Coccidioides Immitis in AIDS Patients

Galgiani, John N.; Ampel, Neil M.; Dols, C L; Fish, Douglas G.

doi:10.1007/978-1-4613-0655-9_17

Cited by 4 publications

(10 citation statements)

References 16 publications

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“…When spherules rupture, the endospores are released, and each is capable of developing into new spherules until the host's immune system (or medical intervention) represses the growth of the fungus. Though the primary route of infection is pulmonary, the organism can disseminate hematogenously to any organ (12)(13)(14).…”

Section: Mycology and Population Structurementioning

confidence: 99%

Recent Advances in Our Understanding of the Environmental, Epidemiological, Immunological, and Clinical Dimensions of Coccidioidomycosis

et al. 2013

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SUMMARY Coccidioidomycosis is the endemic mycosis caused by the fungal pathogens Coccidioides immitis and C. posadasii . This review is a summary of the recent advances that have been made in the understanding of this pathogen, including its mycology, genetics, and niche in the environment. Updates on the epidemiology of the organism emphasize that it is a continuing, significant problem in areas of endemicity. For a variety of reasons, the number of reported coccidioidal infections has increased dramatically over the past decade. While continual improvements in the fields of organ transplantation and management of autoimmune disorders and patients with HIV have led to dilemmas with concurrent infection with coccidioidomycosis, they have also led to advances in the understanding of the human immune response to infection. There have been some advances in therapeutics with the increased use of newer azoles. Lastly, there is an overview of the ongoing search for a preventative vaccine.

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Section: Mycology and Population Structurementioning

confidence: 99%

Recent Advances in Our Understanding of the Environmental, Epidemiological, Immunological, and Clinical Dimensions of Coccidioidomycosis

et al. 2013

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“…1). Endospores are released when the spherule ruptures, and each endospore can develop into a new spherule, and thus the infection progresses (6).…”

Section: Case Reportmentioning

confidence: 99%

Posttransplantation Disseminated Coccidioidomycosis Acquired from Donor Lungs

Miller

Hendren²,

Gilligan

2004

J Clin Microbiol

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A North Carolinian developed fatal coccidioidomycosis immediately after bilateral lung transplantation. The donor had previously traveled to Mexico, and the recipient had no travel history to an area where Coccidioides immitis is endemic. Immunosuppresive therapy of the transplant recipient likely reactivated latent Coccidioides infection in the donor lungs, leading to posttransplant coccidioidomycosis. CASE REPORTA 61-year-old North Carolina resident with chronic obstructive pulmonary disease and emphysema received a bilateral lung transplant. Subsequent immunosuppressive therapy included methylprednisone, azathioprine, and cyclosporine. During hospitalization, the patient also received cefuroxime, clindamycin, piperacillin-tazobactam, and acyclovir as prophylaxis, but no antifungal prophylaxis was initiated. Posttransplantation, the patient was poorly responsive and had complications, including coagulopathy, hypotension, and hypoxia, resulting in increased oxygen requirements. Laboratory findings were consistent with liver, pancreas, and kidney dysfunction, and the patient ultimately required hemodialysis. Chest X-ray images during the first postoperative week indicated bilateral diffuse pulmonary opacities consistent with edema or infection.At 2 weeks posttransplantation, cerebrospinal fluid (CSF) was obtained. CSF analysis showed Ͻ1 red blood cell/mm 3 and 1 total nucleated cell/mm 3 (22% lymphocytes, 63% monocytes, 15% other cells). The CSF contained 32 mg of protein/dl (normal, 15 to 45 mg/dl). A glucose level determination was not performed. The Gram stain showed no polymorphonuclear leukocytes and no organisms. The CSF culture was reported as no growth at 7 days, and peripheral blood cultures were negative after 5 days of incubation. Bronchial washings from the donor lungs at the time of transplantation grew oxacillin-susceptible Staphylococcus aureus. Stenotrophomonas maltophilia and coagulase-negative Staphylococcus spp. were recovered from subsequent washings. The patient's chest X-ray images showed persistent bilateral infiltrates and worsening alveolar consolidation.During the third week posttransplantation, chest X-ray images demonstrated extensive, progressive bilateral air space and interstitial opacities, as well as bilateral apical and lateral pleural thickening. In addition, a brain magnetic resonance image showed multiple areas of enhancement in the region of the gray-white matter junction thought to be consistent with a fungal infection. The patient had multiple line-drawn blood cultures positive with Candida parapsilosis. Further, a KOH preparation of the patient's bronchial washing showed budding yeast with pseudohyphae, and the Gram stain showed polymorphonuclear leukocytes and yeast. Interestingly, this culture not only grew Candida and S. maltophilia but also Coccidioides immitis. In less than 1 month postoperatively, the patient died, and an autopsy was performed.

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“…Thus, both itraconazole and fluconazole were effective at controlling CM, but neither eliminated Coccidioides from tissues. Overall, itraconazole was more efficacious on an mg/kg basis; at high doses they were similarly effective.Meningitis is the most severe form of coccidioidomycosis in humans and is associated with frequent relapses and high mortality (8,9,11,14,23,33,35,41,42). The traditional treatment for coccidioidal meningitis (CM) had been administration of amphotericin B directly into the cerebrospinal fluid (CSF) by the lumbar or cisternal route or into the ventricles or other sites through a reservoir (9, 24, 35).…”

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“…Itraconazole (ICZ) has also shown impressive activities in a small series of patients with refractory disease (37). However, to date no studies have compared FCZ and ICZ for the treatment of CM in humans, and this treatment would be difficult to study in humans because of the relative infrequency of the disease (11,23,33).We have established a murine model of CM by introducing arthroconidia intrathecally (22). This model differs from those reported previously (7,15,27) in the method of central nervous system (CNS) infection and the form of the organism used for infection.…”

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Comparison of Itraconazole and Fluconazole Treatments in a Murine Model of Coccidioidal Meningitis

Kamberi

Sobel

Clemons

et al. 2007

Antimicrob Agents Chemother

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Coccidioidal meningitis (CM) is a devastating disease that requires long-term therapy and for which there is little hope of a cure. A model was used to compare the efficacies of itraconazole and fluconazole. CD-1 mice were infected intrathecally with 30 to 36 viable arthroconidia of Coccidioides. Oral therapy with cyclodextrin (control) or itraconazole or fluconazole at 10, 25, or 50 mg/kg of body weight twice daily (BID) was given for 12 days, from day 3 of infection. Treatment with both antifungals at all doses prolonged survival compared with that of the control treatment (P < 0.01 to 0.0001). At 50 mg/kg, itraconazole and fluconazole were equivalent, whereas itraconazole at 10 or 25 mg/kg prolonged survival compared to that achieved with fluconazole at these dosages (P < 0.05 and 0.01, respectively). Early histologic analysis (10 days of treatment) with 50 mg/kg BID itraconazole or fluconazole showed suppression of CM in all five animals per group; in quantitative cultures, three of three animals from each group had no detectable infection in the brain, spinal cord, or a site of secondary infection, the lungs. In contrast, four of seven controls showed mild to severe meningitis, with arteritis detected in three animals. In a short-term organ clearance study, 5 days of treatment with 10 or 50 mg/kg BID itraconazole or fluconazole reduced the tissue burdens in the brain and spinal cord compared to the tissue burdens in the controls (P < 0.02 to 0.0003). Fluconazole at 10 mg/kg did not reduce the fungal burden in secondary sites, the lungs and kidneys, whereas this itraconazole dose was more effective in clearing the fungi from both organs (P < 0.05 and P < 0.001, respectively). At 50 mg/kg, itraconazole and fluconazole were equivalent in clearing the fungi from the brain and kidney, but itraconazole was superior to fluconazole in clearing the fungi from the spinal cord and lungs (P < 0.05). Thus, both itraconazole and fluconazole were effective at controlling CM, but neither eliminated Coccidioides from tissues. Overall, itraconazole was more efficacious on an mg/kg basis; at high doses they were similarly effective.Meningitis is the most severe form of coccidioidomycosis in humans and is associated with frequent relapses and high mortality (8,9,11,14,23,33,35,41,42). The traditional treatment for coccidioidal meningitis (CM) had been administration of amphotericin B directly into the cerebrospinal fluid (CSF) by the lumbar or cisternal route or into the ventricles or other sites through a reservoir (9, 24, 35). However, this therapy is poorly tolerated and is plagued by toxic side effects, and lifelong treatment is often required.Azoles have increasingly been used as alternative therapies for CM. Data on the efficacy of fluconazole (FCZ) in the treatment of CM have accumulated, and FCZ currently plays an integral role in the treatment (2,4,8,12,13,28,38). Itraconazole (ICZ) has also shown impressive activities in a small series of patients with refractory disease (37). However, to date no studies have compare...

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Coccidioides Immitis in AIDS Patients

Cited by 4 publications

References 16 publications

Recent Advances in Our Understanding of the Environmental, Epidemiological, Immunological, and Clinical Dimensions of Coccidioidomycosis

Recent Advances in Our Understanding of the Environmental, Epidemiological, Immunological, and Clinical Dimensions of Coccidioidomycosis

Posttransplantation Disseminated Coccidioidomycosis Acquired from Donor Lungs

Comparison of Itraconazole and Fluconazole Treatments in a Murine Model of Coccidioidal Meningitis

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