Voriconazole: A New Triazole Antifungal Agent

2003 ◽  
Vol 37 (3) ◽  
pp. 420-432 ◽  
Author(s):  
Margaret M Pearson ◽  
P David Rogers ◽  
John D Cleary ◽  
Stanley W Chapman
Keyword(s):  
Amphotericin B ◽  
Antifungal Agent ◽  
Fungal Pathogens ◽  
Antimicrobial Agents ◽  
Case Reports ◽  
Empirical Therapy ◽  
Immunocompromised Patients ◽  
In Vitro Susceptibility ◽  
Medline Search

OBJECTIVE: To review the pharmacology, in vitro susceptibility, pharmacokinetics, clinical efficacy, and adverse effects of voriconazole, a triazole antifungal agent. DATA SOURCES: A MEDLINE search, restricted to English language, was conducted from 1990 to June 2002. Supplementary sources included program abstracts from the Interscience Conference on Antimicrobial Agents and Chemotherapy and the Infectious Diseases Society of America from 1996 to 2001 and manufacturer information available through the Food and Drug Administration's Web site. DATA EXTRACTION: All published and unpublished trials and abstracts citing voriconazole were selected. DATA SYNTHESIS: Voriconazole has shown in vitro activity against many yeasts and a variety of mold and dermatophyte isolates. Voriconazole can be administered either orally or parenterally. It exhibits good oral bioavailability, wide tissue distribution including distribution into the central nervous system, and hepatic metabolism. Drug interactions occur through inhibition of the CYP2C9, CYP2C19, and CYP3A4 isoenzymes, resulting in alterations in kinetic parameters of either voriconazole or the interacting agent. Efficacy has been illustrated in open, noncomparative studies of aspergillosis in immunocompromised patients. Human case reports describe successful treatment of rare fungal pathogens. The most commonly reported adverse events include visual disturbances and elevations in liver function tests. CONCLUSIONS: Voriconazole is at least as effective as amphotericin B in the treatment of acute invasive aspergillosis in immunocompromised patients. It has similar efficacy as fluconazole in treatment of esophageal candidiasis. Voriconazole did not achieve statistical non-inferiority to liposomal amphotericin B for empirical therapy in patients with neutropenia and persistent fever, diminishing enthusiasm for use in this indication until additional trials are completed. Based on case reports and in vitro efficacy, voriconazole may prove to be a clinically useful agent in the treatment of other fungal disease.

Update on Drug Interactions with Azole Antifungal Agents

1998 ◽  
Vol 32 (9) ◽  
pp. 915-928 ◽  
Author(s):  
Ben M Lomaestro ◽  
Michelle Ann Piatek
Keyword(s):  
Drug Interactions ◽  
Clinical Relevance ◽  
Antimicrobial Agents ◽  
Antifungal Agents ◽  
Fungal Infections ◽  
Case Reports ◽  
Improve Patient Care ◽  
Double Blind ◽  
Medline Search

OBJECTIVE: T o review and update the incidence, mechanism, and clinical relevance of drug interactions with itraconazole, ketoconazole, and fluconazole. DATA SOURCES: Literature was identified by MEDLINE search (from January 1990 to May 1997) using the name of each antifungal and the term “interaction” as MeSH headings. Abstracts were identified by literature citation and by review of Interscience Conference on Antimicrobial Agents and Chemotherapy from 1995 to 1996. STUDY SELECTION: Randomized, controlled, double-blind studies were emphasized; however, uncontrolled studies and case reports were also included. In vitro data were selected from literature review and citations. DATA EXTRACTION: Data were evaluated with respect to study design, clinical relevance, magnitude of interaction, and recommendations provided. DATA SYNTHESIS: The incidence of fungal infections and consequent azole antifungal usage continues to increase. By virtue of their antifungal mechanism (i.e., inhibition of cytochrome P450 fungal enzyme systems), azoles have been investigated and implicated in several drug interactions. The magnitude of interactions can vary from trivial to potentially fatal, and also vary with specific azole and interactant. CONCLUSIONS: The azole antifungal agents represent a commonly used class of agents with a broad range of potential interactions. Recent data have increased our understanding of drug-drug interactions with azoles. Pharmacists are in a unique position to identify these interactions and to intervene to decrease their morbidity and improve patient care.

scholarly journals Isolation of Candida africana in oral candidiasis: First report among cancer patients in Iran

2020 ◽  
Author(s):  
Ensieh Lotfali ◽  
Masoud Mardani ◽  
Sara Abolghasemi ◽  
David Darvishnia ◽  
Mohammad Mahdi Rabiei ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Amphotericin B ◽  
Oral Candidiasis ◽  
Antifungal Susceptibility ◽  
Empirical Therapy ◽  
Antifungal Prophylaxis ◽  
In Vitro Susceptibility ◽  
Molecular Tests ◽  
In Vitro Antifungal Susceptibility

Background and Purpose: Oropharyngeal candidiasis (OPC) is a fungal infection of the oral cavity caused by the members of C. albicans complex. Although C. africana, as a part of the complex, is considered to be mostly responsible for the development of vulvovaginal candidiasis, it may be associated with a wider clinical spectrum. Case report: This report described two cases diagnosed with oral candidiasis during the receipt of treatment for malignancies. Conventional and molecular tests were performed on the samples collected from the patients’ oral cavities. The test results revealed C. africana as the causative agent of oral candidiasis. Furthermore, in vitro antifungal susceptibility test indicated the full susceptibility of all C. africana isolates to caspofungin. However, the data were also suggestive of the resistance against fluconazole and amphotericin B. Caspofungin was used as the main antifungal agent for the treatment of oral candidiasis, resulting in the improvement of thrush in patients. The resistance of C. africana to fluconazole and amphotericin B suggests the necessity of performing in vitro susceptibility testing on the isolates for the selection of appropriate antifungal agents. Conclusion: As the findings indicated, the achievement of knowledge regarding C. africana as an emerging non-albicans Candida species and its antifungal susceptibility profile is crucial to select antifungal prophylaxis and empirical therapy for oral candidiasis in cancer patients undergoing chemotherapy.

scholarly journals Invasive Saprochaete Infections: An Emerging Threat to Immunocompromised Patients

Pathogens ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 922
Author(s):  
Said El Zein ◽  
Joya-Rita Hindy ◽  
Souha S. Kanj
Keyword(s):  
Fungal Pathogens ◽  
Case Reports ◽  
Antifungal Susceptibility ◽  
Case Series ◽  
Source Control ◽  
Immunocompromised Patients ◽  
Tissue Samples ◽  
Flight Mass Spectrometry ◽  
Life Threatening

Saprochaete clavata and Saprochaete capitata are emerging fungal pathogens that are responsible for life threatening infections in immunocompromised patients, particularly in the setting of profound neutropenia. They have been associated with multiple hospital outbreaks mainly in Europe. In this article, we present a comprehensive review of the epidemiology, clinical presentation, diagnosis, antifungal susceptibility and treatment of these organisms. The diagnosis of invasive Saprochaete disease is challenging and relies primarily on the isolation of the fungi from blood or tissue samples. Both species are frequently misidentified as they are identical macroscopically and microscopically. Internal transcribed spacer sequencing and matrix-assisted laser desorption ionization-time of flight mass spectrometry are useful tools for the differentiation of these fungi to a species level. Saprochaete spp. are intrinsically resistant to echinocandins and highly resistant to fluconazole. Current literature suggests the use of an amphotericin B formulation with or without flucytosine for the initial treatment of these infections. Treatment with extended spectrum azoles might be promising based on in vitro minimum inhibitory concentration values and results from case reports and case series. Source control and recovery of the immune system are crucial for successful therapy.

scholarly journals In Vitro Susceptibility of Mycoplasma hyosynoviae and M. hyorhinis to Antimicrobial Agents.

1996 ◽  
Vol 58 (11) ◽  
pp. 1107-1111 ◽  
Author(s):  
Hideki KOBAYASHI ◽  
Nejdet SONMEZ ◽  
Tetsuo MOROZUMI ◽  
Kenji MITANI ◽  
Nobuyoshi ITO ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
In Vitro Susceptibility ◽  
Mycoplasma Hyosynoviae

scholarly journals 1593. Antimicrobial Activity of Ceftazidime-Avibactam and Comparator Agents Against OXA-48 β-lactamase–Producing Enterobacterales Collected in International Medical Centers, Including the United States, in 2017–2018

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S793-S793
Author(s):  
Lynn-Yao Lin ◽  
Dmitri Debabov ◽  
William Chang
Keyword(s):  
Antimicrobial Agents ◽  
The United States ◽  
Resistance Mechanisms ◽  
Clinical Isolates ◽  
Surveillance Program ◽  
Multiple Resistance ◽  
In Vitro Susceptibility ◽  
Medical Centers ◽  
Custom Made

Abstract Background OXA-48 is a carbapenemase with low-level hydrolytic activity toward cephalosporins. This study evaluated in vitro activities of ceftazidime-avibactam (CAZ-AVI), meropenem (MEM), meropenem-vaborbactam (MVB), ceftolozane-tazobactam (C/T), and other antimicrobial agents against 113 OXA-48-producing Enterobacterales with multiple resistance mechanisms collected in a 2017–2018 global surveillance program. Methods Nonduplicate clinical isolates of 113 Enterobacterales were collected from medical centers in 25 countries in 2017–2018. In vitro susceptibility tests were performed by broth microdilution with a custom-made panel consisting of CAZ-AVI, ceftazidime (CAZ), MEM, MVB, C/T, colistin (COL), gentamicin (GEN), levofloxacin (LEV), and amikacin (AMK). Whole genome sequencing or quantitative PCR data were used to analyze resistance mechanisms, such as OXA-48, extended-spectrum β-lactamase (ESBL), original-spectrum β-lactamase (OSBL), and AmpC β-lactamase. Clinical and Laboratory Standards Institute breakpoints were applied for susceptibility interpretations. Results Of 113 OXA-48–producing clinical isolates, 20 carried OXA-48 alone. The remaining 93 isolates carried additional β-lactamases, including 63 with ESBL (CTX-M-15) + OSBL (SHV, TEM), 15 with AmpC (DHA, AAC, CMY) + ESBL (CTX-M-15), and 15 with OSBL (SHV, TEM). 99.1% (all but 1) of all isolates tested were susceptible to CAZ-AVI, whereas 71.7%, 17.7%, and 14.2% were susceptible to MVB, MEM, and C/T, respectively. Among isolates harboring multiple resistance mechanisms (OXA-48 + ESBL + OSBL; n=63), 98.4%, 69.8%, 11.1%, and 7.9% were susceptible to CAZ-AVI, MVB, MEM, and C/T, respectively. Among isolates carrying OXA-48 + AmpC + ESBL + OSBL (n=15), 100%, 66.7%, 13.3%, and 13.3% were susceptible to CAZ-AVI, MVB, MEM, and C/T, respectively (Table). Aminoglycosides (AMK and GEN) and other β-lactams (eg, CAZ) were 20%–90% active against these isolates. COL was the second most effective comparator, inhibiting 83.2% of these isolates. Table Conclusion CAZ-AVI was the most effective agent in this study compared with other antibiotics, including β-lactams, β-lactam–β-lactamase inhibitor combinations, aminoglycosides, and COL, against OXA-48-producing Enterobacterales carrying multiple β-lactamases. Disclosures Lynn-Yao Lin, MS, AbbVie (Employee) Dmitri Debabov, PhD, AbbVie (Employee) William Chang, BS, AbbVie (Employee)

Assessment of Laboratory Performance With Streptococcus pneumoniae Antimicrobial Susceptibility Testing in the United States

1999 ◽  
Vol 123 (4) ◽  
pp. 285-289 ◽  
Author(s):  
Gary V. Doern ◽  
Angela B. Brueggemann ◽  
Michael A. Pfaller ◽  
Ronald N. Jones
Keyword(s):  
United States ◽  
Streptococcus Pneumoniae ◽  
Antimicrobial Agents ◽  
Susceptibility Testing ◽  
Clinical Laboratory ◽  
The United States ◽  
National Committee ◽  
In Vitro Susceptibility ◽  
Susceptibility Tests

Abstract Objective.—To assess the performance of clinical microbiology laboratories in the United States when conducting in vitro susceptibility tests with Streptococcus pneumoniae. Methods.—The results of a nationwide College of American Pathologists Proficiency Survey test sample, in which susceptibility testing of an isolate of S pneumoniae was performed, were assessed with respect to precision and accuracy. Results.—Wide variability was noted among participating laboratories with both minimum inhibitory concentration procedures and disk diffusion susceptibility tests when both methods were applied to S pneumoniae. Despite this high degree of variation, categorical interpretive errors were uncommon. Numerous laboratories reported results for antimicrobial agents that are not recommended by the National Committee for Clinical Laboratory Standards for tests with S pneumoniae. Conclusions.—Current susceptibility testing practices with S pneumoniae in the United States indicate limited precision and a tendency for laboratories to test and report results obtained with antimicrobial agents of questionable therapeutic value against this organism. Continued efforts to standardize susceptibility testing of S pneumoniae in the United States are warranted. In addition, modifications of existing interpretive criteria may be necessary.

scholarly journals In Vitro Susceptibility of Neisseria gonorrhoeae to Nine Antimicrobial Agents

1969 ◽  
Vol 18 (1) ◽  
pp. 21-23 ◽  
Author(s):  
John E. Martin ◽  
Arzell Lester ◽  
Douglas S. Kellogg ◽  
James D. Thayer
Keyword(s):  
Neisseria Gonorrhoeae ◽  
Antimicrobial Agents ◽  
In Vitro Susceptibility
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