Risk factors and outcomes of Pneumocystis pneumonia in solid organ transplant recipients: Impact of posttransplant lymphoproliferative disorder.

BACKGROUND: Pneumocystis jirovecii pneumonia (PJP) is a potentially fatal infection afflicting the immunocompromised population, including solid organ transplant (SOT) recipients. Several risk factors have been described; however, little is known regarding the risk of PJP in SOT recipients with posttransplant lymphoproliferative disorder (PTLD). METHODS: We performed a nested case-control study of SOT recipients diagnosed with PJP from 2000 to 2020. PJP was defined as positive microscopy or polymerase chain reaction testing with compatible symptoms and radiographic findings. Control patients were matched 2:1 by year of first transplant, first transplanted organ, transplant center, and sex. Multivariable conditional logistic regression was performed to test associations with PJP and Cox regression analyzed post-PJP outcomes. RESULTS: Sixty-seven PJP cases were matched to 134 controls. The most common transplant was kidney (55.2%). Fourteen patients had a history of PTLD, 12 of whom developed PJP. After adjusting for age, acute rejection, cytomegalovirus infection, PJP prophylaxis, and lymphopenia (lymphocyte count < .5 × 109 /L), PTLD was independently associated with PJP (OR 14.0, 95% CI 1.7-114.5; p = .014). Lymphopenia was also a significant association (OR 8.2, 95% CI 3.2-20.7; p < .001). PJP was associated with mortality within 90 days of diagnosis (p < .001), but not after 90 days (p = .317). PJP was also associated with 90-day death-censored renal allograft loss (p = .026). CONCLUSIONS: PTLD is independently associated with PJP after adjustment for recognized risk factors. This is likely influenced by PTLD-directed chemotherapy, particularly rituximab-containing regimens. PJP is associated with early mortality, but this effect is not persistent after 90 days. PJP prophylaxis should be considered in SOT recipients with PTLD.

Disseminated mycobacterial infections after tumor necrosis factor inhibitor use, revealing inborn errors of immunity.

Tumor necrosis factor-a inhibitors can be associated with increased risk of infections, particularly reactivation of latent tuberculosis or nontuberculous mycobacterium (NTM). However, because disseminated NTM is rare, inborn errors of immunity should be considered. We present three patients with disseminated NTM after tumor necrosis factor-a inhibitor use who were found to have inborn errors of immunity.

Disseminated Monkeypox Infection in a Kidney Transplant Recipient: A Case Report.

Monkeypox is a rapidly spreading infection worldwide and is a public health concern, especially with newly reported fatality cases. The characteristics and disease course of monkeypox infection in transplant recipients remain elusive because no case reports have been published detailing its clinical presentation and outcome in this population. We report a case of a kidney transplant recipient who developed end-stage renal disease secondary to HIV-associated nephropathy and manifested monkeypox infection after kidney transplantation. The patient had severe clinical manifestations, including disseminated vesicular skin rash, diffuse mucosal involvement, urine retention, proctitis, and bowel obstruction. We also highlight several clinical considerations regarding the use of tecovirimat, a novel antiviral therapy with activity against orthopoxviruses that has been used in the United States to treat monkeypox infection.

Synovitis due to Histoplasma capsulatum: a case series and literature review.

Musculoskeletal manifestations of Histoplasma capsulatum infection are uncommon but can mimic inflammatory arthritis. Early diagnosis of this complication is of critical importance in the era of potent immunosuppression for rheumatologic diseases. We conducted a retrospective chart review for patients with histoplasmosis and tenosynovitis, synovitis, or arthritis, diagnosed and treated at our institution between January 1, 2000, and December 31, 2019. We also reviewed the relevant literature. Four patients with biopsy-proven, culture-proven histoplasma tenosynovitis were identified at our institution. All four patients had wrist or hand involvement in an asymmetric pattern, and one patient had lower extremity involvement as well. Two patients were not immunocompromised at baseline. One patient underwent a lengthy evaluation and received immunosuppression for 4 years without improvement prior to the diagnosis of histoplasmosis. Histoplasma serologic tests varied among patients with localized infection. Pathologic findings revealed non-caseating granulomatous inflammation. Three patients recovered after 6-12 months of antifungal treatment. One patient still had recurrent infection despite 20 months of treatment. Histoplasma tenosynovitis and synovitis are rare causes of inflammatory arthritis. Infectious causes should be considered and carefully evaluated when patients present with asymmetric oligoarthritis. Early recognition is crucial for successful treatment, especially in patients with concomitant rheumatologic diseases receiving immunosuppressive treatment.

Outcomes of bebtelovimab and sotrovimab treatment of solid organ transplant recipients with mild-to-moderate coronavirus disease 2019 during the Omicron epoch.

BACKGROUND: Solid organ transplant recipients (SOTRs) are at high-risk for severe infection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Anti-spike monoclonal antibodies are currently utilized under emergency use authorization to prevent hospitalization in high-risk individuals with coronavirus disease 2019 (COVID-19), including SOTRs. However, clinical data for bebtelovimab, the sole currently available anti-spike monoclonal antibody for COVID-19, is limited. METHODS: We conducted a retrospective cohort study of adult SOTRs diagnosed with mild-to-moderate COVID-19 from January 2022 through May 2022 who received either bebtelovimab or sotrovimab. The primary outcome was COVID-19-related hospitalization within 30 days of COVID-19 diagnosis. Data were analyzed with Fisher's exact test. RESULTS: Among 361 SOTRs, 92 (25.5%) received bebtelovimab and 269 (74.5%) received sotrovimab. The most common organ transplant was a kidney (42.4%). SOTRs who received bebtelovimab had a higher proportion who had received a booster SARS-CoV-2 vaccine dose and had received their last vaccination dose more recently. Eleven (3.0%) SOTRs were hospitalized, and rates of hospitalization were similar between monoclonal antibody groups (3.3% versus 3.0%; p > .99). Three patients required admission to an intensive care unit, all of who received sotrovimab. Four (1.1%) patients died within 30 days of COVID-19 diagnosis, two from each group. CONCLUSIONS: SOTRs with mild-to-moderate COVID-19 who received bebtelovimab had similar rates of COVID-19-related hospitalization as those who received sotrovimab. While differences in vaccination rates and viral subvariants could act as confounders, bebtelovimab appears to be of similar effectiveness as sotrovimab.

Outcomes of B-Cell-Depleted Patients With Coronavirus Disease 2019 Treated With Antispike Monoclonal Antibodies.

Antispike monoclonal antibody treatment of 180 B-cell-depleted patients with mild-to-moderate coronavirus disease 2019 (COVID-19) resulted in good outcomes overall, with only 12.2% progressing to severe disease, 9.4% requiring hospitalization, 0.6% requiring mechanical ventilation, no deaths within 30 days, and 1.8% developing persistent COVID-19. Antispike monoclonal antibodies appear effective in this immunocompromised population.

The first case of Janibacter hoylei bacteremia in an adult.

The Janibacter species are Gram positive, coryneform bacteria that belong to the Actinobacteria phylum and have been linked to bacteremia in immunocompromised children. We present the first documented adult case of Janibacter hoylei bacteremia. The patient was a 52-year-old woman with a history of recurrent Clostridioides difficile infection, sinus tachycardia and high-risk AML who had been admitted one month prior to presentation for matched unrelated donor hematopoietic stem cell transplant with reduced intensity fludarabine-melphalan. Thirty days post-transplant, the infectious disease team was consulted because blood cultures grew Janibacter hoylei, from one of two blood cultures It took nine days to identify the species. She was treated with linezolid and imipenem. Janibacter are rarely implicated in human pathology, and therein, usually identified in the context of malignancy and relative immunosuppression. J. hoylei was only previously reported from the bloodstream of a previously healthy 8-week-old infant without underlying medical conditions. Antimicrobial susceptibility testing is challenging as only in vitro susceptibility testing of Janibacter terrae has been reported. Given these challenges, it is our hope to illustrate the clinical approach to diagnosis as well as subsequent recommendations for treatment in a particularly challenging case of bacteremia in an AML patient.

Monoclonal Antibody Therapy for COVID-19 in Solid Organ Transplant Recipients.

BACKGROUND: Bamlanivimab and casirivimab-imdevimab are authorized for emergency use treatment of mild to moderate coronavirus disease 2019 (COVID-19) in patients at high risk for developing severe disease or hospitalization. Their safety and efficacy have not been specifically evaluated in solid organ transplant recipients. METHODS: We retrospectively reviewed solid organ transplant recipients who received monoclonal antibody infusion for COVID-19 at Mayo Clinic sites through January 23, 2021. Outcomes included emergency department visit, hospitalization, mortality, and allograft rejection. RESULTS: Seventy-three patients were treated, most commonly with bamlanivimab (75.3%). The median age was 59 years, 63% were male, and the median Charlson comorbidity index was 5. Transplant type included 41 kidney (56.2%), 13 liver (17.8%), 11 heart (15.1%), 4 kidney-pancreas (5.5%), 2 lung (2.7%), 1 heart-liver, and 1 pancreas. Eleven (15.1%) patients had an emergency department visit within 28 days of infusion, including 9 (12.3%) who were hospitalized for a median of 4 days. One patient required intensive care unit admission for a nonrespiratory complication. No patients required mechanical ventilation, died, or experienced rejection. Ten adverse events occurred, with 1 seeking medical evaluation. Hypertension was associated with hospital admission (P < .05), while other baseline characteristics were similar. The median time from symptom onset to antibody administration was 4 days in nonhospitalized patients compared with 6 days among hospitalized patients (P < .05). CONCLUSIONS: Monoclonal antibody treatment has favorable outcomes with minimal adverse effects in solid organ transplant recipients with mild to moderate COVID-19. Earlier administration of monoclonal antibody therapy appears to be more efficacious.

V.I.T.A.M. in COVID 19: A Systematic Approach to a Global Pandemic.

INTRODUCTION: In the unprecedented era of COVID-19, ongoing research and evolution of evidence has led to ever-changing guidelines for clinical monitoring and therapeutic options. Formulating treatment protocols requires the understanding and application of the evolving research. OBJECTIVE: The primary objective of this study is to present a systematic evidence-based approach to synthesize the necessary data in order to optimize the management of COVID-19. METHODS: At Mayo Clinic Florida, we developed a multidisciplinary centralized COVID Treatment Review Panel (TRP) of expert pulmonologists, intensivists, infectious disease specialists, anesthesiologists, hematologists, rheumatologists, and hospitalists that in real-time reviews the latest evidence in peer-reviewed journals, the available clinical trials, and help guide the rapid application of therapeutics or interventions to the patient and the bedside provider. RESULTS/CONCLUSIONS: The multi-disciplinary team approach of synthesizing clinical data and coordinating care is effective in responding to rapidly evolving and changing evidence. Systematic data collection and evidence-based treatment algorithms enable physicians to rapidly translate the current literature to clinical practice, and improve care and outcomes of patients.

Epidemiology, risk factors, and association of antifungal prophylaxis on early invasive fungal infection in heart transplant recipients.

BACKGROUND: Invasive fungal infection (IFI) in heart transplant recipients is associated with poor outcomes. Estimated risk of 1-year IFI in heart transplant recipients is 3.4-8.6% with risk factors inconsistently identified in previous studies. The role of antifungal prophylaxis is unclear. The transplant program at Mayo Clinic provides 6 months of universal azole prophylaxis for those heart transplant recipients in Arizona. We sought to define risk factors for 1-year IFI and determine the effect of antifungal prophylaxis. METHODS: We conducted a retrospective cohort study of patients undergoing heart transplantation at Mayo Clinic from January 2000 to March 2019. We analyzed demographics, details of transplant hospitalization, antifungal prophylaxis, and fungal infection. Multivariable Cox analyses were performed to identify risk factors of 1-year IFI and impact of IFI on posttransplant mortality. RESULTS: A total of 966 heart transplant recipients were identified with a median age of 56 years (IQR 47, 62). A total of 444 patients received antifungal prophylaxis. Over 1-year follow-up, 62 patients developed IFI with a cumulative incidence of 6.4%. In multivariable analysis, factors associated with IFI were renal replacement therapy (RRT) (HR 3.24, 95% CI 1.65-6.39), allograft rejection (HR 2.33, 95% CI 1.25-4.34), and antifungal prophylaxis (HR 0.32, 95% CI 0.11-0.96). RRT was also associated with invasive mold infection (HR 3.00, 95% CI 1.29-6.97). CONCLUSIONS: RRT and allograft rejection after transplantation are associated with 1-year IFI, and RRT is also associated with invasive mold infection. Antifungal prophylaxis appears to be protective and further study is needed in the heart transplant population.

A Comparison of Interobserver Reliability Between Orthopedic Surgeons Using the Centers for Disease Control Surgical Wound Class Definitions.

BACKGROUND: The Centers for Disease Control (CDC) created a classification to help stratify surgical wounds based on contamination and risk of developing a surgical site infection. The classification includes four options (I to IV) depending on the level of contamination present. Although universally applied to a variety of surgical specialties, it is unknown whether the current system is reliable when considering orthopaedic surgeries. The purpose of this study was to compare the degree of interobserver reliability between orthopaedic surgeons using the current CDC wound class definitions. METHODS: A questionnaire containing 30 clinical vignettes was completed by 39 orthopaedic surgeons at our institution. After each vignette, respondents were asked to determine the appropriate wound class based on information provided in the vignette. The overall interobserver agreement among all participants was analyzed. In addition, respondents were queried about the adequacy of the current classification system in describing orthopaedic surgical wound class. RESULTS: Interobserver agreement was poor at 66%, with a coefficient of concordance of 0.48. Only six physicians (15.4%) thought that the current wound classification system adequately covered orthopaedic surgery. CONCLUSIONS: There is poor interobserver reliability using the CDC surgical wound class definitions for orthopaedic surgeries. Alternate definitions are needed to improve the validity of the system for subspecialty procedures.

Serologic screening and infectious diseases consultation in renal transplant candidates for measles, mumps, rubella and varicella.

Background. Renal transplant recipients are at increased risk for developing complications of vaccine-preventable diseases. They benefit from a comprehensive pre-transplant evaluation when they might safely receive live vaccines. The primary aim of our study was to investigate the number of renal transplant recipients who were evaluated for serologic status against measles, mumps, rubella (MMR), and varicella. Secondarily, we investigated if pre-transplant Infectious Diseases consultation (IDC) improved vaccination rates.Methods. We retrospectively analyzed 282 kidney-alone and kidney-plus adult transplant recipients who were born in or after 1957. Patients were evaluated at Mayo Clinic, Florida Transplant Center between January 2015 and December 2017. Serologic status evaluation and vaccination rates were compared in two groups created based on IDC and no ID consultation (NIDC).Results. 235 (83%) of a total 282 patients received an IDC pre-transplantation. Varicella IgG levels were screened in all 235 IDC candidates. Among the IDC patients, mumps, measles and rubella IgG serologies were performed in 7 (3%), 143 (61%) and 144 (61%), respectively. Among 44 patients seronegative for any of MMR, 24 (55%) were vaccinated. Ten (66%) of 15 varicella seronegative patients were vaccinated. Zostavax was not given to 18% of IDC patients. Zostavax and MMR were administered more frequently in the IDC group compared to NIDC (p < .001 and p = 0.0016, respectively).Conclusion. Although the majority of patients had IDC, the screening rate for MMR serologies was lower than varicella. A protocol-driven serologic screening similar to the one for VZV is required for MMR. Pre-transplant IDC increases vaccination rates.

Disseminated cryptococcosis in a patient with newly diagnosed HTLV-1 infection.

Infection by human T-lymphotropic virus 1 (HTLV-1) is often seen as the cause of chronic infection or lymphoproliferative disorders, but many clinicians do not recognise its association with severe immunosuppression. We report the case of a woman in her 70s from the Caribbean who sought care at the emergency department for weakness, fatigue and weight loss. Further work-up showed atypical lymphocytosis with floral lymphocytes and smudge cells in the peripheral blood smear and hypercalcaemia. Chest CT demonstrated a moderate right pleural effusion. Results of HIV testing were negative, and screening and confirmatory tests for HTLV-1 were positive. Empiric antibiotic therapy was administered, and the patient was discharged home. Five days later, she was readmitted with shortness of breath and severe abdominal pain. A disseminated infection with Cryptococcus neoformans was diagnosed. Despite aggressive intravenous antifungal therapy, the patient died on day 7 of hospitalisation.

Establishing best practices in measles, mumps, and rubella serologic screening for kidney transplant candidates.

Optimizing immunity against vaccine-preventable diseases improves outcomes in kidney transplant (KT) patients (Arora et al, World J Transplant, 2019, 9:1; Sester et al, Transplant Rev, 2008, 22:274; Fishman, N Engl J Med, 2007, 357:2601). The American Society for Transplantation (AST) Clinical Practice Guidelines advises that serologic screening for measles, mumps, and rubella (MMR) be conducted for all KT candidates, since live-attenuated vaccines are contraindicated post-transplantation (Malinis et al, Clin Transplant, 2019, 33:e13548). Our team at Mayo Clinic Florida (MCF) conducted a quality improvement (QI) initiative to establish a best MMR screening and immunizations clinical practice in KT candidates using a Plan-Do-Study-Act (PDSA) model. By retrospective chart review of all KT candidates evaluated at our institution from January 1, 2016 to December 31, 2017, baseline data determining the rate of MMR serologic screening was established. PDSA cycles were implemented to adopt protocol-driven testing for MMR serologies, immunization documentation, and vaccination in cases of seronegativity to any of the three MMR viruses in all pre-KT candidates. Two PDSA cycles were completed in 4 months. The study population totaled 447 patients (baseline n = 283, PDSA 1 n = 61, PDSA 2 n = 103). Baseline data showed that 83% (n = 235) of pre-KT candidates received infectious disease consultation (IDC). Complete MMR (all three viruses) serological screening in KT candidates improved from baseline 3.9%-87.4% post-PDSA cycle 2 (P < .001). Necessary immunizations per AST guidelines were ordered in only 41.1% (n = 23) of the control cohort vs 100% (n = 12) and 96.9% (n = 31) of PDSA cycles 1 and 2, respectively (P < .001). The data reflect significant practice improvements in MMR screening and immunization rates among KT candidates by using protocol-driven orders combined with our pre-existing IDCs.

Serologic screening and infectious disease consultation (IDC): Indicated in heart, lung, liver (HLL) solid organ transplants (SOT) for measles, mumps, rubella, and varicella.

BACKGROUND: Solid organ transplant (SOT) recipients are a special group of patients who require comprehensive evaluation for preventable infectious diseases before transplantation. The main aim of our study was to investigate the number of heart, lung, and liver (HLL) transplant recipients who were evaluated for their immune status against measles, mumps, rubella (MMR), and varicella (VZV). As a secondary aim, we investigated whether pre-transplant infectious disease consultation (IDC) improves vaccination rates. METHODS: This study was an institution-based retrospective analysis of HLL transplant recipients born in or after 1957 and evaluated at Mayo Clinic, FL Transplant Center between January 1st, 2016 and December 31st, 2017. Data collection was obtained from electronic medical records. The vaccination rates were compared by univariate analysis based on IDC and no ID consultation (NIDC). RESULTS: One hundred and eighty-seven (77%) of a total 242 patients received an IDC pre-transplantation. Varicella IgG levels were screened in all 187 IDC candidates. Among the 187 IDC patients, mumps, measles, and rubella IgG serologies were performed in 9 (5%), 21 (11%), and 51 (27%), respectively. Among all 242 patients, vaccines given included 2 (0.8%) MMR, 10 (4.1%) varicella and 85 (35.12%) Zostavax. Univariate analysis revealed that Zostavax was given to 76 (40.6%) pre-transplant IDC patients and only in 9 (16.7%) NIDC patients (P < .001). CONCLUSIONS: Despite the relatively high IDC rate, patients' screened numbers for MMR IgG levels were low. Results pointed out the need for MMR protocol-driven serologic screening as well as for VZV and IDC prior to transplantation to increase vaccination rates.

Adult Intestinal Botulism: A Rare Presentation in an Immunocompromised Patient With Short Bowel Syndrome.

The cholinergic heat-labile neurotoxin produced by Clostridium species is primarily responsible for the clinical manifestations of botulism. The classic phenotypic presentation of botulism consists of subacute descending flaccid paralysis with intact sensory function. Traditionally, it is classified into 3 main forms (foodborne, wound-related, and infantile) on the basis of primary site of toxin entry into the human nervous system. Toxemia is the common pathophysiology in all forms of botulism. Adult intestinal toxemia botulism is an extremely rare form of the disease with pathogenesis similar to that of infant-type botulism. Symptomatic adults usually have an anatomic abnormality in the gastrointestinal tract leading to changes in normal gut flora. The current case is an addition to the growing literature on this unusual clinical variant of botulism.

Editorial: The Risky Business of Fungal Infections in Patients with Cirrhosis.

Hospitalized patients with cirrhosis have a high rate of mortality. In the report by Bajaj et al., the negative impact of fungal infections (FI) on outcomes in a large US cohort of hospitalized cirrhotics is highlighted. Risk factors for FI are identified. Increasing awareness of FI along with the application of new diagnostic tools in species identification will provide the opportunity to improve patient outcomes.

The epidemiology and outcomes of invasive Candida infections among organ transplant recipients in the United States: results of the Transplant-Associated Infection Surveillance Network (TRANSNET).

BACKGROUND: Invasive candidiasis (IC) is a common cause of mortality in solid organ transplant recipients (OTRs), but knowledge of epidemiology in this population is limited. METHOD: The present analysis describes data from 15 US centers that prospectively identified IC from nearly 17 000 OTRs. Analyses were undertaken to determine predictors of infection and mortality. RESULTS: A total of 639 cases of IC were identified. The most common species was Candida albicans (46.3%), followed by Candida glabrata (24.4%) and Candida parapsilosis (8.1%). In 68 cases >1 species was identified. The most common infection site was bloodstream (44%), followed by intra-abdominal (14%). The most frequently affected allograft groups were liver (41.1%) and kidney (35.3%). All-cause mortality at 90 days was 26.5% for all species and was highest for Candida tropicalis (44%) and C. parapsilosis (35.2%). Non-white race and female gender were more commonly associated with non-albicans species. A high rate of breakthrough IC was seen in patients receiving antifungal prophylaxis (39%). Factors associated with mortality include organ dysfunction, lung transplant, and treatment with a polyene antifungal. The only modifiable factor identified was choice of antifungal drug class based upon infecting Candida species. CONCLUSION: These data highlight the common and distinct features of IC in OTRs.

Morbidity and mortality among patients with respiratory syncytial virus infection: a 2-year retrospective review.

Previous studies have demonstrated high morbidity and mortality for adult patients with respiratory syncytial virus (RSV) infection. We performed a retrospective, multicenter, two-year chart review of all patients (n = 334) testing positive for RSV by the ProFlu + (®) Influenza A/B and RSV assay (Hologic, Bedford, MA). We analyzed indicators of morbidity and mortality in children <6 years old, immunocompetent and immunosuppressed adults, and transplant patients. Significant morbidity and mortality was observed among hematopoietic stem cell transplant patients (7.3%, 60-day mortality), solid organ transplant patients (13.3%, 60-day mortality), and COPD patients (12.8%, 60-day mortality). Of the patients positive for RSV, 144 (43.1%) of 334 received antibacterials or antifungals following diagnosis. Of these patients, a bacterial or fungal pathogen was not recovered from 60% of cases. Despite advances in RSV treatment, certain populations appear to be inadequately treated, while others appear to be inappropriately treated with unnecessary antimicrobials.