deoxycholic-acid and Meningitis

This article summarizes the diagnosis and treatment of coccidioidal meningitis (CM) and its complications. An overview of current and prospective pharmacologic treatment options and monitoring parameters is provided. A consensus has not been reached regarding universally accepted therapeutic serum levels for azoles because of insufficient evidence. We describe the preferred therapeutic drug level ranges that our institution uses to monitor azole therapy.. Ho et al. described the preparation and administration of intrathecally delivered amphotericin B deoxycholate. Thompson et al. described possible benefits of controversial adjuvant corticosteroid therapy for secondary prevention of vasculitic infarction secondary to CM. CM was universally fatal until the advent of intrathecal amphotericin B deoxycholate therapy, the introduction of which changed the natural history of the disease in much the same way as penicillin changed the natural history of bacterial meningitis. Although there was still significant morbidity, survival rates drastically increased to approximately 70%. The introduction of azole therapy has decreased the side effects and burden of treatment but without a significant change in CM-related mortality and morbidity compared with the use of intrathecal amphotericin B deoxycholate therapy.

Topics: Amphotericin B; Antifungal Agents; Coccidioides; Coccidioidomycosis; Cognitive Dysfunction; Deoxycholic Acid; Disease Management; Drug Combinations; Humans; Hydrocephalus; Injections, Spinal; Meningitis; Prospective Studies; Treatment Outcome

Prior to the 1950s no effective therapy for coccidioidomycosis existed. The advent of amphotericin B ushered in the therapeutic era for coccidioidomycosis. Until this time amphotericin B and its lipid congeners have been regarded as the "gold standard" of therapy for severe pulmonary and disseminated coccidioidomycosis. The availability of azoles and later triazoles for the past three decades have relegated the amphotericins into a rescue mode, used mainly in widely disseminated cases, azole intolerance, or when there are contraindications to Azoles, such as pregnancy. In meningitis the intrathecal use of amphotericin B is still used frequently by some clinicians alone or with a triazole. The newer lipid preparations, while more expensive, have significantly reduced toxicity, particularly nephropathy.

Topics: Amphotericin B; Antifungal Agents; Coccidioides; Coccidioidomycosis; Deoxycholic Acid; Drug Combinations; Female; Humans; Kidney Diseases; Lipids; Meningitis; Pregnancy; Treatment Outcome; Triazoles

Cryptococcosis is a common opportunistic infection in patients infected by Human Immunodeficiency Virus (HIV) and is the second leading cause of mortality in Acquired Immunodeficiency Syndrome (AIDS) patients worldwide. The most frequent presentation of cryptococcal infection is subacute meningitis, especially in patients with a CD4+ T Lymphocytes count below 100 cells/μL. However, in severely immunosuppressed individuals Cryptococcus neoformans can infect virtually any human organ, including the bone marrow, which is a rare presentation of cryptococcosis.. A 45-year-old HIV-infected male patient with a CD4+ T lymphocyte count of 26 cells/μL who presented to the emergency department with fever and pancytopenia. Throughout the diagnostic evaluation, the bone marrow aspirate culture yielded encapsulated yeasts in budding, identified as Cryptococcus sp. The bone marrow biopsy revealed a hypocellularity for age and absence of fibrosis. It was observed presence of loosely formed granuloma composed of multinucleated giant cells encompassing rounded yeast like organisms stained with mucicarmine, compatible with Cryptococcus sp. Then, the patient underwent a lumbar puncture to investigate meningitis, although he had no neurological symptoms and neurological examination was normal. The cerebrospinal fluid culture yielded Cryptococcus sp. The species and genotype identification step showed the infection was caused by Cryptococcus neoformans var. grubii (genotype VNI). The patient was initially treated with amphotericin B deoxycholate plus fluconazole for disseminated cryptococcosis, according to guideline recommendations. However, the patient developed acute kidney injury and the treatment was switched for fluconazole monotherapy. The symptoms disappeared completely with recovery of white blood cells and platelets counts. Cerebrospinal fluid cultures for fungi at one and two-weeks of treatment were negative.. Bone marrow infection caused by Cryptococcus neoformans is a rare presentation of cryptococcosis. The cryptococcal infection should be included for differential diagnosis in HIV-infected patients with fever and cytopenias, especially when CD4+ T lymphocytes count is below 100 cells/μL.

Topics: Acute Kidney Injury; Amphotericin B; Antifungal Agents; Bone Marrow; CD4-Positive T-Lymphocytes; Cerebrospinal Fluid; Cryptococcosis; Cryptococcus neoformans; Deoxycholic Acid; Diagnosis, Differential; Drug Combinations; Fluconazole; Genotype; HIV Infections; Humans; Male; Meningitis; Middle Aged

Intrathecal amphotericin B deoxycholate (AmB-d) can be prescribed as an adjunct to systemic therapy for severe or recalcitrant cases coccidioidal meningitis. Recently intravenous (IV) Liposomal amphotericin B (L-AmB) has been recommended as monotherapy therapy for refractory coccidioidal meningitis based on its advantages over (AmB-d), however, its intrathecal use has not been reported. Moreover, there is nothing in the literature quantifying clinical improvement with objective laboratory data in human patients. Consequently, there are no guidelines on how to monitor regularly for improvement of coccidioidal meningitis with treatment of intrathecal L-AmB. The present case addresses both of these. We report intrathecal use of L-AmB for refractory coccidioidal meningitis. Our data demonstrate that there is a correlation between clinical improvement and a decrease in cerebrospinal fluid (CSF) white blood cells (WBC's), protein, and coccidioidal titers with treatment of intrathecal L-AmB with serial collection of CSF studies at the same site, in our case via collection through an external ventricular drain (EVD). As a result, one may postulate that serial CSF collection can be used to monitor the treatment of coccidioidal meningitis; however this case also addresses the risk of developing ventriculitis with sustained EVD placement.

Topics: Adult; Amphotericin B; Antifungal Agents; Coccidioidomycosis; Deoxycholic Acid; Drug Combinations; Humans; Injections, Spinal; Male; Meningitis

Topics: Amphotericin B; Antibodies, Fungal; Antifungal Agents; Brain Damage, Chronic; Brain Edema; Child; Delayed Diagnosis; Deoxycholic Acid; Diagnostic Errors; Drug Combinations; Histoplasma; Histoplasmosis; Humans; Hydrocephalus; Immunocompetence; Itraconazole; Liposomes; Male; Meningitis; Meningitis, Viral; Prognosis; Stroke, Lacunar; Tuberculosis, Meningeal; Ventriculoperitoneal Shunt