Estudio clínico y microbiológico de enfermedades fúngicas invasivas en pacientes con neoplasias hematooncológicas en un centro de referencia de Paraguay
Palabras clave:
infecciones fúngicas invasoras, neoplasias hematológicas, neutropenia febril, aspergilosis, candidiasis
Resumen
Introducción: las enfermedades fúngicas invasivas (EFI) representan una causa importante de morbimortalidad en pacientes con neoplasias hematológicas y trasplantes de progenitores hematopoyéticos.
Objetivo: describir el perfil clínico y microbiológico de los episodios de EFI en pacientes adultos con neoplasias hematooncológicas en el Hospital Central del Instituto de Previsión Social, Asunción, Paraguay.
Materiales y métodos: estudio descriptivo, retrospectivo, realizado en Departamento de Medicina Interna entre 2022 y 2024. Se incluyeron pacientes adultos con neoplasias hematooncológicas o antecedentes de trasplante de progenitores hematopoyéticos, que presentaron EFI. Se utilizaron métodos microbiológicos estandarizados. Se describieron variables clínicas, epidemiológicas y terapéuticas mediante estadística descriptiva.
Resultados: se incluyeron 34 pacientes, con un predominio del sexo femenino. Los diagnósticos más frecuentes fueron la leucemia mieloide aguda y el linfoma no Hodgkin. El 35,2% había recibido trasplante de progenitores hematopoyéticos, predominantemente alogénico. Los factores de riesgo más frecuentes fueron uso reciente de antimicrobianos, quimioterapia, catéter venoso central y corticoterapia en altas dosis. Las EFI más comunes fueron aspergilosis pulmonar invasiva y candidemias por Candida parapsilosis. El tratamiento principal fue voriconazol, aunque en algunos casos se requirió anfotericina B por problemas de disponibilidad. La mortalidad intrahospitalaria fue del 17,6%, concentrada en pacientes con aspergilosis invasiva.
Conclusiones: las EFI presentan características diversas según los factores de riesgo del paciente y el perfil microbiológico institucional. Estos hallazgos destacan la necesidad de estrategias locales de vigilancia, diagnóstico precoz y tratamiento oportuno, así como la implementación de protocolos de profilaxis adaptados a cada contexto.
Citas
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14. Posteraro B, De Carolis E, Criscuolo M, Ballanti S, De Angelis G, Del Principe MI, et al. Candidaemia in haematological malignancy patients from a SEIFEM study: Epidemiological patterns according to antifungal prophylaxis. Mycoses [Internet]. 2020 [cited 2024 Jun 10];63(9):900-10. Available from: https://pubmed.ncbi.nlm.nih.gov/32531854/
15. Gatti M, Rinaldi M, Ferraro G, Toschi A, Caroccia N, Arbizzani F, et al. Breakthrough invasive fungal infections in liver transplant recipients exposed to prophylaxis with echinocandins vs other antifungal agents: A systematic review and meta-analysis. Mycoses [Internet]. 2021 [cited 2024 Jun 10];64(11):1317-27. Available from: https://pubmed.ncbi.nlm.nih.gov/34387004/
16. Jebari M, Mtibaa L, Ghedira H, Baccouchi N, Zriba S, Msadek F, Jemli B. Invasive fungal infection in patients with hematologic malignancies: epidemiology and prognostic factors. Pan Afr Med J [Internet]. 2024 [cited 2024 Jun 10]; 48:130. Available from: https://pubmed.ncbi.nlm.nih.gov/39525547/
17. Patterson TF, Thompson GR 3rd, Denning DW, Fishman JA, Hadley S, Herbrecht R, et al. Practice guidelines for the diagnosis and management of aspergillosis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis [Internet]. 2016 [cited 2024 Jun 10];63(4):e1-e60. Available from: https://pubmed.ncbi.nlm.nih.gov/27365388/
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19. Pagano L, Caira M, Candoni A, Offidani M, Martino B, Specchia G, et al. Invasive aspergillosis in patients with acute myeloid leukemia: a SEIFEM-2008 registry study. Haematologica [Internet]. 2010 [cited 2024 Jun 10];95(4):644-50. Available from: https://pubmed.ncbi.nlm.nih.gov/19850903/
20. Cornely OA, Cuenca-Estrella M, Meis JF, Ullmann AJ. European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Fungal Infection Study Group (EFISG) and European Confederation of Medical Mycology (ECMM) 2013 joint guidelines on diagnosis and management of rare and emerging fungal diseases. Clin Microbiol Infect [Internet]. 2014 [cited 2024 Jun 10];20 [Suppl 3]:1-4. Available from: https://pubmed.ncbi.nlm.nih.gov/24606200/
21. Ullmann AJ, Aguado JM, Arikan-Akdagli S, Denning DW, Groll AH, Lagrou K, et al. Diagnosis and management of aspergillus diseases: executive summary of the 2017 ESCMID-ECMM-ERS guideline. Clin Microbiol Infect [Internet]. 2018 [cited 2024 Jun 10];24 [Suppl 1]:e1-e38. Available from: https://pubmed.ncbi.nlm.nih.gov/29544767/
22. Phillips K, Cirrone F, Ahuja T, Siegfried J, Papadopoulos J. Posaconazole versus voriconazole as antifungal prophylaxis during induction therapy for acute myelogenous leukemia or myelodysplastic syndrome. J Oncol Pharm Pract [Internet]. 2019 [cited 2024 Jun 10];25(2):398-403. Available from: https://pubmed.ncbi.nlm.nih.gov/30319061/ Subscription required
23. Alkan A, Buyukasik Y, Uzun O, Demir AU, Coplu L. Invasive fungal infections in patients with acute leukemia: A retrospective cohort study at a tertiary-care hospital. Medicine (Baltimore) [Internet]. 2024 [cited 2024 Jun 10];103(40):e39959. Available from: https://pubmed.ncbi.nlm.nih.gov/39465746/
2. Cornely OA, Hoenigl M, Lass-Flörl C, Chen SCA, Kontoyiannis DP, Morrissey CO, et al. Defining breakthrough invasive fungal infection-Position paper of the mycoses study group education and research consortium and the European Confederation of Medical Mycology. Mycoses [Internet]. 2019 [cited 2024 Jun 10];62(9):716-29. Available from: https://pubmed.ncbi.nlm.nih.gov/31254420/
3. Oberoi JK, Sheoran L, Sagar T, Saxena S. Invasive fungal infections in hemato-oncology. Indian J Med Microbiol [Internet]. 2023 [cited 2024 Jun 10]; 44:100353. Available from: https://pubmed.ncbi.nlm.nih.gov/37356843/ Subscription required
4. Baliga S, Yadav S, Sagdeo P, Balakrishnan C. Invasive fungal infection in ANCA-associated vasculitis: Between the Devil and Deep blue sea. Case series and review of the literature. Clin Rheumatol [Internet]. 2024 [cited 2024 Jun 10];43(2):785-97. Available from: https://pubmed.ncbi.nlm.nih.gov/37798405/ Subscription required
5. Salmanton-García J, Koehler P, Grothe JH, Mellinghoff SC, Sal E, Simon M, et al. The Cologne ECMM Excellence Center: A two-year analysis of external consultation service for invasive fungal infections. Mycopathologia [Internet]. 2024 [cited 2024 Jun 10];189(2):25. Available from: https://pubmed.ncbi.nlm.nih.gov/38466469/
6. Brizuela Centurión AM, Martí Ruiz ACM, Fusillo Montanaro JD, Oleynick Goncalves AF; Ayala Careaga JB. Aislamiento de gérmenes oportunistas en pacientes internados en Unidad de Cuidados Intensivos. Rev salud publica Parag [Internet]. 2023 [citado 10 Jun 2024];13(1):35–9. Disponible en: doi: https://doi.org/10.18004/rspp.2023.abril.05
7. Arriola A, Arbo A. Factores de riesgo potenciales en infecciones sistémicas por Candida spp. Rev Inst Med Trop [Internet]. 2020 [citado 10 Jun 2024];15(2):5–12. Disponible en: doi: https://doi.org/10.18004/imt/2020.15.2.5
8. Aldama Caballero A, Acosta Sens R, Rivelti V, Insaurralde S, Mendoza de Sánchez G, Celías L. Aspergilosis diseminada con importante afectación cutánea. An Fac Cienc Méd (Asunción) [Internet]. 2016 [citado 10 Jun 2024];49(2):87–96. Disponible en: doi: https://doi.org/10.18004/anales/2016.049(02)87-096
9. Aluán A, Aguayo D, Pérez Bejarano D. Aspergilosis invasiva de vías aéreas. Rev Nac (Itauguá) [Internet]. 2023 [citado 10 Jun 2024];15(2):93–6. Disponible en: doi: https://doi.org/10.18004/rdn2023.dic.02.093.096
10. Rivaldi Montenegro FB, Rodríguez Leiva RR, Gill Oliveira J, Jatchuk Luchuk AM, Barreto Ríos MN. Factores de riesgo de mortalidad en pacientes hematológicos con aspergilosis pulmonar en Clínica Médica del Instituto de Previsión Social -Hospital Central. Año 2016 a 2018. Rev Inst Med Trop [Internet]. 2021 [citado 10 Jun 2024];16(2):61–9. Disponible en: doi: https://doi.org/10.18004/imt/2021.16.2.61
11. Guinea J, Bouza E. Current challenges in the microbiological diagnosis of invasive aspergillosis. Mycopathologia [Internet]. 2014 [cited 2024 Jun 10];178(5-6):403-16. Available from: https://pubmed.ncbi.nlm.nih.gov/24947167/ Subscription required
12. Arvanitis M, Anagnostou T, Fuchs BB, Caliendo AM, Mylonakis E. Molecular and nonmolecular diagnostic methods for invasive fungal infections. Clin Microbiol Rev [Internet]. 2014 [cited 2024 Jun 10];27(3):490-526. Available from: https://pubmed.ncbi.nlm.nih.gov/24982319/
13. Girmenia C, Raiola AM, Piciocchi A, Algarotti A, Stanzani M, Cudillo L, et al. Incidence and outcome of invasive fungal diseases after allogeneic stem cell transplantation: a prospective study of the Gruppo Italiano Trapianto Midollo Osseo (GITMO). Biol Blood Marrow Transplant [Internet]. 2014 [cited 2024 Jun 10];20(6):872-80. Available from: https://pubmed.ncbi.nlm.nih.gov/24631738/
14. Posteraro B, De Carolis E, Criscuolo M, Ballanti S, De Angelis G, Del Principe MI, et al. Candidaemia in haematological malignancy patients from a SEIFEM study: Epidemiological patterns according to antifungal prophylaxis. Mycoses [Internet]. 2020 [cited 2024 Jun 10];63(9):900-10. Available from: https://pubmed.ncbi.nlm.nih.gov/32531854/
15. Gatti M, Rinaldi M, Ferraro G, Toschi A, Caroccia N, Arbizzani F, et al. Breakthrough invasive fungal infections in liver transplant recipients exposed to prophylaxis with echinocandins vs other antifungal agents: A systematic review and meta-analysis. Mycoses [Internet]. 2021 [cited 2024 Jun 10];64(11):1317-27. Available from: https://pubmed.ncbi.nlm.nih.gov/34387004/
16. Jebari M, Mtibaa L, Ghedira H, Baccouchi N, Zriba S, Msadek F, Jemli B. Invasive fungal infection in patients with hematologic malignancies: epidemiology and prognostic factors. Pan Afr Med J [Internet]. 2024 [cited 2024 Jun 10]; 48:130. Available from: https://pubmed.ncbi.nlm.nih.gov/39525547/
17. Patterson TF, Thompson GR 3rd, Denning DW, Fishman JA, Hadley S, Herbrecht R, et al. Practice guidelines for the diagnosis and management of aspergillosis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis [Internet]. 2016 [cited 2024 Jun 10];63(4):e1-e60. Available from: https://pubmed.ncbi.nlm.nih.gov/27365388/
18. Marr KA, Schlamm HT, Herbrecht R, Rottinghaus ST, Bow EJ, Cornely OA, et al. Combination antifungal therapy for invasive aspergillosis: a randomized trial. Ann Intern Med [Internet]. 2015 [cited 2024 Jun 10];162(2):81-9. Available from: https://pubmed.ncbi.nlm.nih.gov/25599346/ Subscription required
19. Pagano L, Caira M, Candoni A, Offidani M, Martino B, Specchia G, et al. Invasive aspergillosis in patients with acute myeloid leukemia: a SEIFEM-2008 registry study. Haematologica [Internet]. 2010 [cited 2024 Jun 10];95(4):644-50. Available from: https://pubmed.ncbi.nlm.nih.gov/19850903/
20. Cornely OA, Cuenca-Estrella M, Meis JF, Ullmann AJ. European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Fungal Infection Study Group (EFISG) and European Confederation of Medical Mycology (ECMM) 2013 joint guidelines on diagnosis and management of rare and emerging fungal diseases. Clin Microbiol Infect [Internet]. 2014 [cited 2024 Jun 10];20 [Suppl 3]:1-4. Available from: https://pubmed.ncbi.nlm.nih.gov/24606200/
21. Ullmann AJ, Aguado JM, Arikan-Akdagli S, Denning DW, Groll AH, Lagrou K, et al. Diagnosis and management of aspergillus diseases: executive summary of the 2017 ESCMID-ECMM-ERS guideline. Clin Microbiol Infect [Internet]. 2018 [cited 2024 Jun 10];24 [Suppl 1]:e1-e38. Available from: https://pubmed.ncbi.nlm.nih.gov/29544767/
22. Phillips K, Cirrone F, Ahuja T, Siegfried J, Papadopoulos J. Posaconazole versus voriconazole as antifungal prophylaxis during induction therapy for acute myelogenous leukemia or myelodysplastic syndrome. J Oncol Pharm Pract [Internet]. 2019 [cited 2024 Jun 10];25(2):398-403. Available from: https://pubmed.ncbi.nlm.nih.gov/30319061/ Subscription required
23. Alkan A, Buyukasik Y, Uzun O, Demir AU, Coplu L. Invasive fungal infections in patients with acute leukemia: A retrospective cohort study at a tertiary-care hospital. Medicine (Baltimore) [Internet]. 2024 [cited 2024 Jun 10];103(40):e39959. Available from: https://pubmed.ncbi.nlm.nih.gov/39465746/
