Aspergillus fumigatus Pneumonia in Neutropenic Patients Receiving Fluconazole for Infection Due to Candida Species: Is Amphotericin B Combined with Fluconazole the Appropriate Answer?

Pahls, Stephan; Schaffner, Andreas

doi:10.1093/clinids/18.3.484

Cited by 17 publications

(5 citation statements)

References 7 publications

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“…This work confirmed earlier findings [13] in which pretreatment with ketoconazole followed by amphotericin B antagonized amphotericin B's effects. Another study also showed that pretreatment with fluconazole antagonized amphotericin B's action but that the isolate regained susceptibility 1 h after the fluconazole was washed off [179].…”

Section: Sequential Therapymentioning

confidence: 86%

Combination and Sequential Antifungal Therapy for Invasive Aspergillosis: Review of Published In Vitro and In Vivo Interactions and 6281 Clinical Cases from 1966 to 2001

2003

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The development of newer antifungal drugs is creating new potential combination therapies to combat the dismal mortality rate associated with invasive aspergillosis (IA). The efficacy of combination therapy for IA has not been established; sparse data on combination or sequential antifungal therapy depict interactions ranging from synergy to antagonism. We reviewed data from all published in vitro studies, animal model studies, and clinical reports and recent abstracts on combination and sequential antifungal therapy for IA from 1966-2001. Among cases of IA during 1966-2001, 249 were treated with 23 different antifungal combinations. Amphotericin B plus 5-fluorocytosine was the most commonly used (49% of cases), followed by amphotericin B plus itraconazole (16%) or plus rifampin (11%). Combination therapy resulted in improvement in 63% of patients, generally with amphotericin B plus 5-fluorocytosine or rifampin and indifference with amphotericin B plus itraconazole. In 27 in vitro reports, we found synergy (in 36% of reports), additivity (in 24%), indifference (in 28%), and antagonism (in 11%). Amphotericin B plus 5-fluorocytosine and amphotericin B plus rifampin showed generally positive interactions and amphotericin B plus itraconazole showed results that were largely indifferent. Eighteen animal model reports demonstrated synergy (in 14% of reports), additivity (in 20%), indifference (in 51%), and antagonism (in 14%). In general, amphotericin B plus 5-fluorocytosine, amphotericin B plus rifampin, and amphotericin B plus itraconazole showed indifferent results, whereas amphotericin B plus micafungin showed positive interactions. Thirty-four cases treated during 1990-2001 with sequential therapy, excluding amphotericin B followed by itraconazole, showed improvement in 68% of cases. Improvement was noted with amphotericin B or itraconazole followed by voriconazole but not with itraconazole followed by amphotericin B.

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Section: Sequential Therapymentioning

confidence: 86%

Combination and Sequential Antifungal Therapy for Invasive Aspergillosis: Review of Published In Vitro and In Vivo Interactions and 6281 Clinical Cases from 1966 to 2001

2003

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“…At the beginning of iv amphotericin B, the study drug was stopped to avoid possible antagonism [13,20].…”

Section: Methodsmentioning

confidence: 99%

Effect of Prophylactic Fluconazole on the Frequency of Fungal Infections, Amphotericin B Use, and Health Care Costs in Patients Undergoing Intensive Chemotherapy for Hematologic Neoplasias

Schaffner

1995

Journal of Infectious Diseases

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108

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Fungal infections are a major problem in patients with hematologic malignancy. Attempts to reduce their frequency with antifungal agents have not been successful. A double-blind, controlled, single-center trial was conducted with 96 consecutive patients undergoing 154 episodes of chemotherapy. Patients received 400 mg of fluconazole or placebo until bone marrow recovery or initiation of intravenous amphotericin B infusions. End points were amphotericin B use, fungal infection, stable neutrophil count >0.5 X 10 9 /L, toxicity precluding further fluconazole use, and death. By KaplanMeier estimation, the time to initiation of amphotericin B therapy was shorter in 76 patients treated with placebo than in 75 treated with fluconazole (P = .003). Also, fluconazole reduced the number of febrile days by 20% (P = .002) and prevented oropharyngeal candidiasis (1/75 vs. 9/76, P = .018).The frequency of deep mycoses (8/76 vs. 8/75) and outcome were unaffected. Fluconazole did not have a favorable effect on infection-related health care costs and was associated with prolonged severe neutropenia (P = .01).

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“…Fluconazole, itraconazole and voriconazole have almost no antifungal activity against mucorales, while isavuconazole and posaconazole are potent against Mucorales and aspergillus ( Nett and Andes, 2016 ; Ellsworth and Ostrosky-Zeichner, 2020 ). Fluconazole has superior activity against cryptococcus and candida than other TADs, but without potency against aspergillus ( Pahls and Schaffner, 1994 ). Emergence of triazole-resistant fungal strains can make treatment of fungal disease problematic.…”

Section: Discussionmentioning

confidence: 99%

Pharmacovigilance of triazole antifungal agents: Analysis of the FDA adverse event reporting system (FAERS) database

Zhou

Wei

et al. 2022

Front. Pharmacol.

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Triazole antifungal drugs (TAD) are widely used to treat invasive fungal infections due to their broad antifungal spectrum and low toxicity. Despite their preference in the clinic, multiple Adverse Events (AE) are still reported each year. Objective: We aimed to characterize the distribution of Adverse Events associated with Triazole antifungal drugs in different systems and to identify Important Medical Events (IME) signals for Triazole antifungal drugs. Methods: The U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) was queried for Adverse Events related to Triazole antifungal drugs from 2012 to 2022. The Adverse Events caused by all other drugs and non-TAD antifungal drugs were analyzed as references. Reporting odds ratio and Bayesian confidence propagation neural network of information components were used to evaluate the association between Triazole antifungal drugs and Important Medical Events. Visual signal spectrum is mapped to identify potential adverse reaction signals. Results: Overall, 10,262 Adverse Events were reported to be associated with Triazole antifungal drugs, of which 5,563 cases were defined as Important Medical Events. Common adverse drug reactions (ADR) mentioned in the instructions such as delirium and hypokalemia were detected, as well as unlabeled ADRs such as rhabdomyolysis and hepatitis fulminant. Cholestasis, drug-induced liver injury, QT interval prolongation and renal impairment have notable signals in all Triazole antifungal drugs, with 50 percent of patients developing a severe clinical outcome. Isavuconazole had the lowest signal intensity and demonstrated a superior safety profile. Conclusion: Most results are generally consistent with previous studies and are documented in the prescribing instructions, but some IMEs are not included, such as hepatitis fulminant. Additional pharmaco-epidemiological or experimental studies are required to validate the small number of unlabeled ADRs. TAD-related Important Medical Eventshave a considerable potential to cause clinically serious outcomes. Clinical use of Triazole antifungal drugs requires more attention.

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Aspergillus fumigatus Pneumonia in Neutropenic Patients Receiving Fluconazole for Infection Due to Candida Species: Is Amphotericin B Combined with Fluconazole the Appropriate Answer?

Cited by 17 publications

References 7 publications

Combination and Sequential Antifungal Therapy for Invasive Aspergillosis: Review of Published In Vitro and In Vivo Interactions and 6281 Clinical Cases from 1966 to 2001

Combination and Sequential Antifungal Therapy for Invasive Aspergillosis: Review of Published In Vitro and In Vivo Interactions and 6281 Clinical Cases from 1966 to 2001

Effect of Prophylactic Fluconazole on the Frequency of Fungal Infections, Amphotericin B Use, and Health Care Costs in Patients Undergoing Intensive Chemotherapy for Hematologic Neoplasias

Pharmacovigilance of triazole antifungal agents: Analysis of the FDA adverse event reporting system (FAERS) database

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