (19.23%) of cases. Conclusions: Staphylococcus sp was the most common causal pathogen of Hip/ Knee PJI in our center. Relatively high rate of culture-negative PJI was observed in this study, further strategies are needed to increase the rate of causal pathogen isolation in hip/ knee PJI cases in our center.

Characteristics and outcomes of culture-negative prosthetic joint infections from the Prosthetic Joint Infection in Australia and New Zealand Observational (PIANO) cohort study

Introduction: Culture-negative (CN) prosthetic joint infections (PJIs) account for approximately 10 % of all PJIs and present significant challenges for clinicians. We aimed to explore the significance of CN PJIs within a large prospective cohort study, comparing their characteristics and outcomes with culture-positive (CP) cases. Methods: The Prosthetic joint Infection in Australia and New Zealand Observational (PIANO) study is a prospective, multicentre observational cohort study that was conducted at 27 hospitals between 2014 and 2017. We compared baseline characteristics and outcomes of all patients with CN PJI from the PIANO cohort with those of CP cases. We report on PJI diagnostic criteria in the CN cohort and apply internationally recognized PJI diagnostic guidelines to determine optimal CN PJI detection methods. Results: Of the 650 patients with 24-month outcome data available, 55 (8.5 %) were CN and 595 were CP. Compared with the CP cohort, CN patients were more likely to be female (32 (58.2 %) vs. 245 (41.2 %); 0.016), involve the shoulder joint (5 (9.1 %) vs. 16 (2.7 %); 0.026), and have a lower mean C-reactive protein (142 mg L vs. 187 mg L ; 0.016). Overall, outcomes were superior in CN patients, with culture negativity an independent predictor of treatment success at 24 months (adjusted odds ratio, aOR, of 3.78 and 95 %CI of 1.65-8.67). Suboptimal diagnostic sampling was common in both cohorts, with CN PJI case detection enhanced using the Infectious Diseases Society of America PJI diagnostic guidelines. Conclusions: Current PJI diagnostic guidelines vary substantially in their ability to detect CN PJI, with comprehensive diagnostic sampling necessary to achieve diagnostic certainty. Definitive surgical management strategies should be determined by careful assessment of infection type, rather than by culture status alone.

An Insight Into Lyme Prosthetic Joint Infection in Knee Arthroplasty: A Literature Review.

Lyme prosthetic joint infection (PJI) is a rare event, but it is imperative to include Lyme disease as a possible cause of PJI in a Lyme-endemic region. The purpose of this article was to review the reported cases of Lyme PJIs in knee arthroplasty and to initiate the development of a treatment strategy. We found five cases of Lyme PJI in the literature. All patients lived in the northeastern region of the United States. Four patients were successfully treated with surgical intervention and postoperative antibiotics. One patient was successfully treated with intravenous and oral antibiotics for 6 weeks, without surgical intervention. Synovial fluid Lyme polymerase chain reaction and serological tests were positive in all patients. On follow-up visits, after completion of their treatment, all patients were asymptomatic with a painless functional knee. We recommend considering Lyme disease as a cause of culture-negative PJIs in endemic regions. Additional research is needed to clearly define a treatment algorithm. Based on our literature review, we cannot recommend a single best treatment modality for the treatment of Lyme PJI. However, early irrigation and débridement with administration of postoperative antibiotics may improve early clinical outcomes.

A Prospective Study to Assess the Optimal Incubation Times for Culture and Aerobic Bacterial Profile in Prosthetic Joint Infections.

Introduction With an increase in the number of total joint arthroplasties, the count of prosthetic joint infections (PJIs) is also increasing and has become a nightmare for an orthopaedic surgeon. Microbiological diagnosis is important for administering definitive antimicrobial treatment. Negative culture reports hamper patient management and prolonged incubation periods have increased the culture yield but at the risk of culture contamination in conventional microbiology settings. Thus, we aimed to optimize the best incubation time for culture and the aerobic bacterial profile of PJIs. Material and Methods Over a year, samples from clinically suspected PJI patients were collected and processed for culture using standard techniques. The samples were incubated for up to 10 days with daily subculturing on to solid media. The bacterial isolates were identified and antibiotic susceptibility was performed. Results Out of 200 patients, 105 were included in the study and samples were collected in triplicate. In 70 cases culture was positive and 35 were culture negative PJIs. Mean incubation days to culture positivity was 3.6 days with 97.14% culture positivity seen by the seventh day of incubation. Twenty-four percent methicillin-resistant Staphylococcus aureus , and more than 50% extended spectrum β lactamase producing Klebsiella pneumoniae and Escherichia coli were isolated. Discussion Culture positivity in PJIs provides definitive evidence of infection and guides the treatment. Increasing the incubation times can help in maximizing the culture yield, and we found that 97.14% pathogens grew within 7 days of incubation. Prolonging it further would not provide an added advantage especially in a resource-constraint setting.

Microbiological pattern of prosthetic hip and knee infections: a high-volume, single-centre experience in China.

Introduction. Prosthetic joint infection (PJI) is a serious complication after arthroplasty, which results in high morbidity, prolonged treatment and considerable healthcare expenses in the absence of accurate diagnosis. In China, microbiological data on PJIs are still scarce.Hypothesis/Gap Statement. The incidence of PJI is increasing year by year, and the proportion of drug-resistant bacteria infection is nicreasing, which brings severe challenges to the treatment of infection.Aim. This study aimed to identify the pathogens in PJIs, multi-drug resistance, and evaluate the effect of the treatment regimen in patients with PJI.Methodology. A total of 366 consecutive cases of PJI in the hip or knee joint were admitted at the Orthopedic Surgery Center in Zhengzhou, China from January 2012 to December 2018. Infections were confirmed in accordance with the Infectious Diseases Society of America and the Musculoskeletal Infection Society (MSIS) criteria. Concurrently, patient demographic data, incidence and antibiotic resistance were investigated. Statistical differences were analysed using Fisher's exact test or chi-square test.Results. Altogether, 318 PJI cases satisfying the inclusion criteria were enrolled in this study, including 148 with hip PJIs and 170 with knee PJIs. The average age of patients with hip PJIs was lesser than that of patients with knee PJIs (56.4 vs. 68.6 years). Meanwhile, coagulase-negative staphylococcus (CNS, n=81, 25.5 %) was the predominant causative pathogen, followed by Staphylococcus aureus (n=67, 21.1 %). Methicillin-resistant Staphylococcus (MRS) was identified in 28.9 % of PJI patients. In addition, fungus accounted for 4.8 % (n=15), non-tuberculosis mycobacterium accounted for 1.6 % (n=5), polymicrobial pathogens accounted for 21.7 % (n=69), and Gram-negative bacteria accounted for 7.9 % (n=25) of the total infections. The results of antibiotic susceptibility testing showed that gentamicin and clindamycin β-lactam antibiotics were poorly susceptible to Gram-positive isolates, but they were sensitive to rifampicin, linezolid and vancomycin. While antibiotics such as amikacin and imipenem were effective against Gram-negative bacteria, there was a high resistance rate of other pathogens to gentamicin, clindamycin and some quinolone antibacterial drugs. Empirical antibiotic treatment should combine vancomycin and cephalosporin, levofloxacin or clindamycin. When the pathogen is confirmed, the treatment should be individualized.Conclusions. The prevalence of culture-negative PJIs is still very high. Gram-positive bacteria are still the main type of pathogens that cause PJIs. Attention should be paid to the high incidence of MRS, such as MRSA and MR-CNS, among PJI patients. Empirical antibiotic treatment should cover Gram-positive isolates, especially Staphylococcus.

Prosthetic joint infection in culture-negative and alpha-defensin-positive patients versus culture-positive and alpha-defensin-negative patients: a retrospective cohort study of the differences in clinical characteristics and outcomes

Background: Culture-negative (CN) prosthetic joint infection (PJI) poses a challenge for the clinician for both diagnosis and management. We compared the clinical presentation and outcomes between patients with CN alpha-defensin-positive PJI and culture-positive (CP) alpha-defensin-negative PJI. Methods: This was a retrospective study of 15 patients who underwent treatment for PJI (four hips and 11 knees) at a tertiary referral center by a single surgeon from 2016 to 2019. Patients were divided into two cohorts based on their culture results: one group had negative cultures but positive alpha-defensin test (n=7) and the other had positive cultures but negative alpha-defensin test (n=8). These two cohorts were compared in terms of clinical presentation, laboratory values, treatment duration, and functional outcome. Statistical analysis was performed on variables of interest. Results: Patients in both PJI groups most commonly presented with pain and swelling of the involved joint. There was a greater proportion of CN PJI patients with a history of infection, such as bacteremia or urinary tract infection (UTI) requiring antibiotics, than CP PJI patients (42.9% vs. 0%). There was no statistically significant difference in inflammatory marker elevation for either group. Only 57% of the CN PJI patients underwent surgical debridement versus all CP PJI patients. There were no differences in outcomes at final follow-up between the two groups. Conclusions: Prior history of infection requiring antimicrobial therapy is a risk factor for negative cultures. CN PJI is not a negative prognostic indicator and results in outcomes similar to CP PJI. Level of Evidence: Level III.

A retrospective analysis of the prosthetic joint infections of the hip and knee at a tertiary care center of India

Introduction: An increase in the number of primary total joint arthroplasties has correspondingly led to an increase in revisions as a result of various complications. The prosthetic joint infection (PJI) is a major complication with concordantly increased morbidity and costs. Through this study, we aimed to determine the bacteriological profiles of PJI diagnosed at our institute and analyze them in the context of patient profiles, joints affected, and the center where the index procedure was done. Materials and Methods: A retrospective study of the revision surgeries for PJI in hip and knee arthroplasties during the period between 2014 and 2019 was conducted. An analysis of 43 patient profiles, with 29 of those being knees and the rest 14 being hips was done, concerning the clinical picture, microbiological profile, and co-morbidities. Results: PJI constituted 31.03% of the revision cases. The knee joint was involved in 67.44% (n = 29) and the hip joint in 32.56% (n = 14). Early infection was seen in 2 (4.65%) and late infections in the remaining 41 (95.34%). 51.66% (n = 22) were culture-positive PJI, whereas 48.34% (n = 21) were culture-negative (CN) PJI. Preoperative C-reactive protein was elevated in 46.51% of the patients (48.27% knees and 42.87% hips). The erythrocyte sedimentation rate was preoperatively elevated by 65.12%. Of the comorbidities PJI was associated with, diabetes mellitus in 30.23%, hypertension in 39.53%, hypothyroidism in 16.28%, skin disorders in 4.65% (psoriasis and eczema), and immunosuppression in 4.65% cases. Conclusions: Microbial growth on routine culture is not mandatorily positive in several clinically suspected PJI. Hence, a stringent protocol requires to be followed in the use of antibiotics, the collection and transportation of samples, and in the selection of media for cultures in the cases of PJI. Notwithstanding the limitations of this study, we conclude that bacterial infections do not follow any predictable patterns, and constant vigilance with a low threshold to suspect and investigate PJI is needed in the management of PJI. We propose based on our study findings that no antibiotics should be used only after a bacteriological diagnosis and antibiotic sensitivity is obtained, else it results in a high rate of CN PJIs.

Metagenomic next-generation sequencing of synovial fluid demonstrates high accuracy in prosthetic joint infection diagnostics: mNGS for diagnosing PJI.

AimsThe aim of this study was to evaluate the performance of metagenomic next-generation sequencing (mNGS) in detecting pathogens from synovial fluid of prosthetic joint infection (PJI) patients.MethodsA group of 75 patients who underwent revision knee or hip arthroplasties were enrolled prospectively. Ten patients with primary arthroplasties were included as negative controls. Synovial fluid was collected for mNGS analysis. Optimal thresholds were determined to distinguish pathogens from background microbes. Synovial fluid, tissue, and sonicate fluid were obtained for culture.ResultsA total of 49 PJI and 21 noninfection patients were finally included. Of the 39 culture-positive PJI cases, mNGS results were positive in 37 patients (94.9%), and were consistent with culture results at the genus level in 32 patients (86.5%) and at the species level in 27 patients (73.0%). Metagenomic next-generation sequencing additionally identified 15 pathogens from five culture-positive and all ten culture-negative PJI cases, and even one pathogen from one noninfection patient, while yielding no positive findings in any primary arthroplasty. However, seven pathogens identified by culture were missed by mNGS. The sensitivity of mNGS for diagnosing PJI was 95.9%, which was significantly higher than that of comprehensive culture (79.6%; p = 0.014). The specificity is similar between mNGS and comprehensive culture (95.2% and 95.2%, respectively; p = 1.0).ConclusionMetagenomic next-generation sequencing can effectively identify pathogens from synovial fluid of PJI patients, and demonstrates high accuracy in diagnosing PJI.Cite this article: Bone Joint Res 2020;9(7):440–449.

Can metagenomic next-generation sequencing identify the pathogens responsible for culture-negative prosthetic joint infection?

BackgroundThe aims of this study were to (1) evaluate the efficacy and safety of targeted antibiotics for the treatment of culture-negative prosthetic joint infection based on metagenomic next-generation sequencing results and (2) verify the accuracy and reliability of metagenomic next-generation sequencing for identifying pathogens related to culture-negative prosthetic joint infection.MethodsNinety-seven consecutive PJI patients, including 27 patients with culture-negative prosthetic joint infection, were treated surgically at our center. Thirteen of the 27 culture-negative prosthetic joint infection patients, who were admitted before June 2017 and treated with empirical antibiotics, comprised the empirical antibiotic group (EA group), and the other 14 patients, who were admitted after June 2017 and treated with targeted antibiotics according to their metagenomic next-generation sequencing results, were classified as the targeted antibiotic group (TA group). The short-term infection control rate, incidence of antibiotic-related complications and costs were compared between the two groups.ResultsTwo of the patients in the EA group experienced debridement and prolonged antimicrobial therapy due to wound infection after the initial revision surgery. No recurrent infections were observed in the TA group; however, no significant difference in the infection control rate was found between the two groups (83.33% vs 100%, P = 0.217). More cases of antibiotic-related complications were recorded in the EA group (6 cases) than in the TA group (1 case), but the difference was not statistically significant (P = 0.0697). The cost of antibiotics obtained for the EA group was 20,168.37 Yuan (3236.38–45,297.16), which was higher than that found for the TA group (10,164.16 Yuan, 2959.54–16,661.04, P = 0.04).ConclusionsTargeted antibiotic treatment for culture-negative prosthetic joint infection based on metagenomic next-generation sequencing results is associated with a favorable outcome, and metagenomic next-generation sequencing is a reliable tool for identifying pathogens related to culture-negative prosthetic joint infection.

Epidemiology and microbiology of prosthetic joint infections: a nine-year, single-center experience in Pavia, Northern Italy.

Prosthetic joint infections (PJIs) are a growing matter of concern due to their economic and social burden on health systems. In Italy, surgical data on PJIs are available in a national registry, but microbiological data are still scarce. We performed a retrospective study at a single center with records of patients treated for primary PJIs of knee or hip from January 1, 2011, to May 30, 2018. Patients with infections of osteosynthesis means and external devices were excluded, as well as PJI recurrences and polytrauma patients. Infections were diagnosed according to IDSA and MSIS criteria. We collected data on demographics, risk factors and microbiology. All patients seen at our center undergo blood cultures and synovial fluid cultures, periarticular biopsy and prosthesis sonication by Bactosonic®. This was used only after 2014. Bacterial identification is achieved by MALDI-TOF, PHOENIX 100 and standard methods. Chi-square or Fisher tests were used to test statistical differences in proportions. Fifty-one patients matched our inclusion criteria. Of these, 16 (31.4%) were enrolled before 2014. The median age was 68.5 (range 22-88). The most common risk factors were obesity (34%), diabetes (21%) and chronic kidney disease (14%). Seventeen patients were diagnosed with a culture-negative PJIs (33.3%). Staphylococcus aureus was the most commonly isolated pathogen (14/51, 27.5%), followed by coagulase-negative staphylococci (7/51, 13.7%). Methicillin-resistant S. aureus rate was 28.6%. The rate of culture-negative PJIs dropped from 56 to 22% after 2014, with a significant difference between the two time periods (p = 0.016). The introduction of sonication dramatically increased our diagnostic accuracy. Our microbiological data are in line with those from other studies conducted in Italy.

383. Rheumatic Disease Patients Have More Culture Negative Prosthetic Joint Infections: Are There Clinical Differences?

BackgroundRheumatic disease (RD) patients are at increased risk for prosthetic joint infections (PJI), however, diagnosis is challenging because active RD may mimic joint infection. We aimed to assess the incidence of culture-negative (CN) PJI in a population of RD and osteoarthritic (OA) PJI using an institutional PJI registry. Baseline clinical differences between CN-RD and culture-positive (CP)-RD as well as the relationship of culture negativity to survivorship of the prosthesis were also evaluated.MethodsA retrospective cohort of hip and knee PJIs, from 2009 to 2016, were identified by ICD codes, and confirmed by chart review. RD cases were identified by ICD code and use of RD-specific medications. CN cases were defined as PJIs with no evidence of microbial growth in intraoperative cultures. Demographics, medications, microbiology, surgical therapy and outcome were abstracted. Baseline characteristics were evaluated using Fisher’s exact and Chi-Square tests. Kaplan–Meier estimates were used to calculate survivorship.Results803 PJI cases were identified including 36 RD (33 rheumatoid arthritis and 3 systemic lupus erythematosus) and 771 OA. A higher proportion of RD PJI were CN (N = 10, 27%) vs. OA PJI (N = 109, 14%, P = 0.02). Fewer CN-RD cases met PJI histopathology criteria compared with CN-OA, (P = 0.08). On average, RD-CN were younger than OA-CN (59 vs 69, P = 0.01), but no different than RD-CP cases. One year survivorship of CN-OA and CN-RD were 87% and 66%, respectively and 47% for CP-RD. Comparing CN-RD vs. CP-RD, no difference was observed in age, smoking, diabetes, or Charlson comorbidities, but a trend toward higher prevalence of prior PJI in the CN-RD group. Clinically, no differences were found in surgical treatment (P = 0.92) or use of biologics and DMARDs (P = 0.12) between CN and CP RD patients.ConclusionRD PJIs are more likely to be culture-negative than OA PJIs. Prior PJI, histopathology and better outcomes suggest biologic differences that should be explored further. Disclosures All authors: No reported disclosures.

A Clinico-Microbiological Study of Prosthetic Joint Infections in an Indian Tertiary Care Hospital: Role of Universal 16S rRNA Gene Polymerase Chain Reaction and Sequencing in Diagnosis.

Background:We determined the magnitude and clinico-microbiological profile of prosthetic joint infection (PJI) at a tertiary hospital. The diagnostic potential of 16S rRNA gene polymerase chain reaction (PCR) and sequencing on periprosthetic tissue samples was evaluated for the diagnosis of PJI.Materials and Methods:This ambispective cohort study consisted of patients who underwent primary or revision hip or knee arthroplasty from June 2013 to June 2017. The patients were classified as either infected or noninfected according to criteria set out by the musculoskeletal infection society (MSIS). Three to five periprosthetic tissue samples were collected from each patient for culture and 16S rRNA gene PCR sequencing.Results:Hundred and six patients were diagnosed to have PJI as per the MSIS Criteria. The cumulative incidence of PJI at our Institute at the end of 36 months was 1.1% (95% confidence interval [CI]: 0.59–2.91). Microorganisms were isolated by periprosthetic tissue culture (PTC) in 84 patients (sensitivity: 79% and specificity: 100%). Gram-negative aerobes were most frequently isolated (61%). Polymicrobial infections were present in 8.3% of cases. The most common infecting microorganism was Staphylococcus aureus (19.5%). Multidrug resistance and methicillin resistance were noted in 54% and 34% of bacterial isolates, respectively. The sensitivity and specificity of 16S rRNA PCR of periprosthetic tissue was 86% (95% CI: 74.9–89.9) and 100% (95% CI: 94.7–100), respectively. Periprosthetic tissue 16S rRNA PCR was more sensitive than PTC (P = 0.008), although both were 100% specific (P = 0.99).Conclusions:The incidence of PJI at our Institute compares well with other published reports. Contrary to previous reports, a predominance of Gram-negative PJI's was found. The preponderance of multidrug-resistant organisms in PJI's is worrisome. The high sensitivity and specificity of the 16S PCR assay used in our study support its use in culture-negative PJI suspected cases.

Evaluation of the CosmosID Bioinformatics Platform for Prosthetic Joint-Associated Sonicate Fluid Shotgun Metagenomic Data Analysis.

We previously demonstrated that shotgun metagenomic sequencing can detect bacteria in sonicate fluid, providing a diagnosis of prosthetic joint infection (PJI). A limitation of the approach that we used is that data analysis was time-consuming and specialized bioinformatics expertise was required, both of which are barriers to routine clinical use. Fortunately, automated commercial analytic platforms that can interpret shotgun metagenomic data are emerging. In this study, we evaluated the CosmosID bioinformatics platform using shotgun metagenomic sequencing data derived from 408 sonicate fluid samples from our prior study with the goal of evaluating the platform vis-à-vis bacterial detection and antibiotic resistance gene detection for predicting staphylococcal antibacterial susceptibility. Samples were divided into a derivation set and a validation set, each consisting of 204 samples; results from the derivation set were used to establish cutoffs, which were then tested in the validation set for identifying pathogens and predicting staphylococcal antibacterial resistance. Metagenomic analysis detected bacteria in 94.8% (109/115) of sonicate fluid culture-positive PJIs and 37.8% (37/98) of sonicate fluid culture-negative PJIs. Metagenomic analysis showed sensitivities ranging from 65.7 to 85.0% for predicting staphylococcal antibacterial resistance. In conclusion, the CosmosID platform has the potential to provide fast, reliable bacterial detection and identification from metagenomic shotgun sequencing data derived from sonicate fluid for the diagnosis of PJI. Strategies for metagenomic detection of antibiotic resistance genes for predicting staphylococcal antibacterial resistance need further development.

Success of Debridement and Implant Retention for Periprosthetic Joint Infection in TKA – Does The Surgeon Matter?

Introduction:Prosthetic joint infection (PJI) is a devastating complication following total knee arthroplasty (TKA). In acute haematogenous and early post-operative PJI, debridement and implant retention (DAIR) is often the initial treatment and reported success rates vary. The aim of this study was to identify factors affecting the success of DAIR and in particular whether involvement of a lower limb arthroplasty surgeon (LLA) can affect outcome.Method:In a multicentre review over a 15 year period we identified 137 patients undergoing DAIR for first episode PJI following primary TKA at one of three tertiary hospitals. Patients receiving arthroscopic washouts, culture negative PJI, and previous PJIs were excluded. Data on patient, hospital, and surgical factors were identified including age of implant, time to theatre, presence of gross purulence, bacterial subtype, inflammatory markers, relevant comorbidities, whether modular component exchange was performed, and whether a lower limb arthroplasty surgeon performed the procedure. Treatment success was defined as infection eradication characterized by no clinical failure (healed wound and painless joint) or infection recurrence, and no mortality or further surgery due to PJI within minimum two-year follow up post DAIR. Multivariate analysis was performed using a logistic regression model to identify factors associated with successful DAIR.Results:Overall failure rate of DAIR in TKA was 42%. A specialist arthroplasty surgeon was present in 49% of cases. Arthroplasty surgeons performed modular exchange in 92% of cases compared to 57% for other surgeons (RR1.6, P <0.01). On multivariate analysis, involvement of a specialist arthroplasty surgeon was the only factor associated with a significant increase in success of DAIR (OR 2.94, P=0.01). Age of prosthesis less than 90 days and the lack of macroscopic purulence (OR 2.44, p=0.04) increased DAIR success on univariate analysis only.Conclusions:Involvement of a specialist arthroplasty surgeon was associated with a 2.9 times higher success rate for DAIR in TKA. Specialist arthroplasty surgeons were more likely to perform modular exchange. This study suggests surgical technique and thorough debridement is likely to be important to the success of DAIR in TKA.

C-reactive protein may misdiagnose prosthetic joint infections, particularly chronic and low-grade infections.

Periprosthetic tissue cultures, sonication and synovial fluid cultures remain the gold standard for prosthetic joint infection (PJI) diagnosis. However, some 15-20% culture-negative PJI are still reported. Therefore, there is the need for other diagnostic criteria. One point of concern relative to the different definitions of PJI is as to the inclusion of the c-reactive protein (CRP) and the erythrocyte sedimentation rate (ESR) as diagnostic criteria for PJI despite them being non-specific inflammatory blood tests. The purpose of the present study was to determine the relevance of CRP and the ESR in the diagnosis of PJI. All PJI with positive cultures over a two-year period in two hospitals were reviewed. The main variables of the present study were the type of prosthesis and the CRP level. More information was recorded in those patients with normal CRP: radiographs, physical examination records and the ESR. Seventy-three patients were included in study. Pre-operative CRP levels were normal (lower than 0.8mg/dl) in 23 patients, representing 32% of all PJI with positive cultures. Low virulence micro-organisms, 12 coagulase-negative staphylococci and four P. acnes, grew in most of them. They represented 70% of all PJI with normal CRP levels. In addition, 17 patients (23% of all PJI with positive cultures) had a normal ESR, a normal physical examination (they only presented with pain) and no clear loosening was observed in the radiographs. Per the American Association of Orthopaedic Surgeons (AAOS) guidelines or the Musculoskeletal Infection Society (MSIS), 23% of the patients in the present study with PJI would never have been identified. Blood inflammatory markers such as the CRP level and ESR may not be accurate as diagnostic tools in PJI, particularly to identify low-grade and chronic PJI.

Preoperative antibiotic prophylaxis in prosthetic joint infections: not a concern for intraoperative cultures

BackgroundCulture negative prosthetic joint infections (PJI) still remain an issue even with the advantages of the new diagnostic tools for PJI. This is why some orthopedic surgeons have reservations relative to the use of preoperative antibiotic prophylaxis when a PJI is suspected. The purpose of the present study was to evaluate the influence of preoperative antibiotic prophylaxis on intraoperative cultures. Material and MethodsAn enhanced diagnostic protocol for PJI (Zimmerli criteria) was used for the inclusion criteria in order to collect all PJI that were seen in a university hospital. Patients were prospectively randomized into two groups. The control group received the classical preoperative antibiotic prophylaxis. The study group did not receive prophylaxis prior to surgery. ResultsThere were 14 patients in each group. They correspond to 13 total hip arthroplasty infections, 12 total knee arthroplasty infections and 3 reverse shoulder prosthesis infections. There were 10 patients in the study group and 10 patients in the control group with at least one positive microbiological criterion (P > 0.05). There were 4 patients in each group with a culture negative PJI (P > 0.05). ConclusionsPreoperative antibiotic prophylaxis does not affect intraoperative cultures in suspected or confirmed PJI. Therefore it is essential to deliver antibiotic prophylaxis in any patient in which a prosthesis is to be implanted in order to protect the prosthesis from infection.

An unusual pathogen for prosthetic joint infection

In 2012, an 84-year-old Chinese man presented with progressive, chronic left atraumatic knee pain and swelling. His medical history was notable for pulmonary tuberculosis treated in China in 1951 and rheumatoid arthritis diagnosed in 2006. His joint pain progressed despite use of disease modifying drugs and steroid injections. Antitumor necrosis factor inhibitors were not used because of concerns of tuberculosis reactivation. Clinical examination showed he had antalgic gait, knee eff usion, stiff ness, and joint-line tenderness. Laboratory results included erythrocyte sedimentation rate of 88 mm/h and C-reactive protein of 205 mg/L. Radiographs showed severe tri-compartmental degenerative arthritis (fi gure A). The patient underwent total knee arthroplasty in August, 2012 (fi gure B). Extensive synovitis was noted and pathological examination showed granulomatous infl ammation (fi gure C). Staining of synovial tissue for acid-fast bacilli and tuberculosis PCR were negative. The patient’s knee symptoms initially improved, but 5 months after total knee arthroplasty he developed a draining sinus from the knee incision. He underwent irrigation and debridement of the knee with exchange of the polyethylene tibial insert. Initial synovial tissue fl uid cultures were negative, but subsequent acid-fast bacilli cultures from synovial tissue and joint fl uid grew Mycobacterium tuberculosis. Sputum cultures were negative for pulmonary tuberculosis. He started a course of antituberculosis therapy including rifampicin, isoniazid, pyrazinamide, and ethambutol for treatment of tuberculosis prosthetic joint infection in February, 2013. He was advised to undergo a two-stage resection-revision arthroplasty but declined further surgery and thus an implant retention strategy was pursued. The patient completed 12 months of antituberculosis therapy in February, 2014. He has since continued rifampicin and isoniazid treatment with a plan for long-term suppressive therapy in the setting of retained prosthesis. At his latest follow-up, 2 years after initial diagnosis of tuberculous prosthetic joint infection, the incision had healed without clinical sign of infection and his knee has a pain-free range of motion from 0–95°. Tuberculous arthritis accounts for 1–5% of people with tuberculosis. Scarce data are available for optimum management of tuberculous prosthetic joint infection. This case illustrates an unusual reactivation of tuberculosis in an isolated extra-pulmonary site after joint replacement surgery. Prompt initiation of antituberculosis therapy might enable implant retention, although continuation of suppressive therapy might be needed. In the setting of globalisation and the increasing use of immunomodulatory therapies and joint replacement surgeries, this case illustrates the need for tuberculosis to be thought about early in the diff erential diagnosis for culture-negative prosthetic joint infection in patients with previous exposures or epidemiological risk factors.

Two-Stage Total Knee Arthroplasty for Prosthetic Joint Infection

PurposeThis retrospective review was conducted to identify prognostic factors for two-stage reimplantation for infected total knee arthroplasty (TKA) and the rate of reinfection following revision TKA.Materials and MethodsOut of 88 patients diagnosed with post-TKA infection between 1998 and 2011, 76 underwent two-stage reimplantation and were reviewed in this study. The 76 patients were divided into two groups-those who experienced reinfection and those who did not. Comorbidities, culture results, and inflammation indices were analyzed and compared between the two groups.ResultsOf the 76 patients who underwent a two-stage reimplantation, 18 (23.7%) experienced reinfection. Patients with more than three comorbidities had significantly higher reinfection rates than those with less than three comorbidities (47.1% vs. 4.8%, p=0.032). The reinfection rate between the culture positive prosthetic joint infection group and the culture negative prosthetic joint infection group was not significantly different (p=0.056). Inflammation indices (erythrocyte sedimentation rate [ESR] and C-reactive protein [CRP]) showed a statistically significant difference between patients with reinfection and those without reinfection at 4 weeks after the first-stage surgery.ConclusionsReimplantation must be carefully performed when the risk of reinfection is high, particularly in patients with more than three systemic or local comorbidities and higher inflammation indices (ESR and CRP) prior to revision TKA.