Real-world experience with available, outpatient COVID-19 therapies in solid organ transplant recipients during the omicron surge.

The SARS-CoV-2 pandemic continues to place a substantial burden on healthcare systems. Outpatient therapies for mild-to-moderate disease have reduced hospitalizations and deaths in clinical trials, but the real-world effectiveness of monoclonal antibodies and oral antiviral agents in solid organ transplant recipients (SOTR) with coronavirus disease-2019 (COVID-19) is largely uncharacterized. We conducted a single-center, retrospective review of 122 SOTR diagnosed with COVID-19 in the outpatient setting during the Omicron surge to address this knowledge gap. The mean age was 54 years, 57% were males, and 67% were kidney transplant recipients. The mean time from transplant to COVID-19 diagnosis was 75 months. Forty-nine (40%) received molnupiravir, 24 (20%) received sotrovimab, and 1 (0.8%) received nirmatrelvir/ritonavir. No outpatient therapy was administered in 48 (39%). All 122 SOTR had >30 days follow-up. Rates of hospitalization within 30 days of initiating therapy for molnupiravir, nirmatrelvir/ritonavir, and sotrovimab were 16% (8/49), 0% (0/1), and 8% (2/24), respectively, compared to 27% (13/48) in patients without outpatient therapy. There were no deaths in those who received any therapy versus 3 (6%) deaths in patients without outpatient therapy (p = .002). Overall, our experience suggests a role for monoclonal antibodies and oral antiviral agents in reducing COVID-19-related morbidity and mortality in SOTR.

Dematiaceous fungal infections in solid organ transplantation: Systematic review and Bayesian meta-analysis.

BACKGROUND: Dematiaceous fungi cause a number of infectious syndromes referred to as phaeohyphomycosis among both immunocompetent and immunocompromised hosts. We performed a systematic review to characterize these infections in solid organ transplant recipients (SOTR). METHODS: We searched PubMed database (last searched 1/6/2022) for English-language reports on dematiaceous fungal infections in SOTR. Included reports needed individualized demographic, treatment, and outcome data; pediatric reports were excluded. A universally applicable bias assessment was performed on reports. Models for infection type and outcome were created using the Bayesian paradigm. RESULTS: We included 149 reports on 201 cases of dematiaceous fungal infections in SOTR. The mean age was 54 years, 72% were men, and kidney recipients accounted for 61% of cases. Skin and soft tissue infection (SSTI) was the most common infectious syndrome (73%). Death from infection occurred in 7% of cases (14/201), with disseminated (32%) cases having the highest mortality. Our model for infection type predicted the relative probability of central nervous system infection to be highest in liver recipients. Across all transplant types, higher relative probabilities of disseminated and pulmonary infections occur in the early post-transplant period, and the predicted probabilities for these infection types decreased after 100 months post-transplantation. DISCUSSION: We identified SSTI as the most common dematiaceous fungal infections in SOTR. Disseminated infections carried the worst prognosis. The evidence in this review is limited by the heterogeneity of included cases. No funding source was used, and this review's protocol was not registered.

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.

Significant Liver Injury During Hospitalization for COVID-19 Is Not Associated With Liver Insufficiency or Death.

BACKGROUND & AIMS: Coronavirus-19 disease (COVID-19) is associated with hepatocellular liver injury of uncertain significance. We aimed to determine whether development of significant liver injury during hospitalization is related to concomitant medications or processes common in COVID-19 (eg, ischemia, hyperinflammatory, or hypercoagulable states), and whether it can result in liver failure and death. METHODS: There were 834 consecutive patients hospitalized with COVID-19 who were included. Clinical, medication, and laboratory data were obtained at admission and throughout hospitalization using an identified database. Significant liver injury was defined as an aspartate aminotransferase (AST) level 5 or more times the upper limit of normal; ischemia was defined as vasopressor use for a minimum of 2 consecutive days; hyperinflammatory state was defined as high-sensitivity C-reactive protein value of 100 mg/L or more, and hypercoagulability was defined as D-dimer 5 mg/L or more at any time during hospitalization. RESULTS: A total of 105 (12.6%) patients developed significant liver injury. Compared with patients without significant liver injury, ischemia (odds ratio [OR], 4.3; range, 2.5-7.4; P < .0001) and tocilizumab use (OR, 3.6; range, 1.9-7.0; P = .0001) were independent predictors of significant liver injury. Although AST correlated closely with alanine aminotransferase (R = 0.89) throughout hospitalization, AST did not correlate with the international normalized ratio (R = 0.10) or with bilirubin level (R = 0.09). Death during hospitalization occurred in 136 (16.3%) patients. Multivariate logistic regression showed that significant liver injury was not associated with death (OR, 1.4; range, 0.8-2.6; P = .2), while ischemic (OR, 2.4; range, 1.4-4.0; P = .001), hypercoagulable (OR, 1.7; range, 1.1-2.6; P = .02), and hyperinflammatory (OR, 1.9; range, 1.2-3.1; P = .02) disease states were significant predictors of death. CONCLUSIONS: Liver test abnormalities known to be associated with COVID-19 are secondary to other insults, mostly ischemia or drug-induced liver injury, and do not lead to liver insufficiency or death.

Fever, pancytopenia, and elevated D-dimer in a 95-year-old woman with ehrlichiosis: a case report.

BACKGROUND: Pancytopenia, fever, and elevated D-dimer are significant clinical findings. The differential diagnosis includes hematological malignancies, severe coronavirus disease 2019 (COVID-19), tick-borne illnesses, and other etiologies. CASE PRESENTATION: We report the case of a 95-year-old woman who presented with high fever (103.6 °F), pancytopenia, and markedly elevated D-dimer (32.21 mg/L; reference range ≤ 0.95 mg/L) in late-autumn during the COVID-19 pandemic at a large academic institution. After remaining persistently febrile, a peripheral blood smear was ordered and revealed parasites consistent with Ehrlichia spp. Doxycycline monotherapy led to symptomatic improvement and resolution of her pancytopenia. During her hospital stay, a computed tomography angiogram of the chest revealed pulmonary emboli, and esophagogastroduodenoscopy uncovered arteriovenous malformations. After appropriate treatment, she was discharged on hospital day 7 and has since done well. CONCLUSIONS: Overall, our case offers a dramatic, unexpected presentation of ehrlichiosis in a nonagenarian. To our knowledge, this is the first report of concurrent ehrlichiosis and pulmonary embolus.

Baryon Acoustic Oscillations from Integrated Neutral Gas Observations: an instrument to observe the 21cm hydrogen line in the redshift range 0.13 < z < 0.45 - status update.

BINGO (BAO from Integrated Neutral Gas Observations) is a unique radio telescope designed to map the intensity of neutral hydrogen distribution at cosmological distances, making the first detection of Baryon Acoustic Oscillations (BAO) in the frequency band 980 MHz - 1260 MHz, corresponding to a redshift range 0.127 < z < 0.449. BAO is one of the most powerful probes of cosmological parameters and BINGO was designed to detect the BAO signal to a level that makes it possible to put new constraints on the equation of state of dark energy. The telescope will be built in Paraíba, Brazil and consists of two \thicksim 40m mirrors, a feedhorn array of 50 horns, and no moving parts, working as a drift-scan instrument. It will cover a 15 ^{\circ} ∘ declination strip centered at \sim \delta ∼ δ =-15 ^{\circ} ∘ , mapping \sim ∼ 5400 square degrees in the sky. The BINGO consortium is led by University of São Paulo with co-leadership at National Institute for Space Research and Campina Grande Federal University (Brazil). Telescope subsystems have already been fabricated and tested, and the dish and structure fabrication are expected to start in late 2020, as well as the road and terrain preparation.

The Tragedy of Names.

The naming of pathogens and their associated syndromes is a thorny process which unfolds in a complex geopolitical environment. This brief piece offers perspective on the multitude of forces that shape the name of a pathogen and summarizes the story of Sin Nombre Virus, with some reference to the ongoing saga of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A monopoly on names and circulating monikers rarely exists, and certain communities become disproportionately impacted by misunderstandings or stigmatization. By acknowledging these processes, we can better serve as allies to affected communities dealing with both pandemic and prejudice.

Bordetella bronchiseptica: a rare cause of meningitis.

BACKGROUND: Bordetella bronchiseptica is a gram-negative, obligate aerobic coccobacillus known to cause disease in domesticated animals and pets. In humans, B. bronchiseptica commonly leads to respiratory infections like pneumonia or bronchitis, and animal contact usually precedes the onset of symptoms. CASE PRESENTATION: We report a case of post-traumatic B. bronchiseptica meningitis without recent surgery in the setting of immunosuppression with a monoclonal antibody. Our case concerns a 77-year-old male with ulcerative colitis on infliximab who sustained a mechanical fall and developed a traumatic cerebrospinal fluid leak complicated by meningitis. He received meropenem then ceftazidime during his hospital course, and temporary neurosurgical drain placement was required. His clinical condition improved, and he was discharged at his baseline neurological status. CONCLUSIONS: B. bronchiseptica is an unusual cause of meningitis that may warrant consideration in immunocompromised hosts with known or suspected animal exposures. To better characterize this rare cause of meningitis, we performed a systematic literature review and summarized all previously reported cases.

Efficacy and safety of chronic antimicrobial suppression therapy for left ventricular assist device driveline infections: A single-center descriptive experience.

BACKGROUND: Driveline infection (DLI) is the most common left ventricular assist device (LVAD) infectious complication. Short-term antimicrobial therapy and local debridement are the cornerstones of management for these infections, but the use of chronic antimicrobial suppression (CAS) therapy is not well characterized. METHODS: To better characterize the efficacy of CAS therapy, we performed a retrospective review of all patients (N = 219) receiving care at our tertiary transplant center with continuous-flow LVADs placed between August 2007 and July 2019. RESULTS: A total of 24 patients were identified as having received CAS therapy as treatment for DLIs. The mean age was 56 years, 50% were female, and chronic kidney disease affected 63% of patients. Staphylococcus aureus accounted for half of all initial DLIs, and the mean length of CAS therapy was 486 days (range 48-2287 days). All patients received per os regimens as suppression therapy. Adverse events impacted 5 of 24 patients (0.43 events per 1000 days). Overall, the use of CAS therapy led to successful outcomes in 50% of patients and 29% experienced treatment failures. The remaining patients experienced stable symptoms. Relapses were the most common cause of treatment failure, and three patients experienced reinfections while on CAS therapy. CONCLUSIONS: Our study suggests that CAS therapy for DLIs can be well tolerated, and future studies are needed to determine which patients merit suppression.

Sankofa pediatric HIV disclosure intervention did not worsen depression scores in children living with HIV and their caregivers in Ghana.

BACKGROUND: The 'Sankofa' pediatric HIV disclosure study (2013-2017) was an intervention that aimed to address the low prevalence of disclosure of HIV status in Ghana. METHODS: We conducted a cross-sectional study at the intervention site in Kumasi, Ghana, in 2019, (2 years after study closure) and administered the 21-item Beck Depression Inventory (BDI) and the 10-item Child Depression Inventory (CDI) to caregiver-child dyads who received the intervention. RESULTS: We enrolled 65% (N = 157) of the original dyads in the present study. Between Sankofa enrollment baseline and the present study, both children and caregivers had significant (p < 0.0001) mean reductions in CDI scores and BDI scores, respectively. CDI scores of the children were significantly correlated with BDI scores of the caregivers (r = 0.019, p = 0.019). No statistically significant associations between disclosure status and either CDI score or BDI score were found. CONCLUSIONS: Our findings did not support caregivers' fears that disclosure leads to depression. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01701635 (date of registration Oct 5, 2012).

Over 870 days of successful antibiotic suppression therapy for VRE-infected left ventricular assist device.

Left ventricular assist devices (LVADs) are used in patients with advanced heart failure. Infections are common complications following device placement; however, the efficacy of chronic antimicrobial suppression therapy for deep-seated infections is not well characterized. We report the case of a 49-year-old male with a HeartMate II LVAD who presented with a methicillin-sensitive Staphylococcus aureus pump pocket infection that was subsequently treated with antibiotics and HeartMate III pump exchange. A vancomycin-resistant Enterococcus faecium (VRE) pump pocket infection then developed and responded to surgical drainage followed by long-term suppression with daptomycin then linezolid for over 870 days. A second pump exchange was not required. To our knowledge, this represents the longest reported use of daptomycin (341 days) without symptomatic adverse events. Managing infections caused by multidrug-resistant pathogens presents a clinical challenge. This case demonstrates the potential for antimicrobial suppression therapy to allow for successful retention of a VRE-infected LVAD.

Nontuberculous mycobacterial infections in left ventricular assist device patients.

Left ventricular assist devices (LVADs) are integral for the management of medically refractory heart failure, and LVAD infections are common following device placement. Most infections are caused by Staphylococcal spp. and Gram-negative enteric bacteria but nontuberculous mycobacterial (NTM) infections have been reported. We present the second-ever reported case of a driveline infection caused by Mycobacterium fortuitum in a 75-year-old male with a continuous-flow LVAD. After receiving meropenem, azithromycin, and ciprofloxacin, he underwent device exchange and ultimately died after failing to recover neurologically. Management of NTM infections presents a clinical challenge due to the propensity for rapidly growing mycobacterial species to form biofilms and the possibility of negative cultures delaying diagnosis. To address the literature gap surrounding NTM infections in LVAD patients, we performed a systematic review and present all previously reported cases.

Repeat exchange transfusion for treatment of severe babesiosis.

We report a case of severe babesiosis presenting with 43% parasitemia in a 73-year-old splenectomized woman on etanercept for rheumatoid arthritis. She initially was treated aggressively with clindamycin and quinine and exchange transfusion. Despite a post-exchange drop in parasitemia to 7.6%, it rebounded to 11.4% on hospital day 5 accompanied by new onset high fevers and hypoxia. She improved after a second exchange transfusion and ultimately resolved her infection after 12 weeks of antibabesial antibiotics. Although exchange transfusion is commonly used in immunocompromised hosts, there is a dearth of information about repeat exchange transfusion, including the risk for and outcome of repeat exchange. We performed a literature search for other cases of repeat exchange transfusion for severe Babesia microti infection and compared our case with those in other published reports.

Antiviral Treatment of Coronavirus Disease-2019 Pneumonia.

Direct acting antivirals and monoclonal antibodies reduce morbidity and mortality associated with severe acute respiratory syndrome coronavirus 2 infection. Persons at higher risk for disease progression and hospitalized patients with coronavirus disease-2019 (COVID-19) benefit most from available therapies. Following an emphasis on inpatient treatment of COVID-19 during the early pandemic, several therapeutic options were developed for outpatients with COVID-19. Additional clinical trials and real-world studies are needed to keep pace with the evolving pandemic.

Splenic Abscess in the New Millennium: A Descriptive, Retrospective Case Series.

Background: Splenic abscess is a rare infection often resulting from hematogenous spread. Immunocompromised states are commonly comorbid, and the microbiology is heterogeneous. Methods: We conducted a retrospective review of 33 cases identified by convenience sampling. Cases were treated in our institution's hospital system between May 2012 and February 2021 and classified as proven or probable based on predetermined criteria. Results: The median age was 57 years, and 58% were men. Common underlying diseases included diabetes mellitus (30%), pancreatic disease (30%), and hematological malignancy (15%). The most common mechanism of pathogenesis was hematogenous spread (n = 13). Escherichia coli, enterococcal spp., and anaerobes were frequently implicated. One case was discovered at autopsy and excluded from subsequent analyses. The median duration of antimicrobial therapy (range) was 45 (5-525) days, and the median length of index hospitalization was 20 days. Percutaneous drainage by interventional radiology was common (17 of 32; 53%), and 6 patients underwent splenectomy. Treatment success was achieved in 14 of 32 cases (44%), with clinical stability in 3 of 32 cases (9%). Failures occurred in 13 of 32 (41%) cases, 2 of whom died from splenic abscesses. Two patients (2 of 32) were lost to follow-up. Conclusions: To our knowledge, this is the largest North American series since the turn of the century and the first to distinguish between proven and probable cases. As reflected in our series, patients with splenic abscess may require prolonged hospitalizations and courses of antimicrobial therapy. Improvements in management are needed.

Real-world assessment of the clinical utility of whole body 18F-FDG PET/CT in the diagnosis of infection.

Few studies have aimed to capture the full spectrum of 18fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG PET/CT) use for evaluation of infections in a real-world context. We performed a retrospective chart review of hospitalized patients who underwent 18F-FDG PET/CT for the workup of infection between April, 2013 and September, 2019. The clinical indications for and impact of 18F-FDG PET/CT on diagnostic and antimicrobial management were evaluated across different infectious indications. Sixty-one patients met the inclusion criteria. The most common indication was identifying a source of a known infection (46%), followed by fever of unknown etiology (FUE)/fever of unknown origin (FUO) (38%), and other (16%). 18F-FDG PET/CT was determined to have had a diagnostic or management clinical impact for a total of 22 patients (36%) including 12/28 (43%) of patients with known infection, 7/23 (30%) of patients with FUE/FUO, and 3/10 (30%) of patients with other indications. 18F-FDG PET/CT confirmed suspected prosthetic endovascular infection for 6/16 (38%) patients. In this study,18F-FDG PET/CT led to a clinical impact on diagnostic and treatment management of hospitalized patients across a variety of syndromes and particularly for source identification in the setting of known infection.

Infectious Disease Images: A Remarkable, Free Resource.

Infectious Disease Images (idimages.org) features several hundred with a vast array of diagnoses. The website is organized by cases and images and boasts an atlas with scores of bacteria, viruses, fungi, parasites, and ectoparasites. As a free resource, Infectious Disease Images lends itself nicely to both learners and educators at all levels.

Pott Disease: A Tale of Two Cases.

Tuberculosis is considered one of the great masqueraders alongside syphilis and vasculitis. Pott disease is recognized as a classic manifestation of tuberculosis, yet it stands as a rare infectious syndrome in regions with low tuberculosis disease burden. To illustrate the challenges of diagnosing Pott disease in these settings, we report two cases and offer a brief overview of management recommendations for vertebral osteomyelitis caused by Mycobacterium tuberculosis. Case one concerns an 81-year-old man with a remote history of incarceration who presented with altered mental status and new pleural effusions. Case two is a 49-year-old man with well-controlled HIV who was transferred to our institution after being found to have extensive destruction of L3-L5 vertebrae and bilateral iliopsoas abscesses on outpatient imaging. These stand as illustrative examples of low and high suspicion for tuberculosis, respectively, and both cases required complex diagnostic and management decisions.