Coccidioidomycosis in Oklahoma: A retrospective case series.

BACKGROUND: Coccidioidomycosis is a systemic fungal disease endemic to arid regions of the Western Hemisphere. In the south-western US, Coccidioides spp. may account for up to 20%-25% of all cases of community acquired pneumonia. Clinical manifestations vary widely, from asymptomatic infection to life-threatening disease, especially in immunocompromised hosts. OBJECTIVES: The primary objective of the study was to characterise cases of coccidioidomycosis in an area of the United States not considered traditionally endemic for the disease. METHODS: We performed a single-centre retrospective study of all cases of coccidioidomycosis from 1 January 2000 to 31 December 2020, in the University of Oklahoma Health Sciences Medical Center. RESULTS: A total of 26 patients were included for analysis. The central nervous system (CNS) and the lungs were the sites most frequently involved. Twenty (77%) had travelled to a coccidioidomycosis endemic region. Most were male (81%) with a median age of 42 years (range: 3-78 years). The majority (46%) were Caucasians, 19% were African American, 19% Hispanic, and 12% Native American. The most common comorbidities were diabetes mellitus and acquired immunodeficiency syndrome, identified in 27% and 23% of patients, respectively. Patients on immunosuppressive therapy accounted for 12% of all cases. CONCLUSION: Our study is one of the largest single-centre case series of coccidioidomycosis from a non-endemic area. Diabetes mellitus was the most frequent comorbidity. Compared to other case series of coccidioidomycosis, our patient population had higher rates of immunosuppression and had both a higher rate of disseminated disease and overall mortality.

Recurrent disseminated coccidioidal meningitis in two subsequent pregnancies.

OBJECTIVE: Recurrent disseminated coccidioidal meningitis in two subsequent pregnancies is rare and can pose a challenge in ensuring the health of both mother and baby. In this unique case we highlight this rare occurrence and subsequent treatment. CASE REPORT: A 29-year-old G4P1021 with a history of disseminated coccidioidomycosis in a previous pregnancy presented at 8 weeks gestation with nausea, headache, and neck pain. Cerebrospinal fluid analysis was positive for recurrent coccidioidal infection. She was started on Amphotericin and discharged. She re-presented at 30 week's gestation with phonophobia and photophobia, emesis, neck pain and swelling. MRI showed evidence of ventriculomegaly with communicating hydrocephalus. She was treated with therapeutic lumbar punctures throughout her pregnancy and a ventriculoperitoneal shunt following delivery. She had a spontaneous vaginal delivery at 38 weeks and 3 days with no complications. CONCLUSION: This unique case highlights the susceptibility of recurrent disseminated coccidioidomycosis in subsequent pregnancies and treatment thereof.

Syndrome of inappropriate antidiuretic hormone release secondary to central nervous system coccidioidomycosis with vasculitis.

A man in his 60s presented to the clinic due to night sweats and weight loss following pneumonia. He was found to have hyponatraemia due to a syndrome of inappropriate antidiuretic hormone (SIADH). CT of the thorax was concerning for pulmonary nodules. He was ultimately diagnosed with pulmonary coccidioidomycosis (CM) and started on fluconazole 400 mg daily with improvement in symptoms. Due to the report of headaches, head MRI was conducted which suggested central nervous system (CNS) involvement. Cerebrospinal fluid analysis was consistent with CNS CM and head magnetic resonance angiography confirmed the presence of CNS vasculitis. Fluconazole dose was increased to 800 mg daily which the patient continued to tolerate and showed improvement. This report depicts a case of SIADH associated with CNS CM with vasculitis and demonstrates the importance of high clinical suspicion for SIADH secondary to CNS CM in the setting of hyponatraemia and headache.

Voriconazole-induced periostitis in a patient with HIV treated for coccidioidomycosis meningitis.

Voriconazole-induced periostitis is a rare adverse effect in patients on long-term therapy, characterised by periosteal inflammation and associated bony pain. The accompanying lab abnormalities (elevated serum alkaline phosphatase and fluoride) and characteristic imaging findings (uptake of radionuclide tracer on nuclear bone scan) are critical for diagnosis. The disease process is thought to be secondary to excess fluoride from voriconazole which stimulates bone formation and decreases osteoclast bone resorption. Management includes stopping voriconazole and switching to another agent.

Early Experiences with Intrathecal Administration of Amphotericin B Liposomal Formulation at a Neurosurgical Center.

BACKGROUND: Intrathecal administration of amphotericin B represents an important adjunctive therapy for management of severe fungal meningitis. Intrathecal preparations have traditionally used amphotericin B deoxycholate. Liposomal amphotericin B is an alternative formulation with good clinical outcomes as systemic therapy, but scant data exist investigating intrathecal use. OBJECTIVE: The aim of this exploratory study was to evaluate outcomes following intrathecal administration of liposomal amphotericin B for treatment of severe fungal meningitis. METHODS: A national shortage of amphotericin B deoxycholate necessitated revision of institutional protocols at a southwestern neurosurgical center in Spring 2023. A starting intrathecal daily dose of 0.125-0.5 mg liposomal amphotericin B was recommended (dependent on insertion device), with 0.125-0.25 mg slow titration every 48 h and up to a 2 mg maximum daily dose. RESULTS: Four cases of fungal meningitis treated with adjunctive intrathecal amphotericin B liposomal formulation were reviewed. This included three cases of coccidioidal meningitis and one case of presumed Fusarium solani meningitis following an outbreak. All patients had initial disease improvement following initiation of intrathecal amphotericin B and were able to tolerate long-term therapy. One coccidioidal meningitis patient expired of neurologic complications shortly after being moved from the intensive care unit (ICU) to a floor unit. All other patients were successfully discharged from the hospital. New headache was the only reported adverse effect, which was managed with dose reduction and did not require therapy discontinuation. CONCLUSIONS: Liposomal amphotericin B may be feasibly administered intrathecally for the adjunctive treatment of severe fungal meningitis.

Cutaneous Coccidiomycosis.

ABSTRACT: Coccidiomycosis is an infectious primary pulmonary disease caused by two highly virulent fungi, Coccidioides immitis and C. Posadasii. Coccidioides spp. are endemic to the southwestern USA, Central America, and South America with infection predominating in the summer and fall seasons. The disease commonly presents with flu-like symptoms. Cutaneous manifestations are rare and are a sign of a more serious infection with poorer outcomes. In this case, a 60-year-old female presented to the dermatology clinic with a 3-month history of a mild, non-pruritic, erythematous rash located on her proximal arms and legs. Two punch biopsies were obtained, and she was found to have a non-endemic case of disseminated coccidiomycosis.

Coccidioides species antifungal susceptibility testing: Experience from a large healthcare system in the endemic region.

The clinical utility of Coccidioides species antifungal susceptibility testing (AST) remains unclear. This study describes the clinical course of eight patients with severe or chronic coccidioidomycosis and subsequent Coccidioides AST. We present the clinical manifestations, antifungal treatment regimens, and clinical outcomes for these patients.

The role of antifungal susceptibility in the management of coccidioidomycosis remains unknown. This report presents cases of complex coccidioidomycosis where clinicians elected to conduct antifungal susceptibility testing as part of the treatment approach.

Diagnostic delays in cutaneous coccidioidomycosis: A report from Central California.

Cutaneous Coccidioidomycosis (CC) infection can present with a wide variety of clinical presentations and is well known as a 'great imitator'. We performed a retrospective analysis of patients with CC in a large referral center in Central Valley, California, from 2010 to 2022 using the ICD9 and ICD10 codes for coccidioidomycosis and CC. We identified 40 patients with CC during the study period. The mean age of the study population was 43 years (with standard deviation of 14.08). Among these, 60% were men and 40% women. The appearance of the lesions varied from ulcers, plaques, nodules, blisters, cellulitis, and abscesses. The most common site of CC lesions was in the lower extremities (42.5%), followed by upper extremities (30%), chest and abdomen, head and neck (25% each). Only 22.5% of the 40 cases were diagnosed as CC and 15% were diagnosed as erythema nodosum. Rest were diagnosed initially as bacterial cellulitis in 37.5%, tinea in 7.5%, and others in 12.5%. There was resolution of the cutaneous lesions in all patients with antifungal treatment. The mean time of diagnosis from onset of symptoms on an average was 12 weeks (8-16 weeks) in our study with 75% cases initially misdiagnosed. Comprehensive knowledge about the manifestations and evaluation of CC among primary care providers and emergency room physicians is essential to prevent delays in diagnosis and treatment.

Cutaneous Coccidioidomycosis (CC) is defined as a fungal infection of the skin and/or subcutaneous tissues caused by the Coccidioides fungus. CC has been classified into primary CC which is caused by direct inoculation of the fungal organism into the skin, reactive CC defined as delayed hypersensitivity reaction, and disseminated CC which involves multiple organs infection. CC infection can present with a wide variety of clinical presentations and is well known as a 'great imitator'. Untreated CC can lead to worsening of local infection and the risk of dissemination to other organs. Coccidioidomycosis may be incorrectly diagnosed, and patients are more likely to receive unnecessary antibacterial drugs, laboratory tests, imaging, and invasive procedures, all of which could contribute to unnecessary costs and additional adverse health consequences. We performed a retrospective analysis of patients with CC in a large referral center in Central Valley, California, from 2010 to 2022. The mean time of diagnosis from onset of symptoms on an average was 12 weeks (8­16 weeks) in our study with 75% cases initially misdiagnosed. There is a need for collaboration between doctors and researchers across multiple counties within the Central Valley of California to develop strategies for diagnosing and treating CC and raising awareness in the community about the elevated risk of this infection for prevention and early detection.

Innovative and potential treatments for fungal central nervous system infections.

Fungal infections of the central nervous system (FI-CNS) are a problematic and important medical challenge considering that those most affected are immunocompromised. Individuals with systemic cryptococcosis (67-84%), candidiasis (3-64%), blastomycosis (40%), coccidioidomycosis (25%), histoplasmosis (5-20%), mucormycosis (12%), and aspergillosis (4-6%) are highly susceptible to develop CNS involvement, which often results in high mortality (15-100%) depending on the mycosis and the affected immunosuppressed population. Current antifungal drugs are limited, prone to resistance, present host toxicity, and show reduced brain penetration, making FI-CNS very difficult to treat. Given these limitations and the rise in FI-CNS, there is a need for innovative strategies for therapeutic development and treatments to manage FI-CNS in at-risk populations. Here, we discuss standards of care, antifungal drug candidates, and novel molecular targets in the blood-brain barrier, which is a protective structure that regulates movement of particles in and out of the brain, to prevent and combat FI-CNS.

Endemic mycoses - are we making progress in management?

PURPOSE OF REVIEW: The endemic fungi are a significant cause of morbidity and mortality in effected patients. The range of endemicity for these are expanding with infections observed outside of traditional locations. Enhanced diagnostic and treatment practices may significantly alter patient outcomes. RECENT FINDINGS: Recently completed clinical trials have focused on an assessment of improving efficacy while minimizing patient toxicity. Practice changing trials have been completed in histoplasmosis showing the utility of a single up-front liposomal amphotericin B dose followed by standard itraconazole dosing. The recent evaluation of several antifungal options including isauvconazole in the treatment of coccidioidomycosis also show promise for additional therapeutic agents. A recently conducted trial has also shown the superiority of amphotericin B therapy over itraconazole in the treatment of talaromycosis. SUMMARY: The increased range of endemic mycoses coupled with the growing immunocompromised patient population mandates continued investigation of improved diagnostic and therapeutic options. Advances in these areas have led to more rapid diagnosis and more efficacious antifungal therapy.

"It's Not Just Bacteria": A Cavitary Lung Lesion in a Patient Living in the Coachella Valley.

Cavitary pulmonary coccidioidomycosis is rare diagnosis with an incidence of 13% to 15% of pulmonary coccidioidomycosis cases. High clinical suspicion is necessary in the setting of geographical location endemicity. We present a 49-year-old male who has lived in the Coachella Valley of California for several years, with a medical history of uncontrolled type 2 diabetes who noted 1 week of right-sided chest pain with shortness of breath, fever, chills, night sweats, and weight loss. A chest X-ray revealed a 4- to 5-cm mass in the right lung. Initial workup revealed negative sputum cultures (aerobic/anaerobic, acid-fast bacilli). However, dedicated fungal cultures (samples from sputum, lymph nodes, lung right lower lobe bronchial swabs), bronchial washings, and surgical tissue biopsy of the right lower lobe revealed mold. The patient underwent right thoracotomy with right lower lobectomy and right mediastinal lymph node dissection for both diagnostic (lung specimen) and therapeutic (removing necrotic lung tissue, source control) purposes. Finally, serum Coccidioides antigens were positive and antibody titers were positive at 1:8; surgical biopsy of the right lower lobe grew mold that came back positive for Coccidioides posadasii. Targeted pharmacotherapy was commenced using intravenous fluconazole and then oral fluconazole for 3 months was prescribed upon discharge. The patient had gradual improvement of his shortness of breath and was instructed to follow-up at an infectious disease clinic.

What You See Is Not What You Get: Germ Cell Tumor Mimicking Disseminated Coccidioidomycosis.

We present the case of a 30-year-old man with no prior medical history who presented to the hospital with a myriad of symptoms such as shortness of breath, generalized weakness, lower limb weakness, and urinary retention. He was recently diagnosed with "disseminated coccidioidomycosis" by an outside provider on an outpatient basis and started on fluconazole orally. However, due to a lack of improvement and significant symptoms, he was sent to the hospital to initiate liposomal amphotericin B treatment. After a comprehensive workup, an alternative diagnosis was suspected and eventually confirmed as metastatic germ cell carcinoma. Due to the vast dissemination and his poor functional status despite chemotherapy initiation, the patient elected for palliative care and expired shortly after at hospice. This case demonstrates the similarity of clinical findings between disseminated infections and malignancies.

Disseminated Coccidioidomycosis With Fungemia and Possible Strongyloides Co-infection.

INTRODUCTION: Coccidioidomycosis is most often an asymptomatic or mild self-limited respiratory infection, but in rare cases it can become disseminated and cause severe disease. CASE PRESENTATION: A 29-year-old man who was originally from Thailand and had been living in Arizona for 2 years presented with intermittent fevers, fatigue, and other nonspecific symptoms, including abdominal pain, nonbloody diarrhea, and pruritic rash. Initial laboratory values showed significant peripheral eosinophilia. Extensive evaluation revealed possible Strongyloides species infection. Shortly after, Coccidioidies species fungemia was found. Fevers and symptoms resolved after adequate treatment. DISCUSSION: Disseminated coccidioidomycosis with fungemia is very rare in immunocompetent individuals. Co-infection with Stronglyloides species is only reported in two other case reports. CONCLUSIONS: We report this case to raise awareness of a rare infection. In adequate epidemiological circumstances, co-infections Coccidioides and Strongyloides species should be considered in presence of fever and eosinophilia.

Coccidioidomycosis lymphadenopathy: an unusual presentation.

Coccidioidomycosis is known to occur around the western hemisphere. In tropical countries, the clinical presentation is atypical presenting with a superficial abscess preceded by respiratory tract involvement often mimicking tuberculosis. Eliciting a history of exposure and high suspicion is imperative for early diagnosis.In the present case report, a man in his early 30s presented with complaints of swelling over the neck for the past 2 months with a recent travel history. With a provisional clinical diagnosis of tuberculosis, a biopsy of the swelling revealed features of granulomas with non-caseating necrosis with Coccidioidomycosis organisms demonstrated by fungal stains. Fungal culture and serology reiterated Coccidioides and he recovered after a course of fluconazole.The case report concludes with a statement that Coccidioidomycosis is known to manifest with lymphadenitis mimicking tuberculosis and must be taken into account as one of the differentials. The current report is presented for its rarity in India with atypical presentation.

Non-shunt Management of Communicating Hydrocephalus in an Immunocompetent Host With Disseminated Central Nervous System Coccidioidomycosis.

Disseminated coccidioidomycosis is associated with significant morbidity and mortality. Involvement of the meninges is often fatal if untreated, typically requiring lifelong antifungal therapy and neurosurgical intervention. We present the case of a young male without any known immunocompromising conditions who opted exclusively for medical management of newly diagnosed coccidioidomycosis meningitis with communicating hydrocephalus and discuss the controversy associated with this approach. This case highlights the importance of shared decision-making between patient and clinician, even if the plan diverges from available guidelines. Furthermore, we discuss clinical considerations in approaching the close outpatient monitoring of patients with central nervous system coccidioidomycosis with hydrocephalus.

Fatal septic shock due to disseminated coccidioidomycosis: a case series and review of the literature.

BACKGROUND: Coccidioidomycosis is a fungal infection endemic to the southwestern United States and regions of Latin America. Disseminated disease occurs in < 1% of cases. Septic shock is even rarer, with high mortality despite therapy. We describe two cases of coccidioidal septic shock. Both patients were older men of Filipino ancestry presenting with respiratory failure and vasopressor-dependent shock. Antifungal drugs were initiated after failure to improve with empiric antibiotics; in both, Coccidioides was isolated from respiratory cultures. Despite aggressive care, both patients ultimately died of their infections. We provide a review of the published literature on this topic. CONCLUSIONS: Most of the 33 reported cases of coccidioidal septic shock occurred in men (88%) of non-white race and ethnicity (78%). The overall mortality rate was 76%. All survivors received amphotericin B as part of their treatment. Coccidioidomycosis-related septic shock is a rare disease with poor outcomes; delays in diagnosis and treatment are common. Improved diagnostic testing for coccidioidomycosis could enhance recognition of this disease in the future. Although data are limited, early treatment with amphotericin B in cases of coccidioidal septic shock may reduce mortality.

Multicentric Case Series and Literature Review of Coccidioidal Otomastoiditis.

Coccidioidomycosis involving the ear, mastoid bone, or both is uncommon. We describe 5 new cases from the United States and review 4 cases reported in the literature of otomycosis and mastoiditis caused by Coccidioides. Of the 9 cases, 8 were linked to residence in or travel to California. Two patients had poorly controlled diabetes mellitus, 7 had otomastoiditis, 1 had otitis externa without mastoid involvement, and 1 had mastoiditis without otic involvement. Four patients had concurrent or prior pulmonary coccidioidomycosis. Ipsilateral facial nerve palsies developed in 2 patients. All patients received antifungal treatment for varying durations, and 8 of the 9 patients underwent surgical debridement. Clinicians should consider coccidioidomycosis as a differential diagnosis for otomastoiditis in patients with geographic risks.