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1.
Eye Contact Lens ; 48(6): 272-275, 2022 Jun 01.
Article in English | MEDLINE | ID: mdl-35703836

ABSTRACT

PURPOSE: To report the clinical profile and treatment outcomes of patients with culture-positive Acremonium keratitis. METHODS: This is a retrospective observational study. Medical records of all patients treated in a tertiary eye hospital for culture positive infective keratitis from March 2016 to February 2021 were screened, of which those positive for Acremonium species on fungal culture were reviewed. Demographic details, clinical presentation, clinical course, treatment given, total follow-up duration, time taken for ulcer to heal, scar size, and final visual acuity in the last follow-up were recorded. RESULTS: Fifty three cases of fungal keratitis caused by Acremonium species were identified, 22 females and 31 males, with average age of 46.39±18.64 years. The mean duration of symptoms being 54.47±50 days. Only five patients had a history of trauma with vegetative matter. Clinical presentation of patients showed a large number of variations, with 2 patients presenting as peripheral ulcerative keratitis and 1 with epithelial plaque. The mean visual acuity of patients at presentation was 2.43±0.46 logMAR units. Thirty-three of 53 patients presented with perforated corneal ulcer and underwent penetrating keratoplasty; 20 patients were medically managed on topical voriconazole 1%, natamycin 5%, and oral voriconazole. The mean duration of healing of epithelial defect was 95±60.62 days (range 60-165 days). CONCLUSION: Acremonium keratitis has a long and indolent course. A prolonged combination therapy of natamycin and voriconazole seems to be effective in the management. A delay in the diagnosis of Acremonium keratitis often leads to clinical worsening requiring keratoplasty.


Subject(s)
Acremonium , Corneal Ulcer , Eye Infections, Fungal , Keratitis , Adult , Aged , Antifungal Agents/therapeutic use , Corneal Ulcer/diagnosis , Corneal Ulcer/drug therapy , Eye Infections, Fungal/diagnosis , Eye Infections, Fungal/drug therapy , Eye Infections, Fungal/microbiology , Female , Humans , Keratitis/diagnosis , Keratitis/drug therapy , Keratitis/microbiology , Male , Middle Aged , Natamycin/therapeutic use , Treatment Outcome , Voriconazole/therapeutic use
2.
Emerg Microbes Infect ; 11(1): 1435-1438, 2022 Dec.
Article in English | MEDLINE | ID: mdl-35536092

ABSTRACT

Aspergillus luchuensis, an industrially important member of Aspergillus species belonging to section Nigri used in fermentation in East Asia, was isolated from an immunocompromised patient with probable invasive pulmonary aspergillosis who failed voriconazole therapy in China. This isolate showed non-wild-type susceptibility to itraconazole, voriconazole, isavuconazole, and posaconazole. A G1378A mutation in cyp51A, resulting in the G441S amino acid substitution, which is the homolog to G448S conferring triazole-resistance in A. fumigatus, was detected in the A. luchuensis isolate.


Subject(s)
Invasive Pulmonary Aspergillosis , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Aspergillus/genetics , Aspergillus/metabolism , Aspergillus fumigatus/genetics , China , Drug Resistance, Fungal/genetics , Fermentation , Fungal Proteins/genetics , Fungal Proteins/metabolism , Humans , Invasive Pulmonary Aspergillosis/drug therapy , Microbial Sensitivity Tests , Triazoles/pharmacology , Triazoles/therapeutic use , Voriconazole/metabolism , Voriconazole/pharmacology , Voriconazole/therapeutic use
3.
Rom J Ophthalmol ; 66(1): 69-74, 2022.
Article in English | MEDLINE | ID: mdl-35531444

ABSTRACT

Objective: Treating fungal keratitis is always a challenge due to limited antifungal medication, their poor penetration, and often, the delay in diagnosis. The purpose of this study is to present new routes of medication delivery, such as intrastromal application for advanced cases not responding to topical therapy. Methods: A 60-year-old female presented with fungal keratitis, complaining of decreased vision, redness in her left eye followed by frequent pain, which got worse a few days prior. Visual acuity was limited to hand motion. Slit-lamp examination showed advanced conjunctival hyperemia, a very deep white feathery lesion in the central cornea, with satellite lesions on the periphery, and pseudohypopyon of 3 mm in the anterior chamber. She was started on oral fluconazole 100 mg b.i.d, followed by corneal debridement and topical hourly voriconazole eye drops and intrastromal voriconazole application as her local findings did not show any improvement. Results: After repeating the procedure three times, the inflammatory reaction was decreased, the central ulcer healed, satellite lesions disappeared and pseudohypopyon did not recur even after discontinuation of the topical therapy. Conclusion: Intrastromal voriconazole application showed its safety and efficacy in treating advanced fungal keratitis with deep intrastromal lesions. Abbreviations: NSAID = non-steroid anti-inflammatory drugs, BCVA = best corrected visual acuity, MIC = mean inhibitory concentration.


Subject(s)
Corneal Ulcer , Eye Infections, Fungal , Keratitis , Antifungal Agents/therapeutic use , Corneal Ulcer/diagnosis , Corneal Ulcer/drug therapy , Corneal Ulcer/microbiology , Eye Infections, Fungal/diagnosis , Eye Infections, Fungal/drug therapy , Eye Infections, Fungal/microbiology , Female , Humans , Keratitis/diagnosis , Keratitis/drug therapy , Keratitis/microbiology , Middle Aged , Voriconazole/therapeutic use
4.
Med Mycol ; 60(5)2022 May 06.
Article in English | MEDLINE | ID: mdl-35511210

ABSTRACT

Studies demonstrated the impact of the COVID-19 pandemic in the prevalence and susceptibility profiles of bacterial and fungal organisms. We analyzed 4821 invasive fungal isolates collected during 2018, 2019, and 2020 in 48 hospitals worldwide to evaluate the impact of this event in the occurrence and susceptibility rates of common fungal species. Isolates were tested using the CLSI broth microdilution method. While the percentage of total isolates that were C. glabrata (n = 710 isolates) or C. krusei (n = 112) slightly increased in 2020, the percentage for C. parapsilosis (n = 542), A. fumigatus (n = 416), and C. lusitaniae (n = 84) significantly decreased (P < .05). Fluconazole resistance in C. glabrata decreased from 5.8% in 2018-2019 to 2.0% in 2020, mainly due to fewer hospitals in the US having these isolates (5 vs. 1 hospital). Conversely, higher fluconazole-resistance rates were noted for C. parapsilosis (13.9 vs. 9.8%) and C. tropicalis (3.5 vs. 0.7%; P < .05) during 2020. Voriconazole resistance also increased for these species. Echinocandin resistance was unchanged among Candida spp. Voriconazole susceptibility rates in A. fumigatus were similar in these two periods (91.7% in 2018 and 2019 vs. 93.0% in 2020). Changes were also noticed in the organisms with smaller numbers of collected isolates. We observed variations in the occurrence of organisms submitted to a global surveillance and the susceptibility patterns for some organism-antifungal combinations. As the COVID-19 pandemic is still ongoing, the impact of this event must continue to be monitored to guide treatment of patients affected by bacterial and fungal infections. LAY SUMMARY: Secondary infections were documented in COVID-19 patients. We compared the prevalence of invasive fungal isolates consecutively collected in 48 worldwide hospitals and their susceptibility patterns between 2020, the year of the global COVID-19 pandemic, and the two prior years.


Subject(s)
COVID-19 , Invasive Fungal Infections , Animals , Antifungal Agents/pharmacology , COVID-19/veterinary , Candida glabrata , Candida parapsilosis , Candida tropicalis , Drug Resistance, Fungal , Fluconazole/pharmacology , Invasive Fungal Infections/veterinary , Microbial Sensitivity Tests/veterinary , Pandemics , Voriconazole/pharmacology , Voriconazole/therapeutic use
5.
BMJ Case Rep ; 15(4)2022 Apr 19.
Article in English | MEDLINE | ID: mdl-35440433

ABSTRACT

A non-diabetic man in his 40s presented with a 4-day history of sudden, painless, rapidly progressive severe vision loss in his right eye. Anterior segment was unremarkable. A dense, solitary vitreous abscess with feathery margins obscured the macula. Retinal haemorrhages, exudates and retinal vasculitis were noted. There was no history of ocular surgery, trauma, intravenous drug abuse or immunocompromise. He received intravenous fluids during a spinal procedure 5 days prior. Prompt diagnostic and therapeutic pars-plana vitrectomy was done and Aspergillus flavus was cultured. Postoperatively, he was treated with oral Voriconazole and four intravitreal Voriconazole injections, till the chorioretinitis lesions had completely healed and was objectively confirmed on follow-up swept-source optical coherence tomography (OCT). He achieved a best-corrected visual acuity of 6/36. A high index of suspicion, early vitrectomy and OCT-based treatment were key to favourable outcomes in this case. Intravenous fluid bottles must be checked for contamination prior to administration.


Subject(s)
Aspergillus flavus , Endophthalmitis , Endophthalmitis/diagnosis , Endophthalmitis/drug therapy , Humans , Male , Tomography, Optical Coherence/methods , Treatment Outcome , Vitrectomy , Voriconazole/therapeutic use
6.
J Infect Dev Ctries ; 16(3): 570-574, 2022 03 31.
Article in English | MEDLINE | ID: mdl-35404865

ABSTRACT

Histoplasmosis is an infection caused by the dimorphic fungus Histoplasma capsulatum. The lungs are the most common site of infection, especially in patients with immune deficiency. We report a case of 62-year-old male patient presented with cough for 3 months and had been taking immunosuppressive drugs for 10 years after heart transplantation. Chest CT scan showed multiple pulmonary nodules. Lung tissue biopsy specimen culture suggested fungal infection, and Histoplasma capsulatum was confirmed by next-generation sequencing (NGS) detection. The patient was diagnosed with pulmonary histoplasmosis. After administration of voriconazole for 46 days, the symptom of cough was markedly relieved and the lesions were partly absorbed. After 13 months of treatment, the lesions completely disappeared, and no significant side-effect of voriconazole was observed. To our knowledge, report of voriconazole as the treatment of histoplasmosis is rare, especially in non-endemic areas. Moreover, this case enriches our experience in the adjustment between immunosuppressive and antifungal agents in treating histoplasmosis.


Subject(s)
Histoplasmosis , Lung Diseases, Fungal , Pneumonia , Cough , Histoplasma , Histoplasmosis/diagnosis , Histoplasmosis/drug therapy , Histoplasmosis/pathology , Humans , Immunosuppressive Agents/therapeutic use , Lung Diseases, Fungal/diagnosis , Lung Diseases, Fungal/drug therapy , Male , Middle Aged , Voriconazole/therapeutic use
7.
Drug Des Devel Ther ; 16: 817-825, 2022.
Article in English | MEDLINE | ID: mdl-35370398

ABSTRACT

Background: Ruxolitinib is newly approved for glucocorticoid-refractory acute graft-versus-host disease (GVHD) in patients undergoing allo-geneic hematopoietic stem-cell transplantation (allo-HSCT), and voriconazole is commonly used in allo-HSCT recipients for the prophylaxis or treatment of invasive fungal infections (IFIs). Drug-drug interaction (DDI) may occur between them because their metabolic pathways overlap and can be inhibited by voriconazole, including cytochrome P450 (CYP) isozymes 3A4 and 2C9. Objective: In the present study, we aimed to investigate the DDI between ruxolitinib and voriconazole in patients with hematological malignancies. Methods: A total of 12 patients with hematologic malignancies were enrolled in this single-arm, single-center, Phase I/II, fixed sequence self-control study. All subjects received 5 mg ruxolitinib alone, followed by the co-administration of ruxolitinib and voriconazole. The plasma concentrations of the two drugs were determined by two well-validated high-performance liquid chromatography-tandem mass spectrometry methods. Phoenix WinNonlin software was used to compare the differences in maximum plasma concentration (Cmax), time to Cmax (Tmax), terminal elimination half-life (T1/2), and apparent plasma clearance (CL/F), as well as area under the curve from time zero to last (AUClast) and AUC from time zero to infinity (AUCinf) between the two periods. Results: After pre-treatment with voriconazole, no significant change existed in Tmax, while Cmax, T1/2, AUClast, and AUCinf of ruxolitinib were significantly increased by 50.4%, 81.3%, 110.1%, and 118.3%, respectively, and CL/F was significantly decreased to 43.6% compared with patients receiving ruxolitinib alone. Conclusion: Our findings confirmed a moderate inhibitory DDI between ruxolitinib and voriconazole as voriconazole decreased the elimination and increased the exposure of ruxolitinib in patients with hematologic malignancies. We recommended a dose reduction regimen when voriconazole and ruxolitinib were coadministered. Drug monitoring might help determine the ruxolitinib treatment concentration for aGVHD patients, improve efficacy, and reduce toxicity.


Subject(s)
Hematologic Neoplasms , Pyrimidines , Hematologic Neoplasms/drug therapy , Humans , Nitriles , Pyrazoles , Voriconazole/therapeutic use
8.
BMJ Case Rep ; 15(3)2022 Mar 29.
Article in English | MEDLINE | ID: mdl-35351742

ABSTRACT

We describe the management of a referred man in his 50s with corneal ulcer in the left eye. Slit-lamp biomicroscopy revealed an infiltrate (4.5×3.5 mm), involving full corneal thickness, corneal melt less than one-third corneal thickness and hypopyon (3.0 mm). Branched septate hypha on direct microscopy and Aspergillus flavus in Sabaraud's dextrose agar confirmed the clinical diagnosis of fungal corneal ulcer. We used natamycin 5% suspension 1 hourly, voriconazole 1% 1 hourly, gatifloxacin 0.5% three times and atropine 1% three times per day, for 2 weeks. However, there was no improvement and the corneal melt increased. We used intracameral plus intracorneal voriconazole injection with voriconazole-impregnated amniotic membrane transplant. We observed a significant decrease in conjunctival congestion, size/depth of infiltrate and hypopyon at the first week of antifungal therapy. Subsequently, at 6 weeks, corneal infiltrate had decreased and superficial corneal vascularisation appeared. Later, at 12 weeks, the patient developed corneal opacity.


Subject(s)
Corneal Ulcer , Eye Infections, Fungal , Antifungal Agents/therapeutic use , Corneal Ulcer/drug therapy , Corneal Ulcer/microbiology , Eye Infections, Fungal/drug therapy , Eye Infections, Fungal/microbiology , Humans , Injections, Intraocular , Male , Voriconazole/therapeutic use
9.
Mycopathologia ; 187(2-3): 249-258, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35267153

ABSTRACT

Aspergillus endocarditis is a rare infection that may affect immunocompetent patients following heart valve replacement or heart surgery. We report the case of a 39 year old woman with a history of intravenous drug use who developed endocarditis with direct examination of the resected valve and vegetation showing the presence of mycelia. Cultures were positive for an Aspergillus of section Nigri, which was subsequently identified as Aspergillus tubingensis by sequencing. The clinical course was favorable following surgery and prolonged antifungal therapy (8 months in total). Antifungal susceptibility testing showed good in vitro activity of amphotericin B, voriconazole and echinocandins against planktonic cells of this A. tubingensis isolate. However, only amphotericin B displayed significant activity against biofilms. In vitro combinations of voriconazole or amphotericin B with echinocandins did not meet the criteria of synergism. Our review of the literature identified 17 other cases of endocarditis attributed to Aspergillus of section Nigri with an overall mortality rate of 57% (100% in the absence of surgery). Endocarditis caused by Aspergillus niger and related cryptic species are rare events, for which surgical management appears to be crucial for outcome. While amphotericin B was the only antifungal drug displaying significant anti-biofilm activity, the type and duration of antifungal therapy remain to be determined.


Subject(s)
Aspergillosis , Endocarditis , Adult , Amphotericin B/pharmacology , Amphotericin B/therapeutic use , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Aspergillosis/diagnosis , Aspergillosis/drug therapy , Aspergillosis/microbiology , Aspergillus , Echinocandins/pharmacology , Echinocandins/therapeutic use , Endocarditis/diagnosis , Endocarditis/drug therapy , Female , Humans , Microbial Sensitivity Tests , Voriconazole/pharmacology , Voriconazole/therapeutic use
10.
J Chin Med Assoc ; 85(3): 381-387, 2022 03 01.
Article in English | MEDLINE | ID: mdl-35259136

ABSTRACT

BACKGROUND: Acanthamoeba keratitis (AK) is a vision-threatening disease, usually associated with contact lens (CL) wear. As overnight orthokeratology (OOK) is increasingly used to control myopia, we have found incidence of OOK-associated AK is increasing. This study aimed to investigate the clinical presentation and visual outcomes of OOK-associated AK. METHODS: Demographic characteristics, clinical features, and treatment outcomes were collected by reviewing the medical charts of CL-associated AK patients (n = 35) diagnosed at Taipei Veterans General Hospital from 2001 to 2016. Cases were OOK-associated AK patients (n = 13), and controls were all other CL-associated AK patients (n = 22). Student t tests and chi-square tests were used to compare cases and controls. Linear regression analyses were used to identify factors associated with the final visual outcome in CL-associated AK. RESULTS: OOK-associated AK accounted for half of all CL-associated AK after 2010. OOK-associated AK patients and other CL-associated patients had similar best-corrected logarithm of the minimum angle of resolution visual acuity (BCLVA) before treatment (1.10 ± 0.75 vs 1.13 ± 0.76, p = 0.893), but OOK-associated AK patients were younger (17.15 ± 3.21 vs 26.36 ± 12.81 years, p = 0.004), had less severe disease (ring infiltration, 0% vs 31.82%, p = 0.023), and had better post-treatment BCLVA (0.06 ± 0.15 vs 0.51 ± 0.95, p = 0.041). Multiple linear regression analysis showed that better BCLVA after treatment in CL-associated AK was associated with initial presentation without ring infiltration (p = 0.002) but not with OOK use itself (p = 0.793). Twenty-six of 35 CL-associated AK patients had final BCLVA equal to or better than 0.10 (Snellen visual acuity of 6/7.5). All 13 OOK-associated AK cases were treated with chlorhexidine 0.02% ± voriconazole 1% ± oral voriconazole, and 12 of these patients had final BCLVA equal to or better than 0.10. CONCLUSION: Most CL-associated AK patients had satisfactory visual outcomes. Half of AK at our hospital is OOK-associated since 2010. Early diagnosis and correct treatment may be the reason why OOK-associated AK patients had better vision prognosis.


Subject(s)
Acanthamoeba Keratitis , Acanthamoeba Keratitis/diagnosis , Acanthamoeba Keratitis/drug therapy , Acanthamoeba Keratitis/etiology , Case-Control Studies , Humans , Retrospective Studies , Risk Factors , Taiwan , Tertiary Care Centers , Voriconazole/therapeutic use
11.
J Med Case Rep ; 16(1): 91, 2022 Mar 04.
Article in English | MEDLINE | ID: mdl-35241155

ABSTRACT

BACKGROUND: Scedosporium apiospermum, an opportunistic and filamentous fungus, is a rarely seen ocular entity that is difficult to identify and heal. We report a challenging case of S. apiospermium keratitis and discuss the treatment modalities in light of previous studies. CASE PRESENTATION: A 30-year-old Turkish farmer with a history of contact lens misuse presented to our clinic with a painful corneal abscess and severe vision loss in his left eye. S. apiospermum was identified by spectrophotometric analysis. The patient was successfully treated with therapeutic penetrating keratoplasty, but was resistant to fluconazole and amphotericin B and susceptible but unresponsive to voriconazole. CONCLUSION: S. apiospermum keratitis should be considered in the differential diagnosis of immunocompromised and immunocompetent patients with history of ocular trauma and contact lens use, especially those who do not respond to treatment.


Subject(s)
Eye Infections, Fungal , Keratitis , Scedosporium , Adult , Antifungal Agents/therapeutic use , Eye Infections, Fungal/diagnosis , Eye Infections, Fungal/drug therapy , Humans , Keratitis/diagnosis , Keratitis/drug therapy , Voriconazole/therapeutic use
13.
J Dermatol ; 49(5): 564-571, 2022 May.
Article in English | MEDLINE | ID: mdl-35218073

ABSTRACT

We encountered two cases of phaeohyphomycosis caused by Exophiala jeanselmei and E. oligosperma that were treated with fosravuconazole and terbinafine, respectively. Our cases were successfully treated with empiric therapy before the pathogen's species or antifungal sensitivity had been determined. We summarized 32 cases of cutaneous and subcutaneous phaeohyphomycosis caused by Exophiala species in Japan. The patients received antifungals, including itraconazole, terbinafine, voriconazole, and fosravuconazole, and the treatment success rates of these monotherapies were 77% (17/22), 67% (8/12), 100% (5/5), and 50% (1/2), respectively. Although the broad-spectrum azole antifungal itraconazole is the first choice for treatment, terbinafine at 125 mg/day might exert the same efficacy. Fosravuconazole is a novel broad-spectrum azole and a moderate inhibitor of Cyp3A4 that causes fewer drug interactions than itraconazole and voriconazole, indicating a promising drug for this disease.


Subject(s)
Exophiala , Phaeohyphomycosis , Antifungal Agents , Azoles/therapeutic use , Humans , Itraconazole/therapeutic use , Phaeohyphomycosis/diagnosis , Phaeohyphomycosis/drug therapy , Phaeohyphomycosis/microbiology , Terbinafine/therapeutic use , Voriconazole/therapeutic use
14.
Lima; IETSI; dic. 2020.
Non-conventional in Spanish | BRISA, BRISA | ID: biblio-1359154

ABSTRACT

INTRODUCCIÓN: El presente dictamen preliminar expone la evaluación de la eficacia y seguridad de las terapias antifúngicas intravenosas para la aspergilosis invasiva, en pacientes adultos con nefrotoxicidad o intolerancia a la anfotericina B deoxicolato y enfermedad aguda o progresiva. La aspergilosis invasiva (AI) es una infección fúngica altamente letal en hospedadores inmunodeprimidos. Se estima que la tasa de mortalidad es de aproximadamente 30 a 80 %. La anfotericina B deoxicolato es el agente antifúngico (intravenoso) con mayor experiencia de uso para tratar la AI; sin embargo, se asocia con importantes toxicidades que limitan su uso, principalmente la nefrotoxicidad. En EsSalud, los pacientes con AI, nefrotoxicidad o intolerancia a anfotericina B deoxicolato y enfermedad aguda, disponen de caspofungina. Sin embargo, el IETSI recibió una solicitud de uso de isavuconazol intravenoso bajo la argumentación de que este fármaco representa la mejor opción terapéutica para este tipo de pacientes, basado en un mejor perfil de eficacia y seguridad. Considerando que, además del isavuconazol, existen otras alternativas antifúngicas intravenosas indicadas para este tipo de pacientes, algunas de las cuales tienen experiencia de uso en EsSalud, el equipo evaluador del IETSI optó por re-evaluar el problema de decisión y realizar una evaluación de múltiples tecnologías sanitarias con el fin de identificar la opción de tratamiento más efectiva, segura y costo-efectiva para la población de interés. METODOLOGÍA: Se realizó una búsqueda sistemática de literatura con el objetivo de identificar evidencia sobre la eficacia y seguridad de las terapias antifúngicas intravenosas para la aspergilosis invasiva, en pacientes adultos con nefrotoxicidad o intolerancia a la anfotericina B deoxicolato y enfermedad aguda o progresiva. Se utilizaron las bases de datos PubMed, Cochrane Library y LILACS, priorizándose la evidencia proveniente de ensayos clínicos controlados aleatorizados. Asimismo, se realizó una búsqueda dentro de bases de datos pertenecientes a grupos que realizan evaluación de tecnologías sanitarias (ETS) y guías de práctica clínica (GPC), incluyendo el Healthcare Improvement Scotland, el National Institute for Health and Care Excellence (NICE), la Canadian Agency for Drugs and Technologies in Health (CADTH), la Haute Autorité de Santé (HAS), el Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen (IQWiG), además de la Base Regional de Informes de Evaluación de Tecnologías en Salud de las Américas (BRISA) y páginas web de sociedades especializadas en aspergilosis como American Thoracic Society (ATS), Infectious Diseases Society of America (IDSA), European Society for Clinical Microbiology and Infectious Diseases (ESCMID) y European Conference on Infections in Leukaemia (ECIL). Se hizo una búsqueda adicional en la página web del Registro administrado por la Biblioteca Nacional de Medicina de los Estados Unidos (https://clinicaltrials.gov/) e International Clinical Trial Registry Platform (ICTRP) (https://apps.who.int/trialsearch/), para poder identificar ensayos clínicos en curso o que no hayan sido publicados para, de este modo, disminuir el riesgo de sesgo de publicación. Para que la búsqueda de información pueda ser empleada para responder a la pregunta PICO se utilizaron estrategias de búsqueda que incluyeron términos relacionados a la población de interés, la intervención, y el comparador. Se emplearon términos MeSH1 y términos libre junto con operadores booleanos acordes a cada una de las bases de datos elegidas para la búsqueda. Con la estrategia de búsqueda diseñada para PubMed, se generaron alertas diarias vía correo electrónico con el objetivo de identificar estudios publicados luego del 09 de octubre de 2020. La búsqueda bibliográfica se limitó a GPC, ETS, revisiones sistemáticas con meta-análisis, y ECA que hayan evaluado la pregunta PICO de interés del presente dictamen. Ante la ausencia de ECA, también se buscaron estudios observacionales comparativos. La búsqueda se limitó a estudios en inglés y español. Se excluyeron las series de casos, los reportes de casos, las cartas al editor, los comentarios, las editoriales, los resúmenes de congresos y los estudios in vitro. La selección de los estudios fue llevada a cabo en dos fases. La primera fase consistió en la revisión de los títulos o los resúmenes a través del aplicativo web Rayyan (https://rayyan.qcri.org), que permitió pre-seleccionar los estudios a incluir y/o los que requerían más información para decidir. En la segunda fase se aplicaron de nuevo los criterios de elegibilidad empleando el texto completo de los estudios que fueron pre-seleccionados. RESULTADOS: Se realizó una búsqueda de la literatura con respecto a la eficacia y seguridad de las terapias antifúngicas intravenosas para la aspergilosis invasiva, en pacientes adultos con nefrotoxicidad o intolerancia a la anfotericina B deoxicolato y enfermedad aguda o progresiva. A continuación, se describe la evidencia disponible según el orden jerárquico del nivel de evidencia o pirámide de Haynes 6S. CONCLUSIONES: El presente dictamen preliminar tuvo como objetivo evaluar la mejor evidencia sobre la eficacia y seguridad de las terapias antifúngicas intravenosas para la aspergilosis invasiva, en pacientes adultos con nefrotoxicidad o intolerancia a la anfotericina B deoxicolato y enfermedad aguda o progresiva (segunda línea de tratamiento). Las intervenciones de interés fueron el isavuconazol intravenoso, el voriconazol intravenoso y la L-AmB (intravenosa), y el comparador de interés fue la caspofungina. Los desenlaces de interés fueron la respuesta clínica, microbiológica y radiológica, la sobrevida global, la mortalidad, la calidad de vida y los eventos adversos. La evidencia disponible sobre la mejor alternativa antifúngica para pacientes con AI y nefrotoxicidad o intolerancia a anfotericina B deoxicolato (o tratamientos antifúngicos convencionales en general) es de baja calidad metodológica. La evidencia disponible sugiere, aunque con una gran incertidumbre, que los antifúngicos de interés para la presente evaluación (isavuconazol, voriconazol, L-AmB y caspofungina) tendrían similar eficacia, en términos de respuesta antifúngica, pero con diferentes perfiles de seguridad. De estos, caspofungina es el que tiene más evidencia en un contexto de intolerancia y sus estudios incluyen a la población de interés del presente dictamen preliminar. Caspofungina es mejor tolerado que otras clases de antifúngicos sistémicos, no habiéndose reportado eventos de nefrotoxicidad. En ese sentido, caspofungina sería el fármaco más adecuado para tratar a la población de interés del presente dictamen. De manera adicional, es importante resaltar que optar por el uso de caspofungina, en lugar de los otros antifúngicos evaluados, es una decisión con mejor perfil de costo-oportunidad; ya que este fármaco tiene los costos más asequibles a nivel institucional. Por lo expuesto, el IETSI no aprueba el uso de isavuconazol intravenoso, voriconazol intravenoso y L-AmB (intravenosa) en pacientes adultos con AI, nefrotoxicidad o intolerancia a la anfotericina B deoxicolato y enfermedad aguda o progresiva.


Subject(s)
Humans , Aspergillosis/drug therapy , Amphotericin B/therapeutic use , Voriconazole/therapeutic use , Caspofungin/therapeutic use , Efficacy , Cost-Benefit Analysis
15.
Biomed Chromatogr ; 36(6): e5356, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35178731

ABSTRACT

Untreated invasive fungal infection is one of the important risk factors affecting the prognosis of pediatric patients with hematologic tumors. Voriconazole (VOR) is the first-line antifungal drug for the treatment of Aspergillus infections. In order to reduce the risk of adverse drug reactions while producing an ideal antifungal effect, therapeutic drug monitoring was performed to maintain the VOR plasma concentration in a range of 1,000-5,500 ng/ml. In the present study, a reliable, accurate, sensitive and quick ultra-high performance liquid chromatograph-tandem mass spectrometry (UPLC-MS/MS) method was developed for the determination of the VOR level. Protein precipitation was performed using acetonitrile, and then the chromatographic separation was carried out by UPLC using a C18 column with the gradient mobile phases comprising 0.1% methanoic acid in acetonitrile (A) and 0.1% methanoic acid in water (B). In the selective reaction monitor mode, the mass spectrometric detection was carried out using an TSQ Endura triple quadruple mass spectrometer. The performance of this UPLC-MS/MS method was validated as per the National Medical Products Administration for Bioanalytical Method Validation. Additionally, the plasma concentrations of VOR in pediatric patients with hematologic tumors were detected using this method, and the analyzed results were used for personalized therapy.


Subject(s)
Hematologic Neoplasms , Tandem Mass Spectrometry , Acetonitriles , Antifungal Agents/therapeutic use , Child , Chromatography, High Pressure Liquid/methods , Chromatography, Liquid/methods , Hematologic Neoplasms/drug therapy , Humans , Reproducibility of Results , Tandem Mass Spectrometry/methods , Voriconazole/therapeutic use
16.
Int J Hematol ; 115(2): 158-162, 2022 Feb.
Article in English | MEDLINE | ID: mdl-35088349

ABSTRACT

Letermovir is commonly used for CMV prophylaxis after allogeneic hematopoietic cell transplantation (HCT). Pharmacokinetic studies have shown an increase in tacrolimus exposure among healthy volunteers who took letermovir. However, studies in HCT recipients are needed because these patients are typically using concomitant antifungals with different degrees of CYP3A4 inhibition that may further interact with tacrolimus pharmacokinetics. In this study, we retrospectively evaluated the kinetics of tacrolimus concentration after letermovir discontinuation by type of concomitant azole antifungal in 57 HCT recipients. The median fold change in tacrolimus concentration-to-dose (C/D) ratio after discontinuing letermovir was 0.64 (range 0.43-0.99) with fluconazole and 1.10 (range 0.59-1.73) with voriconazole (p < 0.001). The tacrolimus C/D ratio decreased ≥ 30% after discontinuing letermovir (p < 0.001) in 66% of patients on fluconazole and 9% on voriconazole. Among patients whose tacrolimus C/D ratio decreased ≥ 30%, three (9%) patients in the fluconazole group and one (4%) in the voriconazole group experienced worsening of GVHD. Careful monitoring of tacrolimus concentration is important after letermovir discontinuation to avoid worsening of GVHD due to decreased tacrolimus concentration.


Subject(s)
Acetates/pharmacology , Antifungal Agents/pharmacology , Fluconazole/pharmacology , Immunosuppressive Agents/pharmacokinetics , Quinazolines/pharmacology , Tacrolimus/pharmacokinetics , Voriconazole/pharmacology , Acetates/therapeutic use , Antifungal Agents/therapeutic use , Female , Fluconazole/therapeutic use , Hematopoietic Stem Cell Transplantation , Humans , Immunosuppressive Agents/therapeutic use , Male , Quinazolines/therapeutic use , Tacrolimus/therapeutic use , Voriconazole/therapeutic use
17.
Medicine (Baltimore) ; 101(4): e28700, 2022 Jan 28.
Article in English | MEDLINE | ID: mdl-35089228

ABSTRACT

RATIONALE: Throughout the clinical course of acute myeloid leukemia (AML), aspergillosis infection remains a significant determinant of treatment outcomes and survival. To emphasize the importance of early diagnosis and appropriate application of integrated therapeutic approaches, we present a case of AML patient who survived through angioinvasive aspergillosis infection causing diaphragmatic rupture with bowel perforation and cerebral aspergillosis during active AML treatment. PATIENT CONCERNS: A 39-year old male with FLT3-mutated AML was transferred to our hospital due to persistent fever after induction therapy. DIAGNOSIS AND INTERVENTIONS: During voriconazole treatment for his invasive pulmonary aspergillosis, the patient was diagnosed with colon perforation at splenic flexure and suspected perforation of left diaphragm with communication with left pleural space. Although pancytopenic, emergency laparotomy was performed with granulocyte transfusion. Also, dual antifungal therapy with voriconazole and micafungin was applied. With supportive care, he was able to successfully complete 3 cycles of consolidation using tyrosine kinase inhibitor. However, 80 days after the last chemotherapy, the patient experienced seizure caused by a single 1.5 cm sized enhancing mass in the right occipital lobe. Diagnostic and therapeutic mass removal was carried out, and pathology-confirmed cerebral aspergillosis was diagnosed. OUTCOMES: The patient's neurologic symptoms are resolved and he is leukemia free, but remains on voriconazole for his cerebral aspergillosis till this day. CONCLUSIONS: Our case highlights the importance of timely integrated intervention and adequate underlying disease control in treatment of invasive aspergillosis in immunocompromised patients. Such rigorous efforts can save even the most seemingly dismal case.


Subject(s)
Antifungal Agents/therapeutic use , Intestinal Perforation/chemically induced , Invasive Pulmonary Aspergillosis/chemically induced , Leukemia, Myeloid, Acute/drug therapy , Thoracic Injuries/chemically induced , fms-Like Tyrosine Kinase 3/genetics , Adult , Antifungal Agents/adverse effects , Humans , Intestinal Perforation/surgery , Invasive Pulmonary Aspergillosis/complications , Leukemia, Myeloid, Acute/complications , Leukemia, Myeloid, Acute/genetics , Male , Micafungin/therapeutic use , Pyrimidines/therapeutic use , Triazoles/therapeutic use , Voriconazole/therapeutic use
18.
JAMA Ophthalmol ; 140(2): 179-184, 2022 Feb 01.
Article in English | MEDLINE | ID: mdl-35024776

ABSTRACT

IMPORTANCE: Antifungal resistance has been shown to impact treatment success, but research analyzing antifungal resistance is scarce. OBJECTIVE: To evaluate changes in antifungal resistance over time. DESIGN, SETTING, AND PARTICIPANTS: Ad hoc analysis of 3 randomized clinical trials including consecutive patients 18 years and older presenting with smear-positive fungal ulcers to Aravind Eye Hospitals in Madurai, Coimbatore, Pondicherry, and Tirunelveli in South India who participated in 1 of 3 clinical trials: the Mycotic Ulcer Treatment Trials (MUTT) I (2010 to 2011) or II (2010 to 2015) or the Cross-Linking Assisted Infection Reduction (CLAIR) trial (2016 to 2018). This post hoc analysis was designed in March 2021 and data were analyzed in May and November 2021. INTERVENTIONS: Minimum inhibitory concentration (MIC) of natamycin and voriconazole was determined from corneal cultures obtained using standardized methods outlined in the Clinical and Laboratory Standards Institute. MAIN OUTCOMES AND MEASURES: The primary outcome of this post hoc analysis was MIC of natamycin and voriconazole. RESULTS: A total of 890 fungal isolates were obtained from 651 patients (mean [SD] age, 49.6 [13.0]; 191 [43.3%] female) from 2010 to 2018. MICs were available for 522 samples in 446 patients. Fungal isolates overall demonstrated a 1.02-fold increase per year in voriconazole resistance as measured by MICs (95% CI, 1.00-1.04; P = .06). In subgroup analyses, Fusarium species demonstrated a 1.04-fold increase in voriconazole resistance per year (95% CI, 1.00-1.06; P = .01). Fungal isolates showed a 1.06-fold increase in natamycin resistance per year overall (95% CI, 1.03-1.09; P < .001). Fusarium species had a 1.06-fold increase in natamycin resistance (95% CI, 1.05-1.08; P < .001), Aspergillus had a 1.09-fold increase in resistance (95% CI, 1.05-1.15; P < .001), and other filamentous fungi had a 1.07-fold increase in resistance to natamycin per year (95% CI, 1.04-1.10; P < .001). CONCLUSIONS AND RELEVANCE: This post hoc analysis suggests that susceptibility to both natamycin and voriconazole may be decreasing over the last decade in South India. While a trend of increasing resistance could impact treatment of mycoses in general and infectious fungal keratitis in particular, further study is needed to confirm these findings and determine their generalizability to other regions of the world. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT00996736 and NCT02570321.


Subject(s)
Corneal Ulcer , Eye Infections, Fungal , Fusarium , Keratitis , Mycoses , Adult , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Corneal Ulcer/drug therapy , Corneal Ulcer/epidemiology , Corneal Ulcer/microbiology , Eye Infections, Fungal/drug therapy , Eye Infections, Fungal/epidemiology , Eye Infections, Fungal/microbiology , Female , Humans , India/epidemiology , Keratitis/drug therapy , Male , Microbial Sensitivity Tests , Middle Aged , Mycoses/drug therapy , Mycoses/epidemiology , Mycoses/microbiology , Natamycin/pharmacology , Natamycin/therapeutic use , Randomized Controlled Trials as Topic , Voriconazole/pharmacology , Voriconazole/therapeutic use
19.
Chest ; 161(1): e5-e11, 2022 01.
Article in English | MEDLINE | ID: mdl-35000717

ABSTRACT

CASE PRESENTATION: A 67-year-old obese man (BMI 38.0) with type 2 diabetes mellitus (DM), chronic atrial fibrillation, and chronic lymphocytic leukemia stage II, stable for 8 years after chemotherapy, and a history of smoking presented to the ED with progressive dyspnea and fever due to SARS-CoV-2 infection. He was admitted to a general ward and treated with dexamethasone (6 mg IV once daily) and oxygen. On day 3 of hospital admission, he became progressively hypoxemic and was admitted to the ICU for invasive mechanical ventilation. Dexamethasone treatment was continued, and a single dose of tocilizumab (800 mg) was administered. On day 9 of ICU admission, voriconazole treatment was initiated after tracheal white plaques at bronchoscopy, suggestive of invasive Aspergillus tracheobronchitis, were noticed. However, his medical situation dramatically deteriorated.


Subject(s)
Acute Kidney Injury/virology , Antifungal Agents/therapeutic use , COVID-19/complications , Mucormycosis/diagnosis , Mucormycosis/drug therapy , Pulmonary Aspergillosis/diagnosis , Pulmonary Aspergillosis/drug therapy , Aged , Amphotericin B/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Atrial Fibrillation/complications , Bronchoscopy , Dexamethasone/therapeutic use , Diabetes Mellitus, Type 2/complications , Fatal Outcome , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/complications , Male , Nitriles/therapeutic use , Obesity/complications , Oxygen Inhalation Therapy , Pyridines/therapeutic use , Respiration, Artificial , SARS-CoV-2 , Smoking/adverse effects , Tomography, X-Ray Computed , Triazoles/therapeutic use , Voriconazole/therapeutic use
20.
Intern Med J ; 51 Suppl 7: 143-176, 2021 11.
Article in English | MEDLINE | ID: mdl-34937136

ABSTRACT

Invasive aspergillosis (IA) in haematology/oncology patients presents as primary infection or breakthrough infection, which can become refractory to antifungal treatment and has a high associated mortality. Other emerging patient risk groups include patients in the intensive care setting with severe respiratory viral infections, including COVID-19. These guidelines present key diagnostic and treatment recommendations in light of advances in knowledge since the previous guidelines in 2014. Culture and histological-based methods remain central to the diagnosis of IA. There is increasing evidence for the utility of non-culture methods employing fungal biomarkers in pre-emptive screening for infection, as well as for IA diagnosis when used in combination. Although azole resistance appears to be uncommon in Australia, susceptibility testing of clinical Aspergillus fumigatus complex isolates is recommended. Voriconazole remains the preferred first-line antifungal agent for treating primary IA, including for extrapulmonary disease. Recommendations for paediatric treatment broadly follow those for adults. For breakthrough and refractory IA, a change in class of antifungal agent is strongly recommended, and agents under clinical trial may need to be considered. Newer immunological-based imaging modalities warrant further study, while surveillance for IA and antifungal resistance remain essential to informing the relevance of current treatment recommendations.


Subject(s)
Aspergillosis , COVID-19 , Adult , Antifungal Agents/therapeutic use , Aspergillosis/diagnosis , Aspergillosis/drug therapy , Aspergillus fumigatus , Child , Drug Resistance, Fungal , Humans , SARS-CoV-2 , Voriconazole/therapeutic use
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