Prospective Activity of PLG0206, an Engineered Antimicrobial Peptide, on Chronic Periprosthetic Joint Infection Total Knee Arthroplasty Components Ex Vivo: The Knee Explant Analysis (KnEA) Study.

PLG0206 is an engineered antimicrobial peptide that has completed phase 1 clinical studies. A prospective study was completed on explanted implants from chronic periprosthetic joint infections (n = 17). At a concentration of 1 mg/mL for 15 min, there was a mean 4-log10 reduction (range, 1 to 7) in the bacterial CFU identified from the implants. IMPORTANCE Chronically infected prosthetics of the knee were exposed to PLG0206, an engineered antimicrobial peptide, at a concentration of 1 mg/mL for 15 min. A mean 4-log10 reduction (range, 1 to 7) in the number of bacteria occurred, which may translate to improved clinical outcomes for persons with prosthetic joint infection of the knee.

Pulmonary Madurella mycetomatis mycetoma secondary to knee eumycetoma, Senegal.

Mycetoma is a neglected tropical disease which is endemic in Senegal. Although this subcutaneous mycosis is most commonly found on the foot, extrapodal localisations have also been found, including on the leg, knee, thigh, hand, and arm. To our knowledge, no case of blood-spread eumycetoma has been reported in Senegal. Here, we report a case of pulmonary mycetoma secondary to a Madurella mycetomatis knee eumycetoma. The patient was a 41-year-old farmer living in Louga, Senegal, where the Sudano-Sahelian climate is characterised by a short and unstable rainy season and a steppe vegetation. He suffered a trauma to the right more than 20 years previously and had received treatment for more than 10 years with traditional medicine. He consulted at Le Dantec University Hospital in Dakar for treatment of a right knee mycetoma which had been diagnosed more than 10 years ago. He had experienced a chronic cough for more than a year; tuberculosis documentation was negative. Grains collected from the knee and the sputum isolated M. mycetomatis, confirmed by the rRNA gene ITS regions nucleotide sequence analysis. An amputation above the knee was performed, and antibacterial and antifungal therapy was started with amoxicillin-clavulanic acid and terbinafine. The patient died within a month of his discharge from hospital.

Ruling out underlying infection in 200 presumed aseptic knee and hip revision arthroplasties using a multiplex PCR system.

Ruling out an infection in one-stage knee and hip revisions for presumed aseptic failure by conventional tissue cultures takes up to 14 days. Multiplex polymerase chain reaction (mPCR) is a quick test (4-5 h) for detecting pathogens. The purpose of this study was to evaluate the diagnostic accuracy of an automated mPCR of synovial fluid obtained intraoperatively in unsuspected knee and hip revisions. A prospective study was conducted with 200 patients undergoing a one-stage knee or hip revision. Synovial fluid was analyzed with the mPCR Unyvero implant and tissue infection G2 cartridge (U-ITI G2) system and compared to intraoperative tissue cultures. The primary outcome measure was the diagnostic accuracy, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), of the mPCR U-ITI G2 system compared to conventional cultures. In the knee revision group, there were no patients with a positive mPCR in combination with positive cultures. This resulted in a non-calculable sensitivity and PPV. The specificity and NPV in the knee revision group of the mPCR compared to tissue cultures was 96.8% and 96.8%, respectively. In the hip revision group, the sensitivity, specificity, PPV, and NPV of the mPCR compared to tissue cultures was 36.4%, 96.6%, 57.1%, and 92.5%, respectively. Sixteen mismatches occurred between the mPCR and tissue cultures. The mPCR U-ITI G2 system is a quick and reliable synovium fluid test for ruling out infection in presumed aseptic knee and hip revisions with a high NPV compared with tissue cultures, although some mismatches were observed. Periprosthetic tissue cultures are still advised as back-up for false negative and positive mPCR test results.

First case report of Cryptococcus laurentii knee infection in a previously healthy patient.

BACKGROUND: The purpose of this case report was to report a case of Cryptococcus laurentii infection in the left knee of a previously healthy 29 year old male patient. CASE PRESENTATION: After an initial misdiagnosis and 7 months of failed treatment, the patient received nearly a month of treatment with voriconazole (200 mg IV q12 h) and knee irrigation with amphotericin B until the infection was controlled. The treatment continued with fluconazole for nearly 7 months and approximately 5 weeks of antibiotic treatment for a skin bacterial coinfection. In the end, the patient's symptoms disappeared completely, the left knee recovered well, and there was no recurrence of infection. CONCLUSION: The key points of successful treatment in this case were the thorough debridement, the adequate course of knee irrigation with antifungal drugs and more than 6 months of oral antifungal drugs that were able to eradicate the infection.

Fungal arthritis with adjacent osteomyelitis caused by Candida pelliculosa: a case report.

BACKGROUND: Candida sp. osteoarticular infection is rare and most often due to hematogenous seeding during an episode of candidemia in immunocompromised patients. However, the diagnosis can be delayed in patients with subtle symptoms and signs of joint infection without a concurrent episode of candidemia. CASE PRESENTATION: A 75-year-old woman presented with a three-year history of pain and swelling of the left knee. Candida pelliculosa was detected from the intraoperative tissue when the patient had undergone left total knee arthroplasty 32 months ago, but no antifungal treatment was performed. One year after the total knee arthroplasty, C. pelliculosa was repeatedly isolated from the left knee synovial fluid and antifungal treatment comprising amphotericin B deoxycholate and fluconazole was administered. However, joint infection had extended to the adjacent bone and led to progressive joint destruction. The patient underwent surgery for prosthesis removal and received prolonged antifungal treatment with micafungin and fluconazole. CONCLUSIONS: This case shows that C. pelliculosa, an extremely rare non-Candida albicans sp., can cause fungal arthritis and lead to irreversible joint destruction owing to delayed diagnosis and treatment.

An atlas overview of characteristic features of tuberculosis that may be encountered at autopsy.

Tuberculosis (TB) is a bacterial infection caused by Mycobacterium tuberculosis. Although primarily a disease of the respiratory system it may be found in any organ or tissue. Global population movements and the emergence of resistant strains are contributing to increasing numbers of cases in certain populations. Subtlety of symptoms and signs, chronicity of disease and failure to seek medical assistance may result in the diagnosis only being made at the time of autopsy. For this reason forensic pathologists need to understand the protean manifestations of the disease and the variable mechanisms by which TB may cause death. This atlas overview provides descriptions of the pathological manifestations of TB in a variety of organs with accompanying illustrations. It serves as a summary of conditions that should be checked for at autopsy in suspected or confirmed cases.

Recurrent arthritis caused by Candida parapsilosis: a case report and literature review.

BACKGROUND: Candida arthritis is extremely rare and also represents a major challenge of diagnosis and treatment. Here we reported a rare case of recurrent arthritis caused by Candida parapsilosis. CASE PRESENTATION: A 56-year-old Chinese male suffered from recurrent pain and swelling in his right knee after several times of "small needle-knife" acupuncture and corticosteroid injection of the joint. Candida parapsilosis was cultured in his synovial fluid and identified by sequencing of its Internal Transcribed Spacer (ITS) gene. Here we present the radiological characteristics, arthroscopic pictures, and synovium pathology of this patient. Also, blood test and chemical analysis of his synovial fluid were listed as well as the ITS sequence of this Candida species identified. The patient underwent thorough arthroscopic debridement and then set on fluconazole 400 mg daily for 12 months. His symptoms resolved and no relapse was observed on the last follow-up. Additionally, a brief but comprehensive review of C. parapsilosis arthritis episodes from past to now were studied. CONCLUSION: With the detailed clinical information reported in this case and our literature review, we hope they would add to our knowledge of C. parapsilosis arthritis - its clinical settings, laboratory features, radiological characteristics, arthroscopic findings and experience of management.

Application of 99mTc-UBI 29-41 scintigraphy in knee periprosthetic infection diagnosis.

AIM: In recent years, the use of total knee arthroplasty (TKA) is considered a safe and cost-effective orthopedic procedure for alleviating the chronic pain and treatment of progressive osteoarthritis. This procedure may have some complications including periprosthetic infection as the most serious and aseptic loosening as the most common one. Differentiating between these entities is important because each has a different therapeutic approach. This study was conducted to investigate the ability of 99mTC-UBI scan to distinguish septic from aseptic loosening in a painful knee prosthesis. METHODS: 34 patients with painful knee prostheses were included. The 99mTC-UBI scan was done immediately after IV administration of 99mTC-UBI in early dynamic and 30-minute static images. Time-activity curve (TAC) was drawn for all patients and target to non-target ratio (T/NT) was calculated on 30-minute images. The final diagnosis was confirmed by surgical findings, microbiologic culture results or active clinical follow up. RESULTS: Using TAC analysis, 24 99mTC-UBI scans were considered negative and 10 positive for an infectious process. Sensitivity, specificity, negative and positive predictive values were 56 %, 80 %, 83 %, and 50 %, respectively. T/NT ratio analysis on 30-minute static images demonstrated 9 positive and 25 negative patterns, with a cut off value of 1.83 for the T/NT ratio. The sensitivity, specificity, negative and positive predictive values, and accuracy of this test modality were all 100 %. CONCLUSIONS: Our findings show 99mTc-UBI scan is an excellent clinical diagnostic test for differentiating septic from aseptic loosening of the knee prostheses with perfect sensitivity and specificity. Highly accurate results were obtained only 30 minutes after injection.

Clinical features of patients with septic arthritis and echocardiographic findings of infective endocarditis.

PURPOSE: Patients with septic arthritis (SA) often undergo echocardiographic evaluation to identify concomitant infective endocarditis (IE). The purpose of this study is to identify distinguishing features of patients with SA and IE by comparing them to patients with SA alone. METHODS: We conducted a retrospective study of all patients 18 and older admitted to a single tertiary hospital between 1998 and 2015 with culture-positive SA. Patients were stratified by echocardiogram status and the presence of vegetations: those who had echocardiographic evaluation with no evidence of infective endocarditis (ECHO + IE-) or with a vegetation present (ECHO + IE+) and those who had no echocardiographic evaluation (ECHO-). Demographic data, clinical characteristics, microbiology data, treatment strategies, and patient outcomes were recorded and compared. RESULTS: We identified 513 patients with SA. Transthoracic echocardiogram and/or transesophageal echocardiogram were performed in 263 patients (51.2%) and demonstrated evidence for IE in 19 patients (3.7%). While most demographic features, comorbidities, and clinical characteristics did not differ significantly between those with and without IE, those with IE had higher rates of sepsis and septic shock. In addition, patients with SA and IE had higher rates of positive blood cultures and Methicillin-sensitive staphylococcus aureus (MSSA) infection when compared to those with SA without IE. Patients with IE had higher rates of intensive care unit admission and increased 30-day mortality. CONCLUSIONS: IE is uncommon among patients with SA. Echocardiography may be overutilized and may be more useful among patients presenting with sepsis, shock, or positive blood cultures, especially when MSSA is isolated.

Tuberculous sacroiliitis in a patient with systemic lupus erythematosus: a case report and literature review.

Systemic lupus erythematosus (SLE) patients are at higher risk of developing opportunistic infections such as tuberculosis (TB), especially extrapulmonary forms like osteoarticular TB, compared to the general population. However, tuberculous sacroiliitis has been scarcely reported in these patients. We present a 34-year-old woman with SLE who developed articular tuberculosis simultaneously affecting the right sacroiliac joint and the left knee. The patient was successfully treated with antituberculosis therapy for nine months. In this case, in addition to the immunological abnormalities of lupus, the long-term glucocorticoid therapy at high dosages was the main risk factor for the development of osteoarticular tuberculosis.

Double invasive fungal infection due to dematiaceous moulds in a renal transplant patient.

Alternaria and Verruconis are two dematiaceous moulds that occasionally cause disease in immunocompromised hosts. We present the case of a 58-year-old man with history of deceased donor renal transplantation 14 months prior, who presented with fevers and cough. He was found to have right upper lobe pneumonia and a non-healing eschar of his right knee. Dematiaceous fungi grew from bronchoalveolar lavage (BAL) and was sent to reference lab for identification. Meanwhile, the eschar on his right knee was biopsied and grew Alternaria spp. Pathology was consistent with invasive mould infection and he was treated as having disseminated Alternaria infection with voriconazole and amphotericin B lipid complex. Later on, the dematiaceous mould from a BAL specimen was identified as Verruconis gallopava The patient was discharged on voriconazole awaiting minimal inhibitory concentrations for V. gallopava but was readmitted 2 days later with high fevers and died from acute respiratory failure.

Septic arthritis of the knee: clinical and laboratory comparison of groups with different etiologies

OBJECTIVES: To clinically and epidemiologically characterize a population diagnosed with and treated for septic arthritis of the knee, to evaluate the treatment results and to analyze the differences between patients with positive and negative culture results, patients with Gram-positive and Gram-negative bacterial isolates and patients with S. aureus- and non-S. aureus-related infections. METHODS: One hundred and five patients with septic knee arthritis were included in this study. The clinical and epidemiological data were evaluated. Statistical analysis was performed to compare patients with and without an isolated causative agent, patients with Gram-positive and Gram-negative pathogens and patients with S. aureus-related and non S. aureus-related infections. RESULTS: Causative agents were isolated in 81 patients. Gram-positive bacteria were isolated in 65 patients and Gram-negative bacteria were isolated in 16 patients. The most commonly isolated bacterium was S. aureus. Comparing cases with an isolated pathogen to cases without an isolated pathogen, no differences between the studied variables were found except for the longer hospital stays of patients in whom an etiological agent was identified. When comparing Gram-positive bacteria with Gram-negative bacteria, patients with Gram-positive-related infections exhibited higher leukocyte counts. Patients with S. aureus-related infections were more frequently associated with healthcare-related environmental encounters. CONCLUSION: S. aureus is the most common pathogen of septic knee arthritis. Major differences were not observed between infections with isolated and non-isolated pathogens and between infections with Gram-positive and Gram-negative bacteria. S. aureus infections were more likely to be associated with a prior healthcare environment exposure.

Successful treatment of methicillin-resistant Staphylococcus aureus osteomyelitis with combination therapy using linezolid and rifampicin under therapeutic drug monitoring.

Linezolid is an effective antibiotic against most gram-positive bacteria including drug-resistant strains such as methicillin-resistant Staphylococcus aureus. Although linezolid therapy is known to result in thrombocytopenia, dosage adjustment or therapeutic drug monitoring of linezolid is not generally necessary. In this report, however, we describe the case of a 79-year-old woman with recurrent methicillin-resistant S. aureus osteomyelitis that was successfully treated via surgery and combination therapy using linezolid and rifampicin under therapeutic drug monitoring for maintaining an appropriate serum linezolid concentration. The patient underwent surgery for the removal of the artificial left knee joint and placement of vancomycin-impregnated bone cement beads against methicillin-resistant S. aureus after total left knee implant arthroplasty for osteoarthritis. We also initiated linezolid administration at a conventional dose of 600 mg/h at 12-h intervals, but reduced it to 300 mg/h at 12-h intervals on day 9 because of a decrease in platelet count and an increase in serum linezolid trough concentration. However, when the infection exacerbated, we again increased the linezolid dose to 600 mg/h at 12-h intervals and performed combination therapy with rifampicin, considering their synergistic effects and the control of serum linezolid trough concentration via drug interaction. Methicillin-resistant S. aureus infection improved without reducing the dose of or discontinuing linezolid. The findings in the present case suggest that therapeutic drug monitoring could be useful for ensuring the therapeutic efficacy and safety of combination therapy even in patients with osteomyelitis who require long-term antibiotic administration.

Septic arthritis of the knee: clinical and laboratory comparison of groups with different etiologies.

OBJECTIVES:: To clinically and epidemiologically characterize a population diagnosed with and treated for septic arthritis of the knee, to evaluate the treatment results and to analyze the differences between patients with positive and negative culture results, patients with Gram-positive and Gram-negative bacterial isolates and patients with S. aureus- and non-S. aureus-related infections. METHODS:: One hundred and five patients with septic knee arthritis were included in this study. The clinical and epidemiological data were evaluated. Statistical analysis was performed to compare patients with and without an isolated causative agent, patients with Gram-positive and Gram-negative pathogens and patients with S. aureus-related and non S. aureus-related infections. RESULTS:: Causative agents were isolated in 81 patients. Gram-positive bacteria were isolated in 65 patients and Gram-negative bacteria were isolated in 16 patients. The most commonly isolated bacterium was S. aureus. Comparing cases with an isolated pathogen to cases without an isolated pathogen, no differences between the studied variables were found except for the longer hospital stays of patients in whom an etiological agent was identified. When comparing Gram-positive bacteria with Gram-negative bacteria, patients with Gram-positive-related infections exhibited higher leukocyte counts. Patients with S. aureus-related infections were more frequently associated with healthcare-related environmental encounters. CONCLUSION:: S. aureus is the most common pathogen of septic knee arthritis. Major differences were not observed between infections with isolated and non-isolated pathogens and between infections with Gram-positive and Gram-negative bacteria. S. aureus infections were more likely to be associated with a prior healthcare environment exposure.

SUCCESSFUL TREATMENT OF MULTIDRUG-RESISTANT ACINETOBACTOR BAUMANII BLISTERS ON THE KNEE.

Acinetobacter baumannii (A. baumannii), nosocomial infections, especially those due to multi-drug resistant (MDR) strains, are increasingly detected. This study reports the case of a 50-year-old man with blisters on the right knee for 8 months, first admitted through the outpatient department for incisional biopsy. Microbiological and histo-pathological examination confirmed the diagnosis of blisters extending deeply up to the knee joint caused by MDR- A. baumannii. A broad spectrum antibiotic therapy was administered and later readjusted according to the results of microbiological culture and biopsy report. Intensive hemodynamic support was required. An extensive surgical debridement was promptly performed and repeated until complete control of the infection with intravenous colistins. Blisters were excised; wounds were dressed daily with chlorhexidine dressings and polymyxine-impregnated dressing. Wounds were finally covered with split-thickness skin grafts. The infection was overcome 120 days after admission. The graft take was 40%. Postoperative rehabilitation was required because of the functional limitation of lower limb movements at the knee joint. Follow-up at 8 months showed no functional deficit and an acceptable aesthetic result. AB-MDR affecting soft tissues is a life-threatening disease, especially in patients with poor immunity and limited access to health facilities, whose clinical diagnosis may sometimes be challenging. Early recognition and treatment represent the most important factors influencing survival.

Multifocal skeletal tuberculosis in an immunocompetent patient: a case report.

BACKGROUND: The occurrence of multifocal skeletal involvement in immunocompetent patients is rare, even in countries where tuberculosis is endemic. Multifocal skeletal lesions may occur as a result of hematogenous dissemination from another primary focus such as cervical lymph nodes, lungs, tonsils or gastrointestinal tract. CASE PRESENTATION: We present a 59 year-old man with a history of intermittent and disabling pain in his left knee for 2 years. The patient in this case presented with lung infection with bilateral skeletal dissemination in the knees and femurs. Immunological examination for the HIV was negative. CONCLUSIONS: Diagnosis of this condition is not always easy because of the disease's insidious character, and it can be confused with other diseases such as osteoarthritis, especially in middle-aged individuals.