Hypoxemic Respiratory Failure and Coccidioidomycosis-Associated Acute Respiratory Distress Syndrome.

Background: Severe coccidioidomycosis presenting with respiratory failure is an uncommon manifestation of disease. Current knowledge of this condition is limited to case reports and small case series. Methods: A retrospective multicenter review of patients with coccidioidomycosis-associated acute respiratory distress syndrome (CA-ARDS) was conducted. It assessed clinical and laboratory variables at the time of presentation, reviewed the treatment course, and compared this cohort with a national database of patients with noncoccidioidomycosis ARDS. Survivors and nonsurvivors of coccidioidomycosis were also compared to determine prognostic factors. Results: In this study, CA-ARDS (n = 54) was most common in males, those of Hispanic ethnicity, and those with concurrent diabetes mellitus. As compared with the PETAL network database (Prevention and Early Treatment of Acute Lung Injury; n = 1006), patients with coccidioidomycosis were younger, had fewer comorbid conditions, and were less acidemic. The 90-day mortality was 15.4% for patients with coccidioidomycosis, as opposed to 42.6% (P < .0001) for patients with noncoccidioidomycosis ARDS. Patients with coccidioidomycosis who died, as compared with those who survived, were older, had higher APACHE II scores (Acute Physiology and Chronic Health Evaluation), and did not receive corticosteroid therapy. Conclusions: CA-ARDS is an uncommon but morbid manifestation of infection. When compared with a national database, the overall mortality appears favorable vs other causes of ARDS. Patients with CA-ARDS had a low overall mortality but required prolonged antifungal therapy. The utility of corticosteroids in this condition remains unconfirmed.

A Clinicopathological Categorization System for Clinical Research in Coccidioidomycosis.

A wide array of clinical manifestations follow infection with Coccidioides immitis or Coccidioides posadasii, ranging from asymptomatic infection to life-threatening pulmonary disease or extrapulmonary dissemination and meningitis. Epidemiological studies require consistent definitions of cases and their comparative clinical features. Understanding host and pathogen determinants of the severity of coccidioidomycosis also requires that specific clinical features (such as coccidioidal meningitis) and their overlap be precisely defined and quantified. Here we propose a system for categorization of outcomes of coccidioidomycosis in individuals who are not overtly immunocompromised that harmonizes clinical assessments during translational research of this increasingly common disease.

Coccidioidal Pulmonary Cavitation: A New Age.

Coccidioides species are thermally dimorphic fungi found in geographically defined areas of the Western Hemisphere. The primary portal of entry is respiratory, with symptomatic pneumonic diseases as the most common presentation. Subsequent pulmonary complications as well as extrapulmonary metastatic infection may occur, either of which may be the presenting disease manifestation. Cavitary lung disease may be found incidentally or when investigating symptoms such as cough or hemoptysis. This study aims to explore the spectrum of coccidioidal cavities and the evaluation and management in a cohort of patients seen at Kern Medical over the last 12 years.

Asymptomatic Coccidioidal Meningitis Relapse: A Demon in Disguise.

Coccidioides spp is a soil-dwelling, dimorphic fungus that causes coccidioidomycosis. It is endemic to the western hemisphere. Although primarily a respiratory disease, it can also cause a myriad of clinical manifestations, from asymptomatic disease to meningitis. In fact, Coccidioides species is probably the most common etiologic agent of long-term meningitis in California and Arizona. Early diagnosis and treatment are critical to avoid fatal complications. With treatment, the cerebral spinal fluid analysis may return to normal. Relapse of coccidioidal meningitis is usually suspected with recurrence of meningitis symptoms. The patient is a 53-year-old man with a 2-decade history of coccidioidal meningitis who was diagnosed with an asymptomatic relapse of coccidioidal meningitis.

Isavuconazole in the Treatment of Chronic Forms of Coccidioidomycosis.

Coccidioidomycosis is a fungal infection with a range of clinical manifestations. Currently used antifungal agents exhibit variable efficacy and toxicity profiles that necessitate evaluation of additional therapeutic options. Improvement was observed in the majority of patients treated with isavuconazole, with clinical failures observed only in those with coccidioidal meningitis.

A Case of Coccidioidal Meningitis With Biofilm Obstructing VP Shunt Due to Cutibacterium acnes.

Herein described is a case of biofilm obstructing ventriculoperitoneal shunt due to Cutibacteirum acnes infection in a patient with coccidioidal meningitis. Cutibacterium acnes infects and obstructs cerebral shunts by the production of biofilm; however, diagnosis is usually missed by routine aerobic cultures. Obtaining anaerobic cultures routinely in patients with foreign body implants leading to central nervous system infections could prevent a missed diagnosis of this pathogen. Penicillin G is the first-line treatment.

Coccidioides Species: A Review of Basic Research: 2022.

Coccidioides immitis and posadasii are closely related fungal species that cause coccidioidomycosis. These dimorphic organisms cause disease in immunocompetent as well as immunocompromised individuals and as much as 40% of the population is infected in the endemic area. Although most infections resolve spontaneously, the infection can be prolonged and, in some instances, fatal. Coccidioides has been studied for more than 100 years and many aspects of the organism and the disease it causes have been investigated. There are over 500 manuscripts concerning Coccidioides (excluding clinical articles) referenced in PubMed over the past 50 years, so there is a large body of evidence to review. We reviewed the most accurate and informative basic research studies of these fungi including some seminal older studies as well as an extensive review of current research. This is an attempt to gather the most important basic research studies about this fungus into one publication. To focus this review, we will discuss the mycology of the organism exclusively rather than the studies of the host response or clinical studies. We hope that this review will be a useful resource to those interested in Coccidioides and coccidioidomycosis.

Controversies in the Management of Central Nervous System Coccidioidomycosis.

Central nervous system infection with Coccidioides spp. is fatal if untreated and complications occur even when therapy is directed by experienced clinicians. We convened a panel of clinicians experienced in the management of coccidioidal meningitis to summarize current controversies and provide consensus for the management of this difficult infection.

A Case of Concurrent Disseminated Coccidioidomycosis and Embryonal Carcinoma When Lice and Fleas Coexist.

Coccidioidomycosis (CM) is a fungal infection endemic to the southwestern United States with a wide range of clinical presentations depending on the infected organ systems. Most infections are asymptomatic. Coccidioidomycosis causes a primary pulmonary infection and when symptoms occur, they most often resemble community-acquired pneumonia. One percent of cases disseminate, typically via hematogenous or lymphatic spread. It is in these cases that more severe symptoms may present and potentially overlap with those characteristics of other systemic illnesses. This is a case of CM disseminated to lymph nodes in a 24-year-old man with concomitant metastatic embryonal carcinoma. It is difficult to identify the primary etiology for many components of this patient's presentation, including diffuse lymphadenopathy and multiple pulmonary nodules. Furthermore, the relationship between these 2 concurrent disease processes is not entirely clear. Factors that may contribute include the well-known phenomenon of locus minoris resistentiae (LMR) or potentially a shared immune failure between infectious organisms and malignant cells.

Two Cases of Miliary and Disseminated Coccidioidomycosis Following Glucocorticoid Therapy and Literature Review.

A 49-year-old man with no significant past medical history received dexamethasone as part of his treatment for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Less than 3 weeks later, the patient developed acute respiratory distress syndrome. Radiological and serological testing led to a diagnosis of acute hypoxic miliary coccidioidomycosis. A 52-year-old man with a past medical history of chronic kidney disease (CKD) was treated with prednisone for focal segmental glomerulosclerosis (FSGS). Within 2 weeks, this patient developed bilateral lower extremity weakness. Radiology, serology, and lumbar puncture proved a diagnosis of reactivated coccidioidomycosis with miliary pattern and coccidioidomycosis meningoencephalitis with arachnoiditis. Whether treatment with glucocorticoids caused reactivation of coccidioidomycosis is discussed in this case series.

Disseminated Coccidioidomycosis: Cutaneous, Soft Tissue, Osseous, and "Shotgun Intraparenchymal" Brain Disease.

Coccidioidomycosis is a disease found in the southwestern United States and caused by inhalation of arthroconidia of Coccidioides immitis and posadasii. Although the disease is most commonly asymptomatic or respiratory, it has a propensity to disseminate to any tissue in the body with the most common being skin, bone, joints, and central nervous system. This case demonstrates the dissemination of coccidioidomycosis to several foci along with a rare form of parenchymal dissemination with an unusual neuroradiological finding.

Coccidioidal Peritonitis: A Review of 17 Cases.

Coccidioidomycosis is the second most common endemic fungal infection in the United States. Prior descriptions of coccidioidal peritonitis include only single cases. We describe 17 new cases previously unreported from healthcare institutions in California. The majority of cases presented with nonspecific abdominal complaints. PubMed and Google Scholar were searched for additional case series and only single case reports and reviews of single cases were found. The diagnosis was confirmed by culture or histopathology and/or serology in each patient. All patients were treated with anti-fungal therapy. This case series demonstrates that coccidioidal peritonitis may be asymptomatic or present with only subtle abdominal symptoms. In a minority of our patients, the diagnosis was established incidentally during surgery. Based on this series, the overall outcome of coccidioidal peritonitis is favorable with long-term triazole treatment. The term cure is not usually used in disseminated coccidioidal disease because of the risk of late relapse.

FDA Public Workshop Summary-Coccidioidomycosis (Valley Fever): Considerations for Development of Antifungal Drugs.

Coccidioidomycosis is a fungal disease endemic to the southwestern United States, Mexico, and Central and South America. Prevalence rates are increasing steadily, and new endemic areas of Coccidioides are emerging. Standard treatment is often administered for months to decades, and intolerance to medications and treatment failures are common. No new treatments for coccidioidomycosis have been approved in the United States in nearly 40 years. On 5 August 2020, the US Food and Drug Administration convened experts in coccidioidomycosis from academia, industry, patient groups, and other government agencies to discuss the disease landscape and strategies to facilitate product development for treatment of coccidioidomycosis. This article summarizes the key topics concerning drug development for coccidioidomycosis presented by speakers and panelists during the workshop, such as unmet need, trial designs, endpoints, incentives, research and development support, and collaborations to facilitate antifungal drug development.

Serum magnesium levels in hospitalized patients with SARS-CoV-2.

Early studies have reported various electrolyte abnormalities at admission in patients with severe COVID-19. 104 out of 193 patients admitted to our institution presented with hypermagnesemia at presentation. It is believed this may be important in the evaluation of severe SARS-CoV-2 infections. This study evaluated the outcomes of hypermagnesemia in patients with COVID-19. A retrospective chart review of patients admitted to the hospital with confirmed SARS-CoV-2 infection was conducted. A review of the medical literature regarding hypermagnesemia, magnesium levels in critical care illness and electrolyte abnormalities in patients with COVID-19 was performed. Differences in demographic and clinical characteristics of patients with hypermagnesemia and normomagnesemia were evaluated using descriptive statistics. Other known variables of disease severity were analyzed. 104 patients (54%) were identified with hypermagnesemia (≥2.5 mg/dL). 48 of those patients were admitted to the intensive care unit (46%, p<0.001). 34 patients required ventilator support (32%, p<0.0001). With age-adjusted logistic regression analysis hypermagnesemia was associated with mortality (p=0.007). This study demonstrates that hypermagnesemia is a significant marker of disease severity and adverse outcome in SARS-CoV-2 infections. We recommend serum magnesium be added to the panel of tests routinely ordered in evaluation of severe SARS-CoV-2 infections.

A randomized, double-blind, placebo-controlled clinical trial of fluconazole as early empiric treatment of coccidioidomycosis pneumonia (Valley Fever) in adults presenting with community-acquired pneumonia in endemic areas (FLEET-Valley Fever).

INTRODUCTION: Coccidioidomycosis is a fungal infection endemic in the southwestern United States (US). Primary pulmonary coccidioidomycosis (PPC) is a leading cause of community-acquired pneumonia (CAP) in this region, although its diagnosis is often delayed, leading to lag in antifungal treatment and subsequent morbidity. The impact of early empiric antifungal therapy as part of treatment for CAP in endemic areas on clinical outcomes is unknown. METHODS: Phase IV randomized, double-blind, placebo-controlled trial in individuals aged 18 years or older with CAP who met all eligibility criteria in Coccidioides endemic regions in the US. Eligible participants with CAP were randomized to receive either fluconazole (400 mg daily) or matching placebo for 42 days and were subsequently monitored for clinical resolution of their illness. OBJECTIVES: The primary objective was to assess the clinical response of early empiric antifungal therapy with fluconazole through Day 22 in subjects with PPC who were adherent to the study intervention. Secondary objectives included: assessments of the impact of early empiric antifungal therapy with fluconazole through Day 22 and 43 in subjects with PPC regardless of adherence, comparisons of the clinical response and its individual components over time by treatment group in subjects with PPC, assessments of days lost from work or school, hospitalization, and all-cause mortality. DISCUSSION: This trial was halted early due to slow enrollment (72 participants in one year, 33 received fluconazole and 39 received placebo). Of those enrolled, eight (11%) met the study definition of PPC. The study design and challenges are discussed.

A Case of S-Variant Hepatitis B Virus: An Immune System Escape Artist.

Genomic variants of the hepatitis B virus (HBV) preS/S protein are well-known to occur. Typically, immunity is gained through recovered HBV infection or by immunization. Very rarely, there are certain mutations that may enable HBV escape from the immune detection. PreS/S mutants may present with unpredictable pathobiologic, clinical, and transmittable implications. Standard laboratory testing for genomic HBV variants is not routinely performed by reference guidelines. s-variant HBV management remains challenging. Herein is a case of s-variant chronic HBV infection in a 55-year-old man. Diagnosis and treatment are described.

Neutrophilic Dermatosis in Myelodysplastic Syndrome and Chronic Active Hepatitis C.

In this article, we describe a case of neutrophilic dermatosis of the dorsal hands (NDDH) complicated with myelodysplastic syndrome and chronic active hepatitis C infection. NDDH was first suggested by Galaria et al in 2000. After comparing features of NDDH with Sweet syndrome in terms of encompassing clinical, laboratory, and histological characteristics, it can be concluded that "distributional or localized variant" of Sweet syndrome is classified as NDDH. Early diagnosis and treatment can improve prognosis. Systemic glucocorticoids are the mainstay of treatment.

Coccidioidal Hepatic Abscess in a Patient With Disseminated Coccidioidomycosis: A Case Report.

Coccidioidomycosis is an infection caused by inhalation of arthroconidia of Coccidioides. Forty percent of patients will develop mild and self-limited respiratory infection, and a small fraction of these individuals will develop extrapulmonary disseminated disease. This is the case of a patient with a known history of disseminated coccidioidomycosis, who initially presented for symptoms of persistent pneumonia. On evaluation, the patient was found to have a hepatic abscess for which he underwent percutaneous drainage. Culture grew Coccidioides immitis, and the patient was treated with systemic antifungal. This is a rare case of disseminated coccidioidomycosis in the liver.

A Case Report of Coccidioidomycosis in the Renal Parenchyma of Unusual Severity.

Coccidioidomycosis (CM) is an endemic fungal infection that is found in the Southwestern United States and adjacent areas of Mexico as well as Central and South America. In the United States, 150 000 to 300 000 infections occur annually. The majority are asymptomatic. Of the symptomatic cases, the majority are primary pneumonic disease that varies from mild to very severe. A minority of persons develop disseminated disease (extrapulmonary disease). These typically manifest as meningitis, osteomyelitis, synovitis, and integumentary. CM has been described in virtually every part of the body, including the genitourinary system. Disseminated CM to the genitourinary tract is well known to occur but is rarely documented. It is believed this is the first case to report disseminated CM to the renal parenchyma. Diagnosis and treatment are described in a 56-year-old Hispanic male.

Coccidioidomycosis: a review.

Coccidioidomycosis is a fungal infection of the Western hemisphere that is endemic to the soil in areas with limited rainfall. Human and animal infections result with inhalation of arthroconidia. Most often, this is an asymptomatic event. When illness occurs, it is primarily a pneumonic presentation. A small minority of infections eventuate in disseminated disease. Predominately, this presents as meningitis or osteoarticular or integumentary disease. Treatment may not be required for the mildest illness. Azoles are commonly prescribed. Severe infections may require amphotericin B.