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Ma Y, Liu Y, Liu X, Li M, Cui J, Guan Z, Pei J, Gao Y. Fluoride exposure and prevalence of osteochondroma in drinking water Endemic fluorosis areas of Heilongjiang Province, China: a cross-sectional study. INTERNATIONAL JOURNAL OF ENVIRONMENTAL HEALTH RESEARCH 2024; 34:2863-2876. [PMID: 37921081 DOI: 10.1080/09603123.2023.2277336] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/13/2023] [Accepted: 10/26/2023] [Indexed: 11/04/2023]
Abstract
To investigate the relationship between fluoride exposure and Osteochondroma (OC) prevalence, a cross-sectional study was conducted in drinking water endemic fluorosis areas of Heilongjiang Province, China. Our study first reported that the prevalence of OC was 2.3% in drinking water endemic fluorosis areas of Heilongjiang Province, China, and no difference in gender. Logistic regression analysis found that compared to 1st quartile participants, the prevalence of OC was 73% lower in the 2nd quartile participants of WF (Water fluoride), and 3.4 times higher among the 2nd quartile UF (Urinary fluoride) participants. Our study suggests that 0.259-0.420 mg/L of WF may be considered an appropriate level for reducing OC prevalence, while UF (≥0.750 mg/L) could slightly increase the prevalence of OC. In summary, the link between fluoride and OC prevalence is complicated and needs to be further investigated in a cohort population.
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Affiliation(s)
- Yongzheng Ma
- Key Laboratory of Etiology and Epidemiology, National Health Commission & Education Bureau of Heilongjiang Province (23618504), Harbin Medical University, Harbin, Heilongjiang Province, China
- Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Harbin Medical University, Harbin, Heilongjiang Province, China
- Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang Province, China
| | - Yang Liu
- Key Laboratory of Etiology and Epidemiology, National Health Commission & Education Bureau of Heilongjiang Province (23618504), Harbin Medical University, Harbin, Heilongjiang Province, China
- Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Harbin Medical University, Harbin, Heilongjiang Province, China
- Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang Province, China
| | - Xiaona Liu
- Key Laboratory of Etiology and Epidemiology, National Health Commission & Education Bureau of Heilongjiang Province (23618504), Harbin Medical University, Harbin, Heilongjiang Province, China
- Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Harbin Medical University, Harbin, Heilongjiang Province, China
- Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang Province, China
| | - Mang Li
- Key Laboratory of Etiology and Epidemiology, National Health Commission & Education Bureau of Heilongjiang Province (23618504), Harbin Medical University, Harbin, Heilongjiang Province, China
- Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Harbin Medical University, Harbin, Heilongjiang Province, China
- Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang Province, China
| | - Jing Cui
- Key Laboratory of Etiology and Epidemiology, National Health Commission & Education Bureau of Heilongjiang Province (23618504), Harbin Medical University, Harbin, Heilongjiang Province, China
- Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Harbin Medical University, Harbin, Heilongjiang Province, China
- Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang Province, China
| | - Zhizhong Guan
- Department of Pathology and Key Lab of Endemic and Ethnic Diseases, Ministry of Education, Guizhou Medical University, Guiyang, Guizhou Province, China
| | - Junrui Pei
- Key Laboratory of Etiology and Epidemiology, National Health Commission & Education Bureau of Heilongjiang Province (23618504), Harbin Medical University, Harbin, Heilongjiang Province, China
- Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Harbin Medical University, Harbin, Heilongjiang Province, China
- Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang Province, China
| | - Yanhui Gao
- Key Laboratory of Etiology and Epidemiology, National Health Commission & Education Bureau of Heilongjiang Province (23618504), Harbin Medical University, Harbin, Heilongjiang Province, China
- Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Harbin Medical University, Harbin, Heilongjiang Province, China
- Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang Province, China
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Jang HM, Kwon H, Choi Y, Kim SH. Bilateral leg pain and swelling with abnormal imaging findings in a patient with voriconazole. Korean J Intern Med 2024; 39:695-696. [PMID: 38798044 PMCID: PMC11236805 DOI: 10.3904/kjim.2024.070] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2024] [Revised: 03/08/2024] [Accepted: 03/11/2024] [Indexed: 05/29/2024] Open
Affiliation(s)
- Hyeon Mu Jang
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Hyeonwoo Kwon
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Yunsuk Choi
- Department of Hematology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sung-Han Kim
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Hoenigl M, Arastehfar A, Arendrup MC, Brüggemann R, Carvalho A, Chiller T, Chen S, Egger M, Feys S, Gangneux JP, Gold JAW, Groll AH, Heylen J, Jenks JD, Krause R, Lagrou K, Lamoth F, Prattes J, Sedik S, Wauters J, Wiederhold NP, Thompson GR. Novel antifungals and treatment approaches to tackle resistance and improve outcomes of invasive fungal disease. Clin Microbiol Rev 2024; 37:e0007423. [PMID: 38602408 PMCID: PMC11237431 DOI: 10.1128/cmr.00074-23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/12/2024] Open
Abstract
SUMMARYFungal infections are on the rise, driven by a growing population at risk and climate change. Currently available antifungals include only five classes, and their utility and efficacy in antifungal treatment are limited by one or more of innate or acquired resistance in some fungi, poor penetration into "sequestered" sites, and agent-specific side effect which require frequent patient reassessment and monitoring. Agents with novel mechanisms, favorable pharmacokinetic (PK) profiles including good oral bioavailability, and fungicidal mechanism(s) are urgently needed. Here, we provide a comprehensive review of novel antifungal agents, with both improved known mechanisms of actions and new antifungal classes, currently in clinical development for treating invasive yeast, mold (filamentous fungi), Pneumocystis jirovecii infections, and dimorphic fungi (endemic mycoses). We further focus on inhaled antifungals and the role of immunotherapy in tackling fungal infections, and the specific PK/pharmacodynamic profiles, tissue distributions as well as drug-drug interactions of novel antifungals. Finally, we review antifungal resistance mechanisms, the role of use of antifungal pesticides in agriculture as drivers of drug resistance, and detail detection methods for antifungal resistance.
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Affiliation(s)
- Martin Hoenigl
- Department of Internal Medicine, Division of Infectious Diseases, ECMM Excellence Center for Medical Mycology, Medical University of Graz, Graz, Austria
- BiotechMed-Graz, Graz, Austria
| | - Amir Arastehfar
- Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, USA
- Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA
| | - Maiken Cavling Arendrup
- Unit of Mycology, Statens Serum Institut, Copenhagen, Denmark
- Department of Clinical Microbiology, Rigshospitalet, Copenhagen, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Roger Brüggemann
- Department of Pharmacy and Radboudumc Institute for Medical Innovation, Radboud University Medical Center, Nijmegen, The Netherlands
- Radboudumc-CWZ Center of Expertise in Mycology, Nijmegen, The Netherlands
| | - Agostinho Carvalho
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal
- ICVS/3B’s - PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - Tom Chiller
- Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Sharon Chen
- Centre for Infectious Diseases and Microbiology Laboratory Services, Institute of Clinical Pathology and Medical Research, NSW South Wales Health Pathology, Westmead Hospital, Westmead, Australia
- The University of Sydney, Sydney, Australia
| | - Matthias Egger
- Department of Internal Medicine, Division of Infectious Diseases, ECMM Excellence Center for Medical Mycology, Medical University of Graz, Graz, Austria
| | - Simon Feys
- Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
- Medical Intensive Care Unit, University Hospitals Leuven, Leuven, Belgium
| | - Jean-Pierre Gangneux
- Centre National de Référence des Mycoses et Antifongiques LA-AspC Aspergilloses chroniques, European Excellence Center for Medical Mycology (ECMM EC), Centre hospitalier Universitaire de Rennes, Rennes, France
- Univ Rennes, CHU Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) UMR_S 1085, Rennes, France
| | - Jeremy A. W. Gold
- Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Andreas H. Groll
- Department of Pediatric Hematology/Oncology and Infectious Disease Research Program, Center for Bone Marrow Transplantation, University Children’s Hospital, Muenster, Germany
| | - Jannes Heylen
- Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
- Medical Intensive Care Unit, University Hospitals Leuven, Leuven, Belgium
| | - Jeffrey D. Jenks
- Department of Public Health, Durham County, Durham, North Carolina, USA
- Department of Medicine, Division of Infectious Diseases, Duke University, Durham, North Carolina, USA
| | - Robert Krause
- Department of Internal Medicine, Division of Infectious Diseases, ECMM Excellence Center for Medical Mycology, Medical University of Graz, Graz, Austria
- BiotechMed-Graz, Graz, Austria
| | - Katrien Lagrou
- Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
- Department of Laboratory Medicine and National Reference Center for Mycosis, University Hospitals Leuven, Leuven, Belgium
| | - Frédéric Lamoth
- Department of Laboratory Medicine and Pathology, Institute of Microbiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
- Department of Medicine, Infectious Diseases Service, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Juergen Prattes
- Department of Internal Medicine, Division of Infectious Diseases, ECMM Excellence Center for Medical Mycology, Medical University of Graz, Graz, Austria
- BiotechMed-Graz, Graz, Austria
| | - Sarah Sedik
- Department of Internal Medicine, Division of Infectious Diseases, ECMM Excellence Center for Medical Mycology, Medical University of Graz, Graz, Austria
| | - Joost Wauters
- Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
- Medical Intensive Care Unit, University Hospitals Leuven, Leuven, Belgium
| | - Nathan P. Wiederhold
- Department of Pathology and Laboratory Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA
| | - George R. Thompson
- Department of Internal Medicine, Division of Infectious Diseases University of California-Davis Medical Center, Sacramento, California, USA
- Department of Medical Microbiology and Immunology, University of California-Davis, Davis, California, USA
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Spec A, Thompson GR, Miceli MH, Hayes J, Proia L, McKinsey D, Arauz AB, Mullane K, Young JA, McGwin G, McMullen R, Plumley T, Moore MK, McDowell LA, Jones C, Pappas PG. MSG-15: Super-Bioavailability Itraconazole Versus Conventional Itraconazole in the Treatment of Endemic Mycoses-A Multicenter, Open-Label, Randomized Comparative Trial. Open Forum Infect Dis 2024; 11:ofae010. [PMID: 38440302 PMCID: PMC10911225 DOI: 10.1093/ofid/ofae010] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Accepted: 01/08/2024] [Indexed: 03/06/2024] Open
Abstract
Background Invasive fungal disease caused by dimorphic fungi is associated with significant morbidity and mortality. Super-bioavailability itraconazole (SUBA-itra) is a novel antifungal agent with pharmacokinetic advantages over currently available formulations. In this prospective comparative study, we report the outcomes of patients with endemic fungal infections (histoplasmosis, blastomycosis, coccidioidomycosis, and sporotrichosis). Methods This open-label randomized trial evaluated the efficacy, safety, and pharmacokinetics SUBA-itra compared with conventional itraconazole (c-itra) treatment for endemic fungal infections. An independent data review committee determined responses on treatment days 42 and 180. Results Eighty-eight patients were enrolled for IFD (SUBA-itra, n = 42; c-itra, n = 46) caused by Histoplasma (n = 51), Blastomyces (n = 18), Coccidioides (n = 13), or Sporothrix (n = 6). On day 42, clinical success was observed with SUBA-itra and c-itra on day 42 (in 69% and 67%, respectively, and on day 180 (in 60% and 65%). Patients treated with SUBA-itra exhibited less drug-level variability at days 7 (P = .03) and 14 (P = .06) of randomized treatment. The concentrations of itraconazole and hydroxyitraconazole were comparable between the 2 medications (P = .77 and P = .80, respectively). There was a trend for fewer adverse events (AEs; 74% vs 87%, respectively; P = .18) and serious AEs (10% vs 26%; P = .06) in the SUBA-itra-treated patients than in those receiving c-itra. Serious treatment-emergent AEs were less common in SUBA-itra-treated patients (12% vs 50%, respectively; P < .001). Conclusions SUBA-itra was bioequivalent, well tolerated, and efficacious in treating endemic fungi, with a more favorable safety profile than c-itra. Clinical Trials Registration NCT03572049.
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Affiliation(s)
- Andrej Spec
- Division of Infectious Disease, Washington University in St Louis School of Medicine, St Louis, Missouri, USA
| | - George R Thompson
- Department of Internal Medicine, Division of Infectious Diseases and Department of Medical Microbiology and Immunology, University of California Davis Medical Center, Sacramento, California, USA
| | - Marisa H Miceli
- Department of Internal Medicine, Division of Infectious Disease, University of Michigan, Ann Arbor, Michigan, USA
| | - Justin Hayes
- Division of Infectious Diseases, University of Arizona College of Medicine, Tucson, Arizona, USA
| | - Laurie Proia
- Department of Medicine, Rochester Regional Health, Rochester, New York, USA
| | - David McKinsey
- Metro Infectious Disease Consultants, Kansas City, Missouri, USA
| | - Ana Belen Arauz
- Department of Medicine, University of Panama and Hospital Santo Tomas, Panama City, Panama
| | - Kathleen Mullane
- Department of Medicine/Section of Infectious Diseases and Global Health, University of Chicago, Chicago, Illinois, USA
| | - Jo-Ann Young
- Department of Medicine, Division of Infectious Disease and International Medicine, Program in Adult Transplant Infectious Disease, University of Minnesota, Minneapolis, Minnesota, USA
| | - Gerald McGwin
- Department of Internal Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Rachel McMullen
- Department of Internal Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, Alabama, USA
- Mycoses Study Group Education and Research Consortium, Birmingham, Alabama, USA
| | - Tyler Plumley
- Department of Internal Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Mary K Moore
- Department of Internal Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | | | - Carolynn Jones
- College of Nursing, The Ohio State University College of Nursing, Columbus, Ohio, USA
- Mycoses Study Group Education and Research Consortium, Birmingham, Alabama, USA
| | - Peter G Pappas
- Department of Internal Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, Alabama, USA
- Mycoses Study Group Education and Research Consortium, Birmingham, Alabama, USA
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Nguyen QP, Wooten D. Voriconazole-induced periostitis in a patient with HIV treated for coccidioidomycosis meningitis. BMJ Case Rep 2024; 17:e257884. [PMID: 38272516 PMCID: PMC10826494 DOI: 10.1136/bcr-2023-257884] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2024] Open
Abstract
Voriconazole-induced periostitis is a rare adverse effect in patients on long-term therapy, characterised by periosteal inflammation and associated bony pain. The accompanying lab abnormalities (elevated serum alkaline phosphatase and fluoride) and characteristic imaging findings (uptake of radionuclide tracer on nuclear bone scan) are critical for diagnosis. The disease process is thought to be secondary to excess fluoride from voriconazole which stimulates bone formation and decreases osteoclast bone resorption. Management includes stopping voriconazole and switching to another agent.
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Affiliation(s)
- Quynh P Nguyen
- School of Medicine, University of California San Diego, La Jolla, California, USA
| | - Darcy Wooten
- Division of Infectious Diseases and Global Public Health, University of California San Diego, La Jolla, California, USA
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Abstract
PURPOSE OF REVIEW The endemic fungi are a significant cause of morbidity and mortality in effected patients. The range of endemicity for these are expanding with infections observed outside of traditional locations. Enhanced diagnostic and treatment practices may significantly alter patient outcomes. RECENT FINDINGS Recently completed clinical trials have focused on an assessment of improving efficacy while minimizing patient toxicity. Practice changing trials have been completed in histoplasmosis showing the utility of a single up-front liposomal amphotericin B dose followed by standard itraconazole dosing. The recent evaluation of several antifungal options including isauvconazole in the treatment of coccidioidomycosis also show promise for additional therapeutic agents. A recently conducted trial has also shown the superiority of amphotericin B therapy over itraconazole in the treatment of talaromycosis. SUMMARY The increased range of endemic mycoses coupled with the growing immunocompromised patient population mandates continued investigation of improved diagnostic and therapeutic options. Advances in these areas have led to more rapid diagnosis and more efficacious antifungal therapy.
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Affiliation(s)
- Nathan C Bahr
- Division of Infectious Diseases, Department of Medicine, University of Kansas Medical Center, Kansas City, Kansas
| | - George R Thompson
- Division of Infectious Diseases, Department of Internal Medicine, University of California Davis Medical Center, Sacramento
- Department of Medical Microbiology and Immunology, University of California Davis, Davis, California, USA
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Heidari A, Sharma R, Shakir Q, Shah M, Clement J, Donnelley MA, Reynolds T, Trigg K, Jolliff J, Kuran R, Johnson R, Thompson GR. Isavuconazole in the Treatment of Chronic Forms of Coccidioidomycosis. Clin Infect Dis 2023; 76:2196-2199. [PMID: 36905151 PMCID: PMC10893960 DOI: 10.1093/cid/ciad146] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2022] [Revised: 02/16/2023] [Accepted: 03/09/2023] [Indexed: 03/12/2023] Open
Abstract
Coccidioidomycosis is a fungal infection with a range of clinical manifestations. Currently used antifungal agents exhibit variable efficacy and toxicity profiles that necessitate evaluation of additional therapeutic options. Improvement was observed in the majority of patients treated with isavuconazole, with clinical failures observed only in those with coccidioidal meningitis.
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Affiliation(s)
- Arash Heidari
- Department of Medicine, Division of Infectious Diseases, Kern Medical Center–University of California–Los Angeles, Bakersfield, California, USA
- Valley Fever Institute, Bakersfield, California, USA
- Department of Medicine, David Geffen School of Medicine, University of California–Los Angeles, Los Angeles, California, USA
| | - Rupam Sharma
- Valley Fever Institute, Bakersfield, California, USA
- Department of Medicine, David Geffen School of Medicine, University of California–Los Angeles, Los Angeles, California, USA
| | - Qusai Shakir
- Valley Fever Institute, Bakersfield, California, USA
| | - Madiha Shah
- Department of Pharmacy, University of California–Davis Medical Center, Sacramento, California, USA
| | - Josh Clement
- Department of Pharmacy, University of California–Davis Medical Center, Sacramento, California, USA
| | - Monica A Donnelley
- Department of Pharmacy, University of California–Davis Medical Center, Sacramento, California, USA
| | - Trina Reynolds
- Department of Internal Medicine, Division of Infectious Diseases, University of California–Davis Medical Center, Sacramento, California, USA
| | - Kate Trigg
- Department of Internal Medicine, Division of Infectious Diseases, University of California–Davis Medical Center, Sacramento, California, USA
| | - Jeff Jolliff
- Department of Medicine, Division of Infectious Diseases, Kern Medical Center–University of California–Los Angeles, Bakersfield, California, USA
- Valley Fever Institute, Bakersfield, California, USA
| | - Rasha Kuran
- Department of Medicine, Division of Infectious Diseases, Kern Medical Center–University of California–Los Angeles, Bakersfield, California, USA
- Valley Fever Institute, Bakersfield, California, USA
- Department of Medicine, David Geffen School of Medicine, University of California–Los Angeles, Los Angeles, California, USA
| | - Royce Johnson
- Department of Medicine, Division of Infectious Diseases, Kern Medical Center–University of California–Los Angeles, Bakersfield, California, USA
- Valley Fever Institute, Bakersfield, California, USA
- Department of Medicine, David Geffen School of Medicine, University of California–Los Angeles, Los Angeles, California, USA
| | - George R Thompson
- Department of Internal Medicine, Division of Infectious Diseases, University of California–Davis Medical Center, Sacramento, California, USA
- Department of Medical Microbiology and Immunology, University of California–Davis, Davis, California, USA
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8
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Chai S, Zhan JL, Zhao LM, Liu XD. Safety of triazole antifungals: a pharmacovigilance study from 2004 to 2021 based on FAERS. Ther Adv Drug Saf 2022; 13:20420986221143266. [PMID: 36545565 PMCID: PMC9761248 DOI: 10.1177/20420986221143266] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Accepted: 11/15/2022] [Indexed: 12/23/2022] Open
Abstract
Background Triazole antifungals are widely used as broad-spectrum antifungal activity; however, there are many undetected and unreported adverse events (AEs). Methods Data from the Food and Drug Administration Adverse Event Reporting System (FAERS) from the first quarter (Q1) of 2004 to the third quarter (Q3) of 2021 were selected for disproportionality analysis to assess the connection between antifungal triazoles, and AEs and important medical events (IMEs). Results A total of 22,566 records associated with triazole antifungals were identified, with 9584 triazole antifungal-IME pairs. The following system organ classes (SOCs) appeared as significant signals: 'Endocrine disorders' [reported odds ratio (ROR) = 167.94], 'Metabolism and nutrition disorders' (ROR = 46.30), and 'Skin and subcutaneous tissue disorders' (ROR = 21.37). Strong signals were observed with respiratory failure, rash, hepatic function abnormal, and hypokalemia. Uncommon security signals included a change in the QT interval, neurotoxicity, pseudoaldosteronism, and hallucinations. Conclusion Various triazole antifungals cause AEs of different types and intensities of association. Our results are broadly consistent with prescribing information and previous studies; however, additional pharmacoepidemiological studies are required to verify AEs with modest incidence but high signal. Plain Language Summary A study on the adverse effects of triazole antifungals Introduction: The triazole antifungals we studied include fluconazole, itraconazole, voriconazole, posaconazole, and isavuconazole. Triazole antifungals are widely used as broad-spectrum antifungals; however, there are many undetected and unreported adverse events (AEs).Materials and Methods: The Food and Drug Administration Adverse Event Reporting System (FAERS) database contains AEs reported to the FDA by different countries regarding post-marketing drugs. Through the FAERS database, we retrieved a total of 22,566 AE reports related to triazole antifungals. We not only counted information about patients' gender, age, weight, reporting country, outcome indicators, and indications but also analyzed the system organ classes (SOCs) of AEs, and the number of reported drug-related AEs and the degree of relevance.Results: We found a total of 22,566 records related to triazole antifungal agents, of which 9584 reports made important medical events (IMEs) about triazole antifungal agents, which are serious AEs. The following SOCs appear as important signals: 'endocrine disorders', 'metabolic and nutritional disorders', and 'skin and subcutaneous tissue disorders'. Triazole antifungals produce AEs, such as respiratory failure, rash, hepatic function abnormal, and hypokalemia. They also produce uncommon AEs, including changes in the QT interval, neurotoxicity, pseudoaldosteronism, and hallucinations.Conclusion: By analyzing data from the FAERS database, we identified more AEs associated with these five triazole antifungals than were indicated in the instructions and our findings provide additional insight into triazole-related AEs to inform clinicians before and during treatment.
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Affiliation(s)
- Shuang Chai
- Department of Pharmacy, Shengjing Hospital of
China Medical University, Shenyang, China,Department of the Second Clinical Pharmacy,
School of Pharmacy, China Medical University, Shenyang, China
| | - Jing-Lun Zhan
- Department of Pharmacy, Shengjing Hospital of
China Medical University, Shenyang, China,Department of the Second Clinical Pharmacy,
School of Pharmacy, China Medical University, Shenyang, China
| | - Li-Mei Zhao
- Department of Pharmacy, Shengjing Hospital of
China Medical University, Shenyang, China,Department of the Second Clinical Pharmacy,
School of Pharmacy, China Medical University, Shenyang, China
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Thompson GR, Ampel NM, Blair JE, Donovan F, Fierer J, Galgiani JN, Heidari A, Johnson R, Shatsky SA, Uchiyama CM, Stevens DA. Controversies in the Management of Central Nervous System Coccidioidomycosis. Clin Infect Dis 2022; 75:555-559. [PMID: 35717645 DOI: 10.1093/cid/ciac478] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Indexed: 11/12/2022] Open
Abstract
Central nervous system infection with Coccidioides spp is fatal if untreated, and complications occur even when therapy is directed by experienced clinicians. We convened a panel of clinicians experienced in the management of coccidioidal meningitis to summarize current controversies and provide consensus for the management of this difficult infection.
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Affiliation(s)
- George R Thompson
- Department of Internal Medicine, Division of Infectious Diseases and the Department of Medical Microbiology and Immunology, University of California-Davis Medical Center; Sacramento, CA USA.,University of California - Davis Center for Valley Fever, Sacramento, CA USA
| | - Neil M Ampel
- Division of Infectious Diseases, Mayo Clinic in Arizona, Phoenix, AZ, USA.,University of Arizona College of Medicine, Tucson, AZ, USA
| | - Janis E Blair
- Division of Infectious Diseases, Mayo Clinic in Arizona, Phoenix, AZ, USA
| | - Fariba Donovan
- University of Arizona College of Medicine, Tucson, AZ, USA.,Valley Fever Center for Excellence, University of Arizona College of Medicine-Tucson, Tucson, AZ, USA
| | - Joshua Fierer
- Division of Infectious Disease, Department of Medicine, University of California San Diego School of Medicine, La Jolla, CA, USA.,Infectious Diseases Section, VA Healthcare San Diego, San Diego, CA, USA
| | - John N Galgiani
- University of Arizona College of Medicine, Tucson, AZ, USA.,Valley Fever Center for Excellence, University of Arizona College of Medicine-Tucson, Tucson, AZ, USA
| | - Arash Heidari
- Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Kern Medical, Bakersfield, CA, USA.,Valley Fever Institute, Kern Medical Center, Bakersfield, CA, USA
| | - Royce Johnson
- Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Kern Medical, Bakersfield, CA, USA.,Valley Fever Institute, Kern Medical Center, Bakersfield, CA, USA
| | | | - Christopher M Uchiyama
- Department of Neurosurgery, Scripps Clinic and Scripps Green Hospital, La Jolla, CA, USA
| | - David A Stevens
- California Institute for Medical Research, San Jose, CA, USA.,Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
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Pulmonary Coccidioidomycosis: A Case Report and Literature Review. Medicina (B Aires) 2022; 58:medicina58050655. [PMID: 35630071 PMCID: PMC9143117 DOI: 10.3390/medicina58050655] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Revised: 04/28/2022] [Accepted: 05/10/2022] [Indexed: 12/03/2022] Open
Abstract
Coccidioidomycosis is an infectious disease caused by Coccidioides immitis or C. posadasii fungus. Humans usually get infected by inhaling spores risen from the soil. Although in 60 percent of cases symptoms are absent, remaining patients can develop various manifestations of the disease, from flu-like symptoms to severe dissemination or meningitis. In endemic regions (California, Arizona, Mexico, Central, and South America), pulmonary coccidioidomycosis causes 25% of community-acquired cases of pneumonia. We present the first registered case of pulmonary coccidioidomycosis in Lithuania. Clinical presentation, pathogenesis, treatment options, and diagnostic alternatives are discussed.
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11
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Li Z, Wu C, Wang C, Deng Z. Spectrum of voriconazole-associated periostitis in clinical characteristics, diagnosis and management. Infection 2022; 50:1217-1224. [PMID: 35288847 DOI: 10.1007/s15010-022-01795-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2021] [Accepted: 02/25/2022] [Indexed: 11/30/2022]
Abstract
PURPOSE Previous knowledge about the relationship between voriconazole exposure and periostitis was mainly based on limited case reports and few retrospective studies. The purpose of this study was to assess the clinical characteristics, diagnosis and management of voriconazole-associated periostitis. METHODS Case reports and case series from 1998 to November 30, 2021 on periostitis induced by voriconazole were collected for retrospective analysis. RESULTS Forty four patients (18 male and 26 female) from 34 studies were included in total. The median age was 58 years (29-74). The majority of patients had undergone organ transplantation (50.0%) or suffered from hematologic malignancy (31.81%). The median onset time of symptoms was 6 months after the start of voriconazole. The most common initial symptom was diffuse skeletal pain (68.28%) which can be severe and even disabling (66.7%). Ribs (37.21%), femurs (32.56%), scapulae (25.58%), humerus (23.26%), and clavicle (23.26%) were the common involved locations. Most cases were accompanied by different degrees of elevated serum alkaline phosphatase and fluoride level, while some presented with elevated bone-specific alkaline phosphatase. The main radiological features included periosteal reaction and multifocal high radiotracer uptake on bone scintigraphy. The formation of new bone was characterized with bilateral, irregular, nodular, as well as high density. The resolution of symptoms was observed with discontinuation of voriconazole in all patients, of whom 18 patients (52.94%) were relieved within a week. Itraconazole, posaconazole or isavuconazole were safe alternatives to voriconazole in voriconazole-induced periostitis. CONCLUSION Voriconazole-induced periostitis is an infrequent complication characterized by bone inflammation involving one or multiple skeletal areas. Bony pain, elevated serum alkaline phosphatase as well as fluoride level are suspicious signs during voriconazole treatment.
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Affiliation(s)
- Zuojun Li
- Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, China
| | - Cuifang Wu
- Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, China
| | - Chunjiang Wang
- Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, China
| | - Zhenzhen Deng
- Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, China.
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12
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Guarascio AJ, Bhanot N, Min Z. Voriconazole-associated periostitis: Pathophysiology, risk factors, clinical manifestations, diagnosis, and management. World J Transplant 2021; 11:356-371. [PMID: 34631468 PMCID: PMC8465512 DOI: 10.5500/wjt.v11.i9.356] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Revised: 07/19/2021] [Accepted: 08/27/2021] [Indexed: 02/06/2023] Open
Abstract
Voriconazole use has been associated with osteoarticular pain and periostitis, likely due to high fluoride content in the drug formulation. This phenomenon has been described primarily with high dosage or prolonged course of voriconazole therapy in immunocompromised and transplant patient populations. Patients typically present with diffuse bony pains associated with elevated serum alkaline phosphatase and plasma fluoride levels in conjunction with radiographic findings suggestive of periostitis. We provide a comprehensive review of the literature to highlight salient characteristics commonly associated with voriconazole-induced periostitis.
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Affiliation(s)
- Anthony J Guarascio
- Department of Pharmacy, Duquesne University School of Pharmacy, Pittsburgh, PA 15282, United States
| | - Nitin Bhanot
- Division of Infectious Disease, Medicine Institute, Allegheny General Hospital, Allegheny Health Network, Pittsburgh, PA 15212, United States
| | - Zaw Min
- Division of Infectious Disease, Medicine Institute, Allegheny General Hospital, Allegheny Health Network, Pittsburgh, PA 15212, United States
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13
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Abstract
Coccidioidomycosis, caused by the dimorphic pathogenic fungi Coccidioides immitis and Coccidioides posadassi, is endemic to the southwestern United states and Central and South America. The incidence of coccidioidomycosis continues to increase. Coccidioidomycosis is typically a self-limiting influenza-like respiratory illness; however, it can lead to disseminated disease outside of the lungs. Not all nondisseminated cases require therapy, but antifungal therapy is typically beneficial requiring treatment ranging from months to lifelong. Clinical factors related to treatment decisions include severity of symptoms, radiography, coccidioidomycosis serologic results, and concurrent medical problems including immunosuppression. This review summarizes the epidemiology, clinical manifestations, and treatment options.
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Affiliation(s)
- Derek J Bays
- Department of Internal Medicine, Division of Infectious Diseases, University of California Davis Medical Center, 4150 V Street, PSSB, Suite G500, Sacramento, CA 95817, USA
| | - George R Thompson
- Department of Internal Medicine, Division of Infectious Diseases, University of California Davis Medical Center, 4150 V Street, PSSB, Suite G500, Sacramento, CA 95817, USA; Department of Medical Microbiology and Immunology, University of California, Davis, Davis, CA, USA.
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14
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Review of Pharmacologic Considerations in the Use of Azole Antifungals in Lung Transplant Recipients. J Fungi (Basel) 2021; 7:jof7020076. [PMID: 33499209 PMCID: PMC7911495 DOI: 10.3390/jof7020076] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2020] [Revised: 01/18/2021] [Accepted: 01/20/2021] [Indexed: 12/15/2022] Open
Abstract
Mold-active azole antifungals are commonly prescribed for the prevention of invasive fungal infections in lung transplant recipients. Each agent exhibits a unique pharmacologic profile, an understanding of which is crucial for therapy selection and optimization. This article reviews pharmacologic considerations for three frequently-used azole antifungals in lung transplant recipients: voriconazole, posaconazole, and isavuconazole. Focus is drawn to analysis of drug-interactions, adverse drug reactions, pharmacokinetic considerations, and the role of therapeutic drug monitoring with special emphasis on data from the post-lung transplant population.
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15
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Ampel NM. Coccidioidomycosis: Changing Concepts and Knowledge Gaps. J Fungi (Basel) 2020; 6:jof6040354. [PMID: 33321746 PMCID: PMC7770576 DOI: 10.3390/jof6040354] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Revised: 12/02/2020] [Accepted: 12/03/2020] [Indexed: 12/11/2022] Open
Abstract
Although first described more than 120 years ago, much remains unknown about coccidioidomycosis. In this review, new information that has led to changing concepts will be reviewed and remaining gaps in our knowledge will be discussed. In particular, new ideas regarding ecology and epidemiology, problems and promises of diagnosis, controversies over management, and the possibility of a vaccine will be covered.
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Affiliation(s)
- Neil M Ampel
- Department of Infectious Diseases, Medicine and Immunobiology University of Arizona, 1501 North Campbell Avenue, Tucson, AZ 85724, USA
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16
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Kelley KD, Thompson GR, Aronowitz P. Mimicking Multiple Myeloma: Voriconazole-Induced Hyperfluorosis and Bone Lesions. J Gen Intern Med 2020; 35:932. [PMID: 31720960 PMCID: PMC7080932 DOI: 10.1007/s11606-019-05551-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2019] [Accepted: 10/31/2019] [Indexed: 11/28/2022]
Affiliation(s)
| | - George R Thompson
- Department of Internal Medicine, Division of Infectious Disease, UC Davis, Sacramento, CA, USA
| | - Paul Aronowitz
- Department of Internal Medicine, UC Davis, Sacramento, CA, USA
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17
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18
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Thompson GR, Lewis JS, Nix DE, Patterson TF. Current Concepts and Future Directions in the Pharmacology and Treatment of Coccidioidomycosis. Med Mycol 2019; 57:S76-S84. [PMID: 30690601 DOI: 10.1093/mmy/myy029] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2018] [Accepted: 04/19/2018] [Indexed: 12/19/2022] Open
Abstract
Coccidioidomycosis remains a significant clinical problem with substantial morbidity and mortality. The vast majority of infections are asymptomatic and the need for early primary therapy remains controversial. The use of triazole antifungals has improved tolerability of therapy but concerns about acute and long-term toxicities among available agents limit their use. In addition, recent findings of decreased in vitro fluconazole susceptibility to as many as 37% of Coccidioides spp. isolates raises concerns regarding optimal therapy for these infections as fluconazole is commonly used for therapy including central nervous system disease. Thus, new agents from novel antifungal classes are currently in preclinical and clinical development aimed at reducing toxicity and improving outcomes of these serious infections.
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Affiliation(s)
- George R Thompson
- Department of Medical Microbiology and Immunology, University of California, Davis; Davis, California, USA.,Department of Internal Medicine, Division of Infectious Diseases, University of California Davis Medical Center; Sacramento, California, USA
| | - James S Lewis
- Department of Pharmacy, Oregon Health & Science University Hospital and Clinics, Portland, Oregon, USA
| | - David E Nix
- Department of Pharmacy Practice and Science, College of Pharmacy, University of Arizona, Tucson, Arizona, USA
| | - Thomas F Patterson
- Division of Infectious Diseases, UT Health San Antonio, and the South Texas Veterans Health Care System; San Antonio, Texas, USA
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19
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Isavuconazole in the Treatment of Coccidioidal Meningitis. Antimicrob Agents Chemother 2019; 63:AAC.02232-18. [PMID: 30559134 DOI: 10.1128/aac.02232-18] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2018] [Accepted: 12/10/2018] [Indexed: 12/17/2022] Open
Abstract
Patients with coccidioidal meningitis require lifelong antifungal therapy. Cumulative toxicity and lack of antifungal efficacy require salvage therapy in the treatment of some patients. In a retrospective review of nine patients with coccidioidal meningitis treated with isavuconazole, successful therapy was seen in three patients and stable disease was confirmed in six patients. Isavuconazole may be a useful addition to the therapeutic choices currently available for coccidioidal meningitis.
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20
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Abstract
A 34-year-old man with history of Hodgkin lymphoma presented 7 months after allogeneic stem cell transplantation with an unexplained severe musculoskeletal pain syndrome. A Tc-MDP bone SPECTCT showed multiple foci with moderate to intense bone uptake across the axial and appendicular skeleton consistent with periostitis. The patient had been on voriconazole daily for 4 months to treat an Aspergillus pneumonia, and in the absence of other causes, a drug-induced periostitis was suspected. Voriconazole was changed to posaconazole with complete resolution of the musculoskeletal symptoms within 3 weeks.
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21
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Bennett N, Maglione PJ, Wright BL, Zerbe C. Infectious Complications in Patients With Chronic Granulomatous Disease. J Pediatric Infect Dis Soc 2018; 7:S12-S17. [PMID: 29746678 PMCID: PMC5985728 DOI: 10.1093/jpids/piy013] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Affiliation(s)
- Nicholas Bennett
- Division of Pediatric Infectious Diseases and Immunology, Connecticut Children’s Medical Center, Hartford
| | - Paul J Maglione
- Division of Clinical Immunology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Benjamin L Wright
- Mayo Clinic Arizona, Scottsdale,Phoenix Children’s Hospital, Phoenix, Arizona
| | - Christa Zerbe
- The National Institutes of Health, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland,Correspondence: Christa S. Zerbe, MD, The National Institute of Allergy and Infectious Diseases, The National Institutes of Health, 10 Center Drive Rm 12C110, Bethesda, MD 20892 ()
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22
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Rausch CR, Kontoyiannis DP. Prolonged voriconazole treatment in a patient with chronic lymphocytic leukemia resulting in a litany of chronic overlapping toxicities. J Oncol Pharm Pract 2018; 25:747-753. [PMID: 29554829 DOI: 10.1177/1078155218762624] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Voriconazole is a triazole antifungal with activity against a number of yeast and mold species including Candida, Aspergillosis, Fusarium, and Coccidioides. Invasive fungal infections are associated with high morbidity and mortality, prolonged treatment courses, and occasionally lifelong suppressive therapy. Voriconazole therapy can result in a number of acute toxicities that clinicians are frequently aware of including hepatotoxicity, visual disturbances, and hallucinations; however, there is limited experience with extended durations of voriconazole therapy. We describe the case of a 62-year-old man who developed Coccidioides meningitis as a result of prolonged neutropenia from treatment for chronic lymphocytic leukemia. He was initially treated with a number of different antifungal agents including voriconazole, liposomal amphotericin B, fluconazole, and itraconazole; however, he developed acute toxicity due to those agents. He was successfully re-challenged with voriconazole, and maintained therapeutic serum concentrations throughout treatment. As a result of prolonged voriconazole exposure of over 14 years, he has suffered a number of toxicities, most significantly including actinic keratosis, squamous cell carcinoma, and skeletal fluorosis. To our knowledge, this is the longest continuous use of voriconazole therapy currently in the literature.
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Affiliation(s)
- Caitlin R Rausch
- 1 Division of Pharmacy, MD Anderson Cancer Center, The University of Texas Houston, TX, USA
| | - Dimitrios P Kontoyiannis
- 2 Department of Infectious Diseases Infection Control and Employee Heath, MD Anderson Cancer Center, The University of Texas Houston, TX, USA
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23
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Voriconazole-induced periostitis: a new rheumatic disorder. Clin Rheumatol 2016; 36:609-615. [DOI: 10.1007/s10067-016-3341-7] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2016] [Revised: 06/22/2016] [Accepted: 06/22/2016] [Indexed: 02/04/2023]
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24
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Patterson TF, Thompson GR, Denning DW, Fishman JA, Hadley S, Herbrecht R, Kontoyiannis DP, Marr KA, Morrison VA, Nguyen MH, Segal BH, Steinbach WJ, Stevens DA, Walsh TJ, Wingard JR, Young JAH, Bennett JE. Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the Infectious Diseases Society of America. Clin Infect Dis 2016; 63:e1-e60. [PMID: 27365388 DOI: 10.1093/cid/ciw326] [Citation(s) in RCA: 1813] [Impact Index Per Article: 201.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2016] [Accepted: 05/11/2016] [Indexed: 12/12/2022] Open
Abstract
It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.
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Affiliation(s)
- Thomas F Patterson
- University of Texas Health Science Center at San Antonio and South Texas Veterans Health Care System
| | | | - David W Denning
- National Aspergillosis Centre, University Hospital of South Manchester, University of Manchester, United Kingdom
| | - Jay A Fishman
- Massachusetts General Hospital and Harvard Medical School
| | | | | | | | - Kieren A Marr
- Johns Hopkins University School of Medicine and the Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland
| | - Vicki A Morrison
- Hennepin County Medical Center and University of Minnesota, Minneapolis
| | | | - Brahm H Segal
- University at Buffalo Jacobs School of Medicine and Biomedical Sciences, and Roswell Park Cancer Institute, New York
| | | | | | - Thomas J Walsh
- New York-Presbyterian Hospital/Weill Cornell Medical Center, New York
| | | | | | - John E Bennett
- Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland
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25
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Voriconazole-Induced Periostitis Mimicking Chronic Graft-versus-Host Disease after Allogeneic Stem Cell Transplantation. Case Rep Infect Dis 2016; 2016:3242196. [PMID: 27403356 PMCID: PMC4923522 DOI: 10.1155/2016/3242196] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2016] [Accepted: 05/24/2016] [Indexed: 01/30/2023] Open
Abstract
Voriconazole is an established first-line agent for treatment of invasive fungal infections in patients undergoing allogeneic stem cell transplantation (ASCT). It is associated with the uncommon complication of periostitis. We report this complication in a 58-year-old female undergoing HSCT. She was treated with corticosteroids with minimal improvement. The symptoms related to periostitis can mimic chronic graft-versus-host disease in patients undergoing HSCT and clinicians should differentiate this from other diagnoses and promptly discontinue therapy.
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26
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Donnelley MA, Zhu ES, Thompson GR. Isavuconazole in the treatment of invasive aspergillosis and mucormycosis infections. Infect Drug Resist 2016; 9:79-86. [PMID: 27330318 PMCID: PMC4898026 DOI: 10.2147/idr.s81416] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
We have a limited arsenal with which to treat invasive fungal infections caused by Aspergillus and Mucorales. The morbidity and mortality for both pathogens remains high. A triazole antifungal, isavuconazole, was recently granted approval by the US Food and Drug Administration and the European Medicines Agency for the treatment of invasive aspergillosis and mucormycosis. A randomized double-blind comparison trial for the treatment of invasive aspergillosis found isavuconazole noninferior to voriconazole. A separate, open-label study evaluating the efficacy of isavuconazole in the treatment of mucormycosis found comparable response rates to amphotericin B and posaconazole treated historical controls. The prodrug isavuconazonium sulfate is commercially available in both an oral and intravenous formulation and is generally well tolerated. Isavuconazole’s broad spectrum of activity, limited side effect profile, and favorable pharmacokinetics will likely solidify its place in therapy.
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Affiliation(s)
- Monica A Donnelley
- Department of Inpatient Pharmacy, University of California - Davis, Sacramento, USA; Department of Clinical Sciences, Touro University College of Pharmacy, Vallejo, USA
| | - Elizabeth S Zhu
- Department of Inpatient Pharmacy, University of California - Davis, Sacramento, USA
| | - George R Thompson
- Department of Medicine, Division of Infectious Diseases, University of California - Davis, Davis, CA, USA
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27
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Metayer B, Bode-Milin C, Ansquer C, Haloun A, Maugars Y, Berthelot JM. Painful and swollen hands 3 months after lungs graft: Suracute voriconazole-induced periostitis and exostosis. Joint Bone Spine 2016; 84:97-98. [PMID: 27117297 DOI: 10.1016/j.jbspin.2015.11.011] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2015] [Accepted: 11/22/2015] [Indexed: 12/14/2022]
Affiliation(s)
- Benoît Metayer
- Rheumatology unit, Hôtel-Dieu, Nantes university hospital, CHU de Nantes, place Alexis-Ricordeau, 44093 Nantes cedex, France
| | - Caroline Bode-Milin
- Nuclear medicine unit, Nantes university hospital, CHU de Nantes, place Alexis-Ricordeau, 44093 Nantes cedex, France
| | - Catherine Ansquer
- Nuclear medicine unit, Nantes university hospital, CHU de Nantes, place Alexis-Ricordeau, 44093 Nantes cedex, France
| | - Alain Haloun
- Chest unit, Nantes university hospital, CHU de Nantes, place Alexis-Ricordeau, 44093 Nantes cedex, France
| | - Yves Maugars
- Rheumatology unit, Hôtel-Dieu, Nantes university hospital, CHU de Nantes, place Alexis-Ricordeau, 44093 Nantes cedex, France
| | - Jean-Marie Berthelot
- Rheumatology unit, Hôtel-Dieu, Nantes university hospital, CHU de Nantes, place Alexis-Ricordeau, 44093 Nantes cedex, France.
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28
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Adwan MH. An update on drug-induced arthritis. Rheumatol Int 2016; 36:1089-97. [DOI: 10.1007/s00296-016-3462-y] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2015] [Accepted: 03/09/2016] [Indexed: 12/17/2022]
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30
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Waugh DT, Potter W, Limeback H, Godfrey M. Risk Assessment of Fluoride Intake from Tea in the Republic of Ireland and its Implications for Public Health and Water Fluoridation. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2016; 13:E259. [PMID: 26927146 PMCID: PMC4808922 DOI: 10.3390/ijerph13030259] [Citation(s) in RCA: 49] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 12/01/2015] [Revised: 02/17/2016] [Accepted: 02/19/2016] [Indexed: 11/16/2022]
Abstract
The Republic of Ireland (RoI) is the only European Country with a mandatory national legislation requiring artificial fluoridation of drinking water and has the highest per capita consumption of black tea in the world. Tea is a hyperaccumulator of fluoride and chronic fluoride intake is associated with multiple negative health outcomes. In this study, fifty four brands of the commercially available black tea bag products were purchased and the fluoride level in tea infusions tested by an ion-selective electrode method. The fluoride content in all brands tested ranged from 1.6 to 6.1 mg/L, with a mean value of 3.3 mg/L. According to our risk assessment it is evident that the general population in the RoI is at a high risk of chronic fluoride exposure and associated adverse health effects based on established reference values. We conclude that the culture of habitual tea drinking in the RoI indicates that the total cumulative dietary fluoride intake in the general population could readily exceed the levels known to cause chronic fluoride intoxication. Evidence suggests that excessive fluoride intake may be contributing to a wide range of adverse health effects. Therefore from a public health perspective, it would seem prudent and sensible that risk reduction measures be implemented to reduce the total body burden of fluoride in the population.
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Affiliation(s)
- Declan T Waugh
- EnviroManagement Services, 11 Riverview, Dohertys Rd, Bandon, Co. Cork P72 YF10, Ireland.
| | - William Potter
- Department of Chemistry and Biochemistry, KEH M2225, University of Tulsa, Tulsa, OK 74104-3189, USA.
| | - Hardy Limeback
- Faculty of Dentistry, University of Toronto, 124 Edward Street, Toronto, ON M5G 1G6, Canada.
| | - Michael Godfrey
- Bay of Plenty Environmental Health, 1416A Cameron Road, Tauranga 3012, New Zealand.
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31
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Rheinboldt M, Delproposto Z, Agarwal R. Voriconazole-induced periostitis post transplant: an illustrative review of thoracic computed tomography imaging manifestations. Transpl Infect Dis 2015; 17:859-63. [DOI: 10.1111/tid.12451] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2015] [Revised: 06/29/2015] [Accepted: 08/13/2015] [Indexed: 11/30/2022]
Affiliation(s)
- M. Rheinboldt
- Department of Radiology; Henry Ford Hospital; Detroit Michigan USA
| | - Z. Delproposto
- Department of Radiology; Henry Ford Hospital; Detroit Michigan USA
| | - R. Agarwal
- Department of Radiology; Northwestern University Hospital; Chicago Illinois USA
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32
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Correlation of Pain and Fluoride Concentration in Allogeneic Hematopoietic Stem Cell Transplant Recipients on Voriconazole. Biol Blood Marrow Transplant 2015; 22:579-83. [PMID: 26524731 DOI: 10.1016/j.bbmt.2015.10.021] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2015] [Accepted: 10/26/2015] [Indexed: 11/23/2022]
Abstract
Supportive care guidelines recommend antimold prophylaxis in hematopoietic stem cell transplant (HSCT) recipients deemed to have high risk for invasive fungal infection, leading to long-term use of voriconazole after allogeneic HSCT in patients who remain immunocompromised. Voriconazole has been associated with periostitis, exostoses, and fluoride excess in patients after solid organ transplantation, HSCT, and leukemia therapy. The aims of this study were to describe the frequency and clinical presentation of patients presenting with pain and fluoride excess among allogeneic HSCT patients taking voriconazole, to identify when a plasma fluoride concentration was measured with respect to voriconazole initiation and onset of pain, and to describe the outcomes of patients with fluoride excess in the setting of HSCT. A retrospective review was conducted of all adult allogeneic HSCT patients receiving voriconazole at Mayo Clinic in Rochester, Minnesota, between January 1, 2009 and July 31, 2012. Of 242 patients included, 32 had plasma fluoride measured to explore the etiology of musculoskeletal pain. In 31 patients with fluoride measurement while on voriconazole, 29 (93.5%) had elevated levels. The median plasma fluoride was 11.1 μmol/L (range, 2.4 to 24.7). The median duration of voriconazole was 163 days (range, 2 to 1327). The median time to fluoride measurement was 128 days after voriconazole initiation (range, 28 to 692). At 1 year after the start of voriconazole after HSCT, 15.3% of patients had developed pain associated with voriconazole use and 35.7% developed pain while on voriconazole after 2 years. Of the patients with an elevated fluoride level, 22 discontinued voriconazole; pain resolved or improved in 15, stabilized in 3, and worsened in 4 patients. Ten patients continued voriconazole; pain resolved or improved in 7, was attributable to alternative causes in 2, and undefined in 1. Serum creatinine, estimated glomerular filtration rate, alkaline phosphatase, and voriconazole concentration did not predict for fluoride excess and associated pain. Periostitis due to fluoride excess is a common adverse effect of voriconazole that should be considered in patients presenting with pain and is often reversible after drug discontinuation. Alternative antifungal agents with a lower risk for fluoride excess should be considered in patients receiving voriconazole who develop fluoride excess and pain.
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Optimizing azole antifungal therapy in the prophylaxis and treatment of fungal infections. Curr Opin Infect Dis 2015; 27:493-500. [PMID: 25229352 DOI: 10.1097/qco.0000000000000103] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
PURPOSE OF REVIEW Azole antifungals are widely used in the prophylaxis and treatment of fungal infections, but are associated with a range of pharmacokinetic challenges and safety issues that necessitate individualized therapy to achieve optimal clinical outcomes. Recent advances in our knowledge of azole exposure-response relationships, therapeutic drug monitoring and individualized dosing strategies are reviewed as follows. RECENT FINDINGS Recent studies have significantly improved the understanding of exposure-response relationships for efficacy and toxicity, increasing confidence in target exposure ranges for azole antifungal agents. Population pharmacokinetic modelling of voriconazole has led to studies demonstrating the feasibility of model-guided dose individualization strategies with the drug, which holds significant promise for optimizing therapy. The recent approval of a solid oral tablet formulation of posaconazole with improved bioavailability and once-daily dosing has significantly improved the clinical utility of this agent. Further clinical experience with the investigational azole isavuconazole is needed to determine the role of individualized therapy. SUMMARY The coordination of CYP2C19 pharmacogenomic testing with model-guided dose individualization holds significant promise for optimizing therapy with voriconazole. Pharmacokinetic challenges with itraconazole, voriconazole and posaconazole oral suspension continue to require therapeutic drug monitoring to individualize therapy and optimize treatment outcomes.
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Davis DL. Voriconazole-related periostitis presenting on magnetic resonance imaging. CLINICAL CASES IN MINERAL AND BONE METABOLISM 2015; 12:78-81. [PMID: 26136804 DOI: 10.11138/ccmbm/2015.12.1.078] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
Painful periostitis is a complication of long-term antifungal therapy with voriconazole. A high clinical suspicion coupled with imaging and laboratory assessment is useful to establish the diagnosis. Prompt discontinuance of voriconazole typically results in the resolution of symptoms and signs. This report describes the presentation of voriconazole-related periostitis on magnetic resonance imaging.
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Affiliation(s)
- Derik L Davis
- Department of Diagnostic Radiology & Nuclear Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA
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Abstract
History A 74-year-old woman presented with multifocal bone pain, including pain in multiple ribs, bilateral shoulders, and bilateral hips. The pain began several months before presentation and was quite severe, ultimately necessitating control with narcotics. At examination, strength in both lower extremities was slightly reduced, sensation and reflexes were intact, and range of motion was full, though painful. There were no notable constitutional symptoms of fever or weight loss. Laboratory work-up was remarkable for elevated alkaline phosphatase level (277 U/L [4.6 mkat/L]). The patient had undergone left lung transplantation 8 years prior for pulmonary fibrosis. A thorough pulmonary work-up for the cause of fibrosis, which included gathering an exposure, occupational, allergy, and previous infectious history, and a rheumatoid work-up were negative. The patient's posttransplantation course was complicated by bronchiolitis obliterans from chronic rejection and by recent pulmonary embolism, for which she was undergoing anticoagulation therapy at the time of presentation. Additionally, the patient experienced repeated pulmonary infections with Aspergillus, leading to multiple hospitalizations and long-term antifungal prophylaxis with voriconazole. A bone scan from an outside hospital was reviewed, and further imaging was performed.
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Affiliation(s)
- Tina D Tailor
- From the Department of Radiology, University of Washington Medical Center, 1959 Pacific St, Box 357115, Seattle, WA 98195-7115
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Rad B, Saleem M, Grant S, Florkowski C, Coates P, Gordon D, Rankin W. Fluorosis and periostitis deformans as complications of prolonged voriconazole treatment. Ann Clin Biochem 2015; 52:611-4. [PMID: 25587196 DOI: 10.1177/0004563214568873] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/29/2014] [Indexed: 12/22/2022]
Abstract
We describe a case of development of painful periostitis deformans in a 39-year-old woman who was receiving long-term voriconazole treatment for Aspergillus infection as a complication of orthotopic liver transplant. Measurement of fluoride levels strongly supports fluorosis to be the mechanism of the voriconazole-induced periostitis deformans and supports the concept that such measurements might be of use in predicting this complication of long-term voriconazole treatment.
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Affiliation(s)
- Babak Rad
- Microbiology & Infectious Diseases, SA Pathology and Flinders Medical Centre, Bedford Park, Australia
| | - Mohamed Saleem
- Division of Chemical Pathology, SA Pathology, Adelaide, Australia
| | - Susan Grant
- Canterbury Health Laboratories, Christchurch, New Zealand
| | | | | | - David Gordon
- Microbiology & Infectious Diseases, SA Pathology and Flinders Medical Centre, Bedford Park, Australia
| | - Wayne Rankin
- Division of Chemical Pathology, SA Pathology, Adelaide, Australia
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Last generation triazoles for imported eumycetoma in eleven consecutive adults. PLoS Negl Trop Dis 2014; 8:e3232. [PMID: 25299610 PMCID: PMC4191942 DOI: 10.1371/journal.pntd.0003232] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2014] [Accepted: 09/01/2014] [Indexed: 11/21/2022] Open
Abstract
Background Optimal management of eumycetoma, a severely debilitating chronic progressive fungal infection of skin, disseminating to bone and viscera, remains challenging. Especially, optimal antifungal treatment and duration are ill defined. Methodology/Principal Findings We conducted a monocentric retrospective study of 11 imported cases of eumycetoma treated by voriconazole or posaconazole for at least 6 months. Response to treatment was assessed through evolution of clinical and magnetic resonance imaging (MRI). (1→3) ß-D-glucan (BG) and positron emission tomography using [18F] fluorodeoxyglucose (PET/CT) results were also assessed. Identified species were Fusarium solani complex (n = 3); Madurella mycetomatis, (n = 3), and Exophiala jeanselmei, (n = 1). Moreover, two coelomycetes and one phaeohyphomycetes strains without species identification were retrieved. Serum BG and PET/CT were abnormal in 7/8 and 6/6 patients tested, respectively. Patients received last generation azoles for a mean duration of 25.9±18 months. Complete response (major clinical and MRI improvement) was observed in 5/11 patients, partial response (minor MRI improvement or stable MRI findings) in 5 and failure (MRI evidence of disease progression) in one, with a 73±39 [6–132] months mean follow-up. Relapse occurred in 2 patients after treatment discontinuation. Optimal outcome was associated with fungal species, initiation of last generation triazole therapy (<65 months since first symptoms), negative serum BG and PET/CT normalization. Conclusions/Significance MRI, PET/CT and serum BG appear as promising tools to assess optimal time of antifungal treatment for eumycetoma. Eumycetoma is a severe chronic progressive fungal infection of skin and ultimately bone or viscera that affect mainly people with low economic status. Optimal treatment of this condition relies on medical and often surgical therapy and remains challenging because of lack of gold standard therapy and high rate of relapse after treatment discontinuation. In this retrospective study we assessed whether modern triazoles (voriconazole and posaconazole) suited to eumycetoma treatment and if tailored treatment duration, based on serial evaluation of a serum biomarker of fungal infection (Serum (1→3) ß-D-Glucan, (BD)), magnetic resonance imaging (MRI) or positron emission tomography using [18F] fluorodeoxyglucose (PET/CT) would be useful. We found that modern triazoles were efficient treatments of eumycetoma, allowing complete or partial response in 10/11 of patients, without significant side effects. Moreover, patients with treatment discontinuation based on normalization of BD, MRI or PET/CT seemed to have better long-term outcome than those with clinical cure but still abnormal BD or imaging results.
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Moon WJ, Scheller EL, Suneja A, Livermore JA, Malani AN, Moudgal V, Kerr LE, Ferguson E, Vandenberg DM. Plasma fluoride level as a predictor of voriconazole-induced periostitis in patients with skeletal pain. Clin Infect Dis 2014; 59:1237-45. [PMID: 24992954 DOI: 10.1093/cid/ciu513] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Voriconazole is a triazole antifungal medication used for prophylaxis or to treat invasive fungal infections. Inflammation of the periosteum resulting in skeletal pain, known as periostitis, is a reported side effect of long-term voriconazole therapy. The trifluorinated molecular structure of voriconazole suggests a possible link between excess fluoride and periostitis, as elevated blood fluoride has been reported among patients with periostitis who received voriconazole. METHODS Two hundred sixty-four patients from Michigan were impacted by the multistate outbreak of fungal infections as a result of contaminated methylprednisolone injections. A retrospective study was conducted among 195 patients who received voriconazole therapy at St Joseph Mercy Hospital during this outbreak. Twenty-eight patients who received both bone scan and plasma fluoride measurements for skeletal pain were included in the statistical analyses. Increased tracer uptake on bone scan was considered positive for periostitis. The primary outcome measure was the correlation between plasma fluoride and bone scan results. RESULTS Blood fluoride (P < .001), alkaline phosphatase (P = .020), daily voriconazole dose (P < .001), and cumulative voriconazole dose (P = .027) were significantly elevated in patients who had periostitis compared with those who did not. Discontinuation or dose reduction of voriconazole resulted in improvement of pain in 89% of patients. CONCLUSIONS High plasma fluoride levels coupled with skeletal pain among patients who are on long-term voriconazole therapy is highly suggestive of periostitis. Initial measurement of fluoride may be considered when bone scan is not readily available. Early detection should be sought, as discontinuation of voriconazole is effective at reversing the disease.
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Affiliation(s)
- Woo J Moon
- Department of Internal Medicine, St Joseph Mercy Hospital
| | - Erica L Scheller
- Department of Molecular and Integrative Physiology, University of Michigan
| | - Anupam Suneja
- Department of Internal Medicine, St Joseph Mercy Hospital
| | | | - Anurag N Malani
- Department of Internal Medicine, St Joseph Mercy Hospital Section of Infectious Diseases
| | - Varsha Moudgal
- Department of Internal Medicine, St Joseph Mercy Hospital Section of Infectious Diseases
| | - Lisa E Kerr
- Department of Pharmacy, St Joseph Mercy Hospital, Ann Arbor, Michigan
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In the Literature. Clin Infect Dis 2013. [DOI: 10.1093/cid/cit344] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
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Tedja R, El-Sherief A, Olbrych T, Gordon S. Multifocal periostitis as a complication of chronic use of voriconazole in a lung transplant recipient. Transpl Infect Dis 2013; 15:424-9. [PMID: 23663268 DOI: 10.1111/tid.12088] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2012] [Revised: 10/18/2012] [Accepted: 12/08/2012] [Indexed: 01/30/2023]
Abstract
Fungal infections are common in solid organ transplantation. An increasing number of transplant recipients receive antifungal therapy for prolonged duration owing to invasive fungal infections. Herein, we describe a diagnosis of periostitis as a complication of chronic use of voriconazole in a lung transplant recipient. The patient was diagnosed with probable pulmonary aspergillosis and was treated with oral voriconazole for a total of 9 months. Evidence of multifocal periostitis was observed in the axial and appendicular skeleton. Early recognition of this phenomenon is important to prevent unnecessary tests and procedures. Prompt discontinuation of voriconazole should result in improvement of symptoms.
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Affiliation(s)
- R Tedja
- Department of Infectious Disease, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
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