Azol Direnci Gelişen İnvaziv Pulmoner Aspergilloz’lu Nadir Bir Lenfoma Olgusu

Öz

Diffüz büyük B-hücreli lenfoma tanılı bir hastada gelişen nadir bir azol-dirençli invaziv pulmoner aspergilloz (İPA) olgusunu sunmayı ve hematolojik malignitelerde ortaya çıkan azol direncinin klinik önemini vurgulamayı amaçladık. İPA gelişen bir hastada klinik, mikrobiyolojik ve radyolojik bulgular geriye dönük olarak değerlendirildi. Antifungal duyarlılık testleri yapıldı ve antifungal tedavide yapılan değişiklik sonrasında klinik yanıt incelendi. Antifungal ajan olarak verilen vorikonazole rağmen azol direnci saptandı. Tedavinin amfoterisin B’ye değiştirilmesi ile belirgin klinik ve radyolojik düzelme gözlendi. Bu bulgular azol-dirençli İPA tanısı ile uyumluydu. Azol direnci nadir görülmekle birlikte, immünsüprese hastalarda giderek daha önemli bir terapötik sorun haline gelmektedir. Direncin erken tanınması ve amfoterisin B gibi alternatif antifungal ajanların zamanında başlanması, klinik sonuçların iyileştirilmesinde kritik rol oynayabilir.

Anahtar Kelimeler

• Aspergilloz
• Vorikonazol
• Azol Direnci
• İnvaziv Pulmoner Aspergilloz
• Hematolojik Malignite

A Rare Case of Lymphoma with Invasive Pulmonary Aspergillosis Developing Azole Resistance

Öz

This study reports a rare case of azole-resistant invasive pulmonary aspergillosis (IPA) in a patient with diffuse large B-cell lymphoma and to underscore the clinical relevance of emerging azole resistance in hematologic malignancies. Clinical, microbiological, and radiological findings were reviewed in a patient who developed IPA. Antifungal susceptibility testing was performed, and the clinical response was evaluated after modification of antifungal therapy. Despite antifungal treatment with voriconazole, azole resistance was detected. Switching back to amphotericin B resulted in marked clinical and radiological improvement, supporting the diagnosis of azole-resistant IPA. Azole resistance, though uncommon, is an increasingly important therapeutic concern in immunocompromised hosts. Early recognition and timely initiation of alternative agents such as amphotericin B may improve outcomes.

Anahtar Kelimeler

• Aspergillosis
• Voriconazole
• Azole Resistance
• Invasive Pulmonary Aspergillosis
• Hematologic Malignancy

Kaynakça

1. 1. van Ingen J, van der Lee HA, Rijs AJMM, et al. High-level pan-azole-resistant aspergillosis. J Clin Microbiol. 2015;53(7):2343-2345. https://doi.org/10.1128/jcm.00502-15
2. 2. Vermeulen E, Lagrou K, Verweij PE. Azole resistance in Aspergillus fumigatus: a growing public health concern. Curr Opin Infect Dis. 2013;26(6):493-500. https://doi.org/ 10.1097/qco.0000000000000005
3. 3. van Ingen J, van der Lee HA, Rijs A, et al. Azole, polyene, and echinocandin MIC distributions for wild type, TR34/L98H, and TR46/Y121F/T289A Aspergillus fumigatus isolates in the Netherlands. J Antimicrob Chemother. 2015;70(1):178-181. https://doi.org/10.1093/jac/dku364
4. 4. Seyedmousavi S, Mouton JW, Melchers WJG, et al. The role of azoles in the management of azole-resistant aspergillosis: from the bench to the bedside. Drug Resist Updat. 2014;17(3):37-50. https://doi.org/10.1016/j.drup.2014.06.001
5. 5. Arendrup MC. Update on antifungal resistance in Aspergillus and Candida. Clin Microbiol Infect. 2014;20(Suppl 6):42-48. https://doi.org/10.1111/1469-0691.12513
6. 6. Verweij PE, Chowdhary A, Melchers WJG, et al. Azole resistance in Aspergillus fumigatus: can we retain the clinical use of mold-active antifungal azoles? Clin Infect Dis. 2016;62(3):362-368. https://doi.org/10.1093/cid/civ885
7. 7. Ener B, Ergin Ç, Gülmez D, et al. Frequency of azole resistance in clinical and environmental strains of Aspergillus fumigatus in Turkey: a multicentre study. J Antimicrob Chemother. 2022;77(7):1894-1898. https://doi.org/10.1093/jac/dkac125
8. 8. Özmerdiven GE, Ak S, Ener B, et al. First determination of azole resistance in Aspergillus fumigatus strains carrying the TR34/L98H mutations in Turkey. J Infect Chemother. 2015;21(8):581-586. https://doi.org/10.1016/j.jiac.2015.04.012

9. 9. Meletiadis J, Siopi M, Kanioura L, et al. Development and multicentre validation of an agar-based screening method for echinocandin susceptibility testing of Aspergillus species. J Antimicrob Chemother. 2019;74(8):2247-2254. https://doi.org/10.1093/jac/dkz154
10. 10. Clinical and Laboratory Standards Institute. Reference Method for Broth Dilution Antifungal Susceptibility Testing of Filamentous Fungi. 3rd edition. CLSI Standard M38. Wayne, PA: Clinical and Laboratory Standards Institute; 2017.
11. 11. Kim SH, Moon SM, Han SH, et al. Epidemiology and clinical outcomes of invasive pulmonary aspergillosis: a nationwide multicenter study in Korea. Infect Chemother. 2012;44(4):282-288. https://doi.org/10.3947/ic.2012.44.4.282
12. 12. Yun JH, Lee SO, Jo KW, et al. Infections after lung transplantation: time of occurrence, sites, and microbiologic etiologies. Korean J Intern Med. 2015;30(4):506-514. https://doi.org/10.3904/kjim.2015.30.4.506
13. 13. Herbrecht R, Denning DW, Patterson TF, et al. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med. 2002;347(6):408-415. https://doi.org/10.1056/nejmoa020191
14. 14. Walsh TJ, Anaissie EJ, Denning DW, et al. Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis. 2008;46:327-360. https://doi.org/10.1086/525258
15. 15.Park SY, Yoon JA, Kim SH, et al. Voriconazole-refractoryinvasive aspergillosis. Korean J Intern Med. 2017;32:805-812. https://doi.org/10.3904/kjim.2017.109
16. 16.Koehler P, Hamprecht A, Bader A, et al. Epidemiology ofinvasive aspergillosis and azole resistance in patients with acute leukaemia: the SEPIA Study. Int J Antimicrob Agents.. 2017;49(2):218-223. https://doi.org/10.1016/j.ijantimicag.2016.10.019