Razonable, Raymund R.

Cytomegalovirus is the classic opportunistic infection after solid organ transplantation. This review will discuss updates and future directions in the diagnosis, prevention and treatment of CMV infection in solid organ transplant recipients. Antiviral prophylaxis and pre-emptive therapy are the mainstays of CMV prevention, but they should not be mutually exclusive and each strategy should be considered depending on a specific situation. The lack of a widely applicable viral load threshold for diagnosis and preemptive therapy is emphasized as a major factor that should pave the way for an individualized approach to prevention. Valganciclovir and intravenous ganciclovir remain as drugs of choice for CMV management, and strategies for managing drug-resistant CMV infection are enumerated. There is increasing use of CMV-specific cell-mediated immune assays to stratify the risk of CMV infection after solid organ transplantation, and their potential role in optimizing CMV prevention and treatment efforts is discussed.

AbstractBackgroundNo consensus exists regarding optimal strategy for antifungal prophylaxis following lung transplant.ObjectiveTo review data regarding antifungal prophylaxis on the development of fungal infections.Study selection/AppraisalWe searched MEDLINE, Embase, and Scopus for eligible articles through December 10, 2019. Observational or controlled trials published after January 1, 2001, that pertained to the prevention of fungal infections in adult lung recipients were reviewed independently by two reviewers for inclusion.MethodsOf 1702 articles screened, 24 were included. Data were pooled using random effects model to evaluate for the primary outcome of fungal infection. Studies were stratified by prophylactic strategy, medication, and duration (short term < 6 months and long term ≥ 6 months).ResultsWe found no difference in the odds of fungal infection with universal prophylaxis (49/101) compared to no prophylaxis (36/93) (OR 0.76, CI: 0.03‐17.98; I2 = 93%) and preemptive therapy (25/195) compared to universal prophylaxis (35/222) (OR 0.91, CI: 0.06‐13.80; I2 = 93%). The cumulative incidence of fungal infections within 12 months was not different with nebulized amphotericin (0.08, CI: 0.04‐0.13; I2 = 87%) compared to systemic triazoles (0.07, CI: 0.03‐0.11; I2 = 21%) (P = .65). Likewise, duration of prophylaxis did not impact the incidence of fungal infections (short term: 0.11, CI: 0.05‐0.17; I2 = 89%; long term: 0.06, CI: 0.03‐0.08; I2 = 51%; P = .39).ConclusionsWe have insufficient evidence to support or exclude a benefit of antifungal prophylaxis.

Abstract Remediation of struggling learners is a challenge faced by all educators. In recognition of this reality, and in light of contemporary challenges facing infectious diseases (ID) fellowship program directors, the Infectious Diseases Society of America Training Program Directors’ Committee focused the 2018 National Fellowship Program Directors’ Meeting at IDWeek on “Remediation of the Struggling Fellow.” Small group discussions addressed 7 core topics, including feedback and evaluations, performance management and remediation, knowledge deficits, fellow well-being, efficiency and time management, teaching skills, and career development. This manuscript synthesizes those discussions around a competency-based framework to provide program directors and other educators with a roadmap for addressing common contemporary remediation challenges.

Abstract Human cytomegalovirus (HCMV) infections are among the most common complications arising in transplant patients, elevating the risk of various complications including loss of graft and death. HCMV infections are also responsible for more congenital infections worldwide than any other agent. Congenital HCMV (cCMV) infections are the leading nongenetic cause of sensorineural hearing loss and a source of significant neurological disabilities in children. While there is overlap in the clinical and laboratory approaches to diagnosis of HCMV infections in these settings, the management, follow-up, treatment, and diagnostic strategies differ considerably. As yet, no country has implemented a universal screening program for cCMV. Here, we summarize the issues, limitations, and application of diagnostic strategies for transplant recipients and congenital infection, including examples of screening programs for congenital HCMV that have been implemented at several centers in Japan, Italy, and the United States.

Abstract Background Demographic and epidemiologic characteristics of Hepatitis E virus (HEV) infected patients in the United States are not well-described. HEV infection may result in severe complications and lead to chronic infection and cirrhosis, especially in immunocompromised patients. There are no widely accepted guidelines for HEV screening and testing in the United States. Identifying traits of known seropositive patients and comorbidities may inform better screening and prevention strategies. In this study, we describe rates of liver disease, transplant status, chronic kidney diseases, and diabetes mellitus among patients serologically tested for HEV at our institution. Methods We retrospectively reviewed all patients for whom HEV IgM or IgG serologic testing was performed across the Mayo Clinic enterprise using the Advanced Cohort Explorer tool. For patients with any documented HEV serologic test, we abstracted baseline patient characteristics and underlying comorbidities at the time of testing. We then grouped subjects according to serologic testing results by antibody type. Survival at one year from date of testing was also assessed. Results A total of 979 unique subjects were identified. The preponderance of subjects was Caucasian (781, 79.8%). Of subjects tested for HEV with serology, 123 (12.6%) had any positive serology. Breakdown of baseline characteristics and selected comorbidities are summarized in Table 1. The largest proportion of subjects, 458 (46.8%), were both IgG and IgM negative and 432 subjects received only IgM or IgG testing. Liver disease was more prevalent in patients with positive vs. negative testing (5.8% vs. 2.1%) as was higher age (average 55.1 years vs. 52.2). One-year survival was similar in all groups. Conclusion HEV serology is not commonly tested. Among those tested, seropositivity is uncommon. Our data show higher HEV seropositivity in older adults, which may represent increase risk of exposure over time. Higher percentage of positive testing was also observed in subjects with liver disease, which may indicate a possible etiologic association. Further population-based studies are needed to estimate prevalence of HEV infection and associated liver disease, outcomes in infected patients, and indications for testing in at-risk populations. Disclosures All authors: No reported disclosures.

Abstract Background Quantitative nucleic acid amplification (QNAT) tests are cornerstone for the management of CMV disease after organ transplantation. We assessed the potential impact of viral load results obtained by two commercial WHO international standard-calibrated NAT in solid-organ (SOT) and hematopoietic stem cell transplant (HSCT) recipients. Methods Sixty-four patients (36 SOT and 28 HSCT) had plasma CMV viral load assessed using the COBAS AmpliPrep/COBAS TaqMan CMV Test (CAP/CTM; lower limit of quantification [LLoQ] at 137 IU/mL) and cobas 6800 System (cobas CMV; LLoQ at 35 IU/mL). Viral load values were correlated with clinical course and outcomes. Results Forty-three of 64 patients (67.2%) had CMV infection or disease (asymptomatic, 67.4%; gastrointestinal disease, 16.3%; pneumonitis 4.7%) at median of 4.4 months (IQR 1.4 to 7.7) from transplantation. At CMV infection diagnosis, viral load results (mean ± SD) were almost two-fold higher when measured by cobas CMV (19,456 ± 51,618 IU/mL) compared with CAP/CTM (10,504 ± 27,744 IU/mL; P = 0.04). Time to onset of CMV viremia was significantly shorter (11.5 days; P < 0.001) while viral clearance was significantly longer (12.75 days; P < 0.001) by cobas CMV when compared with CAP/CTM. Persistent viremia was observed with cobas CMV in 44% of patients at the time of first negative results by CAP/CTM. Patients with negative results by cobas CMV at the end of antiviral treatment had a significantly lower need for re-treatment (OR 0.26, 95% CI 0.04 to 0.99, P = 0.05). Conclusion Our study highlights significant differences between CMV QNAT assays despite calibration to the WHO-international standard. The significant differences in the degree (almost two-fold), time to onset (12 days difference) and clearance (13 days difference) of CMV viremia between two automated commercial QNAT assays have direct implications in the care of transplant recipients. Persistence of low-level viremia was observed in samples that reached negative threshold by CAP/CTM, when tested using the more sensitive cobas CMV. Clearance of CMV viremia, when assessed by the more sensitive cobas CMV, was significantly associated with a lower need for re-treatment. Disclosures All authors: No reported disclosures.

Abstract Background Cryptococcus sp. is a major cause of opportunistic infections in immunocompromised patients, with nearly all cases due to C. neoformans or C. gattii. There are occasional reports of other Cryptococcus species causing invasive human disease. However, their epidemiology and clinical significance are not fully defined. We sought to describe the patients with cultures positive for Cryptococcus species other than neoformans and gattii. Methods A retrospective descriptive review of patients with cultures growing Cryptococcus species other than neoformans and gattii from November 2011 to February 2019. Clinical and laboratory data were analyzed. Results Out of 177 cases with a culture positive for Cryptococcus sp., 54 patients (mean age, 53.3 years; 61% men) had a culture for Cryptococcus other than neoformans and gattii. The most common species were unspecified non-neoformans/gattii (10), magnus (9), laurentii (8), and ater (7). Three patients had active malignancies and 15 were on immunosuppressive drugs, 6 due to transplant. The most common sites or specimens were skin (16), respiratory (16), urine (7), joint (3), intravascular catheter (2), cerebrospinal fluid (2), oral (2), peritoneal fluid, donor liver transplant, bone marrow, sinus, nail, and cornea. Whereas 21 (38.9%) cultures were obtained due to local symptoms, there was only one case of invasive disease, affecting the peritoneum, while the majority was either unaddressed (25) or considered contaminants (17). Only 12 patients received antifungal treatment, where sources were skin (4), oral (2), peritoneum, donor liver, respiratory, vascular catheter, urine, and nail. Antifungal drugs were fluconazole, itraconazole, clotrimazole, caspofungin, and griseofulvin, for a mean duration of 37.6 days. Among patients who were not treated, four died within 6 months but mostly of unrelated causes (3) or not known (1). Conclusion This large series of patients with Cryptococcus sp. other than neoformans and gattii suggests that these species rarely cause clinically significant infection in humans. Only one case of invasive disease was found. Disclosures All authors: No reported disclosures.