The pre-transplant evaluation: Considerations for trainees and early career transplant infectious diseases clinician.

Transplant infectious disease (TID) clinicians are integral to the pre-transplantation evaluation. Pre-transplant evaluations allow clinicians to assess risk factors for latent infections and relevant exposures to potential pathogens, address immunizations, and optimize patients' health and understanding of life after transplant. However, there is not a standardized approach to the pre-transplant evaluation. This article reviews the details of performing successful pre-transplant evaluations, including updated recommendations on available vaccines and contemporary opinions on marijuana use. This resource can be used for teaching with trainees or for early career TID clinicians.

Safety of fluconazole in kidney transplant recipients for prevention of coccidioidomycosis.

Coccidioides is an endemic fungus that causes infections ranging from mild respiratory illness to life-threatening disease, and immunocompromised hosts such as solid organ transplant recipients are at higher risk for disseminated infection and mortality. Our center administers fluconazole prophylaxis to kidney transplant recipients residing in geographic areas with higher incidences of coccidioidomycosis. However, because drug-drug interactions occur between triazoles and immunosuppressants used in transplant medicine, we undertook a study to ascertain whether fluconazole prophylaxis was associated with any important safety outcomes in kidney transplant recipients. This retrospective study evaluated patients who had undergone kidney transplantation between 2016 and 2019. Data on patient demographics, transplant-related clinical information, use of fluconazole prophylaxis (200 mg daily for 6-12 months post-transplant), and patient outcomes were obtained. The primary outcome was mean estimated glomerular filtration rate (eGFR) at 12 months, comparing those who received fluconazole prophylaxis to those who did not. Secondary outcomes included mean eGFR at 3 months, 6 months, and 9 months post-transplant, patient survival, biopsy-proven graft rejection, graft loss, or a new requirement for post-transplant dialysis, all within 12 months post-transplant. The mean eGFR at 12 months was similar between both groups, with 66.4 ml/min/1.73 m² in the fluconazole prophylaxis group vs. 64.3 ml/min/1.73 m² in the non-fluconazole prophylaxis group (P = 0.55). Secondary outcomes were similar across both groups. Multivariable linear regression found no significant association between fluconazole use and graft function. Fluconazole prophylaxis for prevention of coccidioidomycosis was not associated with adverse graft outcomes in kidney transplant recipients.

Solid organ transplant recipients can be highly immune suppressed, and infection with Coccidioides (valley fever) after transplant can lead to severe infections in these patients. Our study showed that fluconazole was safe and effective for preventing Coccidioides in kidney transplant recipients.

Entrapment Syndrome in a Kidney Transplant Recipient with Cryptococcal Meningitis.

Cryptococcus neoformans primarily affects immunocompromised individuals and the central nervous system (CNS) is the most common site of dissemination. Entrapped temporal horn syndrome (ETH) remains a rare CNS manifestation and has not previously been described in solid organ transplant recipients. Here, we present a case of ETH in a 55-year-old woman with history of renal transplant and prior treated Cryptococcal meningitis.

Endogenous Endophthalmitis From Methicillin-Resistant Staphylococcus aureus Bacteremia Treated With Ceftaroline.

Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia may lead to endogenous endophthalmitis (EE), an uncommon disease process described mainly in case series and case reports. It is considered an ophthalmologic emergency requiring prompt diagnosis and treatment with systemic intravenous and intravitreal antibiotics to improve mortality and prevent blindness. The management of MRSA EE represents a challenge, as there are no established guidelines for treatment or outcomes. In our case report, we demonstrate that ceftaroline may be considered as an alternative option to treat MRSA EE in lieu of vancomycin due to drug-induced rash, given the promising penetration of the blood brain barrier and low minimum inhibitory concentration (MIC) values for most Staphylococcus aureus isolates.

Axillary Adenopathy Secondary to SARS-CoV-2 Vaccination: a Case Report.

SARS-CoV-2 mRNA vaccines are safe and effective for the prevention of COVID-19 infection, though local reactions are commonly reported. Axillary lymphadenopathy has also been reported, which has the potential of causing diagnostic confusion and unnecessary testing and procedures. A 58-year-old female with untreated latent tuberculosis was noted to have a pulmonary nodule on chest radiograph. Evaluation for Mycobacterium tuberculosis was undertaken, and a FDG PET/CT was performed to rule out malignancy. While the nodule demonstrated low avidity, highly avid lymph nodes were noted in the left axillary region. Further questioning elicited a recent history of mRNA-1273 (Moderna) COVID-19 vaccination in her left deltoid muscle 3 weeks prior and a sensation of axillary fullness. She was managed conservatively with spontaneous resolution of her lymphadenopathy. Axillary lymphadenopathy following mRNA vaccination has been reported and appears to be more common with mRNA-1273 (Moderna) than BNT162b2 vaccine (Pfizer-BioNTech), in those aged 18 to 64 as compared to age ≥ 65, and following the second vaccine dose compared to the first dose. Vaccination should be considered in the differential diagnosis of axillary lymphadenopathy, particularly ipsilateral to the vaccination site, to avoid unnecessary testing, treatment, and patient anxiety. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s42399-022-01143-y.

Rectal screening for azole non-susceptible Candida species in patients undergoing liver transplantation.

INTRODUCTION: Candidiasis is the most common invasive fungal infection in solid organ transplant recipients, and liver transplant (LT) recipients are at heightened risk. We hypothesized that pre-transplant screening for azole non-susceptible Candida (ANSC) allows for tailored antifungal prophylaxis to reduce the incidence of post-LT ANSC infection. METHODS: We performed a retrospective chart review of adult (age ≥18 years) patients who underwent LT at Yale New Haven Hospital from April 2019 to March 2021. Screening for ANSC, defined as Candida glabrata or Candida krusei, was performed using a rectal swab prior to or at the time of LT. RESULTS: During the study period, ANSC screening was performed in 47 patients who underwent a total of 48 LTs, with 46/48 (96%) primary LTs and two re-transplantations. Ten of 48 screened cases (21%) had ANSC-positive rectal swabs. Only seven of 10 ANSC-colonized patients received appropriate antifungal prophylaxis (i.e., anidulafungin), and one of these seven patients developed candidemia within 30 days of LT. The median number of candidiasis risk factors was one, and 29% of the cohort had two or more risk factors. DISCUSSION: Routine ANSC screening of LT candidates may assist in selecting appropriate antifungal prophylaxis but may be insufficient to prevent infection in those with multiple risk factors for Candida infection.

Genetic and Epidemiologic Analyses of an Outbreak of Pneumocystis jirovecii Pneumonia Among Kidney Transplant Recipients in the United States.

BACKGROUND: Pneumocystis jirovecii is an opportunistic fungus that causes Pneumocystis pneumonia (PCP) in immunocompromised hosts. Over an 11-month period, we observed a rise in cases of PCP among kidney-transplant recipients (KTR), prompting an outbreak investigation. METHODS: Clinical and epidemiologic data were collected for KTR diagnosed with PCP between July 2019 and May 2020. Pneumocystis strain typing was performed using restriction fragment length polymorphism analyses and multilocus sequence typing in combination with next-generation sequencing. A transmission map was drawn, and a case-control analysis was performed to determine risk factors associated with PCP. RESULTS: Nineteen cases of PCP in KTR were diagnosed at a median of 79 months post-transplantation; 8 received monthly belatacept infusions. Baseline characteristics were similar for KTR on belatacept versus other regimens; the number of clinic visits was numerically higher for the belatacept group during the study period (median 7.5 vs 3). Molecular typing of respiratory specimens from 9 patients revealed coinfection with up to 7 P. jirovecii strains per patient. A transmission map suggested multiple clusters of interhuman transmission. In a case-control univariate analysis, belatacept, lower absolute lymphocyte count, non-White race, and more transplant clinic visits were associated with an increased risk of PCP. In multivariate and prediction power estimate analyses, frequent clinic visits was the strongest risk factor for PCP. CONCLUSIONS: Increased clinic exposure appeared to facilitate multiple clusters of nosocomial PCP transmission among KTR. Belatacept was a risk factor for PCP, possibly by increasing clinic exposure through the need for frequent visits for monthly infusions.

Mycobacterium tuberculosis in solid organ transplant donors and recipients.

PURPOSE OF REVIEW: Due to impaired immune response, solid organ transplant (SOT) recipients are susceptible to tuberculosis (TB) and its subsequent morbidity and mortality. Current prevention strategies, diagnostic and treatment approach to TB infection in donors and recipients were reviewed in this article. RECENT FINDINGS: Screening of latent tuberculosis infection (LTBI) in donors and recipients is the cornerstone of TB-preventive strategy in recipients and requires an assessment of TB risk factors, TB-specific immunity testing, and radiographic evaluation. Interferon-gamma release assay has superseded the tuberculin skin test in LTBI evaluation despite its recognized limitations. LTBI treatment should be offered to transplant candidates and living donors before transplantation and donation, respectively. Diagnosis of TB disease can be challenging because of nonspecific clinical presentation in the recipient and is limited by the sensitivity of current diagnostics. The approach to LTBI and TB disease treatment is similar to the general population, but can be challenging because of potential drug interactions and toxicities. SUMMARY: The appropriate evaluation of donors and recipients for TB can mitigate posttransplant TB disease. Current approaches to diagnosis and treatment parallels that of immunocompetent hosts. Future research evaluating existing and novel diagnostics and treatment in transplant recipients is needed.

Prolonged incubation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a patient on rituximab therapy.

The incubation period of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is rarely >14 days. We report a patient with hypogammaglobulinemia who developed coronavirus disease 2019 (COVID-19) with a confirmed incubation period of at least 21 days. These findings raise concern for a prolonged presymptomatic transmission phase, necessitating a longer quarantine duration in this patient population.

Repurposing antimicrobial stewardship tools in the electronic medical record for the management of COVID-19 patients.

During the COVID-19 pandemic, the antimicrobial stewardship module in our electronic medical record was reconfigured for the management of COVID-19 patients. This change allowed our subspecialist providers to review charts quickly to optimize potential therapy and management during the patient surge.

Tocilizumab Treatment for Cytokine Release Syndrome in Hospitalized Patients With Coronavirus Disease 2019: Survival and Clinical Outcomes.

BACKGROUND: Tocilizumab, an IL-6 receptor antagonist, can be used to treat cytokine release syndrome (CRS), with observed improvements in a coronavirus disease 2019 (COVID-19) case series. RESEARCH QUESTION: The goal of this study was to determine if tocilizumab benefits patients hospitalized with COVID-19. STUDY DESIGN AND METHODS: This observational study of consecutive COVID-19 patients hospitalized between March 10, 2020, and March 31, 2020, and followed up through April 21, 2020, was conducted by chart review. Patients were treated with tocilizumab using an algorithm that targeted CRS. Survival and mechanical ventilation (MV) outcomes were reported for 14 days and stratified according to disease severity designated at admission (severe, ≥ 3 L supplemental oxygen to maintain oxygen saturation > 93%). For tocilizumab-treated patients, pre/post analyses of clinical response, biomarkers, and safety outcomes were assessed. Post hoc survival analyses were conducted for race/ethnicity. RESULTS: Among the 239 patients, median age was 64 years; 36% and 19% were black and Hispanic, respectively. Hospital census increased exponentially, yet MV census did not. Severe disease was associated with lower survival (78% vs 93%; P < .001), greater proportion requiring MV (44% vs 5%; P < .001), and longer median MV days (5.5 vs 1.0; P = .003). Tocilizumab-treated patients (n = 153 [64%]) comprised 90% of those with severe disease; 44% of patients with nonsevere disease received tocilizumab for evolving CRS. Tocilizumab-treated patients with severe disease had higher admission levels of high-sensitivity C-reactive protein (120 vs 71 mg/L; P < .001) and received tocilizumab sooner (2 vs 3 days; P < .001), but their survival was similar to that of patients with nonsevere disease (83% vs 91%; P = .11). For tocilizumab-treated patients requiring MV, survival was 75% (95% CI, 64-89). Following tocilizumab treatment, few adverse events occurred, and oxygenation and inflammatory biomarkers (eg, high-sensitivity C-reactive protein, IL-6) improved; however, D-dimer and soluble IL-2 receptor (also termed CD25) levels increased significantly. Survival in black and Hispanic patients, after controlling for age, was significantly higher than in white patients (log-rank test, P = .002). INTERPRETATION: A treatment algorithm that included tocilizumab to target CRS may influence MV and survival outcomes. In tocilizumab-treated patients, oxygenation and inflammatory biomarkers improved, with higher than expected survival. Randomized trials must confirm these findings.

Daptomycin perioperative prophylaxis for the prevention of vancomycin-resistant Enterococcus infection in colonized liver transplant recipients.

BACKGROUND: Vancomycin-resistant Enterococcus (VRE)-colonized liver transplantation (LT) recipients have increased post-LT morbidity, mortality, and higher rates of VRE infections compared with their non-colonized counterparts. Pre-LT screening for VRE colonization and inclusion of daptomycin in the perioperative antibiotic prophylaxis regimen may mitigate this risk. METHODS: We performed a retrospective chart review of liver transplant recipients aged ≥ 18 years between 2013 and August 2019 to identify pre-LT VRE-colonized recipients and whether they received daptomycin perioperative prophylaxis (DPP). Demographic and clinical characteristics, including risk factors for VRE infection, were collected. Outcomes measured were VRE-related infection and all-cause mortality within 90 days of LT. RESULTS: Of the 27 VRE-colonized liver transplant recipients within the study period, 25 received DPP. All recipients were admitted to the intensive care unit postoperatively, six (24%) required reoperation, fifteen (60%) required renal replacement therapy, and eight (32%) experienced postoperative hemorrhage within 90 days post-transplant. Two recipients (8%) experienced acute cellular rejection, but no primary graft failure was seen within 90 days. Among those who received DPP, no infections related to VRE or death was seen within 90 days of LT. The two VRE-colonized recipients who did not receive DPP both developed VRE bacteremia in the early post-LT period. CONCLUSION: Despite having multiple risk factors for post-LT VRE infection, VRE-colonized recipients who received DPP did not develop VRE-related infections in the first 90 days post-LT. Our experience demonstrates that pre-LT VRE screening and DPP may be associated with a reduction in VRE infection in the early post-LT period, but this strategy warrants further evaluation in prospective studies.

Diagnosing peritoneal tuberculosis.

Peritoneal tuberculosis (TB) is one of the most challenging forms of extrapulmonary tuberculosis to diagnose. This challenge can be compounded in low incidence regions, and in patients with cirrhosis in whom the presence of ascites alone may not prompt further investigation. A delay in the diagnosis and treatment of peritoneal tuberculosis may lead to worse clinical outcomes. This case describes a 64-year-old Italian male with decompensated cirrhosis being evaluated for liver transplantation, who developed abdominal pain and a persistent inflammatory ascites with peritoneal thickening despite antibiotic therapy. Peritoneal tuberculosis was suspected, although non-invasive and invasive direct mycobacterial testing remained negative. A constellation of positive QuantiFERON-TB Gold In-Tube test, elevated ascitic adenosine deaminase and dramatic symptomatic and radiographic response to empiric anti-tuberculous therapy confirmed the diagnosis of peritoneal tuberculosis. This paper will review the approach to the diagnosis of peritoneal tuberculosis.

Condomless sex and HIV transmission among serodifferent couples: current evidence and recommendations.

Human immunodeficiency virus (HIV) infection remains a global pandemic. The primary driver of HIV incidence is sexual transmission between serodifferent individuals. Condoms, when used consistently and correctly, are effective at preventing sexually transmitted HIV infections and are considered an integral component of a comprehensive approach to HIV prevention. However, the demonstrated effectiveness of antiretroviral therapy (ART) to prevent HIV transmission, known as treatment as prevention and of pre-exposure prophylaxis, have raised an intriguing dilemma on the necessity and additive preventive benefit of condom use among individuals in serodifferent relationships utilizing these prevention strategies. Recent published evidence, although of limited follow-up duration, has shown no linked HIV transmissions with condomless sex among serodifferent couples where the infected partner was on ART and virologically suppressed. This paper will review the evidence surrounding HIV transmission risk among serodifferent couples with and without the use of condoms and will highlight factors that increase or attenuate this risk. It will also address the important benefits that condomless sex offers couples. This paper aims to provide a template for providers to have personalized discussions with their patients, particularly those with an HIV-positive sexual partner, around their individual risk of HIV transmission and the role of condom use.