Characteristics and management of periprosthetic joint infections caused by rapidly growing mycobacteria: a retrospective study and a review of the literature.

Background: Periprosthetic joint infection (PJI) following total joint arthroplasty is a serious complication associated with significant morbidity. While Gram-positive cocci are the predominant causative organisms, PJIs caused by rapidly growing mycobacteria (RGM) have been reported, albeit at a lower frequency. This study aimed to investigate the characteristics and management of PJI caused by RGM. Methods: A retrospective review was conducted using an institutional PJI database to identify patients diagnosed with PJI due to RGM from January 2010 to December 2021. Clinical data, including demographics, symptoms, comorbidity information, laboratory parameters, surgical procedures, medical treatment and outcomes, were collected and analyzed. Results: A total of eight patients were identified with PJI caused by RGM during the study period. The median age was 66 years old, and most cases occurred in patients with total knee arthroplasty (n=6). The isolated RGM species included Mycobacterium abscessus (three cases), M. fortuitum (three cases), and one case each of M. immunogenum and M. mageritense. Surgical debridement was performed in all cases, with six patients undergoing two-stage revision and two patients requiring amputation. Combination antimicrobial therapy was administered based on antimicrobial susceptibility testing, and the median duration of treatment was 7.5 months. Adverse events related to therapy occurred in 75 % of cases. No relapses were observed during the median follow-up period of 39.6 months. Conclusions: PJI caused by RGM is a rare complication of total joint arthroplasty. Surgical debridement and combination antimicrobial therapy are the mainstays of treatment. Although clinical cure rates are high, amputation may be required in severe cases.

Clinical features, treatment, and outcomes of mpox in solid organ transplant recipients: A multicenter case series and literature review.

In 2022, the largest global outbreak of mpox to date emerged. In the immunocompetent host, mpox generally presents as a self-limiting illness. However, immunosuppression, such as that seen with advanced HIV, has been associated with significant morbidity and mortality related to mpox infection. To evaluate the impact of immunosuppression related to solid organ transplantation on clinical features and outcomes of mpox we established a multicenter case registry. Eleven cases from 7 participating centers in the USA were submitted. All cases occurred in males. The majority were kidney transplant recipients (91%, n = 10). Median duration of symptoms at presentation was 6 days (range, 3-14 days). Rates of hospitalization were high (73%, n = 8) with a median length of stay of 4.5 days (range, 1-10 days). Mpox in solid organ transplant recipients was associated with a high burden of skin lesions and systemic symptoms. Fever, fatigue, pharyngitis, and proctitis were commonly reported. Other clinical features included headache, myalgia, epididymo-orchitis, urinary retention, hematemesis, pneumonitis, and circulatory shock. All patients received treatment with tecovirimat. There was 1 mpox-related death in the cohort. Infection was reported to have resolved at 30-day follow-up in all other cases.

Sex-specific analysis of clinical features and outcomes in staphylococcal periprosthetic joint infections managed with two-stage exchange arthroplasty.

Background: Differences in susceptibility and response to infection between males and females are well established. Despite this, sex-specific analyses are under-reported in the medical literature, and there is a paucity of literature looking at differences between male and female patients with periprosthetic joint infection (PJI). Whether there are sex-specific differences in presentation, treatment tolerability, and outcomes in PJI has not been widely evaluated. Methods: We undertook a retrospective case-matched analysis of patients with staphylococcal PJI managed with two-stage exchange arthroplasty. To control for differences other than sex which may influence outcome or presentation, males and females were matched for age group, causative organism category (coagulase-negative staphylococci vs. Staphylococcus aureus), and joint involved (hip vs. knee). Results: We identified 156 patients in 78 pairs of males and females who were successfully matched. There were no significant baseline differences by sex, except for greater use of chronic immunosuppression among females (16.4 % vs. 4.1 %; p = 0.012 ). We did not detect any statistically significant differences in outcomes between the two groups. Among the 156 matched patients, 16 recurrent infections occurred during a median follow-up time of 2.9 (IQR 1.5-5.3) years. The 3-year cumulative incidence of relapse was 16.1 % for females, compared with 8.8 % for males ( p = 0.434 ). Conclusions: Success rates for PJI treated with two-stage exchange arthroplasty are high, consistent with previously reported literature. This retrospective case-matched study did not detect a significant difference in outcome between males and females with staphylococcal PJI who underwent two-stage exchange arthroplasty.

Non-tuberculous mycobacteria infection presenting as a hepatic allograft abscess.

Nontuberculous mycobacteria (NTM) are mycobacterial species other than Mycobacterium tuberculous and Mycobacterium leprae [1]. They are environmental organisms which have been implicated in a wide array of clinical syndromes. Here we describe a case of a Mycobacterium fortuitum complex liver abscess in a liver transplant recipient.

Real-world experience of tixagevimab-cilgavimab pre-exposure prophylaxis in orthotopic heart transplant recipients.

BACKGROUND: Pre-exposure prophylaxis with tixagevimab-cilgavimab (tix-cil) may be associated with cardiovascular adverse events. Also, in vitro studies have reported a reduced activity of tix-cil against emerging SARS-CoV-2 Omicron subvariants. Our study aimed to report the real-world outcomes of tix-cil prophylaxis in orthotopic heart transplant (OHT) recipients METHODS: We retrospectively studied all OHT recipients who received one dose of tix-cil (150-150 mg or 300-300 mg) at Mayo Clinic in Arizona, Florida, and Minnesota, between February 5, 2022 and September 8, 2022. We collected data on cardiovascular adverse events and breakthrough COVID-19 following tix-cil administration. RESULTS: One hundred sixty-three OHT recipients were included. The majority were male (65.6%), and the median age was 61 years (IQR 48, 69). During the median follow-up of 164 days (IQR 123, 190), one patient presented an episode of asymptomatic hypertensive urgency that was managed with outpatient antihypertensive treatment optimization. Twenty-four patients (14.7%) experienced breakthrough COVID-19 at the median of 63.5 days (IQR 28.3, 101.3) after tix-cil administration. The majority (70.8%) completed the primary vaccine series and received at least one booster dose (70.8%). Only one patient with breakthrough COVID-19 required hospitalization. All patients survived. CONCLUSIONS: In this cohort of OHT recipients, no patients developed severe cardiovascular events related to tix-cil. The high incidence of breakthrough COVID-19 could be due to the reduced activity of tix-cil against current circulating SARS-CoV-2 Omicron variants. These results emphasize the need for a multimodal prevention strategy against SARS-CoV-2 in these high-risk patients.

Polymicrobial Infections in the Immunocompromised Host: The COVID-19 Realm and Beyond.

Immunosuppression changes both susceptibility to and presentation of infection. Infection with one pathogen can also alter host response to a different, unrelated pathogen. These interactions have been seen across multiple infection domains where bacteria, viruses or fungi act synergistically with a deleterious impact on the host. This phenomenon has been well described with bacterial and fungal infections complicating influenza and is of particular interest in the context of the COVID-19 pandemic. Modulation of the immune system is a crucial part of successful solid organ and hematopoietic stem cell transplantation. Herein, we present three cases of polymicrobial infection in transplant recipients. These case examples highlight complex host-pathogen interactions and the resultant clinical syndromes.

Enhancing Diagnostics in Orthopedic Infections.

Accurate diagnosis of orthopedic infection is crucial in guiding both antimicrobial therapy and surgical management in order to optimize patient outcomes. A variety of microbiological and nonmicrobiological methods are used to establish the presence of a musculoskeletal infection. In this minireview, we examine traditional culture-based and newer molecular methodologies for pathogen detection, as well as systemic and localized assays to assess host response to maximize diagnostic yield.

Prevalence of antibodies to SARS-CoV-2 in Irish hospital healthcare workers.

Hospital healthcare workers (HCWs) are at increased risk of contracting COVID-19 infection. We aimed to determine the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in HCWs in Ireland. Two tertiary referral hospitals in Irish cities with diverging community incidence and seroprevalence were identified; COVID-19 had been diagnosed in 10.2% and 1.8% of staff respectively by the time of the study (October 2020). All staff of both hospitals (N = 9038) were invited to participate in an online questionnaire and blood sampling for SARS-CoV-2 antibody testing. Frequencies and percentages for positive SARS-CoV-2 antibody were calculated and adjusted relative risks (aRR) for participant characteristics were calculated using multivariable regression analysis. In total, 5788 HCWs participated (64% response rate). Seroprevalence of antibodies to SARS-CoV-2 was 15% and 4.1% in hospitals 1 and 2, respectively. Thirty-nine percent of infections were previously undiagnosed. Risk for seropositivity was higher for healthcare assistants (aRR 2.0, 95% confidence interval (CI) 1.4-3.0), nurses (aRR: 1.6, 95% CI 1.1-2.2), daily exposure to patients with COVID-19 (aRR: 1.6, 95% CI 1.2-2.1), age 18-29 years (aRR: 1.4, 95% CI 1.1-1.9), living with other HCWs (aRR: 1.3, 95% CI 1.1-1.5), Asian background (aRR: 1.3, 95% CI 1.0-1.6) and male sex (aRR: 1.2, 95% CI 1.0-1.4). The HCW seroprevalence was six times higher than community seroprevalence. Risk was higher for those with close patient contact. The proportion of undiagnosed infections call for robust infection control guidance, easy access to testing and consideration of screening in asymptomatic HCWs. With emerging evidence of reduction in transmission from vaccinated individuals, the authors strongly endorse rapid vaccination of all HCWs.

Prevalence of Antibodies to SARS-CoV-2 Following Natural Infection and Vaccination in Irish Hospital Healthcare Workers: Changing Epidemiology as the Pandemic Progresses.

BACKGROUND: In October 2020 SARS-CoV-2 seroprevalence among hospital healthcare workers (HCW) of two Irish hospitals was 15 and 4. 1%, respectively. We compare seroprevalence in the same HCW population 6 months later, assess changes in risk factors for seropositivity with progression of the pandemic and serological response to vaccination. METHODS: All staff of both hospitals (N = 9,038) were invited to participate in an online questionnaire and SARS-CoV-2 antibody testing in April 2021. We measured anti-nucleocapsid and anti-spike antibodies. Frequencies and percentages for positive SARS-CoV-2 antibodies were calculated and adjusted relative risks for participant characteristics were calculated using multivariable regression analysis. RESULTS: Five thousand and eighty-five HCW participated. Seroprevalence increased to 21 and 13%, respectively; 26% of infections were previously undiagnosed. Black ethnicity (aRR 1.7, 95% CI 1.3-2.2, p < 0.001), lower level of education (aRR 1.4 for secondary level education, 95% CI 1.1-1.8, p = 0.002), living with other HCW (aRR 1.2, 95% CI 1.0-1.4, p = 0.007) were significantly associated with seropositivity. Having direct patient contact also carried a significant risk being a healthcare assistant (aRR 1.8, 95% CI 1.3-2.3, p < 0.001), being a nurse (aRR 1.4, 95% CI 1.0-1.8, p = 0.022), daily contact with COVID-19 patients (aRR 1.4, 95% CI 1.1-1.7, p = 0.002), daily contact with patients without suspected or confirmed COVID-19 (aRR 1.3, 95% CI 1.1-1.5, p = 0.013). Breakthrough infection occurred in 23/4,111(0.6%) of fully vaccinated participants; all had anti-S antibodies. CONCLUSION: The increase in seroprevalence reflects the magnitude of the third wave of the pandemic in Ireland. Genomic sequencing is needed to apportion risk to the workplace vs. the household/community. Concerted efforts are needed to mitigate risk factors due to ethnicity and lower level of education, even at this stage of the pandemic. The undiagnosed and breakthrough infections call for ongoing infection prevention and control measures and testing of HCW in the setting of close contact. Vaccinated HCW with confirmed infection should be actively assessed, including SARS-CoV-2 whole genome sequencing (WGS), serology testing and assessment of host determinants, to advance understanding of the reasons for breakthrough infection.

Calreticulin and other components of endoplasmic reticulum stress in rat and human inflammatory demyelination.

BACKGROUND: Calreticulin (CRT) is a chaperone protein, which aids correct folding of glycosylated proteins in the endoplasmic reticulum (ER). Under conditions of ER stress, CRT is upregulated and may be displayed on the surface of cells or be secreted. This 'ecto-CRT' may activate the innate immune response or it may aid clearance of apoptotic cells. Our and other studies have demonstrated upregulation of ER stress markers CHOP, BiP, ATF4, XBP1 and phosphorylated e-IF2 alpha (p-eIF2 alpha) in biopsy and post-mortem human multiple sclerosis (MS) samples. We extend this work by analysing changes in expression of CRT, BiP, CHOP, XBP1 and p-eIF2 alpha in a rat model of inflammatory demyelination. Demyelination was induced in the spinal cord by intradermal injection of recombinant mouse MOG mixed with incomplete Freund's adjuvant (IFA) at the base of the tail. Tissue samples were analysed by semi-quantitative scoring of immunohistochemically stained frozen tissue sections. Data generated following sampling of tissue from animals with spinal cord lesions, was compared to that obtained using tissue derived from IFA- or saline-injected controls. CRT present in rat serum and in a cohort of human serum derived from 14 multiple sclerosis patients and 11 healthy controls was measured by ELISA. RESULTS: Stained tissue scores revealed significantly (p<0.05) increased amounts of CRT, CHOP and p-eIF2 alpha in the lesion, lesion edge and normal-appearing white matter when compared to controls. CHOP and p-eIF2 alpha were also significantly raised in regions of grey matter and the central canal (p<0.05). Immunofluorescent dual-label staining confirmed expression of these markers in astrocytes, microglia or neurons. Dual staining of rat and human spinal cord lesions with Oil Red O and CRT antibody showed co-localisation of CRT with the rim of myelin fragments. ELISA testing of sera from control and EAE rats demonstrated significant down-regulation (p<0.05) of CRT in the serum of EAE animals, compared to saline and IFA controls. This contrasted with significantly increased amounts of CRT detected in the sera of MS patients (p<0.05), compared to controls. CONCLUSION: This data highlights the potential importance of CRT and other ER stress proteins in inflammatory demyelination.