A case of orbital cryptococcosis.

Purpose: This report describes a case of Cryptococcus neoformans found in an unlikely location, the orbit, in an apparently immunocompetent host. Observations: A coordinated, multi-disciplinary approach between the ophthalmology, neurosurgery, pathology, and infectious disease departments was integral to saving both vision and life. Conclusions and Importance: This is the first case of primary orbital cryptococcosis described in the medical literature, to the authors' knowledge. The case draws attention to the possibility that Cryptococcus neoformans can indeed invade the orbit and should be considered part of the differential diagnosis for patients presenting with orbital masses of uncertain etiology.

Prediction of the need for intensive oxygen supplementation during hospitalisation among subjects with COVID-19 admitted to an academic health system in Texas: a retrospective cohort study and multivariable regression model.

OBJECTIVE: SARS-CoV-2 has caused a pandemic claiming more than 4 million lives worldwide. Overwhelming COVID-19 respiratory failure placed tremendous demands on healthcare systems increasing the death toll. Cost-effective prognostic tools to characterise the likelihood of patients with COVID-19 to progress to severe hypoxemic respiratory failure are still needed. DESIGN: We conducted a retrospective cohort study to develop a model using demographic and clinical data collected in the first 12 hours of admission to explore associations with severe hypoxemic respiratory failure in unvaccinated and hospitalised patients with COVID-19. SETTING: University-based healthcare system including six hospitals located in the Galveston, Brazoria and Harris counties of Texas. PARTICIPANTS: Adult patients diagnosed with COVID-19 and admitted to one of six hospitals between 19 March and 30 June 2020. PRIMARY OUTCOME: The primary outcome was defined as reaching a WHO ordinal scale between 6 and 9 at any time during admission, which corresponded to severe hypoxemic respiratory failure requiring high-flow oxygen supplementation or mechanical ventilation. RESULTS: We included 329 participants in the model cohort and 62 (18.8%) met the primary outcome. Our multivariable regression model found that lactate dehydrogenase (OR 2.36), Quick Sequential Organ Failure Assessment score (OR 2.26) and neutrophil to lymphocyte ratio (OR 1.15) were significant predictors of severe disease. The final model showed an area under the curve of 0.84. The sensitivity analysis and point of influence analysis did not reveal inconsistencies. CONCLUSIONS: Our study suggests that a combination of accessible demographic and clinical information collected on admission may predict the progression to severe COVID-19 among adult patients with mild and moderate disease. This model requires external validation prior to its use.

Antibiotic Stewardship and Inpatient Clostridioides difficile Testing in Solid Organ Transplant Recipients: The Need for Multilevel Checks and Balances.

BACKGROUND: Diarrhea among recipients of solid organ transplants is a commonly encountered problem and is often multifactorial in etiology. Owing to the combination of perioperative antibiotic administration and the immunosuppressed status of transplant recipients, a high degree of suspicion for Clostridioides difficile (C. difficile) colitis is prudent. The purpose of this study is to demonstrate the association of an institutional integrated stewardship program with C. difficile testing practices after abdominal solid organ transplantation. METHODS: Starting in July 2017, a diagnostic stewardship was enacted in our institution requiring the ordering provider to answer a series of questions within the electronic medical record before ordering a C. difficile toxin test. The charts were reviewed for all solid organ transplant recipients on whom a test was ordered between January 2016 and September 2019. RESULTS: Orders for C. difficile toxin per quarter significantly decreased in the postintervention era (18 vs 8.5, P = .038). Median cost of inpatient treatment and days of therapy per thousand patient days was significantly lower in the postintervention era (median cost, $2,944.55 vs $416.92; P = .01) (days of therapy per thousand patient days, 521.9 vs 300.5; P < .01). Quarterly rates of negative tests were similar between the pre- and postintervention eras (65% vs 73%, P = .38). CONCLUSIONS: Although no orders were blocked based on the responses, this multilevel intervention was associated with a 47% decrease in C. difficile testing without effecting the rate of negative testing. These results suggest that we have achieved significant cost savings, in testing and isolation, without sacrificing critical aspects of clinical care.

Early Clinical Experience with Delafloxacin: A Case Series.

BACKGROUND: The most recently approved fluoroquinolone for use in the US and Europe, delafloxacin (DLX) provides broad-spectrum coverage, improved side effect profile, and excellent potency. Currently approved for the treatment of acute bacterial skin infections and community-acquired pneumonia, DLX may be useful in the treatment of other infections given the longstanding versatility of other fluoroquinolones. MATERIALS AND METHODS: This is a retrospective review of adult patients treated with DLX at The University of Texas Medical Branch, Galveston, TX from January 1, 2018 to February 1, 2020 using pre-existing electronic medical records. Simple statistics were calculated using Microsoft Excel. RESULTS: Five patients were prescribed DLX (median age 59 years, 40% female, 100% outpatient) with a median treatment duration of seven days. Prescriptions were initiated by infectious diseases specialists (2/5, 40%), emergency medicine physicians (2/5, 40%), and ophthalmologists (1/5, 20%).  The most common conditions treated were prosthetic joint infections (PJI) and acute skin and soft tissue infections (each n = 2). Both PJIs were caused by multi-drug-resistant Staphylococcus epidermidis. Off-label utilization was high (3/5, 60%). No patient experienced any documented treatment failure due to delafloxacin and there were zero reported adverse events. CONCLUSIONS: A new antibiotic with valuable characteristics, DLX treatment was highly successful in this case series, including with multiple off-label indications. Real-world clinical data with delafloxacin are currently scant. Prospective data would be useful for identifying future clinical niches for this new fluoroquinolone.

Comparison of Coronary Artery Involvement and Mortality in STEMI Patients With and Without SARS-CoV-2 During the COVID-19 Pandemic: A Systematic Review and Meta-Analysis.

BACKGROUND: Cardiovascular injury with SARS-CoV-2 infection is well known. Several studies have outlined baseline characteristics in patients presenting with STEMI and SARS-CoV-2. Paucity in data exists in selective coronary involvement in patients with STEMI and SARS-CoV-2 during the COVID-19 pandemic. METHODS: A systematic search and meta-analysis of studies meeting the inclusion and exclusion criteria obtained from MEDLINE, Scopus, and Cochrane databases was performed utilizing PRISMA criteria. The main outcome was likelihood of coronary artery involvement among patients with STEMI and SARS-CoV-2 versus without SARS-CoV-2. The primary adverse outcome measured was in-hospital mortality. RESULTS: The final analysis included 5 observational studies with a total of 2,266 patients. There was no statistical significance in LM (OR 1.40; 95% CI: 0.68, 2.90), LAD (OR 1.09; 95% CI 0.83, 1.43), LCX (OR 1.17; 95% CI: 0.75, 1.85), or RCA (OR 0.59; 95% CI: 0.30, 1.17) disease among the 2 groups. LAD disease was the most prevalent coronary involvement among patients with STEMI and SARS-CoV-2 (49.6%). Higher in-hospital mortality was observed in the STEMI and SARS-CoV-2 group (OR 5.24; 95% CI: 3.63, 7.56). CONCLUSIONS: Our analysis demonstrated no statistical significance in selective coronary involvement in patients with STEMI and SARS-CoV-2 during the COVID-19 pandemic. The higher mortality among patients with SARS-CoV-2 and STEMI has been noted in prior studies with concerns being late presentation due to fear of infection, delayed care time, and poor resource allocation. Focus should be placed on identifying and managing comorbidities to reduce mortality.

Extensively Drug-Resistant Acinetobacter baumannii Nosocomial Pneumonia Successfully Treated with a Novel Antibiotic Combination.

Extremely drug-resistant (XDR) Acinetobacter baumannii causes challenging nosocomial infections. We report the case of a patient with XDR A. baumannii pneumonia and septic shock successfully treated with cefiderocol and a novel antibiotic obtained via expanded access protocol. With focused research and drug development efforts, the poor outcomes associated with these infections may be mitigated.

Native and Prosthetic Valve Staphylococcus capitis Endocarditis: A Review of the Literature.

Infective endocarditis (IE) is a rare but serious disease. Coagulase-negative staphylococci (CoNS) are among the least prevalent causes of IE. Staphylococcus capitis, a species of CoNS, although described in the literature before has only been seen in a few cases. Even with such few cases, complications and mortality have still been demonstrated. In our review, we look at the epidemiology, diagnosis, management, and literature prevalence of CoNS in native and prosthetic valve IE.

Extensively drug-resistant Salmonella Typhi in a patient returning from Pakistan, complicated by relapse with meropenem monotherapy.

In developing countries, typhoid fever is a common cause of febrile illness accompanied by abdominal pain and weakness. It is caused by Salmonella enterica serovar Typhi. Humans are the only known reservoir of infection, and typhoid fever is common in regions where access to clean water and sanitation is limited. The antimicrobials of choice for a case of typhoid fever acquired outside Pakistan are third generation cephalosporins. Lately, cases of extensively drug-resistant (XDR) Salmonella Typhi have been reported in people with a travel history to Pakistan. We present a case of XDR typhoid fever which relapsed after treatment with meropenem.

Life-Threatening Intraventricular Rupture of Brain Abscess in a Patient With Undiagnosed Hereditary Hemorrhagic Telangiectasia.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant genetic condition associated with mucocutaneous and visceral arteriovenous malformations (AVMs), including pulmonary AVMs, which predispose patients to systemic paradoxical emboli that can lead to brain abscesses. Intraventricular rupture of brain abscess (IVROBA) is a feared complication with a high mortality rate. Here, we present a case with brain abscesses complicated by IVROBA and ventriculitis as the initial presentation of HHT in an undiagnosed patient. We also discuss the diagnostic and therapeutic approach that resulted in this patient's clinical improvement.

Unexpected Cholera Bacteremia in a 91 Year Old Caucasian Male Patient.

Cholera is an illness caused by Vibrio cholerae; its main symptom is acute watery diarrhea. Some infections are asymptomatic or result in patients presenting with mild diarrhea, but complications, such as bacteremia, can be fatal. Being endemic in Africa, Southeast Asia, and Haiti, V. cholerae infection cases in the United States are primarily considered travel-related. Herein, we report a case of a 91 year old Caucasian man, a Texas Gulf Coast resident, who developed bacteremia due to V. cholerae despite having no international travel history. Culture workup by mass spectrometry, automated biochemical system, and 16S ribosomal RNA (rRNA) gene sequencing confirmed V. cholerae. This case conveys an important reminder to clinicians and laboratory professionals regarding potentially serious cholera illnesses due to the domestic prevalence of V. cholerae in the coastal regions of the United States.

Adjunctive ceftaroline in combination with daptomycin or vancomycin for complicated methicillin-resistant Staphylococcus aureus bacteremia after monotherapy failure.

BACKGROUND: Methicillin-resistant Staphylococcus aureus bacteremia (MRSA-B) may fail to improve with standard monotherapy, particularly in patients with multifocal infection, incomplete source control, or persistent bacteremia. Synergy observed in vitro between ceftaroline (CPT) and daptomycin (DAP) or vancomycin (VAN) may translate into clinical benefit. Here, we describe our experience with DAP/CPT and VAN/CPT for complicated MRSA-B after monotherapy failure. METHODS: Single-center, retrospective review of consecutive patients treated with DAP/CPT or VAN/CPT for MRSA-B after monotherapy failure from 1 January 2016 to 30 November 2018. RESULTS: We identified 11 instances of combination therapy in 10 patients (DAP/CPT = 6, VAN/CPT = 5) with 1 patient receiving VAN/CPT followed by DAP/CPT. Rates of multifocal infection, incomplete source control, persistent bacteremia, and infective endocarditis were high (100%, 80%, 60%, and 60%, respectively). Combination therapy was initiated most commonly for persistent bacteremia (60%). When patients were persistently bacteremic, median preceding duration was 13 days and median time to clearance was 3 days. Total microbiologic cure rate was 100%. There were zero instances of bacteremia relapse at 30 days (30D) or 60 days (60D). All-cause 30D and 60D mortality rates were 11.1% and 33.3%, respectively. CONCLUSIONS: Combination therapy demonstrated success in diverse cases of refractory MRSA-B, including instances of persistent bacteremia paired with incomplete source control. Optimal timing and therapeutic cadence for combination therapy remain unclear. Our findings suggest that DAP/CPT and VAN/CPT can be considered for complicated MRSA bacteremia when other treatment options fail or are unavailable. We propose persistent bacteremia with incomplete source control to be a clinical niche particularly worthy of further investigation.

Adiponectin and the steatosis marker Chi3L1 decrease following switch to raltegravir compared to continued PI/NNRTI-based antiretroviral therapy.

BACKGROUND: People with HIV are at for metabolic syndrome (MetS) and fatty liver disease, but the role of Antiretroviral therapy (ART) is poorly understood. MetS and fatty liver disease been associated with changes in adiponectin, soluble ST2 (sST2), chitinase 3-like 1 (Chi3L1), hyaluronic acid (HA), tissue inhibitor of metalloproteinase-1 (TIMP-1), lysyl oxidase-like-2 (LOXL2) and transforming growth factor ß (TGF-ß) concentrations in HIV-uninfected populations. Protease (PI) and non-nucleoside reverse transcriptase inhibitors (NNRTI) may contribute to these comorbidities, but the effects of switching from PI- or NNRTI to raltegravir (RAL) on these biomarkers is unknown. METHODS: Cryopreserved plasma was obtained from a completed, prospective trial of HIV-infected women with central adiposity on NNRTI- or PI-based ART during which they were randomized to remain on their current ART or switch to a RAL based regimen. Biomarker concentrations were quantified using ELISA and Multiplex assays at baseline and 24 weeks after randomization. Wilcoxon-signed rank test evaluated within-group changes, Spearman and linear regression models evaluated correlations between biomarkers and clinical covariates. RESULTS: Participants had a median age of 43 years, CD4+ T lymphocyte count 558 cells/mm3 and BMI 32 kg/m2; 35% met criteria for MetS. At baseline, higher adiponectin levels correlated with higher Chi3L1 levels (r = 0.42, p = 0.02), as did declines after 24 weeks (r = 0.40, p = 0.03). Changes in sST2 correlated with changes in Chi3L1 (r = 0.43, p = 0.02) and adiponectin (r = 0.40, p = 0.03). Adiponectin and Chi3L1 levels decreased significantly in women switched to RAL vs continue PI/NNRTI. CONCLUSION: In women with HIV and central obesity, the hepatic steatosis/fibrosis marker Chi3L1 and adiponectin decrease in conjunction with sST2 decreases following switch to RAL. Whether switching from NNRTI/PI-based regimens to RAL can improve hepatic steatosis and dysmetabolism requires further study. TRIAL REGISTRATION: Clinicaltrials.gov NCT00656175.

Prevalence of bovine subclinical mastitis, its etiology and diagnosis of antibiotic resistance of dairy farms in four municipalities of a tropical region of Mexico.

A region-wide survey was conducted in the tropical area of Tierra Caliente, State of Guerrero, Mexico to estimate the prevalence of subclinical bovine mastitis (SCM), distribution of mastitis pathogens, and in vitro antimicrobial susceptibility of different mastitis pathogens in dairy farms. In total, 1036 quarter milk samples were obtained from 259 cows at 87 different dairy farms. Collected quarter milk samples were submitted for California Mastitis Test (CMT), bacteriological examination, and testing for antimicrobial susceptibility. Overall prevalence of SCM in the studied area was 20.5 %. Prevalence in the different regions was as follows: 28 % in Arcelia municipality, 21 % in Tlalchapa municipality, 19.4 % in Pungarabato municipality, and 14.3 % in Finch Cutzamala municipality. Of all positive isolates, 97.5 % were Gram-negative bacteria. Moreover, of all positive isolates, 37.5 % were Proteus vulgaris, 25 % Salmonella spp., 12.5 % Enterobacter aerogenes, and 10 % Escherichia coli. Klebsiella pneumonia and E. coli were sensitive for netilmicin antimicrobial. However, E. coli was sensitive for pefloxacin and gentamicin with a sensitivity for pefloxacin for E. aerogenes, while Staphylococci were sensitive for gentamicin and dicloxacillin. It could be concluded that practices such as the implementation of mastitis control programs, improved milking hygiene together with an intramammary treatment with netilmicin, pefloxacin, and gentamicin antimicrobials should be considered for mastitis prevention in the study area of Tierra Caliente, in the tropical area of Guerrero, Mexico.

Anti-tumor effects of the Notch pathway in gastrointestinal stromal tumors.

Gastrointestinal stromal tumors (GISTs) are driven by gain-of-function mutations of KIT or PDGFRa. The introduction of imatinib has significantly extended survival for patients. However, most patients develop resistances. Notch signaling is a conserved developmental pathway known to play a critical role in the development of several cancers, functioning as a tumor promoter or a tumor suppressor. Given that the normal progenitor cell for GIST, the interstitial cell of Cajal, has characteristics similar to those of cells of neuroendocrine origin, we hypothesized that Notch pathway impacts the biology of GIST cells. In this study, we retrovirally and pharmacologically manipulated the Notch pathway in human GIST cells. We also performed a retrospective analysis of a cohort on 15 primary tumors to determine the role of Hes1, a major target gene of Notch, as a prognostic marker for GIST. Constitutively, active intracellular domain of Notch1 (ICN1) expression potently induced growth arrest and downregulated KIT expression in vitro. Additionally, treatment with the histone deacetylase inhibitor suberoylanilide hydroxamic acid caused dose-dependent upregulation of Notch1 expression and a parallel decrease in viability in these cells. Retroviral silencing of downstream targets of Notch (dominant-negative Hes1) and pharmacological inhibition of Notch activation (γ-secretase inhibition) partially rescued GIST cells from suberoylanilide hydroxamic acid treatment. GIST patients with high Hes1 mRNA levels have a significantly longer relapse-free survival. These results identify a novel anti-tumor effect of Notch1 and cross talk between the Notch and KIT pathways. Thus, activation of this pathway by treatment with histone deacetylase inhibitors is an appealing potential therapeutic strategy for GISTs. Précis: This study is the first report of the tumor suppressor effects of Notch pathway in gastrointestinal stromal tumors via a negative feedback with the oncogene KIT and may lead the development of new therapeutic strategies for GISTs patients.