Disseminated tuberculosis in a lung transplant recipient presenting as tenosynovitis, subcutaneous nodules, and liver abscesses.

Tuberculosis is of particular concern in lung transplant recipients. We present the case of a patient who received a double lung transplant from a deceased donor from Mexico and developed disseminated tuberculosis 60 days post-transplant manifested as tenosynovitis, liver abscesses, and subcutaneous nodules with no definitive lung allograft involvement. The recipient did not have evidence of tuberculosis on explanted lungs, had a negative interferon gamma release assay pre-transplant, and did not have risk factors for this infection. Mycobacterium tuberculosis should remain in the differential diagnosis of early post-transplant infections with atypical presentations, evidence of dissemination, or lack of improvement with appropriate antimicrobial coverage, even in the absence of typical lung findings.

Real-World Comparison of Bezlotoxumab to Standard of Care Therapy for Prevention of Recurrent Clostridioides difficile Infection in Patients at High Risk for Recurrence.

BACKGROUND: Bezlotoxumab (BEZ) is a monoclonal antibody used to prevent recurrent Clostridioides difficile infection (rCDI). This study investigates BEZ effectiveness in relation to rCDI and patient-specific risk factors in a real-world setting. METHODS: A matched, retrospective cohort study was conducted from 2015 to 2019 to compare BEZ to historical standard of care (SoC) therapy with vancomycin or fidaxomicin. The primary outcome was incidence of 90-day rCDI. Secondary outcomes were incidence of all-cause hospital readmission and all-cause mortality at 90 days, infusion-related reactions, and incidence of heart failure exacerbation. Baseline confounding was addressed using inverse probability of treatment weighting (IPTW). RESULTS: Overall, 107 participants were included (54 BEZ and 53 SoC). Mean number of prior CDI episodes was 2, median number of risk factors for rCDI was 4, and 28% of participants had severe CDI. Incidence of 90-day rCDI was 11% BEZ vs 43% SoC (P = < .001) and 90-day all-cause readmission was 40% BEZ vs 64% SoC (P = .011). In IPTW-adjusted analyses, BEZ was associated with significantly reduced odds of rCDI (odds ratio [OR], 0.14 [95% confidence interval {CI}: .05-.41]) and all-cause readmission (OR, 0.36 [95% CI: .16-.81]). No safety signals were detected with BEZ use. CONCLUSIONS: BEZ is effective for the prevention of rCDI and reduction in all-cause hospital readmission for patients at high risk for recurrence, supporting current guideline recommendations.

Carbapenemase-producing Enterobacterales in solid organ transplantation: Tip of the iceberg?

A liver transplant recipient developed a urinary tract infection with Citrobacter freundii complex and Klebsiella aerogenes, both producing dual carbapenemases (KPC-3/NDM-1). Whole-genome sequencing suggested plasmid transfer between organisms. Silent plasmid transmission highlights emergent threats to infection prevention, with implications for screening and antimicrobial stewardship.

Effectiveness of Bezlotoxumab for Prevention of Recurrent Clostridioides difficile Infection Among Transplant Recipients.

BACKGROUND: Bezlotoxumab significantly reduces the incidence of recurrent Clostridioides difficile infection (CDI); however, limited data are available in solid organ transplant (SOT) and hematopoietic cell transplant (HCT) recipients. METHODS: We conducted a single-center retrospective analysis comparing recurrent CDI in SOT and HCT recipients receiving standard of care alone (oral vancomycin, fidaxomicin, or metronidazole) or bezlotoxumab plus standard of care. The primary outcome was 90-day incidence of recurrent CDI, and secondary outcomes included 90-day hospital readmission, mortality, and incidence of heart failure exacerbation. RESULTS: Overall, 94 patients received bezlotoxumab plus standard of care (n = 38) or standard of care alone (n = 56). The mean age was 53 years; patients had a median of 3 prior Clostridioides difficile episodes and 4 risk factors for recurrent infection. Most patients were SOT recipients (76%), with median time to index CDI occurring 2.7 years after transplantation. Ninety-day recurrent CDI occurred in 16% (6/38) in the bezlotoxumab cohort compared to 29% (16/56) in the standard of care cohort (P = .13). Multivariable regression revealed that bezlotoxumab was associated with significantly lower odds of 90-day recurrent CDI (odds ratio, 0.28 [95% confidence interval, .08-.91]). There were no differences in secondary outcomes, and no heart failure exacerbations were observed. CONCLUSIONS: In a cohort of primarily SOT recipients, bezlotoxumab was well tolerated and associated with lower odds of recurrent CDI at 90 days. Larger, prospective trials are needed to confirm these findings among SOT and HCT populations.

Coronavirus Disease 2019 in Solid Organ Transplant: A Multicenter Cohort Study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has led to significant reductions in transplantation, motivated in part by concerns of disproportionately more severe disease among solid organ transplant (SOT) recipients. However, clinical features, outcomes, and predictors of mortality in SOT recipients are not well described. METHODS: We performed a multicenter cohort study of SOT recipients with laboratory-confirmed COVID-19. Data were collected using standardized intake and 28-day follow-up electronic case report forms. Multivariable logistic regression was used to identify risk factors for the primary endpoint, 28-day mortality, among hospitalized patients. RESULTS: Four hundred eighty-two SOT recipients from >50 transplant centers were included: 318 (66%) kidney or kidney/pancreas, 73 (15.1%) liver, 57 (11.8%) heart, and 30 (6.2%) lung. Median age was 58 (interquartile range [IQR] 46-57), median time post-transplant was 5 years (IQR 2-10), 61% were male, and 92% had ≥1 underlying comorbidity. Among those hospitalized (376 [78%]), 117 (31%) required mechanical ventilation, and 77 (20.5%) died by 28 days after diagnosis. Specific underlying comorbidities (age >65 [adjusted odds ratio [aOR] 3.0, 95% confidence interval [CI] 1.7-5.5, P < .001], congestive heart failure [aOR 3.2, 95% CI 1.4-7.0, P = .004], chronic lung disease [aOR 2.5, 95% CI 1.2-5.2, P = .018], obesity [aOR 1.9, 95% CI 1.0-3.4, P = .039]) and presenting findings (lymphopenia [aOR 1.9, 95% CI 1.1-3.5, P = .033], abnormal chest imaging [aOR 2.9, 95% CI 1.1-7.5, P = .027]) were independently associated with mortality. Multiple measures of immunosuppression intensity were not associated with mortality. CONCLUSIONS: Mortality among SOT recipients hospitalized for COVID-19 was 20.5%. Age and underlying comorbidities rather than immunosuppression intensity-related measures were major drivers of mortality.

Cryptococcal pericarditis in a heart transplant recipient.

We present a case of Cryptococcus neoformans pericarditis in a cardiac transplant recipient. This article reviews the diagnosis, treatment, and complications of cryptococcosis specifically in transplant patients. While pericarditis is a rare manifestation of Cryptococcus infection, this case highlights that cryptococcosis should be considered in the differential diagnosis for solid organ transplant and immunocompromised patients presenting with pericardial effusions.

Cytomegalovirus myocarditis in solid organ transplant recipients: A case series and review of literature.

Cytomegalovirus (CMV) is a DNA virus of the Herpesviridae family and is estimated to affect 15%-30% of high-risk solid organ transplant recipients. Typical manifestations of CMV end-organ disease in this population include colitis, esophagitis, and pneumonitis, and myocarditis is a rarely reported manifestation. We describe two cases of CMV myocarditis in solid organ transplant recipients and review the literature regarding previously published cases of CMV myocarditis.

Letermovir prophylaxis through day 100 post transplant is safe and effective compared with alternative CMV prophylaxis strategies following adult cord blood and haploidentical cord blood transplantation.

We compared CMV outcomes of three prophylactic approaches used for CBT and haploidentical cord transplants from December 2009 through 2018: letermovir (n = 32) through day 100 post transplant, "valacyclovir day 100" (valacyclovir 2 g orally three times daily through day 100) (n = 60), and "valacyclovir hospital discharge" (valacyclovir 2 g orally three times daily through hospital discharge then acyclovir 800 mg twice daily) (n = 41). Through day 100, none in the letermovir group, six (10%) in the "valacyclovir day 100," and nine (22%) in the "valacyclovir hospital discharge" group required CMV directed treatment (p = 0.005 and 0.06 comparing letermovir to "valacyclovir hospital discharge" and "valacyclovir day 100"). Fewer patients in the letermovir group (n = 7, 22%) had any CMV reactivation versus the "valacyclovir day 100" group (n = 20, 33%) versus the "valacyclovir hospital discharge" group (n = 23, 57%) (p = 0.003 and 0.21 comparing letermovir to "valacyclovir hospital discharge" and "valacyclovir day 100"). Among patients not reactivating CMV before 100 days, reactivation rates between day 100 and 180 were higher in the letermovir and "valacyclovir day 100" groups than the "valacyclovir hospital discharge" group. Letermovir is safe and effective compared with alternative prophylaxis approaches following CBT through day 100. Reactivation and monitoring after day 100 remain potential concerns.

Severe acute Q fever pneumonia complicated by presumed persistent localized Q fever endocarditis in a renal transplant recipient: A case report and review of the literature.

Q fever in solid organ transplant (SOT) recipients is rarely described in the medical literature. We present a case of severe acute Q fever pneumonia that evolved into persistent localized Q fever endocarditis in a renal transplant recipient.

Toxoplasmosis in non-cardiac solid organ transplant recipients: A case series and review of literature.

The risk of toxoplasmosis in high-risk cardiac transplant recipients is well recognized prompting universal donor and candidate screening with administration of targeted post-transplant chemoprophylaxis in high-risk (D+/R-) cardiac transplant patients. In contrast, until recently, there have been neither well-defined recommendations nor consensus regarding toxoplasmosis preventive strategies among non-cardiac solid organ transplant recipients. We report 3 cases of post-transplant toxoplasmosis in non-cardiac transplant recipients (one lung and two liver); all 3 infections presumed to be donor-derived. Not surprisingly, pre-transplant Toxoplasma serology was negative in all the patients. None of the patients were on trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis at the time of diagnosis of toxoplasmosis. The median time from transplant to onset of infection was 90 days (range: 30-120 days). Clinical presentations included cerebral (n = 1) and disseminated infections (n = 2). Two of the 3 patients, both with disseminated infection died (mortality ~ 67%).

Oral Vancomycin Prophylaxis as Secondary Prevention Against Clostridioides difficile Infection in the Hematopoietic Stem Cell Transplantation and Hematologic Malignancy Population.

Clostridioides difficile infection (CDI) is a common complication in the hematopoietic stem cell transplantation (HSCT) and hematologic malignancy (HM) population. CDI is associated with increased hospital length of stay, health care and societal costs, morbidity, and mortality. Identifying strategies for secondary prevention of CDI is of extreme importance in the HSCT/HM population. In this study, our primary objective was to evaluate the effectiveness and safety of an oral vancomycin prophylaxis (OVP) protocol for secondary prevention of CDI in a retrospective cohort of adult autologous/allogeneic HSCT recipients and patients with HM who did not undergo HSCT with a first CDI episode treated with concomitant broad-spectrum antibiotics (BSA). Patients were diagnosed and treated for CDI as inpatients and/or outpatients and were divided into 2 groups based on a preprotocol versus postprotocol analysis: the OVP group, comprising patients who received planned monotherapy with oral vancomycin 125 mg every 6 hours for 14 days for a first episode of CDI and subsequently received OVP posttreatment and a no OVP (NOVP) group, comprising patients who received planned monotherapy with oral vancomycin 125 mg every 6 hours for 14 days for a first episode of CDI and subsequently did not receive OVP posttreatment. OVP was defined as vancomycin 125 mg every 12 hours for up to 7 days after BSA discontinuation. The primary endpoint was recurrent CDI (rCDI), defined as symptoms of loose stools/diarrhea with high clinical suspicion for CDI prompting empiric therapy within 60 days of completion of treatment/prophylaxis for the first CDI episode. The incidence of vancomycin-resistant enterococcal (VRE) infection and 60-day mortality were also compared between the 2 groups. Multivariate logistic regression was created from associated variables to identify independent associations with rCDI. A total of 50 patients were included, 21 in the OVP group (42%) and 29 in the NOVP group (58%). The mean patient age was 58 years, and the cohort was 60% male and 86% Caucasian. HSCT was performed in 60% of the patients, and 76% of CDI cases were diagnosed during hospitalization. The rate of rCDI was significantly lower in the OVP group compared with the NOVP group (5% [1 of 21] versus 35% [10 of 29]; P= .016), with no subsequent increase in VRE infection rate (14% [3 of 21] versus 10% [3 of 29]; P = .686). By multivariable logistic regression, rCDI was inversely associated with OVP (odds ratio [OR], .14; 95% confidence interval [CI], .007 to .994; P = .049) and directly associated with outpatient CDI diagnosis (OR, 8.72; 95% CI, 1.816 to 49.158; P = .007). No between-group differences were found in 60-day mortality (10% [2 of 21] for OVP versus 7% [2 of 29] for NOVP; P > 0.999). OVP appears to be safe and effective for secondary prevention of CDI in the HSCT/HM population. Prospective trials are needed to validate the effectiveness of OVP in this vulnerable population to prevent rCDI.