Comparison of fluconazole and itraconazole for treatment of rhinomaxillary mucormycosis

Yıl 2019, , 476 - 480, 29.07.2019

Omer Sefvan Janjua Sarah Shah , Ammara Afzal Sana Mehmood Qureshi

https://doi.org/10.28982/josam.521374

Öz

Aim: Rhinomaxillary mucormycosis (RMM) is a detrimental and progressive deep fungal infection which predominantly affects immunocompromised patients. The disease has heterogeneity in clinical manifestation and presents with unfavorable consequences. Despite recent advances in the diagnosis and treatment, the disease has inadequate prognosis overall. The aim of our study is to compare Fluconazole vs. Itraconazole for the management of RMM.

Methods: We retrieved demographic, clinical, radiological and histopathological data of patients affected with osteomyelitis in head and neck region and 33 patients exclusively affected with RMM were separated from departmental records. Several characteristics such as Gender, age, Diabetic status, co-morbidity were observed. Patients were randomly distributed in two groups with respect to the azole drug prescribed to them. Group A was given Fluconazole while group B was given Itraconazole. Aggressive surgery with concomitant use of antifungal drug was the mandatory treatment in all patients. Regular monitoring of side effects of drugs and recurrence was carried out for prolonged time.

Results: Overall, 18 patients were male and 15 patients were female with a ratio of M:F 1.2. Mean age of patients was 48.21 (11.66) with the age range from 25 years to 70 years. Out of 33 patients, 30 of the patients (90.9%) were diabetic. Fifteen patients in Group A were managed with Fluconazole while 18 patients in group B were treated with Itraconazole. There was no statistically significant difference observed in most of the clinical signs and symptoms presented in both groups as p>0.05 except for bone necrosis (P=0.381). In group A, 4 patients exhibited recurrence (26.6%) while in group B, 5 (27.7%) patients presented with recurrence (p=0.943).

Conclusion: Aggressive surgical approach along with supportive antifungal medication remained the mainstay of the treatment. Between Fluconazole and Itraconazole there was no difference observed.

Anahtar Kelimeler

Fluconazole, Rhinomaxillary mucormycosis, Itraconazole

Rhinomaksiler mukormikoz tedavisinde flukonazol ve itrakonazolun karşılaştırılması

Öz

Amaç: Çalışmamızın amacı, rhinomaksiler mukormikoz (RMM) tedavisi için Fluconazole - Itraconazole uygulamasını karşılaştırmaktır.

Yöntemler: Baş ve boyun bölgesinde osteomiyelit ile etkilenen hastaların demografik, klinik, radyolojik ve histopatolojik verilerini aldık ve sadece RMM'den etkilenen 33 hasta bölümsel kayıtlardan ayrıldı. Cinsiyet, yaş, diyabetik durum, komorbidite gibi çeşitli özellikler kaydedildi. Hastalar, kendilerine verilen azol ilacı açısından rastgele iki gruba ayrıldı. A grubuna Flukonazol, B grubuna Itrakonazol verildi. Antifungal ilacın birlikte kullanılması ile yapılan agresif cerrahi, tüm hastalarda zorunlu tedavi idi. İlaçların yan etkilerinin düzenli olarak izlenmesi ve tekrarlama uzun süre takip edildi.

Bulgular: Toplamda 18 hasta erkek, 15 hasta kadındı (E/K 1,2). Hastaların yaş ortalaması 48.21 (11,66), yaşları 25 ile 70 arasında değişmekteydi. 33 hastanın 30'u (%90,9) diyabetikti. Grup A'da 15 hasta Fluconazole ile tedavi edilirken, grup B'de 18 hasta Itraconazole ile tedavi edildi. Kemik nekrozu dışında her iki grupta da sunulan klinik belirti ve semptomların çoğunda p>0.05 düzeyinde istatistiksel olarak anlamlı bir fark bulunmadı (P=0.381). Grup A'da 4 hastada nüks görüldü (%26,6), grup B'de ise 5 hastada (%27,7) nüks saptandı (p=0,943).

Sonuç: Destekleyici antifungal ilaçlar ile birlikte agresif cerrahi yaklaşım tedavinin dayanak noktası olarak kaldı. Flukonazol ve Itrakonazol arasında anlamlı bir fark gözlenmedi.

Anahtar Kelimeler

Flukonazol, Itrakonazol, Rhinomaksiler mukormikoz

Kaynakça

• 1. Al Ruoppi P, Dietz A, Nikanne E, Seppaè J, Markkanen H and Nuutinen J. Paranasal Sinus Mucormycosis: a Report of Two Cases. Acta Otolaryngol 2001 Dec;121(8):948-52.
• 2. Vijayabala GS, Annigeri RG, Sudarshan R. Mucormycosis in a diabetic ketoacidosis patient. Asian Pac J Trop Biomed 2013 Oct;3(10):830-3.
• 3. Spellberg B & Ibrahim AS. Recent Advances in the Treatment of Mucormycosis. Curr Infect Dis Rep. 2010 Nov;12(6):423-9.
• 4. Swain SK, Sahu MC, Baisakh MR. Mucormycosis of the Head and Neck. Apollo Med 2018 Apr;15:6-10.
• 5. Oladeji S, Amusa Y, Olabanji J, Adisa A. Rhinocerebral Mucormycosis in a Diabetic - Case Report. J West Afr Coll Surg. 2013 Jan;3(1):93-102.
• 6. Camara-Lemarroy CR, González-Moreno EI, Rodríguez-Gutiérrez R, Rendón-Ramírez EJ, Ayala-Cortés AS, Fraga-Hernández ML, et al. Clinical Features and Outcome of Mucormycosis. Interdiscip Perspect Infect Dis. 2014 Aug;2014:1-5.
• 7. Petrikkos G, Skiada A, Lortholary O, Roilides E, Walsh TJ, Kontoyiannis DP. Epidemiology and clinical manifestations of mucormycosis.Clin Infect Dis. 2012 Feb;54 Suppl 1:S23-34.
• 8. Mignogna MD, Fortuna G, Leuci S, Adamo D, Ruoppo E, Siano M, Mariani U. Mucormycosis in immunocompetent patients: a case-series of patients with maxillary sinus involvement and a critical review of the literature. Int J Infect Dis. 2011 Aug;15(8):e533-40.
• 9. Ibrahim AS, Spellberg B, Walsh TJ, and Kontoyiannis DP. Pathogenesis of Mucormycosis.Clin Infect Dis. 2012 Feb 1;54(Suppl 1):S16–S22.
• 10. Bhansali A, Bhadada S, Sharma A, Suresh V, Gupta A, Singh P, Chakarbarti A, Dash RJ. Presentation and outcome of rhino-orbital-cerebral mucormycosis in patients with diabetes. Postgrad Med J. 2004 Nov;80(949):670-4.
• 11. Alobid I, Bernal M, Calvo C, Vilaseca I, Berenguer J, Alós L. Treatment of Rhinocerebral Mucormycosis by Combination of Endoscopic Sinus Debridement and Amphotericin B. Am J Rhinol. 2001 Sep-Oct;15(5):327-31.
• 12. Leonardis FD, Perillo T, Giudice G, Favia G and Santoro N. Recurrent rhino-ocular-cerebral mucormycosis in a leukemic child: a case report and review of pediatric literature. Pediatr Rep. 2015 Sep 28;7(3):5938.
• 13. Roden MM, Nelson LD, Knudsen TA, Jarosinski PF, Starling JM, Shiflett SE, et al. Triad of Acute Infusion-Related Reactions Associated with Liposomal Amphotericin B: Analysis of Clinical and Epidemiological Characteristics. Clin Infect Dis. 2003 May 15;36(10):1213-20.
• 14. Rai S, Yadav S, Kumar D, Kumar V, Rattan V. Management of Rhinomaxillary mucormycosis with Posaconazole in immunocompetent patients. J Oral Biol Craniofac Res. 2016 Nov;6(Suppl 1):S5–S8.
• 15. Hosseini SM, Borghei P. Rhinocerebral mucormycosis: pathways of spread. Eur Arch Otorhinolaryngol. 2005 Nov;262(11):932-8.
• 16. Hadzri MH, Azarisman SM, Fauzi AR, Kahairi A. Invasive rhino cerebral Mucormycosis with orbital extension in poorly controlled diabetes mellitus. Singapore Med J. 2009 Mar;50(3):e107-9.
• 17. Casqueiro J, Casqueiro J, Alves C. Infections in patients with diabetes mellitus: A review of pathogenesis. Indian J Endocrinol Metab. 2012 Mar;16(Suppl 1):S27–S36.
• 18. Vaezi A, Moazeni M, Rahimi MT, Hoog SD, Badali H. Mucormycosis in Iran: a systematic review. Mycoses. 2016 Jul;59(7):402-15.
• 19. Chakrabarti A, Das A, Mandal J, Shivaprakash MR, George VK, Tarai B, et al. The rising trend of invasive zygomycosis in patients with uncontrolled diabetes mellitus. Med Mycol. 2006 Jun;44(4):335-42.
• 20. Pandey A, Bansal V, Asthana AK, Trivedi V, Madan M, Das A. Maxillary osteomyelitis by mucormycosis: report of four cases. Int J Infect Dis. 2011 Jan;15(1):e66-9.
• 21. Kolekar JS. Rhinocerebral Mucormycosis: A Retrospective Study. Indian J Otolaryngol Head Neck Surg. 2015 Mar;67(1):93–6.
• 22. Reed C, Bryant R, Ibrahim AS, Edward Jr J, Filler SG, Goldberg R, et al. Combination Polyene-Caspofungin Treatment of Rhino-Orbital-Cerebral Mucormycosis. Clin Infect Dis. 2008 Aug 1;47(3):364–71.
• 23. Mohammadi R, Nazeri M, Sayedayn SMA, Ehteram H. A successful treatment of rhinocerebral mucormycosis due to Rhizopus oryzae. J Res Med Sci. 2014 Jan;19(1):72-4.
• 24. Laniado-Laborín R, Cabrales-Vargas MN. Amphotericin B: side effects and toxicity. Rev Iberoam Micol. 2009 Dec 31;26(4):223-7.
• 25. Çagatay AA, Öncü SS, Çalangu SS, Yildirmak TT, Özsüt HH, Eraksoy HH. Rhinocerebral mucormycosis treated with 32 gram liposomal amphotericin B and incomplete surgery: a case report. BMC Infect Dis. 2001 Nov;1:22.
• 26. Handzel O1, Landau Z, Halperin D. Liposomal amphotericin B treatment for Rhinocerebral mucormycosis: How much is enough? Rhinology. 2003 Sep;41(3):184-6.
• 27. Brüggemann RJ, Alffenaar JW, Blijlevens NM, Billaud EM, Kosterink JG, Verweij PE, Burger DM. Clinical Relevance of the Pharmacokinetic Interactions of Azole Antifungal Drugs with Other Coadministered Agents. Clin Infect Dis. 2009 May 15;48(10):1441-58.
• 28. Mehta R, Panda NK, Mohindra S, Chakrabarti A, Singh P. Comparison of Efficacy of Amphotericin B and Itraconazole in Chronic Invasive Fungal Sinusitis. Indian J Otolaryngol Head Neck Surg. 2013 Aug;65(Suppl 2):288–94.
• 29. Reed C, Ibrahim A, Edwards Jr JE. Deferasirox, an Iron-Chelating Agent, as Salvage Therapy for Rhinocerebral Mucormycosis. Antimicrob Agents Chemother. 2006 Nov;50(11):3968–9.