Treatment of Histoplasmosis With Fluconazole in Patients With Acquired Immunodeficiency Syndrome

Wheat, Joe; MaWhinney, Samantha; Hafner, Richard; McKinsey, David S.; Chen, Dafeng; Korzun, Ann H.; Shakan, Kenneth J.; Johnson, P. C.; Hamill, Richard J.; Bamberger, David M.; Pappas, Peter G.; Stansell, John; Koletar, Susan L.; Squires, Kathleen; Larsen, Robert A.; Cheung, Tony; Hyslop, Newton E.; Lai, Kwan Kew; Schneider, Debra; Kauffman, Carol A.; Saag, Michael S.; Dismukes, William E.; Powderly, William G.

doi:10.1016/s0002-9343(97)00151-4

Cited by 138 publications

(18 citation statements)

References 15 publications

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“…In humans, itraconazole is known to be more effective than fluconazole for the treatment of histoplasmosis, as 30.5% of patients on maintenance therapy with fluconazole relapsed vs <5% on itraconazole. 9 , 10 Reduced susceptibility to fluconazole has been documented during therapy, with one older study showing at least a four-fold increase in MIC in the isolates from more than half of patients with paired pretreatment and relapse/failure samples. 3 The mechanism of this increase in MIC is reduced inhibition of ergosterol synthesis due to be decreased sensitivity of cytochrome P450-dependent enzymes 14α-demethylase (CYP51p; encoded by ERG11 ) and 3-ketosteroid reductase to fluconazole.…”

Section: Discussionmentioning

confidence: 99%

Reduced susceptibility to fluconazole in a cat with histoplasmosis

Renschler¹,

Norsworthy²,

Rakian

et al. 2017

Journal of Feline Medicine and Surgery Open Reports

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Case summaryAn 11-year-old neutered male domestic longhair cat was diagnosed with histoplasmosis from fine-needle aspirates of an abdominal lymph node. Lymph node size initially decreased with fluconazole therapy (11.8 mg/kg PO q12h); however, after 13 months of continuous fluconazole therapy, lymphadenomegaly worsened and samples were collected for culture and antifungal susceptibility. The Histoplasma capsulatum isolate had a very high fluconazole minimum inhibitory concentration (MIC) of 64 µg/ml and an itraconazole MIC of 0.06 µg/ml. The owner declined a change to itraconazole and, ultimately, the cat developed neurologic signs and was euthanized. Owing to the initial response to fluconazole followed by treatment failure and high MIC value, acquired fluconazole resistance was suspected. Clinical breakpoints for fluconazole for the dimorphic fungi are not available to define true antifungal resistance.Relevance and novel informationThis is the first published report of reduced susceptibility to fluconazole in a cat being treated for histoplasmosis. Fluconazole failure and increases in MIC between pretreatment and long-term treatment isolates are known to occur in humans with histoplasmosis. Practitioners should be aware of this possibility when treating cats with fluconazole (particularly in cases with long-term [>1 year] fluconazole therapy or in cases with disease recrudescence).

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Section: Discussionmentioning

confidence: 99%

Reduced susceptibility to fluconazole in a cat with histoplasmosis

Renschler¹,

Norsworthy²,

Rakian

et al. 2017

Journal of Feline Medicine and Surgery Open Reports

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“…Fluconazole is less active than itraconazole against dimorphic fungi especially histoplasmosis, probably explaining the lack of clinical response until amphotericin B deoxycholate was commenced. 9 , 10 Currently there are no treatment guidelines for HIV-associated disseminated Emmonsia infection. Our regimen of amphotericin B deoxycholate followed by maintenance itraconazole therapy was extrapolated from treatment guidelines for other dimorphic fungal infections.…”

Section: Discussionmentioning

confidence: 99%

A case of emmonsiosis in an HIV-infected child

Lochan

Naicker

Maphanga

et al. 2015

South. Afr. j. HIV med.

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Opportunistic fungal infections can cause significant morbidity and mortality in immunocompromised patients. We describe a paediatric case of an unusual disseminated fungal infection. A three-year-old HIV-infected child with severe immunosuppression (CD4+ T-cell count 12 × 106/L) was admitted to hospital with pneumonia, gastroenteritis and herpes gingivostomatitis. Despite antibacterial and antiviral therapy, he experienced high fevers and developed an erythematous maculopapular rash and abdominal tenderness. The child's condition progressively worsened during the admission. A thermally dimorphic fungus was cultured from bone marrow and identified as an Emmonsia species on DNA sequencing. The patient made a good recovery on amphotericin B deoxycholate and antiretroviral therapy. Itraconazole was continued for a minimum of 12 months, allowing for immune reconstitution to occur. This case is the first documented description of disseminated disease caused by a novel Emmonsia species in an HIV-infected child in South Africa.

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“…For mild to moderate disease, the current recommendation places itraconazole above fluconazole. Itraconazole demonstrated an 85% response in 1 study whereas fluconazole showed a 74% response in a separate study [ 11 , 12 ]. In the absence of a head-to-head comparison, and considering the excellent pharmacokinetic properties of fluconazole, which eliminates the need for therapeutic drug monitoring, fluconazole arguably becomes a reasonable choice in resource-constrained settings.…”

Section: Discussionmentioning

confidence: 99%

Challenges in the Management of Disseminated Progressive Histoplasmosis in Human Immunodeficiency Virus-Infected Patients in Resource-Limited Settings

Murphy

Gounder

Manzini

et al. 2015

Open Forum Infectious Diseases

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The diagnosis of histoplasmosis in patients with human immunodeficiency virus in southern Africa is complicated by the nonspecific presentation of the disease in this patient group and the unavailability of sensitive diagnostics including antigen assays. Treatment options are also limited due to the unavailability of liposomal amphotericin and itraconazole, and the inability to perform therapeutic drug monitoring further confounds management. We present 3 clinical cases to illustrate the limits of diagnosis and management in the southern African context, and we highlight the need for additional diagnostic tools and treatment options in resource-limited settings.

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Treatment of Histoplasmosis With Fluconazole in Patients With Acquired Immunodeficiency Syndrome

Cited by 138 publications

References 15 publications

Reduced susceptibility to fluconazole in a cat with histoplasmosis

Reduced susceptibility to fluconazole in a cat with histoplasmosis

A case of emmonsiosis in an HIV-infected child

Challenges in the Management of Disseminated Progressive Histoplasmosis in Human Immunodeficiency Virus-Infected Patients in Resource-Limited Settings

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