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.

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.

Cerebral vasospasm due to Fusarium solani meningitis: A complication from medical tourism. Case report and literature review.

OBJECTIVES: Medical tourism is expanding globally, with patients seeking cosmetic procedures abroad. To date, little information is known regarding the risks and outcomes of cosmetic tourism, especially potential stroke complications. Here, we present a case of fungal meningitis in the setting of medical tourism leading to ischemic strokes and vasospasm. MATERIAL AND METHODS: We describe an immunocompetent 29-year-old female patient who initially presented with intractable headaches and an abnormal cerebrospinal fluid (CSF) profile who was eventually diagnosed with Fusarium solani meningitis as a part of a common source outbreak in Matamoros, Mexico. These patients were part of a cohort who underwent cosmetic procedures requiring spinal anesthesia. This report also highlights the unusual clinical course leading to poor outcomes in such conditions. RESULTS: The patient initially presented with headaches, papilledema, elevated opening pressure on the spinal tap, abnormal CSF studies, and eventually developed ischemic strokes and hydrocephalus. CSF showed positive beta D-Glucan with repeated negative CSF fungal cultures. A cerebral angiogram revealed extensive basilar artery vasospasm that led to ischemic strokes. Continued clinical worsening and lack of response to antifungal treatment prompted further imaging that revealed significant non-obstructive hydrocephalus subsequently complicated by spontaneous intracranial hemorrhage. CSF PCR for Fusarium solani species was positive days after her passing. CONCLUSION: This novel case highlights fungal meningitis caused by Fusarium solani complicated by bilateral ischemic strokes stemming from basilar artery vasospasm. Complications from medical tourism impact not only individual patients but also the health systems of both countries. Professional and regulatory entities for cosmetic surgeries must highlight and educate patients on the risks and complications of cosmetic surgeries happening abroad. Physicians should be aware of ongoing outbreaks and possible complications of these procedures.

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.

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.

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.

Candida meningitis in an infant after abdominal surgery successfully treated with intrathecal and intravenous amphotericin B: A case report.

RATIONALE: Studies on Candida infections in the central nervous system, especially in infants and young children that did or did not have postoperative surgery, are rarely reported. Thus far, intrathecal (i.t.) amphotericin B (AmB) is not routinely recommended as a therapy for Candida meningitis. We report the first case of Candida meningitis in an infant who underwent abdominal surgery and was successfully treated with i.t. and intravenous (i.v.) AmB in the mainland of China. PATIENT CONCERNS: Candida meningitis was confirmed by culture and immunoserological tests in a 1-day-old girl after surgery. She was treated with fluconazole for 1 month, but the patient's symptoms showed no improvement. DIAGNOSES: After surgery, the infant started having recurrent attacks of fever, and laboratory tests of the cerebrospinal fluid (CSF) revealed antigens of Candida tropicalis. CSF tests revealed a high total protein level and a low glucose level. She was diagnosed with a secondary Candida meningitis. INTERVENTIONS: After azole therapy failure, intrathecal and intravenous AmB therapy were used as rescue therapies. OUTCOMES: After nearly 2 months of AmB treatment, all repeat CSF cultures were negative, the infant was deemed stable and was discharged home, and she continued taking voriconazole orally as an outpatient. LESSONS: The combination of i.t. and i.v. administration of AmB can provide a safe and effective alternative to managing this rare but severe disease.

Rhino-orbital-cerebral-mucormycosis in COVID-19: A systematic review.

Since the onset of COVID-19 pandemic, parallel opportunistic infections have also been emerging as another disease spectrum. Among all these opportunistic infection, mucormycosis has become a matter of concern with its rapid increase of cases with rapid spread as compared to pre-COVID-19 era. Cases have been reported in post-COVID-19-related immune suppression along with the presence of comorbidity which adds on the deadly outcome. There is no systematic review addressing the issue of COVID-19-associated mucormycosis. This is the first systematic review of published studies of mucormycosis associated with COVID-19. The aim was to analyze the real scenario of the disease statement including all the published studies from first November 2019 to 30th June to analyze the contemporary epidemiology, clinical manifestations, risk factor, prognosis, and treatment outcome of COVID-19 associated rhino-orbito-cerebral-mucormycosis. A comprehensive literature search was done in following databases, namely, PubMed, Google Scholar, Scopus, and EMBASE using keywords mucormycosis, rhino orbital cerebral mucormycosis, COVID-19, and SARS-CoV-2 (from November 01, 2019 to June 30, 2021). Our study shows that, while corticosteroids have proved to be lifesaving in severe to critical COVID-19 patients, its indiscriminate use has come with its price of rhino-orbito-cerebral mucormycosis epidemic, especially in India especially in patients with preexisting diabetes mellitus with higher mortality. Corticosteroid use should be monitored and all COVID-19 patients should be closely evaluated/monitored for sequelae of immunosuppression following treatment.

Isavuconazole for treatment of refractory coccidioidal meningitis with concomitant cerebrospinal fluid and plasma therapeutic drug monitoring.

Coccidioidal meningitis (CM) is a life-threatening infection with limited treatment options. Small series have reported success with isavuconazole; however, limited data exist on cerebrospinal fluid (CSF) penetration. Paired plasma and CSF isavuconazole concentrations were measured. Eleven CSF levels were tested, (7 ventricular, 4 lumbar) in three CM patients. Ventricular CSF levels were undetectable despite detectable plasma levels. All lumbar CSF levels were detectable (mean 1.00 µg/ml). Three pairs of lumbar CSF/plasma concentrations taken within 1 h of each other yielded a mean CSF/plasma ratio of 0.31. Isavuconazole was detectable in lumbar but not ventricular CSF in three patients treated for refractory CM. LAY SUMMARY: Isavuconazole is a triazole antifungal that has been used as salvage therapy in the treatment of coccidioidal meningitis (CM). Few data exist characterizing its concentration in the cerebrospinal fluid (CSF). We report tandem plasma and CSF concentrations of isavuconazole in three patients with CM.

Disseminated coccidioidomycosis in a patient with juvenile idiopathic arthritis receiving infliximab.

BACKGROUND: Coccidioides immitis is a dimorphic fungus endemic to the arid climates of the Southwest United States, Mexico and parts of Central and South America. Human infection occurs through inhalation of spores with less than half of exposures progressing to a symptomatic state that primarily consists of pulmonary manifestations. Disseminated coccidioidomycosis is exceedingly rare, occurring in fewer than 1 % of symptomatic infections. Through hematogenous spread, the fungus can infect most organ systems and may be fatal without systemic antifungal treatment. Individuals with impaired cell-mediated immunity either from primary immunodeficiency disorders or secondary to immunosuppression with medications such as tumor necrosis factor alpha (TNF-α) inhibitors have increased risk of disseminated coccidioidomycosis and previous cases of coccidioidomycosis have been reported with biologic therapy. CASE PRESENTATION: We present a case of disseminated coccidioidomycosis in a 16-year-old female with polyarticular juvenile idiopathic arthritis (JIA) being treated with prednisone, methotrexate, and infliximab. The patient presented with symptoms of meningeal irritation, bilateral choroidal lesions, and necrotizing peripheral pneumonia. Her infection was thought to be a reactivation of coccidioidomycosis given her history of resolved pneumonia that occurred after traveling to Arizona, New Mexico, and El Paso one year prior to presentation. Following diagnosis, she improved with discontinuation of her immunosuppressive medications and two weeks of intravenous amphotericin B and fluconazole with plans for lifetime treatment with fluconazole while immunosuppressed. Due to worsening arthritis, she will begin tofacitinib and continue close monitoring of chest x-rays and coccidioides antibody. CONCLUSIONS: Patients undergoing immunosuppressive therapy for rheumatological conditions are at increased risk of disseminated coccidioidomycosis and should be evaluated with high suspicion when presenting with atypical symptoms and history of travel to endemic regions.

First case report of fungal meningitis due to a polypore mushroom Irpex lacteus.

A 73-year-old Japanese man with a medical history of sarcoidosis was diagnosed with meningitis caused by an undetermined fungus. For further identification, the cerebrospinal fluid sample was analyzed for the rDNA internally transcribed spacer regions, and the fungus was identified as Irpex lacteus. I. lacteus is classified under phylum Basidiomycota and is a wood-rotting bracket mushroom. Although there is no standard treatment regimen for I. lacteus infections, amphotericin B was effective in this patient. Herein, we present, to our knowledge, the first reported case of fungal meningitis caused by I. lacteus, its treatment course, and review relevant published literature.

Isavuconazole as Salvage Therapy for Refractory Pediatric Coccidioidal Meningitis.

Coccidioidal meningitis remains difficult to treat. The newer triazole, isavuconazole, has demonstrated efficacy in invasive fungal disease with less side effects than other azoles. We describe a case of refractory pediatric coccidioidal meningitis with disease stabilization and improvement on isavuconazole after failing treatment with other antifungal agents.

Case Report: Chronic Fungal Meningitis Masquerading as Tubercular Meningitis.

Phaeohyphomycosis causes a wide spectrum of systemic manifestations and can affect even the immunocompetent hosts. Involvement of the central nervous system is rare. A 48-year-old farmer presented with chronic headache, fever, and impaired vision and hearing. Serial MRIs of the brain showed enhancing exudates in the basal cisterns, and lesions in the sella and perichiasmatic and cerebellopontine angle regions along with enhancement of the cranial nerves and leptomeninges. Cerebrospinal fluid (CSF) showed lymphocytic pleocytosis with elevated protein and decreased glucose on multiple occasions. Clinical, imaging, and CSF abnormalities persisted despite treatment with antitubercular drugs and steroids for 2 years. Biopsy of the dura mater at the cervicomedullary junction revealed necrotizing granulomatous lesions, neutrophilic abscesses, and giant cells containing slender, pauci-septate, pigmented fungal hyphae. Fungal culture showed growth of Fonsecaea pedrosoi, which is classically known to cause brain abscesses. Here, we report the diagnostic odyssey in a patient with chronic meningitis from a region endemic for tuberculosis and describe the challenges in establishing the accurate diagnosis. Lack of therapeutic response to an adequate trial of empirical antitubercular therapy warrants search for alternative causes, including fungal meningitis. We highlight the uncommon manifestation of F. pedrosoi with chronic meningitis as well as the protracted clinical course despite not receiving antifungal therapy.

Aspergillus fumigatus meningitis in an immunocompetent young woman.

Aspergillus meningitis is a rare clinical entity that is much more frequently observed among immunocompetent patients. Here we present the case of a 28 year old immunocompetent lady with Aspergillus fumigatus meningitis possibly following spinal anaesthesia for her caesarean section. The diagnosis of Aspergillus meningitis is very difficult and challenging. Even after diagnosis, clinical outcomes remain poor with treatment. We wish to highlight the need for high index of suspicion for Fungal meningitis in patients presenting with meningism after Neurosurgeries and procedures involving invasion into the CSF compartment.

Antifungal drugs: An updated review of central nervous system pharmacokinetics.

Invasive fungal infections (IFIs) in the central nervous system (CNS) are particularly hard to treat and are associated with high morbidity and mortality rates. Four chemical classes of systemic antifungal agents are used for the treatment of IFIs (eg meningitis), including polyenes, triazoles, pyrimidine analogues and echinocandins. This review will address all of these classes and discuss their penetration and accumulation in the CNS. Treatment of fungal meningitis is based on the antifungal that shows good penetration and accumulation in the CNS. Pharmacokinetic data concerning the entry of antifungal agents into the intracranial compartments are faulty. This review will provide an overview of the ability of systemic antifungals to penetrate the CNS, based on previously published drug physicochemical properties and pharmacokinetic data, for evaluation of the most promising antifungal drugs for the treatment of fungal CNS infections. The studies selected and discussed in this review are from 1990 to 2019.

Sporotrichosis in renal transplant patients: two case reports and a review of the literature.

INTRODUCTION: Sporotrichosis is a rare fungal infection in transplant patients; among these patients, it occurs mostly in renal transplant patients. Sporothrix schenkii is the primary pathogen responsible. A high index of suspicion is required to make the diagnosis keeping important differential diagnoses in mind. History of trauma through recreational or occupational exposure to the fungus may assist in making the diagnosis. Treatment is difficult, with long-term use of potentially nephrotoxic and cytochrome P450 inhibitor antifungal agents leading to potential calcineurin inhibitors toxicity. We describe two renal transplant patients presenting with distinct sporotrichosis infection: "Case 2" being only the second reported case ever of meningeal sporotrichosis. We subsequently review the general aspects of sporotrichosis, specifically in renal transplant patients as described in the medical literature. CASE PRESENTATION: Case 1, a 43-year-old mixed ancestry male patient presented with a non-healing ulcer on the left arm for 1 year, he was diagnosed with cutaneous sporotrichosis and was successfully treated with itraconazole monotherapy. Case 2, a 56-year-old mixed ancestry male patient presented with a slow decline in functions, confusion, inappropriate behavior, rigors and significant loss of weight and appetite over the past 4 months, he was diagnosed with meningeal sporotrichosis and was successfully treated with a combination of deoxycholate amphotericin B and itraconazole. CONCLUSION: Physicians taking care of renal transplant patients should have a high index of suspicion for sporotrichosis infection particularly when conventional therapy for common conditions fails. Susceptibility testing is recommended to identify the most effective antifungal agent and its dose. The slow nature of growth of Sporothrix schenkii necessitates patients to be on amphotericin B until the time results are available. Finally, there is a need to be aware of potential drug-drug interactions of the azoles with calcineurin inhibitors and the required dose adjustments to prevent therapy related adverse events.

Coccidioidal meningitis in non-AIDS patients. A case series at a Mexican neurological referral center.

BACKGROUND: Coccidioidal meningitis is a life-threatening condition and a diagnostic challenge in cases of chronic meningitis. It is associated to severe complications, like basal arachnoiditis, hydrocephalus, and secondary vasculitis. OBJECTIVE: To present a 20-year retrospective clinical series of coccidioidal meningitis cases at a Mexican neurological referral center. RESULTS: The clinical records of 11 patients, predominantly males, were retrieved. Weight loss and night sweats were observed in 64 % of cases. Neurological signs included intracranial hypertension in 91 % of cases, altered alertness and meningeal syndrome in 72 %, and neuropsychiatric symptoms in 64 %. Mean CSF glucose levels were 30 ± 25 mg/dL, and pleocytosis ranged from 0 to 2218 cells/mm3. The diagnosis was confirmed by coccidioidal antigen latex agglutination in 91 % of cases. Radiological findings were hepatomegaly in 55 % of cases and pneumonia in 45 %. Neuroimaging findings included leptomeningitis in 73 % of cases, pachymeningitis in 45 %, and vascular involvement in 91 %. Less common findings included spinal cord lesion and mycotic aneurism, found in 18 % of cases. A molecular coccidioidal DNA test confirmed the predominance of Coccidioides immitis, detected in 64 % of cases. With respect to the clinical outcome, 46 % of patients died. The survivors suffered from sequels like chronic headache, cognitive alterations, and depression. CONCLUSIONS: Coccidioidal meningitis is an entity with high mortality rates. More than one half of patients suffered disseminated disease. Although meningeal signs are not frequent in chronic meningitis, more than two-thirds of our patients showed mild nuchal rigidity. In addition, cerebral and cerebellar volume loss, associated with cognitive impairment and depression, was often observed in surviving patients during the clinical-radiological follow-up.

Aspergillus meningitis in a patient with chronic lymphocytic leukemia.

Central nervous system aspergillosis is relatively rare and difficult to diagnose. Here, we report a case of 90-year-old man with chronic lymphocytic leukemia who presented with a month-long gradually worsening headache followed by 3 days of low-grade fever associated with altered mental status. Aspergillus meningitis diagnosed using Aspergillus galactomannan antigen in the cerebrospinal fluid and treated with voriconazole. Delayed diagnosis and treatment of Aspergillus meningitis is typically associated with high mortality; therefore, it is imperative to include this disease in the differential diagnoses of subacute meningitis.

A case report of Coccidioides posadasii meningoencephalitis in an immunocompetent host.

BACKGROUND: Coccidioides spp. are dimorphic fungi endemic to Central America, regions of South America and southwestern USA. Two species cause most human disease: Coccidioides immitis (primarily California isolates) and Coccidioides posadasii. Coccidioidomycosis is typically acquired through inhalation of soil or dust containing spores. Coccidioidal meningitis (CM), most common in the immunocompromised host, can also affect immunocompetent hosts. CASE PRESENTATION: We report a case of C. posadasii meningoencephalitis in a previously healthy 42-year-old Caucasian male who returned to Canada after spending time working in New Mexico. He presented with a 3-week history of headache, malaise and low-grade fevers. He developed progressive confusion and decreasing level of consciousness following hospitalization. Evidence of hydrocephalus and leptomeningeal enhancement was demonstrated on magnetic resonance imaging (MRI) of his brain. Serologic and PCR testing of the patient's CSF confirmed Coccidioides posadasii. Despite appropriate antifungal therapy he continues to have significant short-term memory deficits and has not returned to his full baseline functional status. CONCLUSIONS: Travel to endemic regions can result in disease secondary to Coccidioides spp. and requires physicians in non-endemic areas to have a high index of suspicion. Effective therapeutic options have reduced the mortality rate of CM, however, it is still associated with significant morbidity and requires life-long therapy.