Culture-positive Periprosthetic Joint Infection Research Articles

Clinical applications of metagenomic next-generation sequencing in the identification of pathogens in periprosthetic joint infections: a retrospective study

BackgroundThis study aimed to evaluate the application of metagenomic next-generation sequencing (mNGS) technology to identify pathogens in periprosthetic joint infection (PJI).MethodsA retrospective analysis was conducted on 65 patients suspected of having PJI between April 2020 and July 2023. The patients were categorized into PJI (46 patients) and non-PJI (19 patients) groups based on the 2018 International Consensus Meeting criteria. Clinical data were collected, and both conventional bacterial culture and mNGS were performed. The diagnostic performance of the two methods was compared and analyzed.ResultsmNGS exhibited a sensitivity of 89.13%, a specificity of 94.74%, a positive predictive value of 97.62%, a negative predictive value of 78.26%, and an overall diagnostic accuracy of 90.77%. Compared to microbial culture, mNGS demonstrated superior diagnostic sensitivity while maintaining similar specificity. A total of 48 pathogens were successfully identified using mNGS, with Coagulase-negative staphylococci, Streptococci, Staphylococcus aureus, and Cutibacterium acnes being the most common infectious agents. Notably, mNGS was used to identify 17 potential pathogens in 14 culture-negative PJI samples, highlighting its ability to detect rare infectious agents, including Cutibacterium acnes (n = 5), Granulicatella adiacens (n = 1), Mycobacterium tuberculosis complex (n = 1), and Coxiella burnetii (n = 1), among others, which are not detectable by routine culture methods. However, mNGS failed to detect the pathogen in 4 culture-positive PJI patients, indicating its limitations. Among the 46 PJI patients, 27 had positive culture and mNGS results. The results of mNGS were concordant with those of culture at the genus level in 6 patients with PJI and at the species level in 18 patients. Furthermore, the present study revealed a significantly greater proportion of Staphylococcus aureus in the sinus tract group (45.45%) than in the non-sinus tract group (14.29%), indicating the association of this pathogen with sinus formation in PJI (P = 0.03). Additionally, there was no significant difference in the occurrence of polymicrobial infections between the sinus tract group (27.27%) and the non-sinus tract group (33.33%) (P = 0.37).ConclusionsMetagenomic next-generation sequencing can serve as a valuable screening tool in addition to traditional culture methods to improve diagnostic accuracy through optimized culture strategies.

Efficacy and safety of two-stage revision for patients with culture-negative versus culture-positive periprosthetic joint infection: a single-center retrospective study

BackgroundThe safety and efficacy of two-stage revision for culture-negative PJI remain controversial. This study analyzed outcomes after two-stage revision in patients with culture-negative and culture-positive periprosthetic joint infection (PJI) during follow-up lasting at least two years.MethodsData were retrospectively analysed patients who underwent hip or knee revision arthroplasty from January 2008 to October 2020 at our medical center. The primary outcome was the re-revision rate, while secondary outcomes were the rates of reinfection, readmission, and mortality. Patients with culture-negative or culture-positive PJI were compared in terms of these outcomes, as well as survival time without reinfection or revision surgery, based on Kaplan‒Meier analysis.ResultsThe final analysis included 87 patients who were followed up for a mean of 72.3 months (range, 24–123 months). The mean age was 58.1 years in the culture-negative group (n = 24) and 59.1 years in the culture-positive group (n = 63). The two groups (culture-negative versus culture-positive) did not differ significantly in rates of re-revision (0.0% vs. 3.2%, p > 0.05), reinfection (4.2% vs. 3.2%, p > 0.05), readmission (8.4% vs. 8.0%, p > 0.05), or mortality (8.3% vs. 7.9%, p > 0.05). They were also similar in survival rates without infection-related complications or revision surgery at 100 months (91.5% in the culture-negative group vs. 87.9% in the culture-positive group; Mantel‒Cox log-rank χ2 = 0.251, p = 0.616).ConclusionThe two-stage revision proves to be a well-tolerated and effective procedure in both culture-negative and culture-positive PJI during mid to long-term follow-up.

Second-Line Antibiotic Agents in Patient-Reported Penicillin or Cephalosporin Allergy Have No Negative Impact on Antibiotic Resistance After Hip and Knee Arthroplasty

BackgroundThe aim of the present study was to compare causative bacteria and their antibiotic resistance profiles in patients developing a periprosthetic joint infection (PJI) based on preoperative prophylactic antibiotic regimens in primary total hip (THA) and primary total and unicompartmental knee arthroplasty (TKA/UKA). MethodsWe reviewed all cases of PJI occurring after primary THA and primary TKA/UKA, between 2011 and 2020 in a tertiary referral hospital. The standard preoperative prophylactic antibiotic for primary joint arthroplasty was cefuroxime and recommended second-line agent was clindamycin. Patients were divided by the replaced joint and analyzed independently. ResultsIn the THA group, culture-positive PJI was detected in 61 of 3,123 (2.0%) cefuroxime-administered cases and 6 of 206 (2.9%) noncefuroxime-administered cases. In the TKA/UKA group, culture positive PJI was identified in 21 of 2,455 (0.9%) cefuroxime-administered cases and in 3 of 211 (1.4%) noncefuroxime administered cases. The most commonly isolated bacteria in both groups were coagulase negative staphylococci (CNS). There were no statistically significant differences of pathogen spectrum depending on the preoperative antibiotic regimen detected. Antibiotic resistance of isolated bacteria was significantly different in 4 of 27 (14.8%) analyzed antibiotics in THA and in 3 of 22 (13.6%) analyzed antibiotics in TKA/UKA. In all cohorts, a high occurrence of oxacillin-resistant CNS (50.0 to 100.0%) and clindamycin-resistant CNS (56.3 to 100.0%) has been observed. ConclusionThe use of the second-line antibiotic did not influence the pathogen spectrum or antibiotic resistance. However, an alarmingly high proportion of CNS strains was resistant to clindamycin.

Multiplex PCR-based next generation sequencing as a novel, targeted and accurate molecular approach for periprosthetic joint infection diagnosis.

Periprosthetic joint infection (PJI) diagnosis remains challenging, and the identification of the causative microorganism is, by far, the most important aspect. Here, we use multiple PCR-based targeted next-generation sequencing (tNGS) to detect pathogens in PJI. To explore 1. the ability of targeted next-generation sequencing (tNGS) to detect pathogens in PJI; 2. the consistency of tNGS, metagenomic NGS (mNGS), and culture results; and 3. the ability of tNGS to detect drug resistance genes in PJI. PJI was diagnosed according to the Musculoskeletal Infection Society (MSIS) criteria. The microorganisms were detected by culture, mNGS and tNGS to compare the diagnostic effectiveness of the three methods for PJI and to compare their consistency in detecting microorganisms. Drug resistance genes were detected using tNGS. The costs and turnaround times of mNGS and tNGS were compared. Forty-three patients with PJI, 21 patients without PJI and 10 negative control cases were included. The culture, tNGS, and mNGS sensitivities for PJI diagnosis were 74.41%, 88.37%, and 93.02%, respectively, with no significant differences. The specificities were 90.48%, 95.24%, and 95.24%, respectively, with no significant differences. tNGS detected drug resistance genes in 37.5% of culture-positive PJIs. tNGS was superior to mNGS for turnaround time (14.5 h vs. 28 h) and cost ($150 vs. $260). tNGS can effectively identify PJI pathogens and may provide drug resistance information, while tNGS is superior to mNGS regarding cost and turnaround time. A multidisciplinary, multi-technology based algorithm to diagnose PJI is appropriate. 298 microorganisms and 86 drug resistance genes were included in the tNGS panel.Diagnostic efficacy of tNGS is not inferior to that of commonly used indicators.tNGS is superior to mNGS in cost and turnaround time.

Clinical outcomes of two-stage revision for chronic periprosthetic joint infection of the knee: culture-negative versus culture-positive

BackgroundThe effect of negative culture on the treatment outcomes of chronic periprosthetic joint infection (PJI) is still controversial. The purpose of this study is to evaluate whether the outcomes of two-stage revision in culture-negative chronic PJI differ from those in culture-positive PJI.MethodsThe patients who received two-stage revisions due to chronic PJI during the period between 2007 and 2017 were retrospectively reviewed. The culture-negative and culture-positive PJI group included 57 cases and 79 cases, respectively. The demographic data, as well as reoperation, mortality, reinfection, and failure rates of each group were evaluated.ResultsThere was a significant difference in reoperation rate between the two groups for the period from the first-stage surgery to the second-stage revision arthroplasty (p = 0.045). The reoperation rate of the culture-positive group was 25.3% (20/79) whereas that of the culture-negative group was 10.5% (6/57). Among the 136 PJI cases, 97 cases (71.3%) received reimplantation surgery (culture-negative group, 43 cases; culture-positive group, 54 cases). No significant difference was noted between the culture-negative and culture-positive groups with respect to the number of cases that did not undergo reimplantation surgery and the reoperation, reinfection, mortality, and failure rates after two-stage surgery (p > 0.05, all parameters).ConclusionsThe culture outcome had no significant effect on the outcome of the two-stage revision in patients with chronic PJI. The reoperation rate after first-stage surgery was significantly higher in the culture-positive group, but the overall failure rate did not significantly differ in both the groups. The presence of a negative culture might be a good prognostic factor for chronic PJI.

Emergence of Antibiotic Resistance Across Two-Stage Revision for Periprosthetic Joint Infection

BackgroundThe current preferred treatment for chronic hip and knee periprosthetic joint infection (PJI) involves both surgical intervention and antibiotic treatment as part of a two-stage revision. The purpose of this study is to determine how often patients who underwent a two-stage revision for chronic PJI developed a subsequent antibiotic-resistant infection. MethodsWe retrospectively reviewed the clinical records of 142 patients who underwent a two-stage revision for a chronic culture-positive PJI from January 2014 to May 2019. Demographic data and risk factors for PJI were identified. Resistance was defined in accordance with microbiology laboratory report and minimum inhibitory concentration. Statistical analysis consisted of descriptive statistics and univariate analysis. ResultsOnly 10 of the 142 patients (7.04%) demonstrated emergence of resistance to antibiotics across their two-stage revision. At reimplantation, 25 (17.6%) patients had positive cultures. Of these, 16 patients presented with a novel organism and 9 patients had positive culture for the same organism as the initial infection. During the entire course of the two-stage revision, including spacer exchanges and irrigation and debridement procedures, 15 (10.56%) patients demonstrated persistent infections, whereas 25 (17.6%) patients presented with novel infections. 26 (18.3%) patients had reinfection of the same joint within one year. ConclusionIn the given cohort, there does not appear to be a major emergence of antibiotic resistant organisms in patients undergoing two-stage exchange arthroplasty and antibiotic treatment.

Presentation and Outcomes of Peri-Prosthetic Joint Infection: A Comparison of Culture-Positive and Culture-Negative Disease.

Background: Peri-prosthetic joint infection (PJI) is a debilitating and costly complication of joint replacement. Synovial fluid cultures are negative in up to 25% of PJI cases. The purpose of this study was to compare the clinical characteristics and outcomes of culture negative and culture positive PJI. Patients and Methods: We conducted a retrospective study including all patients aged 18 and older admitted to a single tertiary-care hospital between 1998 and 2015 diagnosed with PJI and treated with antibiotic agents and surgery. Results: One hundred ninety-six patients with PJI were identified; 48 (24.5%) were culture-negative (CN) and 148 (75.5%) were culture-positive (CP). The groups were similar in age and presence of associated comorbidities. Fever was more common among the CP patients (CN, 23.8%; CP, 38.4%; p = 0.03) as was sepsis defined by Sepsis-2 criteria (CN, 12.8%; CP, 28.7%; p = 0.03). Patients who were CP had higher synovial white blood cell (WBC) count (CN, 30,500 per milliliter; CP, 95,400 per milliliter; p < 0.01), a longer length of stay (CN, 3.8%; CP,7.9%; p = 0.02), and fewer alternative diagnoses established within one year (CN, 25.0%; CP, 2.7%; p < 0.01). Our logistic regression models also found that CP patients had an adjusted odds ratio (OR) of 2.59 for rehabilitation placement with 95% confidence interval (CI) of 1.15-5.83 and adjusted OR of 0.04 for an alternative diagnosis within one year with 95% CI, 0.009-0.22 compared with their CN counterparts. Conclusions: This study suggests that patients with CN PJI have less severe disease, better outcomes, and higher rates of alternative diagnoses within one year.

Preoperative synovial fluid culture poorly predicts the pathogen causing periprosthetic joint infection

PurposeWe investigated the value of preoperative pathogen detection and evaluated its concordance with intraoperative cultures in patients with culture-positive periprosthetic joint infection (PJI).MethodsCulture-positive PJI episodes with available preoperative (synovial fluid) and intraoperative cultures (periprosthetic tissue, synovial or sonication fluid) were analyzed. The pathogen detection rate in preoperative and intraoperative cultures was compared using Fisher’s exact test and their concordance was calculated.ResultsAmong 167 included PJI episodes, 150 were monomicrobial with coagulase-negative staphylococci (n = 55, 37%), S. aureus (n = 34, 23%), and streptococci (n = 21, 14%) being the most common pathogens. Seventeen episodes (10%) were polymicrobial infections. The pathogen(s) grew in preoperative culture in 110 and in intraoperative cultures in 153 episodes (66% vs. 92%, p < 0.001). The pathogen detection rate was lower in preoperative compared to intraoperative cultures for low-virulent pathogens (40% vs. 94%, p < 0.001), polymicrobial infections (59% vs. 100%, p = 0.007), and in delayed and late PJI (63% vs. 94%, and 66% vs. 91%, respectively, p < 0.001). Full concordance of preoperative and intraoperative cultures was found in 87 episodes (52%). The pathogen was detected solely preoperatively in 14 episodes (8%) and solely intraoperatively in 57 cases (34%); an additional pathogen was found in 3 episodes (2%) preoperatively and in 6 episodes (4%) intraoperatively.ConclusionThe concordance of preoperative and intraoperative cultures was poor (52%). The sole or an additional pathogen was found exclusively in intraoperative cultures in 38% of PJI episodes, hence preoperative synovial fluid cultures are considered unreliable for pathogen detection in PJI.

Outcome of Debridement, Antibiotics, and Implant Retention With Modular Component Exchange in Acute Culture-Negative Periprosthetic Joint Infections

BackgroundModular component exchange and culture-directed antibiotic treatment is routinely employed for acute periprosthetic joint infection (PJI). However, as many as 7%-23% of PJIs have been reported to yield negative culture results. The efficacy of debridement, antibiotics, and implant retention (DAIR) with modular component exchange in the setting of acute culture negative PJI remains largely unknown. The aim of our study is to evaluate the outcomes of DAIR with modular component exchange in acute culture-positive and culture-negative PJI. MethodsA total of 149 consecutive patients with primary total joint replacements (90 total knee arthroplasties and 59 total hip arthroplasties) who underwent DAIR with modular component exchange for acute PJI with at least 3 years of follow-up were evaluated: (1) 46 culture-negative PJI patients and (2) 103 culture-positive PJI patients. Reinfection and aseptic revision rates along with complication rates were compared. ResultsThe reinfection rate for DAIR in acute culture-negative PJI was 13.0% compared to 19.4% in culture-positive PJI (P = .48). Mean survival time from reinfection between culture-negative (7.7 ± 0.4 years) and culture-positive (7.4 ± 0.3 years) PJI groups did not differ significantly (P = .40). Aseptic revision rates were 8.7% and 4.9% (P = .46), respectively, with loosening being the primary reason for implant failure in both cohorts. ConclusionsDespite lack of an identifying organism to guide postoperative antibiotic therapy, DAIR with modular component exchange for acute culture-negative PJI was associated with similar reinfection rates compared to acute culture-positive PJI, suggesting that culture negativity may not be a contraindication to DAIR in patients with acute PJI.

Detection of periprosthetic joint infection pathogens by metagenomic next-generation sequencin

Objective To investigate and compare the capability of metagenomic next-generation sequencing (mNGS) in detecting pathogens and diagnosing of periprosthetic joint infection (PJI) from synovial fluid and sonicate fluid of patients who underwent revision arthroplasty. Methods Thirty-five consecutive patients who underwent revision arthroplasty from May 2018 to November 2018 were included prospectively. There were 22 males and 13 females, 11 hip revisions and 24 knee revisions. All the patients were divided into the PJI group and aseptic loosening (AL) group. Synovial fluid and sonicate fluid of the explanted prostheses were obtained for microbiological culture and mNGS tests. Periprosthetic tissues were only collected for culture. Synovial fluid of three patients undergoing primary arthroplasty been treated by sonication as the negative control group concurrently. Comparisons of microbiological results and diagnostic value from mNGS and culture tests were performed. Results In the 13 culture-positive PJI patients, mNGS results of synovial fluid were positive in 12 cases, while culture and mNGS results were completely consistent at species level in 7 cases, consistent at the genus level in 1 case. mNGS results of sonicate fluid were positive in 13 cases, while culture and mNGS results were completely consistent at species level in 9 cases, consistent at the genus level in 1 case. In 7 culture-negative PJI patients, 6 cases had consistent mNGS results at species level both from synovial fluid and sonicate fluid, however, one case had positive mNGS result only from sonicate fluid. All culture results and mNGS results of synovial fluid were negative in all 15 AL patients, however, mNGS results of sonicate fluid was positive in 1 AL case. Cultures and mNGS results were negative in all three pairs of negative-control samples. In all 70 samples, mNGS detected 24 pathogens in sonicate fluids and 22 pathogens in synovial fluids. There was no significant difference in number of raw reads and human reads ratio between mNGS of sonicate fluid and synovial fluid. mNGS of sonicate fluid generated significantly higher number of microbial reads and of stringently mapped reads of pathogen in species-level than that of synovial fluids. There was no significant difference in diagnostic sensitivity of PJI between mNGS of sonicate fluids and synovial fluids (90.0% vs 100.0%). Both of them were significantly higher than that of culture of synovial fluid, periprosthetic tissues. Diagnostic sensitivity of sonicate fluid mNGS was not significantly higher than that in culture of sonicate fluid (65%). The specificities were similar among various microbiological testing methods. Conclusion mNGS of either synovial fluid or sonicate fluid from patients who underwent revision arthroplasty can be used to detect the presence of pathogens effectively and diagnose PJI accurately. mNGS can identify more pathogens and generate a higher number of pathogenic reads from sonicate fluids than synovial fluid. mNGS of synovial fluids has met the clinical diagnostic demands for most PJI patients. mNGS of sonicate fluid could be applied in some cases. Key words: Metagenomics; Prosthesis-related infections; Molecular diagnostic techniques; Sonication

Long-term clinical outcome of two-stage revision surgery for infected hip arthroplasty using cement spacer: Culture negative versus culture positive.

Periprosthetic joint infection (PJI) is a terrible complication after hip arthroplasty. Clinical feature of culture-negative PJI (CN-PJI) has not been well studied till now. In our study, we retrospectively analyzed long-term clinical results after two-stage revision arthroplasty using an antibiotic-impregnated cement spacer for CN-PJI. The purpose of this study is to investigate the clinical features and prognosis of CN-PJI after hip arthroplasty and to compare these with those of culture-positive PJI (CP-PJI). We retrospectively reviewed 15 CN-PJI cases and 70 CP-PJI cases following hip arthroplasty. The average follow-up period was 7.4 years (5-11.7 years). The demographics, laboratory findings, the time interval between antibiotic-impregnated cement spacer insertion and revision arthroplasty, and recurrence of infection were analyzed. The CN-PJI group showed a significantly higher incidence of prior antibiotic use ( p = 0.004) and lower serum C-reactive protein (CRP) level ( p = 0.001) than the CP-PJI group. Normalized time interval of CRP level in CN-PJI was shorter than that of CP-PJI group. The mean interval time for two-stage exchange arthroplasty was also significantly lower ( p = 0.049) in the CN-PJI group than the CP-PJI group. There was no case of treatment failure or major complication in CN-PJI group. The CN-PJI group after total hip arthroplasty could be treated successfully by two-stage exchange arthroplasty without any complications. Clinical course and prognosis of CN-PJI group was also better compared with that of CP-PJI group. Therefore, culture negativity of PJI cannot be always a poor prognostic factor for the treatment.

Direct Detection and Identification of Prosthetic Joint Pathogens in Synovial Fluid (SF) by Metagenomic Shotgun Sequencing

BackgroundDetection and identification of microorganism(s) involved in periprosthetic joint infection (PJI) can inform surgical management and directed antibiotic therapy. Metagenomic shotgun sequencing is a powerful tool with the potential to change how many PJIs are diagnosed as it allows direct detection and identification of pathogens in clinical specimens. In the largest series to date, we utilized a metagenomics-based approach applied to SF to define potential microbial etiologies of failed total knee arthroplasties (TKAs).MethodsSynovial fluid was collected from 112 failed TKAs [74 PJI and 38 aseptic implant failure (AF)] via preoperative arthrocentesis. Cell count and differential, standardized culture and DNA-based metagenomic shotgun sequencing were performed. Human DNA was depleted using the MolYsis basic kit prior to DNA extraction, whole genome amplification, and sequencing. Taxonomic assignment of reads and pathogen identification was achieved using a pipeline incorporating k-mer- and marker gene-based classification software. A scheme for analysis and filtration of false-positives was created and applied, incorporating cut-offs for the number of reads, quality scores, and coverage across a reference genome. Patients were classified as having PJI using the IDSA criteria and expert review. Analyses were recorded as percent agreement, with 95% confidence intervals (CI), of metagenomics to SF culture.ResultsMetagenomic analysis identified the known pathogen in 54 (90%) (CI, 79.5%–96.2%) of the 60 culture-positive PJIs analyzed and one (2%) (CI, 0.0%–8.9%) potential polymicrobial infection not detected by culture. For the 14 culture-negative PJIs tested, metagenomics showed 79% (CI, 49.2%–95.3%) agreement for negative findings; potential pathogens were identified in three (21%) (CI, 4.7%–50.8%) culture-negative PJI cases, with one being polymicrobial. Of the 37 culture-negative AF cases, metagenomics showed 97% (CI, 85.8%–99.9%) agreement with negative culture and identified one (3%) (CI, 0.0%–14.2%) potential pathogen. For the one culture-positive AF case, metagenomic results were negative, suggesting possible culture contamination.ConclusionMetagenomic shotgun sequencing performed on SF can be used to diagnose PJI and may be particularly useful for culture-negative PJI.Disclosures R. Patel, ASM: Board Member, None; CD Diagnostics, BioFire, Curetis, Merck, Hutchison Biofilm Medical Solutions, Accelerate Diagnostics, Allergan, and The Medicines Company: Grant Investigator, Grant recipient; Curetis: Consultant, Monies paid to my employer; A patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic, and a patent on an anti-biofilm substance issued: Patents, Patents, any money is paid to my employer; Actelion: DSMB, Money paid to my employer; ASM and IDSA: Editor’s stipends, Editor’s stipends; NBME, Up-to-Date and the Infectious Diseases Board Review Course: NBME, Up-to-Date and the Infectious Diseases Board Review Course, Honoraria; Roche, ASM, and IDSA: Travel reimbursement, Travel reimbursement

Culture-negative Periprosthetic Joint Infection Does Not Preclude Infection Control

Periprosthetic joint infection (PJI) is a devastating complication after total joint arthroplasty. Lack of confirmation of an infecting organism poses a challenge with regard to the selection of an appropriate antibiotic agent and surgical treatment. It is unclear whether patients with negative cultures presumed to have infections achieve similar rates of infection-free survival as those with positive cultures. The purposes of this study were (1) to report the infection control rates using irrigation and débridement and two-stage exchange for treatment of culture-negative PJIs; and (2) to compare infection control rates in culture-negative cases with those in culture-positive cases. We retrospectively reviewed 55 patients with culture-negative PJI treated between 2000 and 2007. We compared the infection-free survival rate in the culture-negative patients with that of 295 culture-positive cases of PJI. Overall infection control rate in culture-negative cases was 73% at minimum 1-year followup (mean, 47 months; range, 12-119 months). We found similar infection control rates in culture-negative and culture-positive PJI. Infection-free survival rates in both groups were highest after two-stage exchange arthroplasty and postoperative vancomycin therapy. Our observations suggest aggressive two-stage exchange arthroplasty and postoperative parenteral vancomycin therapy in patients with culture-negative PJI achieves similar rates of infection-free survival as with patients having culture-positive PJI. Level III, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.