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We evaluated use of maribavir (MBV) for treatment of 15 episodes of refractory/resistant cytomegalovirus infection in 13 solid organ transplant recipients. Treatment failure due to treatment-emergent MBV resistance or early virological recurrence after MBV discontinuation occurred in 7 (47%) episodes. Sustained viral clearance was achieved in 6 (40%) episodes. [ABSTRACT FROM AUTHOR]

Background The 2022 mpox outbreak disproportionately affected men who have sex with men and persons living with HIV (PLWH). A 2-dose mpox vaccine series was deployed in mid-2022. Structural racism and insurance status may have affected equitable vaccination. Methods We defined 3 cohorts: PLWH with at least 1 clinic visit between 1 July 2021 and 1 July 2022 (n = 2066), HIV preexposure prophylaxis (PrEP) recipients as of 1 January 2022 (n = 262), and all mpox-vaccinated patients in our health system between 1 July 2022 and 30 November 2022 (n = 807). We identified patients with prior diagnosed sexually transmitted infections (STIs) as having a positive test result for gonorrhea, chlamydia, or syphilis between 1 July 2021–1 July 2022. The primary outcome was receipt of at least 1 dose of mpox vaccine. Results We identified 224 (10.8%) PLWH and 50 (19.0%) PrEP patients who received at least 1 dose of mpox vaccine. Among PLWH, White race (odds ratio [OR], 1.55; 95% CI, 1.11–2.16), private insurance (OR, 1.83; 95% CI, 1.01–3.34), prior STI (OR, 3.04; 95% CI, 2.16–4.27), prior COVID-19 vaccination (OR, 3.17; 95% CI, 1.93–5.20), and prior influenza vaccination (OR, 1.42; 95% CI, 1.30–1.96) independently predicted mpox vaccination. Within the PrEP cohort, prior COVID-19 vaccination and seasonal influenza vaccination predicted mpox vaccination. Uninsured patients were vaccinated later in the outbreak than patients with private insurance (median time to vaccination, 41 days in the privately insured group vs 83 days in the uninsured group; P <.0001). Conclusions Race, insurance status, prior STI, and previous receipt of other vaccines influenced uptake of mpox vaccine. Addressing health disparities and vaccine acceptance will be essential in improving future outbreak response. [ABSTRACT FROM AUTHOR]

Coinfection with sexually transmitted infections (STIs) and mpox is common. We evaluated concurrent STI testing among Duke Health patients tested for mpox. We found that most patients tested for mpox were not comprehensively tested for STIs, despite concurrent STIs being diagnosed in 15% of patients when testing was performed. [ABSTRACT FROM AUTHOR]

Background Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectious virus isolation in outpatients with coronavirus disease 2019 (COVID-19) has been associated with viral RNA levels and symptom duration, little is known about the host, disease, and viral determinants of infectious virus detection. Methods COVID-19 adult outpatients were enrolled within 7 days of symptom onset. Clinical symptoms were recorded via patient diary. Nasopharyngeal swabs were collected to quantitate SARS-CoV-2 RNA by reverse transcriptase polymerase chain reaction and for infectious virus isolation in Vero E6-cells. SARS-CoV-2 antibodies were measured in serum using a validated ELISA assay. Results Among 204 participants with mild-to-moderate symptomatic COVID-19, the median nasopharyngeal viral RNA was 6.5 (interquartile range [IQR] 4.7–7.6 log10 copies/mL), and 26% had detectable SARS-CoV-2 antibodies (immunoglobulin (Ig)A, IgM, IgG, and/or total Ig) at baseline. Infectious virus was recovered in 7% of participants with SARS-CoV-2 antibodies compared to 58% of participants without antibodies (prevalence ratio [PR] = 0.12, 95% confidence interval [CI]:.04,.36; P  = .00016). Infectious virus isolation was also associated with higher levels of viral RNA (mean RNA difference +2.6 log10, 95% CI: 2.2, 3.0; P  < .0001) and fewer days since symptom onset (PR = 0.79, 95% CI:.71,.88 per day; P  < .0001). Conclusions The presence of SARS-CoV-2 antibodies is strongly associated with clearance of infectious virus. Seropositivity and viral RNA levels are likely more reliable markers of infectious virus clearance than subjective measure of COVID-19 symptom duration. Virus-targeted treatment and prevention strategies should be administered as early as possible and ideally before seroconversion. Clinical Trials Registration NCT04405570. [ABSTRACT FROM AUTHOR]

This post hoc analysis of the Adaptive Coronavirus Disease 2019 (COVID-19) Treatment Trial-1 (ACTT-1) shows a treatment effect of remdesivir (RDV) on progression to invasive mechanical ventilation (IMV) or death. Additionally, we create a risk profile that better predicts progression than baseline oxygen requirement alone. The highest risk group derives the greatest treatment effect from RDV. [ABSTRACT FROM AUTHOR]

Background There are no antiviral therapies for parainfluenza virus (PIV) infections. DAS181, a sialidase fusion protein, has demonstrated activity in in vitro and in animal models of PIV. Methods Adult immunocompromised patients diagnosed with PIV lower respiratory tract infection (LRTI) who required oxygen supplementation were randomized 2:1 to nebulized DAS181 (4.5 mg/day) or matching placebo for up to 10 days. Randomization was stratified by need for mechanical ventilation (MV) or supplemental oxygen (SO). The primary endpoint was the proportion of patients reaching clinical stability survival (CSS) defined as returning to room air (RTRA), normalization of vital signs for at least 24 hours, and survival up to day 45 from enrollment. Results A total of 111 patients were randomized to DAS181 (n = 74) or placebo (n = 37). CSS was achieved by 45.0% DAS181-treated patients in the SO stratum compared with 31.0% for placebo (P =.15), whereas patients on MV had no benefit from DAS181. The proportion of patients achieving RTRA was numerically higher for SO stratum DAS181 patients (51.7%) compared with placebo (34.5%) at day 28 (P =.17). In a post hoc analysis of solid organ transplant, hematopoietic cell transplantation within 1 year, or chemotherapy within 1 year, more SO stratum patients achieved RTRA on DAS181 (51.8%) compared with placebo (15.8%) by day 28 (P =.012). Conclusions The primary endpoint was not met, but post hoc analysis of the RTRA component suggests DAS181 may have clinical activity in improving oxygenation in select severely immunocompromised patients with PIV LRTI who are not on mechanical ventilation. Clinical Trials Registration. NCT01644877. [ABSTRACT FROM AUTHOR]

Background We recently mitigated a clonal outbreak of hospital-acquired Mycobacterium abscessus complex (MABC), which included a large cluster of adult patients who developed invasive infection after exposure to heater-cooler units during cardiac surgery. Recent studies have detailed Mycobacterium chimaera infections acquired during cardiac surgery; however, little is known about the epidemiology and clinical courses of cardiac surgery patients with invasive MABC infection. Methods We retrospectively collected clinical data on all patients who underwent cardiac surgery at our hospital and subsequently had positive cultures for MABC from 2013 through 2016. Patients with ventricular assist devices or heart transplants were excluded. We analyzed patient characteristics, antimicrobial therapy, surgical interventions, and clinical outcomes. Results Ten cardiac surgery patients developed invasive, extrapulmonary infection from M. abscessus subspecies abscessus in an outbreak setting. Median time from presumed inoculation in the operating room to first positive culture was 53 days (interquartile range [IQR], 38–139 days). Disseminated infection was common, and the most frequent culture-positive sites were mediastinum (n = 7) and blood (n = 7). Patients received a median of 24 weeks (IQR, 5–33 weeks) of combination antimicrobial therapy that included multiple intravenous agents. Six patients required antibiotic changes due to adverse events attributed to amikacin, linezolid, or tigecycline. Eight patients underwent surgical management, and 6 patients required multiple sternal debridements. Eight patients died within 2 years of diagnosis, including 4 deaths directly attributable to MABC infection. Conclusions Despite aggressive medical and surgical management, invasive MABC infection after cardiac surgery caused substantial morbidity and mortality. New treatment strategies are needed, and compliance with infection prevention guidelines remains critical. [ABSTRACT FROM AUTHOR]

The opioid epidemic has resulted in an increase in organ donors with hepatitis C virus (HCV) infection in the United States. With the development of direct-acting antiviral regimens that offer high sustained virologic response rates even in the setting of immunosuppression after transplantation, these HCV-viremic organs are now being offered to transplant candidates with or without preexisting HCV infection. Strategies for HCV treatment with HCV-viremic organs have included delayed and preemptive approaches. This review will discuss key studies in the different solid organ transplants, recent reports of adverse events, and ethical and regulatory considerations. The efficacy of current HCV therapies has created this important opportunity to improve survival for patients with end-organ failure through greater access to organ transplantation and decreased waitlist mortality rate. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 69-year-old man with amyloid cardiomyopathy presented an uncomplicated orthotopic heart transplant with history of malaise, nausea and vomiting, diarrhea, and headache. It discussed the diagnosis of Acanthamoeba encephalitis and through the microscopic examination revealed the presence of large amoebic trophozoites.

These clinical practice guidelines are an update of the guidelines published by the Infectious Diseases Society of America (IDSA) in 2009, prior to the 2009 H1N1 influenza pandemic. This document addresses new information regarding diagnostic testing, treatment and chemoprophylaxis with antiviral medications, and issues related to institutional outbreak management for seasonal influenza. It is intended for use by primary care clinicians, obstetricians, emergency medicine providers, hospitalists, laboratorians, and infectious disease specialists, as well as other clinicians managing patients with suspected or laboratory-confirmed influenza. The guidelines consider the care of children and adults, including special populations such as pregnant and postpartum women and immunocompromised patients. [ABSTRACT FROM AUTHOR]

Background. Nontuberculous mycobacteria (NTM) commonly colonize municipal water supplies and cause healthcare-associated outbreaks. We investigated a biphasic outbreak of Mycobacterium abscessus at a tertiary care hospital. Methods. Case patients had recent hospital exposure and laboratory-confirmed colonization or infection with M. abscessus from January 2013 through December 2015. We conducted a multidisciplinary epidemiologic, field, and laboratory investigation. Results. The incidence rate of M. abscessus increased from 0.7 cases per 10 000 patient-days during the baseline period (January 2013-July 2013) to 3.0 cases per 10 000 patient-days during phase 1 of the outbreak (August 2013-May 2014) (incidence rate ratio, 4.6 [95% confidence interval, 2.3-8.8]; P < .001). Thirty-six of 71 (51%) phase 1 cases were lung transplant patients with positive respiratory cultures. We eliminated tap water exposure to the aerodigestive tract among high-risk patients, and the incidence rate decreased to baseline. Twelve of 24 (50%) phase 2 (December 2014-June 2015) cases occurred in cardiac surgery patients with invasive infections. Phase 2 resolved after we implemented an intensified disinfection protocol and used sterile water for heater-cooler units of cardiopulmonary bypass machines. Molecular fingerprinting of clinical isolates identified 2 clonal strains of M. abscessus; 1 clone was isolated from water sources at a new hospital addition. We made several water engineering interventions to improve water flow and increase disinfectant levels. Conclusions. We investigated and mitigated a 2-phase clonal outbreak of M. abscessus linked to hospital tap water. Healthcare facilities with endemic NTM should consider similar tap water avoidance and engineering strategies to decrease risk of NTM infection. [ABSTRACT FROM AUTHOR]

Background. Oseltamivir resistance among 2009 pandemic influenza A (H1N1) viruses (pH1N1) is rare. We investigated a cluster of oseltamivir-resistant pH1N1 infections in a hospital ward.Methods. We reviewed patient records and infection control measures and interviewed health care personnel (HCP) and visitors. Oseltamivir-resistant pH1N1 infections were found with real-time reverse-transcription polymerase chain reaction and pyrosequencing for the H275Y neuraminidase (NA) mutation. We compared hemagglutinin (HA) sequences from clinical samples from the outbreak with those of other surveillance viruses.Results. During the period 6–11 October 2009, 4 immunocompromised patients within a hematology-oncology ward exhibited symptoms of pH1N1 infection. The likely index patient became febrile 8 days after completing a course of oseltamivir; isolation was instituted 9 days after symptom onset. Three other case patients developed symptoms 1, 3, and 5 days after the index patient. Three case patients were located in adjacent rooms. HA and NA sequences from case patients were identical. Twelve HCP and 6 visitors reported influenza symptoms during the study period. No other pH1N1 isolates from the hospital or from throughout the state carried the H275Y mutation.Conclusions. Geographic proximity, temporal clustering, presence of H275Y mutation, and viral sequence homology confirmed nosocomial transmission of oseltamivir-resistant pH1N1. Diagnostic vigilance and prompt isolation may prevent nosocomial transmission of influenza. [ABSTRACT FROM PUBLISHER]

Background In the United States, all deceased donors (DD) are evaluated for behavioral risk factors for human immunodeficiency virus (HIV), hepatitis B (HBV), and hepatitis C (HCV) infection during the past 12 months. DD with behavioral risk factors or hemodilution are designated as PHS increased risk donors (IRD). Since 2013, the number of IRD has increased from 13.4% of DD to 27% in 2018. Despite a low residual risk of disease transmission after a negative nucleic acid test for HIV/HBV/HCV, the considerable underutilization of IRD has driven an interest in revising the PHS IRD 2013 guidelines. The objective of this study was to describe the epidemiology of IRD with the goal of guiding policy change and maximize organ use. Methods This is a retrospective cohort study of DD during 2018. Characteristics of IRD were compared with non-IRD. A random 10% sample of IRD was selected for manual review of text narratives and donor questionnaires submitted by organ procurement organizations to determine specific PHS IRD factors. Categorical variables were compared using the χ 2 test and continuous variables were compared using a 2-sample t -test for independent samples. Results Among 10,721 DD in 2018, 2,904 were designated IRD (27.1%) with regional variability noted (Figure). Compared with non-IRD, IRD were younger (median age 35 vs. 45 years, P < 0.001) and more often died from drug intoxication (33.2 vs. 5.6%, P < 0.001). Hemodilution was found in 6.8% of all IRD and was the only factor for IRD designation in 60% of pediatric donors <12 years old. The random sample of IRD (N = 288) was similar to IRD population for age, gender, ethnicity, cause of death, and region of recovery (table). Descriptive analysis of the random sample showed that intravenous drug use was the most common behavioral risk factor (N = 124, 43.1%), followed by incarceration (N = 108, 37.5%). Most DD met only 1 criterion (N = 179, 62%); 21% met 2 criteria; and 17% had > 3 criteria. Conclusion This study represents the most detailed description of PHS IRD factors since the adoption of the new guidelines in 2013. Understanding the prevalence of factors that lead to IRD designation will help inform future policy development, optimize safe DD use, and increase the number of transplants. Disclosures All Authors: No reported Disclosures. [ABSTRACT FROM AUTHOR]

Background Mycoplasma and Ureaplasma species can cause invasive infections early after lung transplant that are difficult to diagnose and associated with substantial morbidity, including hyperammonemia syndrome. Data on the epidemiology and clinical outcomes of these infections are needed to inform clinical management and screening protocols for donors and recipients. Methods We retrospectively collected clinical data on all patients who underwent lung transplantation at our hospital from January 1, 2010 to April 15, 2019 and subsequently had positive cultures or PCR studies for M. hominis or Ureaplasma spp. Patients with positive studies from only the genitourinary tract were excluded. We analyzed donor and recipient clinical characteristics, treatment courses, and outcomes for up to 2 years after transplant. Results Of 1055 total lung transplant recipients, 20 (1.9%) patients developed invasive infection with M. hominis or Ureaplasma spp. M. hominis caused the first 10 infections (2010–2016), and Ureaplasma spp. caused 10 subsequent infections (2017–2019). Date of first positive culture or PCR study occurred a median of only 19 days after transplant (range, 4–90 days). Median donor age was 31 years (range, 18–45 years), and chest imaging for 16 (80%) donors revealed airspace disease compatible with aspiration. Infection outside of the respiratory tract was confirmed for 13 (65%) recipients, including 8 patients with M. hominis empyemas (Figure 1). Ten (50%) patients developed altered mental status that was temporally associated with infection; 8 (80%) of these patients had elevated serum ammonia levels, including 3 patients with M. hominis infection. Median duration of therapy was 6 weeks (IQR, 4–9 weeks), consisting of combination antimicrobial regimens for nearly all patients. Additional postoperative complications were common, and 11 (55%) patients died within 1 year after transplant (median, 117 days; IQR, 65–255 days) (Figure 2). Conclusion Ureaplasma and M. hominis infections occurred early after lung transplant and were associated with substantial morbidity and mortality. Transplant clinicians should have low thresholds for performing specific diagnostic testing for these organisms. Protocols for donor and recipient screening and management need to be developed. Disclosures Rachel Miller, MD, Synexis: Research Grant. [ABSTRACT FROM AUTHOR]

Background Ventricular assist devices (VADs) are increasingly used for the management of end-stage heart failure, but infection is a complication that has not been thoroughly studied. The purpose of our study was to compare patients who had surgical debridement vs. medical therapy alone for VAD-related/specific infections. Methods We performed a retrospective chart review on patients at Duke University Hospital (DUH) from 2015 to 2017. Patients with VAD-related/specific infections were included, per 2011 ISHLT definitions. We reviewed electronic medical records for demographics, VAD implantation data, infectious episodes, surgical debridements and mortality. Descriptive statistics compared patients with and without debridement and compared with and without relapse. Results We found 94 infections in 72 patients. Descriptive statistics of the cohort and comparisons with and without debridement can be seen in Table 1. Sixty-one cases (65%) included debridement and 5 (5%) required pump exchange. Notably, patients with fever or bacteremia were more likely to undergo debridement. Of the patients that had a preoperative CT, sensitivity for deep infection (pump, pocket, or deep to the muscle) was 38%, yet specificity was 95%. For superficial infections (involving the driveline or superficial to the muscle), preoperative CT sensitivity was 95%; specificity 65%. Table 2 shows intraoperative culture data. When the preoperative driveline culture grew Staphylococcus species or Pseudomonas aeruginosa there was strong correlation with intraoperative organism (matched in >75% of cases). Table 3 compares treatments among patients with and without infective relapse. Relapse rate appeared the same if patients received 2, 4, or ≥6 weeks of intravenous antibiotics. Conclusion We present a large single-center cohort [DCWM1] examining VAD-related/-specific infections. While patients chosen for debridement may be sicker, these patients had a longer hospital stay and relapsed more often. Preoperative CT should be used with caution as it underestimates the extent of disease. However, preoperative driveline cultures correlated strongly with intraoperative cultures for most common pathogens. There was no association between initial intravenous therapy duration and infection relapse. Table 1. demographic characteristics of total cohort and comparisons among patients who underwent debridement for treatment of infection and patients who did not undergo debridement for treatment of infection Table 2. Organisms found intraoperatively and the number of organisms found preoperatively that are the same as the intraoperative cultures Table 3. Comparing treatment and cultures in patients who suffered an infection relapse Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background Donor-derived toxoplasmosis (DDT) is a severe and potentially life-threatening infection after solid-organ transplantation (SOT). Serologic testing for Toxoplasma gondii is required for all deceased donors per OPTN policy as of 4/6/17. To assess the impact of universal donor testing and the optimal approach to DDT prevention, we analyzed potential DDT cases reviewed by DTAC. Methods All potential Toxoplasma donor-derived transmission events adjudicated by DTAC from 2008 to 2018 were reviewed. A standardized classification algorithm was used to adjudicate each event as proven, probable, possible, unlikely, excluded or intervention without disease transmission. Results Twenty-eight potential DDT events were reported between 2008 and 2018. Proven or probable (p/p) DDT developed in 16 organ recipients from 15 donors. In the 9 years prior to the new testing requirement (January 2008–March 2017) 11 organ recipients from 10 donors had p/p DDT (0.13 transmissions per 1,000 donors); in the first 21 months of the new testing requirement 5 recipients from 5 donors had p/p DDT (0.27 transmissions per 1,000 donors), rate ratio 2.15; 95% CI 0.577, 6.90;P = 0.18. 10.2% of 18,328 donors tested between April 6, 2017 and December 31, 2018 were Toxoplasma IgG seropositive. Recipient pre-SOT serostatus was unknown in 4 of 5 and negative in 1 case of p/p DDT. Trimethoprim/sulfamethoxazole prophylaxis was either stopped at < 3 months or not used in all 5 cases. Infection was diagnosed a median of 103 days (range 42–153) post-transplant. Four of the 5 recipients died. Conclusion DDT remains a morbid infection in both heart and non-heart recipients. Despite an apparent increase in DDT reporting to DTAC, it is unlikely that the actual incidence of this donor-derived event is increasing. Rather, with universal serologic screening of deceased donors and wider access to molecular diagnostics, DDT is increasingly recognized and diagnosed. To decrease risk for illness and death related to DDT, broader pre-transplant recipient serologic testing and use of prophylaxis or monitoring for high-risk serostatus recipients (Toxoplasm a D+/R−) is critical. The optimal duration of prophylaxis is uncertain at this time and warrants further study. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Electronic medical record platforms fail to support provider alerts when a drug is discontinued. Protease inhibitors, often boosted by ritonavir or cobicistat, increase the serum concentration of calcineurin inhibitors. This case demonstrates acute liver transplant rejection in an HIV-positive recipient due to a failure to recognize the loss of protease inhibitor interaction with his immunosuppressive regimen. [ABSTRACT FROM AUTHOR]

Presented is a case of chronic methicillin-resistant Staphylococcus aureus osteomyelitis, which was unsuccessfully treated with multiple courses of debridement and potent antibiotic therapies. Amputation of the patient's lower limb was believed to be the only option remaining. A compassionate access program, with approval from the US Food and Drug Administration and the institutional review board, enabled the patient to undergo a course of treatment with oral fusidic acid (CEM-102). The patient tolerated the drug well, with no significant toxicities noted to date. His infection improved rapidly, his flap healed, he has returned to work part-time, and he continues to take daily suppressive doses of oral CEM-102. [ABSTRACT FROM PUBLISHER]