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2.
Clin Chest Med ; 44(2): 279-297, 2023 06.
Article En | MEDLINE | ID: mdl-37085220

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.


COVID-19 , Coronavirus , Hepatitis C, Chronic , Pneumonia , Humans , Antiviral Agents/therapeutic use
3.
PLoS One ; 17(11): e0277403, 2022.
Article En | MEDLINE | ID: mdl-36374789

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.


Fever of Unknown Origin , Positron Emission Tomography Computed Tomography , Humans , Positron Emission Tomography Computed Tomography/methods , Fluorodeoxyglucose F18 , Positron-Emission Tomography/methods , Fever of Unknown Origin/diagnostic imaging , Fever of Unknown Origin/etiology , Retrospective Studies , Radiopharmaceuticals
4.
Am J Transplant ; 22(10): 2458-2463, 2022 10.
Article En | MEDLINE | ID: mdl-35583664

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.


COVID-19 , Organ Transplantation , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Neutralizing , Antiviral Agents/therapeutic use , COVID-19/epidemiology , COVID-19 Testing , Cytidine/analogs & derivatives , Female , Humans , Hydroxylamines , Male , Middle Aged , Organ Transplantation/adverse effects , Ritonavir , SARS-CoV-2 , Transplant Recipients
5.
Transpl Infect Dis ; 24(2): e13819, 2022 Apr.
Article En | MEDLINE | ID: mdl-35253959

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.


Mycoses , Organ Transplantation , Antifungal Agents/therapeutic use , Bayes Theorem , Child , Humans , Male , Middle Aged , Mycoses/drug therapy , Mycoses/epidemiology , Organ Transplantation/adverse effects , Transplant Recipients
6.
Open Forum Infect Dis ; 9(4): ofac085, 2022 Apr.
Article En | MEDLINE | ID: mdl-35299986

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.

7.
Transpl Infect Dis ; 24(2): e13811, 2022 Apr.
Article En | MEDLINE | ID: mdl-35184347

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.


Candida , Liver Transplantation , Adolescent , Adult , Antifungal Agents/therapeutic use , Azoles/therapeutic use , Humans , Liver Transplantation/adverse effects , Retrospective Studies
9.
Open Forum Infect Dis ; 8(12): ofab560, 2021 Dec.
Article En | MEDLINE | ID: mdl-34888400

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.

10.
IDCases ; 26: e01322, 2021.
Article En | MEDLINE | ID: mdl-34786341

Beta-D-glucan (BDG) testing can expedite the diagnosis of invasive fungal infections in immunocompromised hosts. Elevated BDG levels have been reported in both in-vitro studies assessing cross-reactivity with Nocardia spp. and published cases of patients with nocardiosis, but there is little data on this association in solid organ transplantation (SOT) recipients. To explore this association, we conducted a case series of SOT recipients with culture-proven nocardiosis and BDG testing who received their care at our institution between 2016 and 2021. We found thirteen cases of nocardiosis in SOT recipients, of which three cases met our case definition of an elevated BDG. Their clinical courses are detailed in the present report. We found that BDG may be elevated in SOT with nocardiosis with no identified cause of false positive BDG, though a causal association cannot be determined. Future prospective studies that better evaluate the association between nocardiosis and BDG are warranted, as are studies that better characterize the possible variability in reactivity amongst Nocardia spp.

11.
Pathogens ; 10(9)2021 Sep 09.
Article En | MEDLINE | ID: mdl-34578190

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.

12.
Yale J Biol Med ; 94(2): 375-378, 2021 06.
Article En | MEDLINE | ID: mdl-34211356

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.


Terminology as Topic , COVID-19/virology , Humans , SARS-CoV-2/physiology , Sin Nombre virus/physiology , World Health Organization
13.
World J Transplant ; 11(6): 244-253, 2021 Jun 18.
Article En | MEDLINE | ID: mdl-34164299

BACKGROUND: Bartonellosis is a rare but challenging condition to diagnose with a spectrum of clinical presentations in the immunocompromised host. AIM: To further characterize the presentation of Bartonella henselae (B. henselae) infections in solid organ and hematopoietic stem cell transplant recipients. METHODS: We conducted a single-center retrospective study of all B. henselae testing for 5012 transplant recipients receiving care at a single institution between 2011 and 2018. RESULTS: We identified 38 patients who underwent testing for B. henselae, and three of 38 were found to have bartonellosis. Two of the patients were renal transplant recipients who presented with visceral bartonellosis and symptoms concerning for post-transplant lymphoproliferative disorder. One autologous stem cell transplant recipient presented with cat scratch disease. We detail the clinical courses of these three cases and review the literature concerning the clinical presentations, differential diagnosis, and limitations of diagnostic tests for B. henselae infections in transplant recipients. CONCLUSION: Although the incidence of B. henselae infection in transplant recipients is unknown, it merits inclusion in the differential diagnosis for fever of unknown origin in this population.

14.
An Acad Bras Cienc ; 93(suppl 1): e20201096, 2021.
Article En | MEDLINE | ID: mdl-34076206

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.

16.
Clin Gastroenterol Hepatol ; 19(10): 2182-2191.e7, 2021 10.
Article En | MEDLINE | ID: mdl-34004326

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.


COVID-19 , Hepatic Insufficiency , Hospitalization , Humans , Retrospective Studies , SARS-CoV-2
17.
Open Forum Infect Dis ; 8(4): ofab098, 2021 Apr.
Article En | MEDLINE | ID: mdl-33884279

BACKGROUND: Pyomyositis is a bacterial infection of skeletal muscle that classically leads to abscess formation. A related, but distinct, entity is infectious myositis. The epidemiology of these infections has changed in recent years. METHODS: To better characterize both pyomyositis and infectious myositis, we conducted a retrospective study at our tertiary care institution. We identified 43 cases of pyomyositis and 18 cases of infectious myositis treated between January 2012 and May 2020. RESULTS: The mean age of patients was 48 years, and 66% were male. Diabetes mellitus affected one third of patients, and 16% had other immunocompromising comorbidities. Staphylococcal species accounted for 46% of all infections, and common symptoms included muscle pain (95%) and subjective fever (49%). Altered mental status was a presenting symptom in 16% of cases. Approximately half of all patients received >1 class of antibiotic, and the median length of antimicrobial therapy was 18 days. Open and percutaneous drainage procedures figured prominently in the management of these infections, with 28% of patients requiring multiple procedures. Pathology specimens were available for 12 of 61 cases. Overall, the treatment success rate was 84%. CONCLUSIONS: Gram-positive bacteria accounted for most infections at our institution, and management commonly involved open or percutaneous drainage procedures. Future studies that prospectively evaluate treatment strategies for pyomyositis and infectious myositis are warranted.

18.
BMC Geriatr ; 21(1): 178, 2021 03 12.
Article En | MEDLINE | ID: mdl-33711942

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.


COVID-19 , Ehrlichiosis , Pancytopenia , Aged, 80 and over , Ehrlichiosis/diagnosis , Ehrlichiosis/drug therapy , Female , Fibrin Fibrinogen Degradation Products , Humans , Pancytopenia/diagnosis , Pancytopenia/etiology , Pandemics , SARS-CoV-2
19.
BMC Infect Dis ; 20(1): 922, 2020 Dec 03.
Article En | MEDLINE | ID: mdl-33272197

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.


Anti-Bacterial Agents/therapeutic use , Bordetella Infections/drug therapy , Bordetella bronchiseptica/isolation & purification , Ceftazidime/therapeutic use , Meningitis/drug therapy , Meningitis/surgery , Meropenem/therapeutic use , Aged , Animals , Bordetella Infections/microbiology , Cerebrospinal Fluid Leak/complications , Colitis, Ulcerative/drug therapy , Drainage/methods , Humans , Immunocompromised Host , Immunosuppressive Agents/therapeutic use , Infliximab/therapeutic use , Male , Meningitis/etiology , Meningitis/microbiology , Neurosurgical Procedures/methods , Treatment Outcome
20.
Pathogens ; 9(12)2020 Nov 29.
Article En | MEDLINE | ID: mdl-33260314

Infective endocarditis classically involves non-sterile vegetations on valvular surfaces in the heart. Feared complications include embolization and acute heart failure. Surgical intervention achieves source control and alleviates valvular regurgitation in complicated cases. Vegetations >1 cm are often intervened upon, making massive vegetations uncommon in modern practice. We report the case of a 39-year-old female with history of intravenous drug abuse who presented with a serpiginous vegetation on the native tricuspid valve and methicillin-resistant Staphylococcus aureus bacteremia. The vegetation grew to 5.6 cm by hospital day two, and she successfully underwent a tricuspid valvectomy. Six weeks of intravenous vancomycin therapy were completed without adverse events. To better characterize other dramatic presentations of infective endocarditis, we performed a systematic literature review and summarized all case reports involving ≥4 cm vegetations.

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