Comprehensive assessment of Indonesian Pharmacy Student’s knowledge and perceptions of nanotechnology and its practical applications in pharmaceutical sciences

Meiliyana Wijaya Rexel Kuatama Monika Venilia Maria Gabriela A. I. Kedang Daniel Edbert   

Open Access   

Published:  Jul 07, 2025

DOI: 10.7324/JAPS.2025.247191
Abstract

Invasive aspergillosis (IA) is a life-threatening infection, particularly in immunocompromised patients, with an estimated annual incidence exceeding 300,000 cases worldwide. This study compares the antifungal drugs of azoles, amphotericin B, and echinocandins based on primary and salvage treatment outcomes. This systematic review and meta-analysis included studies using IA diagnostic criteria from the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium. The review followed the Preferred Reported Items for Systematic Review and Meta-analysis 2020 guidelines. Data were analyzed for response and survival outcomes. A total of 264 studies (1997–2019) were screened, with 10 studies included for analysis, consisting of six randomized controlled trials (RCTs) and four non-RCTs/ cohorts involving 2,162 patients. New triazoles demonstrated a significantly higher favorable response in salvage treatment [odds ratio (OR) 2.31, p = 0.003] but not in primary treatment. Echinocandins exhibited no superiority in either setting. Survival rates after 6–12 weeks were higher with new triazoles (OR 1.59, p < 0.001), while echinocandins showed no significant advantage. Voriconazole remains the preferred primary treatment for IA, while posaconazole is superior for salvage therapy, with isavuconazole as an alternative due to fewer adverse effects. Amphotericin B has roles in treatment but requires careful consideration due to toxicity risks.


Keyword:     Invasive aspergillosis antifungal primary salvage response survival


Citation:

Wijaya M, Kuatama R, Venilia M, Kedang MGAI, Edbert D. Comprehensive assessment of Indonesian Pharmacy Student’s knowledge and perceptions of nanotechnology and its practical applications in pharmaceutical sciences. J Appl Pharm Sci. 2025. Article in Press. https://doi.org/10.7324/JAPS.2025.247191

Copyright: © The Author(s). This is an open-access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Reference

1. Zaragoza R, Sole-Violan J, Cusack R, Rodriguez A, Reyes LF, MartinLoeches I. Invasive pulmonary aspergillosis: not only a disease affecting immunosuppressed patients. Diagnostics. 2023;13(3):440. doi: https://doi.org/10.3390/DIAGNOSTICS13030440

2. Ledoux MP, Herbrecht R. Invasive pulmonary aspergillosis. J Fungi (Basel). 2023;9(2):131. doi: https://doi.org/10.3390/JOF9020131

3. Song L, Qiu L, Wang G, Zou W, Zhang S, Sai L. Investigation of risk factors for invasive pulmonary aspergillosis among patients with COVID-19. Sci Rep. 2024;14(1):1–8. doi: https://doi.org/10.1038/s41598-024-71455-7

4. Kuo CW, Wang SY, Tsai HP, Su PL, Cia CT, Lai CH, et al. Invasive pulmonary aspergillosis is associated with cytomegalovirus viremia in critically ill patients - A retrospective cohort study. J Microbiol Immunol Infect. 2022;55(2):291–9. doi: https://doi.org/10.1016/J. JMII.2021.03.005

5. Marr KA, Carter RA, Boeckh M, Martin P, Corey L. Invasive aspergillosis in allogeneic stem cell transplant recipients: changes in epidemiology and risk factors. Blood. 2002;100(13):4358–66. doi: https://doi.org/10.1182/BLOOD-2002-05-1496

6. Firacative C. Invasive fungal disease in humans: are we aware of the real impact? Mem Inst Oswaldo Cruz. 2020;115(9):e200430. doi: https://doi.org/10.1590/0074-02760200430

7. Bongomin F, Gago S, Oladele RO, Denning DW. Global and multinational prevalence of fungal diseases—estimate precision. J Fungi (Basel). 2017;3(4):57. doi: https://doi.org/10.3390/JOF3040057

8. Chandrasekar P. Riches usher dilemmas: antifungal therapy in invasive aspergillosis. Biol Blood Marrow Transplant. 2005;11(2):77–84. doi: https://doi.org/10.1016/J.BBMT.2004.11.021

9. Cavassin FB, Baú-Carneiro JL, Vilas-Boas RR, Queiroz-Telles F. Sixty years of amphotericin B: an overview of the main antifungal agent used to treat invasive fungal infections. Infect Dis Ther. 2021;10(1):115–47. doi: https://doi.org/10.1007/S40121-020- 00382-7

10. Boyer J, Feys S, Zsifkovits I, Hoenigl M, Egger M. Treatment of invasive aspergillosis: how it’s going, where it’s heading. Mycopathologia. 2023;188(5):667–81. doi: https://doi.org/10.1007/S11046-023-00727-Z

11. Aruanno M, Glampedakis E, Lamoth F. Echinocandins for the treatment of invasive aspergillosis: from laboratory to bedside. Antimicrob Agents Chemother. 2019;63(8):e00399–19. doi:

https://doi.org/10.1128/AAC.00399-19

12. Jenks JD, Hoenigl M. Treatment of aspergillosis. J Fungi (Basel). 2018;4(3):98. doi: https://doi.org/10.3390/JOF4030098

13. Cheng MP, Orejas JL, Arbona-Haddad E, Bold TD, Solomon IH, Chen K, et al. Use of triazoles for the treatment of invasive aspergillosis: a three-year cohort analysis. Mycoses. 2020;63(1):58– 64. doi: https://doi.org/10.1111/MYC.13013

14. Szymanski M, Chmielewska S, Czyzewska U, Malinowska M, Tylicki A. Echinocandins – structure, mechanism of action and use in antifungal therapy. J Enzyme Inhib Med Chem. 2022;37(1):876. doi: https://doi.org/10.1080/14756366.2022.2050224

15. Ascioglu S, Rex JH, De Pauw B, Bennett JE, Bille J, Crokaert F, et al. Defining opportunistic invasive fungal infections in immunocompromised patients with cancer and hematopoietic stem cell transplants: an international consensus. Clin Infect Dis. 2002;34(1):7–14. doi: https://doi.org/10.1086/323335

16. De Pauw B, Walsh TJ, Donnelly JP, Stevens DA, Edwards JE, Calandra T, et al. Revised definitions of invasive fungal disease from the European organization for research and treatment of cancer/invasive fungal infections cooperative group and the national institute of allergy and infectious diseases mycoses study group (EORTC/MSG) consensus group. Clin Infect Dis. 2008;46(12):1813. doi: https://doi.org/10.1086/588660

17. Donnelly JP, Chen SC, Kauffman CA, Steinbach WJ, Baddley JW, Verweij PE, et al. Revision and update of the consensus definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium. Clin Infect Dis. 2020;71(6):1367–76. doi: https://doi.org/10.1093/cid/ciz1008

18. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. doi: https://doi.org/10.1136/BMJ.N71

19. Sterne JAC, Savovic J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366:l4898. doi:

https://doi.org/10.1136/BMJ.L4898

20. Sterne JA, Hernán MA, Reeves BC, Savovic J, Berkman ND, Viswanathan M, et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ. 2016;355:i4919. doi: https://doi.org/10.1136/BMJ.I4919

21. Walsh TJ, Raad I, Patterson TF, Chandrasekar P, Donowitz GR, Graybill R, et al. Treatment of invasive aspergillosis with posaconazole in patients who are refractory to or intolerant of conventional therapy: an externally controlled trial. Clin Infect Dis. 2007;44(1):2–12. doi: https://doi.org/10.1086/508774

22. Raad II, Hanna HA, Boktour M, Jiang Y, Torres HA, Afif C, et al. Novel antifungal agents as salvage therapy for invasive aspergillosis in patients with hematologic malignancies: posaconazole compared with high-dose lipid formulations of amphotericin B alone or in combination with caspofungin. Leukemia. 2008;22(3):496–503. doi: https://doi.org/10.1038/SJ.LEU.2405065

23. Maertens JA, Rahav G, Lee DG, Ponce-de-León A, Ramírez Sánchez IC, Klimko N, et al. Posaconazole versus voriconazole for primary treatment of invasive aspergillosis: a phase 3, randomised, controlled, non-inferiority trial. Lancet. 2021;397(10273):499–509. doi: https://doi.org/10.1016/S0140-6736(21)00219-1

24. Maertens JA, Raad II, Marr KA, Patterson TF, Kontoyiannis DP, Cornely OA, et al. Isavuconazole versus voriconazole for primary treatment of invasive mould disease caused by Aspergillus and other filamentous fungi (SECURE): a phase 3, randomised-controlled, non-inferiority trial. Lancet. 2016;387(10020):760–9. doi: https://doi.org/10.1016/S0140-6736(15)01159-9

25. Cornely OA, Meems L, Herbrecht R, Viscoli C, van Amsterdam RGM, Ruhnke M. Randomised, multicentre trial of micafungin vs. an institutional standard regimen for salvage treatment of invasive aspergillosis. Mycoses. 2015;58(1):58–64. doi: https://doi.org/10.1111/MYC.12274

https://doi.org/10.1111/MYC.12274

26. Marr KA, Boeckh M, Carter RA, Hyung WK, Corey L. Combination antifungal therapy for invasive aspergillosis. Clin Infect Dis. 2004;39(6):797–802. doi: https://doi.org/10.1086/423380

27. Singh N, Limaye AP, Forrest G, Safdar N, Muñoz P, Pursell K, et al. Combination of voriconazole and caspofungin as primary therapy for invasive aspergillosis in solid organ transplant recipients: a prospective, multicenter, observational study. Transplantation. 2006;81(3):320–6. doi: https://doi.org/10.1097/01.TP.0000202421.94822.F7

28. 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. 2015;162(2):81–9. doi: https://doi.org/10.7326/M13-2508

29. Caillot D, Thiébaut A, Herbrecht R, De Botton S, Pigneux A, Bernard F, et al. Liposomal amphotericin B in combination with caspofungin for invasive aspergillosis in patients with hematologic malignancies: a randomized pilot study (Combistrat trial). Cancer. 2007;110(12):2740–6. doi: https://doi.org/10.1002/CNCR.23109

https://doi.org/10.1002/CNCR.23109

30. Herbrecht R, Denning DW, Patterson TF, Bennett JE, Greene RE, Oestmann J-W, et al. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med. 2002;347(6):408– 15. doi: https://doi.org/10.1056/NEJMOA020191

31. Rogacheva YA, Markelov VV, Popova MO, Volkova AG, Nikolaev IY, Pinegina ON, et al. Invasive aspergillosis in allogeneic hematopoietic stem cell transplantation recipients: a large cohort single-center study. Blood. 2021;138(Supplement 1):1801. doi: https://doi.org/10.1182/BLOOD-2021-153762

32. Reichenberger F, Habicht JM, Gratwohl A, Tamm M. Diagnosis and treatment of invasive pulmonary aspergillosis in neutropenic patients. Eur Respir J. 2001;19(4):743–55. doi: https://doi.org/10.1 183/09031936.02.00256102

33. Stafylidis C, Diamantopoulos P, Athanasoula E, Solomou E, Anastasopoulou A. Acute lymphoblastic leukemia and invasive mold infections: a challenging field. J Fungi (Basel). 2022;8(11):1127. doi: https://doi.org/10.3390/JOF8111127

https://doi.org/10.3390/JOF8111127

34. Colombo AL, Bergamasco MD, Nouér SA, Oliveira e Castro P de T, Pasqualotto AC, de Queiroz-Telles F, et al. Invasive aspergillosis in patients with acute leukemia: comparison between acute myeloid and acute lymphoid leukemia. Mycopathologia. 2022;188(1–2):1–8. doi: https://doi.org/10.1007/S11046-022-00684-Z

35. Egger M, Hoenigl M, Thompson GR, Carvalho A, Jenks JD. Let’s talk about sex characteristics—As a risk factor for invasive fungal diseases. Mycoses. 2022;65(6):599–612. doi: https://doi.org/10.1111/MYC.13449

https://doi.org/10.1111/MYC.13449

36. Shekhova E, Salazar F, Da Silva Dantas A, Chakraborty T, Wooding EL, White PL, et al. Age difference of patients with and without invasive aspergillosis: a systematic review and meta-analysis. BMC Infect Dis. 2024;24(1):220. doi: https://doi.org/10.1186/S12879- 024-09109-2

37. Lee SO. Diagnosis and treatment of invasive mold diseases. Infect Chemother. 2023;55(1):10–21. doi: https://doi.org/10.3947/IC.2022.0151

https://doi.org/10.3947/IC.2022.0151

38. Douglas AP, Smibert OC, Bajel A, Halliday CL, Lavee O, McMullan B, et al. Consensus guidelines for the diagnosis and management of invasive aspergillosis, 2021. Intern Med J. 2021;51(S7):143–76. doi: https://doi.org/10.1111/IMJ.15591

39. Patterson TF, Thompson GR, 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. 2016;63(4):e1–60. doi: https://doi.org/10.1093/CID/CIW326

https://doi.org/10.1093/CID/CIW326

40. Douglas AP, Smibert OC, Bajel A, Halliday CL, Lavee O, McMullan B, et al. Consensus guidelines for the diagnosis and management of invasive aspergillosis, 2021. Intern Med J. 2021;51(S7):143–76. doi: https://doi.org/10.1111/IMJ.15591

41. Heinz WJ, Egerer G, Lellek H, Boehme A, Greiner J. Posaconazole after previous antifungal therapy with voriconazole for therapy of invasive aspergillus disease, a retrospective analysis. Mycoses. 2013;56(3):304–10. doi: https://doi.org/10.1111/MYC.12023

42. Van Matre ET, Evans SL, Mueller SW, MacLaren R, Fish DN, Kiser TH. Comparative evaluation of isavuconazonium sulfate, voriconazole, and posaconazole for the management of invasive fungal infections in an academic medical center. Ann Clin Microbiol Antimicrob. 2019;18(1):13. doi: https://doi.org/10.1186/S12941- 019-0311-3

43. Batista MV, Ussetti MP, Jiang Y, Neofytos D, Cortez AC, Feriani D, et al. Comparing the real-world use of isavuconazole to other anti-fungal therapy for invasive fungal infections in patients with and without underlying disparities: a multi-center retrospective study. J Fungi (Basel). 2023;9(2):166. doi: https://doi.org/10.3390/JOF9020166

44. Cavassin FB, Baú-Carneiro JL, Vilas-Boas RR, Queiroz-Telles F. Sixty years of amphotericin b: an overview of the main antifungal agent used to treat invasive fungal infections. Infect Dis Ther. 10(1):115–47. doi: https://doi.org/10.1007/S40121-020-00382-7

https://doi.org/10.1007/S40121-020-00382-7

45. Aguirre B, Restrepo JP, Am H, Aguirrejp B, Restrepo H. Amphotericin B deoxycholate versus liposomal amphotericin B: effects on kidney function. Cochrane Database Syst Rev. 2015;2015(11):CD010481. doi: https://doi.org/10.1002/14651858.CD010481.PUB2

46. Martín MT, Gavaldà J, López P, Gomis X, Ramírez JL, Rodríguez D, et al. Efficacy of high doses of liposomal amphotericin B in the treatment of experimental aspergillosis. J Antimicrob Chemother. 2003;52(6):1032–4. doi: https://doi.org/10.1093/JAC/DKH003

47. Alabdullah MN, Yousfan A. Is low dose of liposomal amphotericin B effective in management of acute invasive fungal rhinosinusitis? Our conclusions from Al-Mowassat University Hospital, Syria: a prospective observational study. BMC Infect Dis. 2023;23(1):1–14. doi: https://doi.org/10.1186/S12879-023-08177-0/FIGURES/8

48. Stover KR, Jordan TE, Wagner JL, Barber KE. High-dose amphotericin: yay or nay? A case series and literature review. Drugs Context. 2024;13:2023-9-1. doi: https://doi.org/10.7573/dic.2023-9-1

49. Aruanno M, Glampedakis E, Lamoth F. Echinocandins for the treatment of invasive aspergillosis: from laboratory to bedside. Antimicrob Agents Chemother. 2019;63(8):e00399–19. doi: https://doi.org/10.1128/AAC.00399-19

50. Lamberink H, Huygens S, Aerts R, Lagrou K, Van LeeuwenSegarceanu E, Lodewyck T, et al. Superiority trials in invasive aspergillosis: a harsh reality check with the ia-duet (HOVON502) trial. Clinical Infectious Diseases. 2025;80(2):367–70. doi: https://doi.org/10.1093/CID/CIAE501

https://doi.org/10.1093/CID/CIAE501

51. Jacobs SE, Chaturvedi V. CAF to the rescue! potential and challenges of combination antifungal therapy for reducing morbidity and mortality in hospitalized patients with serious fungal infections. Open Forum Infect Dis. 2024;11(11):ofae646. doi: https://doi.org/10.1093/OFID/OFAE646

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