García-Ortega S, Soto-Manzano AV, Martínez-Sánchez LM

Language: Spanish
References: 47
Page: 42-47
PDF size: 158.78 Kb.

ABSTRACT

Introduction. Invasive fungal infections (ifis) are a frequent cause of morbidity and mortality in immunocompromised patients, such as those with leukemia or who have undergone hematopoietic stem cell transplantation. The main risk factors include prolonged neutropenia and corticosteroid use. The most common ifis are candidiasis and aspergillosis, which is usually acquired by inhaling spores. Their treatment and prophylaxis can present a medical challenge due to adverse effects and resistance to currently available antifungal agents.
Materials and methods. A review of the literature was carried out in databases such as PubMed and Elsevier. We reviewed 100 articles published in recent years, of which 47 were selected to be part of this review, limiting participation to those that were not available in Spanish or English, or that spoke specifically of the pediatric population.
Conclusion. Invasive fungal infections remain a threat to immunocompromised patients, such as those with hematologic malignancies or stem cell transplants. Despite advances in diagnosis, treatments face challenges such as antifungal resistance and side effects. Azole prophylaxis has been effective, but the choice of treatment must be tailored to the individual patient. Research into new antifungals and optimization of prophylactic therapies are key to improving outcomes in these patients.

REFERENCES

1. Donnelly, J.P., Chen, S.C., Kauffman, C.A., Steinbach,W.J., Baddley, J.W. Verweij, P.E. et al., “Revision andupdate of the consensus definitions of invasive fungaldisease from the European Organization for Researchand Treatment of Cancer and the Mycoses Study GroupEducation and Research Consortium”, Clin Infect Dis, 2020, 71 (6): 1367-1376. doi: 10.1093/cid/ciz1008.

2. Busca, A., Cinatti, N., Gill, J., Passera, R., Dellacasa,C.M., Giaccone, L. et al., “Management of invasivefungal infections in patients undergoing allogeneichematopoietic stem cell transplantation: the Turin experience”,Front Cell Infect Microbiol, 2022, 11: 805514.doi: 10.3389/fcimb.2021.805514.

3. Akan, H., Antia, V.P., Kouba, M., Sinkó, J., Tănase, A.D.,Vrhovac, R. et al., “Preventing invasive fungal diseasein patients with haematological malignancies and therecipients of haematopoietic stem cell transplantation:practical aspects”, J Antimicrob Chemother, 2013, 68Suppl 3: iii5-16. doi: 10.1093/jac/dkt389.

4. Kontoyiannis, D.P., Marr, K.A., Park, B.J., Alexander, B.D.,Anaissie, E.J., Walsh, T.J. et al., “Prospective surveillancefor invasive fungal infections in hematopoietic stemcell transplant recipients, 2001-2006: overview of theTransplant-Associated Infection Surveillance Network(transnet) Database”, Clin Infect Dis, 2010, 50 (8): 1091-1100. doi: 10.1086/651263.

5. Shafiee, F., Soltani, R. y Meidani, M., “Invasive fungalinfections in hematologic malignancies: incidence,management, and antifungal therapy”, J Res Med Sci,2023, 28: 73. doi: 10.4103/jrms.jrms_1072_21.

6. Worth, L.J. y Slavin, M.A., “Bloodstream infections inhaematology: risks and new challenges for prevention”,Blood Rev, 2009, 23 (3): 113-122. doi: 10.1016/j.blre.2008.10.003.

7. Rüping, M.J., Vehreschild, J.J. y Cornely, O.A., “Patientsat high risk of invasive fungal infections: when andhow to treat”, Drugs, 2008, 68 (14): 1941-1962. doi:10.2165/00003495-200868140-00002.

8. Cordonnier, C., Pautas, C., Maury, S., Vekhoff, A., Farhat,H., Suárez, F. et al., “Empirical versus preemptiveantifungal therapy for high-risk, febrile, neutropenicpatients: a randomized, controlled trial”, Clin Infect Dis,2009, 48 (8): 1042-1051. doi: 10.1086/597395.

9. Montagna, M.T., Giglio, O., Napoli, C., Lovero, G., Caggiano,G. Delia, M. et al., “Invasive fungal infections in patientswith hematologic malignancies (Aurora project): lightsand shadows during 18-months surveillance”, Int J MolSci., 2012, 13 (1): 774-787. doi: 10.3390/ijms13010774.

10. Caira, M., Girmenia, C., Fadda, R.M., Mitra, M.E., Picardi,M., Van Lint, M.T. et al., “Invasive fungal infections inpatients with acute myeloid leukemia and in those submittedto allogeneic hemopoietic stem cell transplant:who is at highest risk?”, Eur J Haematol, 2008, 81 (3):242-243. doi: 10.1111/j.1600-0609.2008.01096.x.

11. Lehrnbecher, T., Groll, A.H., Cesaro, S., Alten, J., Attarbaschi,A., Barbaric, D. et al., “Invasive fungal diseasesimpact on outcome of childhood all: an analysis of theinternational trial aieop-bfm all 2009”, Leukemia, 2023,37 (1): 72-78. doi: 10.1038/s41375-022-01768-x.

12. Martino, R. y Subirà, M., “Invasive fungal infections inhematology: new trends”, Ann Hematol, 2002, 81 (5):233-243. doi: 10.1007/s00277-002-0466-3.

13. Pagano, L., Akova, M., Dimopoulos, G., Herbrecht, R.,Drgona, L. y Blijlevens, N., “Risk assessment and prognosticfactors for mould-related diseases in immunocompromisedpatients”, J Antimicrob Chemother, 2011,66 Suppl 1: i5-14. doi: 10.1093/jac/dkq437.

14. Zhang, X., Zhang, L., Li, Y., Wang, N. y Zhang, Y., “Clinicalperformance of metagenomic next-generation sequencingfor diagnosis of invasive fungal disease after hematopoieticcell transplant”, Front Cell Infect Microbiol,2024, 14: 1210857. doi: 10.3389/fcimb.2024.1210857.

15. Ledoux, M.P. y Herbrecht, R., “Invasive pulmonaryaspergillosis”, J Fungi (Basilea), 2023, 9 (2): 131. doi:10.3390/jof9020131.

16. Girmenia, C., Raiola, A.M., Piciocchi, A., Algarotti, A.,Stanzani, M., Cudillo, L. et al., “Incidence and outcomeof invasive fungal diseases after allogeneic stemcell transplantation: a prospective study of the GruppoItaliano Trapianto Midollo Osseo (gitmo)”, Biol BloodMarrow Transplant, 2014, 20 (6): 872-880. doi: 10.1016/j.bbmt.2014.03.004.

17. Schuster, M.G., Cleveland, A.A., Dubberke, E.R., Kauffman,C.A., Avery, R.K., Husain, S. et al., “Infections inhematopoietic cell transplant recipients: results fromthe organ transplant infection project, a multicenter,prospective, cohort study”, Open Forum Infect Dis,2017, 4 (2): ofx050. doi: 10.1093/ofid/ofx050.

18. Maertens, J., Lodewyck, T., Donnelly, J.P., Chantepie, S.,Robin, C., Blijlevens, N. et al., “Empiric vs preemptive antifungalstrategy in high-risk neutropenic patients on fluconazoleprophylaxis: a randomized trial of the EuropeanOrganization for Research and Treatment of Cancer”, ClinInfect Dis, 2023, 76 (4): 674-682. doi: 10.1093/cid/ciac623.

19. Erb, T., Mihai, S., Strauß, R., Herbst, L., Castellanos, I.,Diesch, K. et al., “β-(1→3)-D-glucan- and mannan-guidedearly termination of antifungal therapy in icu patients:a randomized controlled study”, Antimicrob AgentsChemother, 2023, 67 (11): e0072523. doi: 10.1128/aac.00725-23.

20. Locke, J.B., Pillar, C.M., Castanheira, M., Carvalhaes,C.G., Andes, D., Aram, J.A. et al., “Outcomes by Candidaspp. in the restore phase 3 trial of rezafunginversus caspofungin for candidemia and/or invasive candidiasis”,Antimicrob Agents Chemother, 2024, 68 (5):e0158423. doi: 10.1128/aac.01584-23.

21. Thompson, G.R. 3rd, Soriano, A., Honore, P.M., Bassetti,M., Cornely, O.A., Kollef, M. et al., “Efficacy and safetyof rezafungin and caspofungin in candidaemia and invasivecandidiasis: pooled data from two prospectiverandomised controlled trials”, Lancet Infect Dis, 2024,24 (3): 319-328. doi: 10.1016/S1473-3099(23)00551-0.

22. Saber-Moghaddam, N., Nodeh, M.M., Ghavami, V.,Rahimi, H., Azimi, S.A., Seddigh-Shamsi, M. et al., “Theevaluation of atorvastatin as an adjunct to fluconazolefor the anti-fungal prophylaxis in acute myeloid leukemia:a multicenter, triple-blinded, randomized clinicaltrial”, Naunyn Schmiedebergs Arch Pharmacol, 2024,397 (6): 4355-4364. doi: 10.1007/s00210-023-02892-w.

23. Veringa, A., Brüggemann, R.J., Span, L.F.R., Biemond,B.J., De Boer, M.G.J., Van den Heuvel, E.R. et al., “Therapeuticdrug monitoring-guided treatment versus standarddosing of voriconazole for invasive aspergillosisin haematological patients: a multicentre, prospective,cluster randomised, crossover clinical trial”, Int J AntimicrobAgents, 2023, 61 (2): 106711. doi: 10.1016/j.ijantimicag.2023.106711.

24. Khardori, N. y Bodey, G.P., “Infections in hematologicmalignancies”, Hematology, 1991, 14: 363-424.

25. Verfaillie, C., Weisdorf, D., Haake, R., Hostetter, M.,Ramsay, N.K. y McGlave, P., “Candida infections in bonemarrow transplant recipients”, Bone Marrow Transplant,1991, 8 (3): 177-184.

26. Wolff, S.N., Fay, J., Stevens, D., Herzig, R.H., Pohlman,B., Bolwell, B. et al., “Fluconazole vs low-dose amphotericinb for the prevention of fungal infections in patientsundergoing bone marrow transplantation: a study ofthe North American Marrow Transplant Group”, BoneMarrow Transplant, 2000, 25 (8): 853-859. doi: 10.1038/sj.bmt.1702233.

27. Krüger, W., Sobottka, I., Stockschläder, M., Mross, K.,Hoffknecht, M., Rüssmann, B. et al., “Fatal outcome ofdisseminated candidosis after allogeneic bone marrowtransplantation under treatment with liposomal and conventionalamphotericin-b. A report of 4 cases with determinationof the Mic values”, Scand J Infect Dis, 1996, 28(3): 313-316. doi: 10.3109/00365549609027181.

28. Sastry, P.S., Parikh, P.M., Kulkarni, P.S., Bhagwat, R. yGadade, H., “Use of liposomal amphotericin b in bonemarrow transplant”, J Postgrad Med, 2005, 51 Suppl 1:S49-52.

29. Wang, J., Zhan, P., Zhou, R., Xu, J., Shao, X., Yang, Y. etal., “Prophylaxis with itraconazole is more effective thanprophylaxis with fluconazole in neutropenic patientswith hematological malignancies: a meta-analysis ofrandomized-controlled trials”, Med Oncol, 2010, 27 (4):1082-1088. doi: 10.1007/s12032-009-9339-0.

30. Xu, S.X., Shen, J.L., Tang, X.F., Feng, B. y Xu, H.Q.,“Newer antifungal agents micafungin and voriconazolefor fungal infection prevention during hematopoieticcell transplantation: a meta-analysis”, Eur Rev MedPharmacol Sci, 2016, 20 (2): 381-390.

31. Bow, E.J., Vanness, D.J., Slavin, M., Cordonnier, C.,Cornely, O.A., Marks, D.I. et al., “Systematic review andmixed treatment comparison meta-analysis of randomizedclinical trials of primary oral antifungal prophylaxisin allogeneic hematopoietic cell transplant recipients”,bmc Infect Dis, 2015, 15: 128. doi: 10.1186/s12879-015-0855-6.

32. Flowers, C.R., Seidenfeld, J., Bow, E.J., Karten, C., Gleason,C., Hawley, D.K. et al., “Antimicrobial prophylaxisand outpatient management of fever and neutropenia inadults treated for malignancy: American Society of ClinicalOncology clinical practice guideline”, J Clin Oncol,2013, 31 (6): 794-810. doi: 10.1200/JCO.2012.45.8661.

33. Patterson, T.F., Thompson, G.R. 3rd, Denning, D.W., Fishman,J.A., Hadley, S., Herbrecht, R. et al., “PracticeGuidelines for the Diagnosis and Management of Aspergillosis:2016 Update by the Infectious Diseases Societyof America”, Clin Infect Dis, 2016, 63 (4): e1-e60.doi: 10.1093/cid/ciw326.

34. Ruiz-Campos, I., Aguado, J.M., Almirante, B., Bouza,E., Ferrer-Barbera, C.F., Len, O. et al., “Guidelines forthe prevention of invasive mould diseases caused byfilamentous fungi by the Spanish Society of InfectiousDiseases and Clinical Microbiology (seimc)”, Clin MicrobiolInfect, 2011, 17 Suppl 2: 1-24. doi: 10.1111/j.1469-0691.2011.03477.x.

35. Barberán, J., Mensa, J., Llamas, J.C., Ramos, I.J., Ruiz,J.C., Marín, J.R. et al., “Recommendations for the treatmentof invasive fungal infection caused by filamentousfungi in the hematological patient”, Rev Esp Quimioter,2011, 24 (4): 263-270.

36. Su, H.C., Hua, Y.M., Feng, I.J. y Wu, H.C., “Comparativeeffectiveness of antifungal agents in patients withhematopoietic stem cell transplantation: a systematicreview and network meta-analysis”, Infect Drug Resist,2019, 12: 1311-1324. doi: 10.2147/IDR.S203579.

37. Wang, J., Zhou, M., Xu, J.Y., Zhou, R.F., Chen, B. yWan, Y., “Comparison of antifungal prophylaxis drugsin patients with hematological disease or undergoinghematopoietic stem cell transplantation: a systematicreview and network meta-analysis”, jama Netw Open,2020, 3 (10): e2017652. doi: 10.1001/jamanetworkopen.2020.17652.

38. Guarascio, A.J. y Slain, D., “Review of the new delayed-release oral tablet and intravenous dosage formsof posaconazole”, Pharmacotherapy, 2015, 35 (2): 208-219. doi: 10.1002/phar.1533.

39. Pappas, P.G., Kauffman, C.A., Andes, D.R., Clancy, C.J.,Marr, K.A., Ostrosky-Zeichner, L. et al., “Clinical practiceguideline for the management of candidiasis: 2016update by the Infectious Diseases Society of America”,Clin Infect Dis, 2016, 62 (4): e1-50. doi: 10.1093/cid/civ933.

40. Leonart, L.P., Tonin, F.S., Ferreira, V.L., Penteado, S.T.S.,Wiens, A. et al., “A network meta-analysis of primaryprophylaxis for invasive fungal infection in haematologicalpatients”, J Clin Pharm Ther, 2017, 42 (5): 530-538.doi: 10.1111/jcpt.12579.

41. Wingard, J.R., Carter, S.L., Walsh, T.J., Kurtzberg, J.,Small, T.N., Baden, L.R. et al., “Randomized, double-blind trial of fluconazole versus voriconazole forprevention of invasive fungal infection after allogeneichematopoietic cell transplantation”, Blood, 2010, 116(24): 5111-5118. doi: 10.1182/blood-2010-02-268151.vv.

42. Van Burik, J.A., Ratanatharathorn, V., Stepan, D.E., Miller,C.B., Lipton, J.H. Vesole, D.H. et al., “Micafungin versusfluconazole for prophylaxis against invasive fungalinfections during neutropenia in patients undergoinghematopoietic stem cell transplantation”, Clin InfectDis, 2004, 39 (10): 1407-16. doi: 10.1086/422312.

43. De Laurenzi, A., Matteocci, A., Lanti, A., Pescador, L.,Blandino, F. y Papetti, C., “Amphotericin b prophylaxisagainst invasive fungal infections in neutropenicpatients: a single center experience from 1980 to1995”, Infection, 1996, 24 (5): 361-366. doi: 10.1007/BF01716080.

44. Perfect, J.R., Klotman, M.E., Gilbert, C.C., Crawford,D.D., Rosner, G.L., Wright, K.A. et al., “Prophylactic intravenousamphotericin b in neutropenic autologous bonemarrow transplant recipients”, J Infect Dis, 1992, 165(5): 891-897. doi: 10.1093/infdis/165.5.891.

45. Yan, X., Huang, Y., Xie, J., Wu, Q., Yang, S., Yang, X. et al.,“Safety, tolerability, and pharmacokinetics of hrs9432(a)injection in healthy Chinese subjects: a phase-i randomized,double-blind, dose escalation, placebo-controlledstudy”, Antimicrob Agents Chemother, 2024, 68 (7):e0052424. doi: 10.1128/aac.00524-24.

46. Sohn, H.S., Lee, T.J., Kim, J. y Kim, D., “Cost-effectivenessanalysis of micafungin versus fluconazole forprophylaxis of invasive fungal infections in patientsundergoing hematopoietic stem cell transplantation inKorea”, Clin Ther, 2009, 31 (5): 1105-1115; discussion1066-1068. doi: 10.1016/j.clinthera.2009.05.011.

47. Cornely, O.A., Bassetti, M., Calandra, T., Garbino, J., Kullberg,B.J., Lortholary, O. et al., “escmid* guideline for thediagnosis and management of Candida diseases 2012:non-neutropenic adult patients”, Clin Microbiol Infect,2012, 18 Suppl 7: 19-37. doi: 10.1111/1469-0691.12039.