The Clinical Challenge of Prosthetic Valve Endocarditis: JACC Focus Seminar 3/4.

During the past 6 decades, there have been numerous changes in prosthetic valve endocarditis (PVE), currently affecting an older population and increasing in incidence in patients with transcatheter-implanted valves. Significant microbiologic (molecular biology) and imaging diagnostic (fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography) advances have been incorporated into the 2023 Duke-International Society for Cardiovascular Infectious Diseases infective endocarditis diagnostic criteria, thus increasing the diagnostic sensitivity for PVE without sacrificing specificity in validation studies. PVE is a life-threatening disease requiring management by multidisciplinary endocarditis teams in cardiac centers to improve outcomes. Novel surgical options are now available, and an increasing set of patients may avoid surgical intervention despite indication. Selected patients may complete parenteral or oral antimicrobial treatment at home. Finally, patients with prosthetic valves implanted surgically or by the transcatheter approach are candidates for antibiotic prophylaxis before invasive dental procedures.

Optimal selection of specimens for metagenomic next-generation sequencing in diagnosing periprosthetic joint infections.

Objective: This study aimed to assess the diagnostic value of metagenomic next-generation sequencing (mNGS) across synovial fluid, prosthetic sonicate fluid, and periprosthetic tissues among patients with periprosthetic joint infection (PJI), intending to optimize specimen selection for mNGS in these patients. Methods: This prospective study involved 61 patients undergoing revision arthroplasty between September 2021 and September 2022 at the First Affiliated Hospital of Zhengzhou University. Among them, 43 cases were diagnosed as PJI, and 18 as aseptic loosening (AL) based on the American Musculoskeletal Infection Society (MSIS) criteria. Preoperative or intraoperative synovial fluid, periprosthetic tissues, and prosthetic sonicate fluid were collected, each divided into two portions for mNGS and culture. Comparative analyses were conducted between the microbiological results and diagnostic efficacy derived from mNGS and culture tests. Furthermore, the variability in mNGS diagnostic efficacy for PJI across different specimen types was assessed. Results: The sensitivity and specificity of mNGS diagnosis was 93% and 94.4% for all types of PJI specimens; the sensitivity and specificity of culture diagnosis was 72.1% and 100%, respectively. The diagnostic sensitivity of mNGS was significantly higher than that of culture (X2 = 6.541, P=0.011), with no statistically significant difference in specificity (X2 = 1.029, P=0.310). The sensitivity of the synovial fluid was 83.7% and the specificity was 94.4%; the sensitivity of the prosthetic sonicate fluid was 90.7% and the specificity was 94.4%; and the sensitivity of the periprosthetic tissue was 81.4% and the specificity was 100%. Notably, the mNGS of prosthetic sonicate fluid displayed a superior pathogen detection rate compared to other specimen types. Conclusion: mNGS can function as a precise diagnostic tool for identifying pathogens in PJI patients using three types of specimens. Due to its superior ability in pathogen identification, prosthetic sonicate fluid can replace synovial fluid and periprosthetic tissue as the optimal sample choice for mNGS.

Identification of prosthetic joint infections with 16S amplicon metagenomic sequencing - comparison with standard cultivation approach.

Prosthetic joint infections (PJIs) are commonly diagnosed via culture-based methods, which may miss hard-to-grow pathogens. This study contrasts amplicon metagenomic sequencing (16S AS) with traditional culture techniques for enhanced clinical decision-making. We analyzed sonicate fluid from 27 patients undergoing revision arthroplasty using both methods, emphasizing the distinction between contaminants and true positives. Our findings show moderate agreement between the two methods, with a Cohen's kappa of 0.490, varying across bacterial genera (Cohen's kappa -0.059 to 1). The sensitivity of 16S AS compared to culture was 81% (95% CI, 68% to 94%). Sequencing revealed greater microbial diversity, including anaerobic genera like Anaerococcus and Citrobacter. Interestingly, several culture-negative PJI samples showed diverse bacteria via 16S AS. Despite rigorous controls and algorithms to eliminate contaminants, confirming bacteria presence with 16S AS remains a challenge. This highlights the need for improved PJI diagnostic methods, while also pointing out the limitations of next-generation sequencing (NGS) as a clinical diagnostic tool.

Rapid high-throughput processing of tissue samples for microbiological diagnosis of periprosthetic joint infections using bead-beating homogenization.

Enrichment of periprosthetic tissue samples in blood culture bottles (BCBs) for microbiological diagnosis of periprosthetic joint infections (PJI) is more reliable than the use of an enrichment broth. Nevertheless, the extremely time-consuming homogenization of the samples for BCB processing has so far limited its use, especially in high-throughput settings. We aimed to establish a highly scalable homogenization process of tissue samples for long-term incubation in BCBs. A protocol for homogenization of tissue samples using bead beating was established and validated. In a second step, the use of the homogenate for enrichment in BCBs was compared to the use of thioglycolate broth (TB) in terms of diagnostic accuracy using clinical tissue samples from 150 patients with suspected PJI. Among 150 analyzed samples, 35 samples met the microbiological criteria for PJI. Using BCB, 32 of 35 (91.4%) PJI were detected compared to 30 of 35 (85.7%) by TB. The use of BCB had a lower secondary contamination rate (2/115; 1.7% vs 4/115; 3.5%) but the trend was not significant due to low numbers of samples (P = 0.39). The time to process a batch of 12 samples using the established homogenization method was 23 ± 5 min (n = 10 batches). We established and validated a homogenization workflow that achieves the highest sensitivity in the microbiological diagnostic of PJI. The enrichment of the tissue homogenate in BCBs showed equally good results as the use of enrichment broth and allows semi-automated high-throughput processing while demonstrating lower contamination rates in our study.

Organism profile and C-reactive protein (CRP) response are different in periprosthetic joint infection in patients with hepatitis.

PURPOSE: Hepatitis B and C are important and relatively common health issues. It is known that many patients who underwent total knee and hip arthroplasty were also diagnosed with hepatitis. These patients are at higher risk of periprosthetic joint infection (PJI). This study aimed to investigate the differences in PJI cases in hepatitis B and C patients. METHODS: This is a retrospective case-controlled single-center study. A total of 270 patients with hepatitis and non-hepatitis (control group) who underwent one-stage septic exchange to the hip and knee joints were included in the study. All patients' previous surgical histories, infective organisms, C-reactive protein (CRP) values before septic exchange, and demographic data were evaluated. All microbiological and laboratory evaluations were performed separately for knee and hip arthroplasty. RESULTS: The mean CRP levels of Hep B- and C-positive patients, who underwent one-stage septic exchange in the knee joint, were 23.6 mg/L. In the control group, this value was 43.1 mg/L and a statistically significant difference was found between the groups (p = 0.004). Gram-negative organisms were identified in a larger proportion of patients with hepatitis who developed PJI in both hip and knee joints and underwent one-stage septic exchange (p = 0.041/p = 0.044). CONCLUSION: PJIs caused by Gram-negative bacteria are encountered more frequently in patients with hepatitis than in the control group. In addition, the CRP rise is less in patients with hepatitis compared to PJI cases in the control group. Patient-specific evaluation is required in cases of PJI in patient groups with co-existing hepatitis.

Periprosthetic joint infection and immunity: Current understanding of host-microbe interplay.

Periprosthetic joint infection (PJI) is a major complication of total joint arthroplasty. Even with current treatments, failure rates are unacceptably high with a 5-year mortality rate of 26%. Majority of the literature in the field has focused on development of better biomarkers for diagnostics and treatment strategies including innovate antibiotic delivery systems, antibiofilm agents, and bacteriophages. Nevertheless, the role of the immune system, our first line of defense during PJI, is not well understood. Evidence of infection in PJI patients is found within circulation, synovial fluid, and tissue and include numerous cytokines, metabolites, antimicrobial peptides, and soluble receptors that are part of the PJI diagnosis workup. Macrophages, neutrophils, and myeloid-derived suppressor cells (MDSCs) are initially recruited into the joint by chemokines and cytokines produced by immune cells and bacteria and are activated by pathogen-associated molecular patterns. While these cells are efficient killers of planktonic bacteria by phagocytosis, opsonization, degranulation, and recruitment of adaptive immune cells, biofilm-associated bacteria are troublesome. Biofilm is not only a physical barrier for the immune system but also elicits effector functions. Additionally, bacteria have developed mechanisms to evade the immune system by inactivating effector molecules, promoting killing or anti-inflammatory effector cell phenotypes, and intracellular persistence and dissemination. Understanding these shortcomings and the mechanisms by which bacteria can subvert the immune system may open new approaches to better prepare our own immune system to combat PJI. Furthermore, preoperative immune system assessment and screening for dysregulation may aid in developing preventative interventions to decrease PJI incidence.

Therapeutic efficacy of vancomycin-loaded carbon fiber-reinforced polyetheretherketone hip stem for periprosthetic joint infection: A pilot study.

A carbon fiber-reinforced polyetheretherketone (CFR/PEEK) hip stem with a special antibiotic elution mechanism is under development to treat periprosthetic joint infection (PJI). The antibiotic elution characteristics of intramedullary implants were experimentally investigated, and the efficacy of revision surgery using a therapeutic stem in treating ovine PJI was examined. To evaluate elution characteristics, the intramedullary vancomycin-loaded CFR/PEEK cylindrical implants were inserted in the distal femur of nine sheep, and the vancomycin elution rate was measured at 2, 7, and 21 days. To evaluate therapeutic efficacy, the PJI model with staphylococcus aureus was attempted to create for five sheep. Moreover, the therapeutic vancomycin-loaded CFR/PEEK stem was implanted during one-stage revision surgery. Three weeks after revision surgery, the treatment efficacy was evaluated based on bacterial cultures and wound findings. In addition, the vancomycin elution rate from the stem was measured. On average, the cylindrical implants eluted approximately 70% vancomycin in 21 days. Of the five sheep attempting to create a PJI model, three were successfully infected with S. aureus as intended for verification of treatment efficacy. In all three joints, negative bacterial cultures and no purulence were observed 3 weeks after revision surgery. The vancomycin elution rates from the stems were >70%. Efficient elution of vancomycin was confirmed by the experimental implant inserted into the bone marrow and the stem in actual PJI treatment. Using a novel therapeutic stem with an antibiotic elution mechanism in one-stage revision surgery, successful treatment was demonstrated in all S. aureus-induced PJIs.

Isolated mitral valve endocarditis: Patient, disease, and surgical factors that influence outcomes.

OBJECTIVE: The objectives of this study were to investigate patient characteristics, valve pathology, bacteriology, and surgical techniques related to outcome of patients who underwent surgery for isolated native (NVE) or prosthetic (PVE) mitral valve endocarditis. METHODS: From January 2002 to January 2020, 447 isolated mitral endocarditis operations were performed, 326 for NVE and 121 for PVE. Multivariable analysis of time-related outcomes used random forest machine learning. RESULTS: Staphylococcus aureus was the most common causative organism. Of 326 patients with NVE, 88 (27%) underwent standard mitral valve repair, 43 (13%) extended repair, and 195 (60%) valve replacement. Compared with NVE with standard repair, patients who underwent all other operations were older, had more comorbidities, worse cardiac function, and more invasive disease. Hospital mortality was 3.8% (n = 17); 0 (0%) after standard valve repair, 3 (7.0%) after extended repair, 8 (4.1%) after NVE replacement, and 6 (5.0%) after PVE re-replacement. Survival at 1, 5, and 10 years was 91%, 75%, and 62% after any repair and 86%, 62%, and 44% after replacement, respectively. The most important risk factor for mortality was renal failure. Risk-adjusted outcomes, including survival, were similar in all groups. Unadjusted extended repair outcomes, particularly early, were similar or worse than replacement in terms of reinfection, reintervention, regurgitation, gradient, and survival. CONCLUSIONS: A patient- and pathology-tailored approach to surgery for isolated mitral valve endocarditis has low mortality and excellent results. Apparent superiority of standard valve repair is related to patient characteristics and pathology. Renal failure is the most powerful risk factor. In case of extensive destruction, extended repair shows no benefit over replacement.

Prosthetic joint infections: 6 weeks of oral antibiotics results in a low failure rate.

BACKGROUND: Need for parenteral administration and total duration of antibiotic therapy for prosthetic joint infection (PJI) are debated. We report our PJI management, in which outpatient care is privileged. METHODS: This was a retrospective multicentre cohort study of PJI managed from January 2017 to Jun 2021. Microbial diagnosis was based on surgical samples. Surgical procedures and antibiotic treatments were reported. Chronic PJI was defined by a course >1 month. Oral antibiotic therapy (OAT) was defined by exclusive use of oral antibiotics or by ≤3 days of parenteral treatments. Management failure was defined by clinical and/or microbial relapse of PJI over 24 months after surgical treatment. RESULTS: One hundred and seventy-two patients from 13 institutions were included: 103 were male (60%) and mean age was (±SD): 73 ±â€Š12 years. Sites for PJI were mainly hip (50%) and knee (35%), being chronic infections in 70 cases (41%). The main bacterial genus in monomicrobial infections was Staphylococcus spp. (60%). We recorded 41 (24%) implant exchanges. An OAT was prescribed in 76 cases (44%), and the median (range) course for parenteral route was 6 days (4-180) for 96 cases. Median (range) duration of antimicrobials was 42 days (21-180). Management failure was observed in 7/76 (9.2%) cases treated with OAT and 15/96 (15.6%) treated with prolonged parenteral therapy. In multivariate analysis, risk factors for failure were a knee PJI [adjusted OR (95% CI) = 3.27 (1.27-8.40)] and a polymicrobial infection [4.09 (1.46-11.49)]. CONCLUSIONS: OAT for 6 weeks for PJI was associated with a low rate of management failure.

Do All Prosthetic Joint Infection Clinical Isolates Form Aggregates in Synovial Fluid That Are Resistant to Antibiotic Agents?

Background: Chronic prosthetic joint infections (PJI) are associated with substantial morbidity because conventional antibiotic agents lack activity to bacteria in biofilms that necessitates prosthetic removal to attempt definitive cure. However, these are complex infections that go beyond biofilms and bacteria can be present in various other different states such as synovial fluid aggregates. Consequently, the purpose of this study was to assess the propensity of historically preserved PJI clinical isolates to form synovial fluid aggregates and if aggregation occurred then what is proclivity to be tolerant to high doses of antibiotic agents. Patients and Methods: Historically preserved chronic PJI clinical isolates from 2021 were evaluated for their ability to form synovial fluid aggregates under static and dynamic conditions in 24-microwell plates. Tolerance to vancomycin, gentamicin, or amphotericin was conducted by adding high concentrations of these antibiotic agents to synovial fluid microbial aggregates. Results: All clinical isolates formed synovial fluid aggregates under dynamic conditions, which with the use of scanning electron microscopy showed dense collections of bacteria with synovial fluid polymers. However, under static conditions only Staphylococcus aureus formed aggregates. Importantly, all the microbes in these aggregates were tolerant to high concentrations of antibiotic agents. Conclusions: This study demonstrates that synovial fluid aggregation occurred with all bacterial and fungal species assessed. Therefore, the findings here have important clinical ramifications given the extent that this phenomenon occurs across microbial species and the propensity for the microbes in these aggregates to be tolerant to antibiotic agents.

Isothermal microcalorimetry improves accuracy and time to bacterial detection of periprosthetic joint infection after total joint arthroplasty.

Isothermal microcalorimetry (IMC) was evaluated compared to conventional cultures to determine the clinical performance for diagnosing periprosthetic joint infection (PJI) of hip/knee replacements. We prospectively collected three to five deep tissue samples per patient from 152 patients undergoing conversion or revision hip/knee arthroplasty from July 2020 to November 2022. Cultures and IMC for each sample were compared for concordance, median time to detection (TTD), and diagnostic performance based on 2013 Musculoskeletal Infection Society criteria. Secondary analyses involved patients on antibiotics at sampling. The 152 total patients had 592 tissue samples (mean 3.9 ± 0.3) with sample concordance between cultures and IMC of 90%. IMC demonstrated a sensitivity of 83%, specificity of 100%, negative predictive value (NPV) of 89%, and positive predictive value (PPV) of 100% for PJI. Cultures resulted in 69% sensitivity, 100% specificity, 81% NPV, and 100% PPV. The accuracy of IMC was 93% compared to 87% for cultures (P < 0.001). The median TTD of PJI by cultures was 51 (21-410) hours compared to 10 (0.5-148) hours for IMC (P < 0.001). For 39 patients on chronic antibiotics, sensitivity in PJI detection was 93%, specificity 100%, NPV 85%, and PPV 100% by IMC compared to 79% sensitivity, 100% specificity, 65% NPV, and 100% PPV for cultures. The accuracy was 95% for IMC compared to 85% for cultures (P < 0.001) with median TTD of 12 (0.5-127) hours compared to 52 (21-174) hours (P < 0.001). Utilizing IMC for PJI detection improves TTD by nearly 2 days while improving diagnostic accuracy compared to cultures, particularly in patients on chronic antibiotics.

Rare Bipolaris Species Fungal Periprosthetic Hip Infection in an Immunocompetent Host: A Case Report.

CASE: We present a case report of a 64-year-old man who developed a rare Bipolaris species fungal periprosthetic joint infection (PJI) after revision arthroplasty for complications associated with a metal-on-metal total hip arthroplasty. The patient underwent a 2-stage debridement with antibiotic bead placement and implant retention, along with chronic antifungal suppression. At the 2-year follow-up, the patient remained asymptomatic. CONCLUSION: Fungal PJI with filamentous fungi such as Bipolaris species is a rare clinical entity. This case report highlights the clinical presentation and management of this rare condition.

Management of Biofilm with Breast Implant Surgery.

LEARNING OBJECTIVES: After studying this article, the participant should be able to: 1. Understand how bacteria negatively impact aesthetic and reconstructive breast implants. 2. Understand how bacteria infect breast implants. 3. Understand the evidence associated with common implant infection-prevention strategies, and their limitations. 4. Understand why implementation of bacteria-mitigation strategies such as antibiotic administration or "no-touch" techniques may not indefinitely prevent breast implant infection. SUMMARY: Bacterial infection of aesthetic and reconstructive breast implants is a common and expensive problem. Subacute infections or chronic capsular contractures leading to device explantation are the most commonly documented sequelae. Although bench and translational research underscores the complexities of implant-associated infection, high-quality studies with adequate power, control groups, and duration of follow-up are lacking. Common strategies to minimize infections use antibiotics-administered systemically, in the breast implant pocket, or by directly bathing the implant before insertion-to limit bacterial contamination. Limiting contact between the implant and skin or breast parenchyma represents an additional common strategy. The clinical prevention of breast implant infection is challenged by the clean-contaminated nature of breast parenchyma, and the variable behavior of not only specific bacterial species but also their strains. These factors impact bacterial virulence and antibiotic resistance.

Falsarthrobacter nasiphocae periprosthetic joint infection.

We report the isolation of a rare Gram-positive coccobacillary bacterium from synovial fluids of a patient with periprosthetic joint infection on three occasions over an 8-month period. As routine microbiological methods were not able to identify the isolate definitely, sequence analyses of the bacterial 16S ribosomal RNA gene and whole genome were performed. Analysis of the bacterial 16S ribosomal RNA gene showed the highest similarity (98.1%) with that of Falsarthrobacter (previously known as Arthrobacter) nasiphocae, which was first isolated from the nasal cavities of common seals (Phoca vitulina). The genome size of the strain (designated as UM1) is 2.4 Mb. With a high G+C content (70.4 mol%), strain UM1 is phylogenetically most closely related to F. nasiphocae based on whole genome analysis. Strain UM1 was susceptible to vancomycin, linezolid, trimethoprim-sulfamethoxazole, doxycycline, and intermediate to penicillin and ciprofloxacin. Ceftriaxone resistance was noted. The patient who was also on hemodialysis for his end stage kidney disease died approximately 3 weeks following implant removal and fusion with an external fixator. This study describes the first isolation of F. nasiphocae from human clinical samples. The use of emerging technologies has supported more definitive etiological diagnosis associated with rarely encountered organisms in periprosthetic joint infection.

A rare case of periprosthetic joint infection of the hip due to Kocuria spp.

BACKGROUND: Kocuria spp. are ubiquitous bacteria that have gained recent attention as potential infectious agents. The most common bacteria in PJI are S. aureus und S. epidermidis. CASE PRESENTATION: We present the case of a 72-year-old woman who received total hip arthroplasty after a traumatic medial femoral neck fracture. Postoperatively, due to the clinical presentation of periprosthetic joint infection (PJI) revision surgery was performed twice. The microbiological tissue samples were positive for Kocuria spp. Initially, this was considered contamination and the patient was treated with various antibiotic regimens as well as prednisolone due to the differential diagnosis of pyoderma gangraenosum. However, a specialized histopathology lab performed further testing which substantiated the suspicion of a rare case of PJI due to Kocuria spp. CONCLUSIONS: To our knowledge, this is the first reported case of a PJI caused by Kocuria spp. Further clinical research is necessary to assess whether Kocuria spp. are an underestimated cause of PJI.

Patient Characteristics, Microbiology, and Mortality of Infective Endocarditis After Transcatheter Aortic Valve Implantation.

BACKGROUND: Infective endocarditis (IE) after transcatheter aortic valve implantation (TAVI) is associated with high mortality and surgery is rarely performed. Thus, to inform on preventive measures and treatment strategies, we investigated patient characteristics and microbiology of IE after TAVI. METHODS: Using Danish nationwide registries, we identified patients with IE after TAVI, IE after non-TAVI prosthetic valve (nTPV), and native valve IE. Patient characteristics; overall, early (≤12 m), and late IE (>12 m) microbiology; and unadjusted and adjusted mortality were compared. RESULTS: We identified 273, 1022, and 5376 cases of IE after TAVI, IE after nTPV, and native valve IE. Age and frailty were highest among TAVI IE (4.8%; median age: 82 y; 61.9% frail). Enterococcus spp. were common for IE after TAVI (27.1%) and IE after nTPV (21.2%) compared with native valve IE (11.4%). Blood culture-negative IE was rare in IE after TAVI (5.5%) compared with IE after nTPV (15.2%) and native valve IE (13.5%). The unadjusted 90-day mortality was comparable, but the 5-year mortality was highest for IE after TAVI (75.2% vs 57.2% vs 53.6%). In Cox models adjusted for patient characteristics and bacterial etiology for 1-90 days and 91-365 days, there was no significant difference in mortality rates. CONCLUSIONS: Patients with IE after TAVI are older and frailer, enterococci and streptococci are often the etiologic agents, and are rarely blood culture negative compared with other IE patients. Future studies regarding antibiotic prophylaxis strategies covering enterococci should be considered in this setting.

Fibrinolytic and antibiotic treatment of prosthetic vascular graft infections in a novel rat model.

OBJECTIVES: We developed a rat model of prosthetic vascular graft infection to assess, whether the fibrinolytic tissue plasminogen activator (tPA) could increase the efficacy of antibiotic therapy. MATERIALS AND METHODS: Rats were implanted a polyethylene graft in the common carotid artery, pre-inoculated with approx. 6 log10 colony forming units (CFU) of methicillin resistant Staphylococcus aureus. Ten days after surgery, rats were randomized to either: 0.9% NaCl (n = 8), vancomycin (n = 8), vancomycin + tPA (n = 8), vancomycin + rifampicin (n = 18) or vancomycin + rifampicin + tPA (n = 18). Treatment duration was seven days. Approximately 36 hours after the end of treatment, the rats were euthanized, and grafts and organs were harvested for CFU enumeration. RESULTS: All animals in the control group had significantly higher CFU at the time of euthanization compared to bacterial load found on the grafts prior to inoculation (6.45 vs. 4.36 mean log10 CFU/mL, p = 0.0011), and both the procedure and infection were well tolerated. Vancomycin and rifampicin treatment were superior to monotherapy with vancomycin, as it lead to a marked decrease in median bacterial load on the grafts (3.50 vs. 6.56 log10 CFU/mL, p = 0.0016). The addition of tPA to vancomycin and rifampicin combination treatment did not show a further decrease in bacterial load (4.078 vs. 3.50 log10 CFU/mL, p = 0.26). The cure rate was 16% in the vancomycin + rifampicin group vs. 37.5% cure rate in the vancomycin + rifampicin + tPA group. Whilst interesting, this trend was not significant at our sample size (p = 0.24). CONCLUSION: We developed the first functional model of an arterial prosthetic vascular graft infection in rats. Antibiotic combination therapy with vancomycin and rifampicin was superior to vancomycin monotherapy, and the addition of tPA did not significantly reduce bacterial load, nor significantly increase cure rate.

Periprosthetic joint infection:A South African perspective.

BACKGROUND: South African data on the bacteriology and sensitivity profile of periprosthetic joint infection is lacking.  Current regimens for systemic and local antibiotic therapy are based on international literature. These regimens are different for the United States of America and Europe and might thus not be relevant to South Africa. OBJECTIVES: To determine the characteristics of periprosthetic joint infection in a South African clinical setting by identifying the most common organisms cultured and establishing their antibiotic sensitivities in order to propose the most appropriate empiric antibiotic treatment regimen. In the case of two-stage revision procedures, we aim to compare the organisms cultured during the first stage versus organisms cultured during the second stage in second-stage procedures that had positive cultures.  Furthermore, in these culture-positive second-stage procedures we aim to correlate the bacterial culture with the erythrocyte sedimentation rate/ C-reactive protein result. METHODS: We performed a retrospective cross-sectional study looking at all hip and knee periprosthetic joint infections in patients 18 years and older, treated at a government institution and a private revision practice in Johannesburg, South Africa between January 2015 and March 2020. Data were collected from the Charlotte Maxeke Johannesburg Academic Hospital hip and knee and the Johannesburg Orthopaedic hip and knee databanks. RESULTS: We included 69 patients whom underwent 101procedures relating to periprosthetic joint infection. Positive cultures were found in 63 samples, 81 different organisms were identified. The most common organisms cultured were Staphylococcus aureus (n = 16, 19.8%) and Coagulase negative Staphylococcus (n = 16, 19.8%), followed by Streptococci species (n = 11, 13.6%).  The positive yield in our cohort was 62.4% (n = 63). A polymicrobial growth was found in 19% (n = 12) of the culture positive specimens. Of all the microorganisms cultured, 59.2% (n = 48) were Gram-positive versus 35.8% (n = 29) Gram-negative. The remainder were fungal and anaerobic organisms at 2.5% (n = 2) each. Gram-positive cultures displayed 100% sensitivity to Vancomycin and Linezolid, whereas Gram-negative organisms displayed 82% sensitivity towards Gentamycin and 89% sensitivity towards Meropenem respectively. CONCLUSION: Our study identifies the bacteriology of periprosthetic joint infections and their sensitivities in a South African setting. We recommend that empiric antibiotic-loaded cement spacers and systemic antibiotic regimens should consist of Meropenem or Gentamycin; Vancomycin and Rifampicin to achieve the broadest spectrum of coverage and most likely success in eradicating infection.