In Vitro Susceptibility of Aflatoxigenic and Non-aflatoxigenic Aspergillus flavus Strains to Conventional Antifungal Agents
Presently appearance of resistance to antifungal agents among Aspergillus species is dramatically increasing. The objective of this study was to look at the in vitro activities of antifungal drugs against Iranian clinical (from nail, bronchoalveolar lavage, paranasal sinus) isolated A. flavus strains. The susceptibility of 45 aflatoxigenic and non-aflatoxigenic Aspergillus flavus strains were evaluated to six antifungal agents (caspofungin, itraconazole, amphotericin B, ketoconazole, fluconazole, nystatin) using CLSI M38-A2 broth microdilution method. The results indicated that 57.1%, 28.6% of aflatoxigenic and 25.8%, 6.5% of non-aflatoxigenic isolates were susceptible to caspofungin, amphotericin B respectively. All isolates but one aflatoxigenic strain were sensitive to ketoconazole. All 45 strains showed to be resistant to nystatin. Also 64.28%, 92.9% of aflatoxigenic and 64.51%, 100% of non-aflatoxigenic isolates were resistant to fluconazole and itraconazole in ranking order. There was no statistically significant difference between the susceptibilities of aflatoxigenic and non-aflatoxigenic strains of A. flavus to tested antifungal agents.
Christensen M, Tothill DE. Aspergillus: an overview. 1985; 195-209. In: Samson, RA & J.I Pitt (Eds) advances in penicillium and Aspergillus systematic New York:Plenum press.
Domsch KA, Gams W, Anderson TH. Compendium of soil fungi academi. Press, London, New York. Torroute, Sydney, Sanfransisco 1980; 859.
Iwen PC, Rupp ME and Hinrichs SH. Invasive mold sinusitis: 17 cases in immunocompromised patients and review of the literature. Clin Infect Dis 1997;24(6): 1178-84.
Iwen PC, Rupp ME, Langna LN, Reed EC, Hinrichs SH. Invasive pulmonary aspergillosis due to Aspergillus terreus: 12 years experience and review of literature. Clin Infect Dis 1998;26(5): 1092-7.
Lortholary O, Meyohas MC, Dupont B, Cadranel J, Salmon-Deron D, Peyramond D, Simoni D and centre d' information’s et de soins de l'lmmunodefficience humaine de l'Est parisien. Invasive aspergillosis in patients with acquired immunodeficiency syndrome: Report of 33 cases. Am J Med 1993; 95(2): 177-86.
Denning DW. Invasive aspergillosis. Clin Infect Dis 1998;26: 781-803.
Morgan J, Wannemuehler KA, Marr kA, Hadley S, Kontoyiannis DP, Walsh TJ, Fridkin SK, Pappas PG,Warnock DW. Incidence of invasive aspergillosis following hematopoietic stem cell and solid organ transplantation: Interim results of prospective multicenter surveillance program. Med Mycol 2005; 43(suppl 1): S49-S58.
Kontoyiannis DP, Bodey GP. Invasive aspergillosis in2002: An update. Eur J Clin Microbiol Infect Dis 2002;21(3): 161-72.
Chen KY, kO SC, Hsueh PR, Luh kT, Yang PC. Pulmonary fungal infection: Emphasis on microbiological spectra, patient outcome and prognostic factors. Chest 2001;120(1): 177-84.
Hsueh R, Lau Y, Chuang Y, Wan J, Huang W, Shyr J, Yan J, Yu K, Wu J, KO W, Yang Y. Antifungal susceptibilities of clinical isolates of candida species, Cryptococcus neoformans and Aspergillus species from Taiwan: Surveillance of multicenter antimicrobial resistance in Taiwan. Program Data from 2003. Antimicrob Agents Chemother 2005; 49(2): 512-7.
Verweij PE, Oakley KL, Morrissey J, Morrissey G, Denning DW. Efficacy of LY 303366 against amphotericin B susceptible and resistant Aspergillus fumigatus in a murine model of invasive aspergillosis. Antimicrob Agents Chemoter 1998;42(4): 873-6.
Odd FC, Geruen FV, Espinel-Ingroff A, Bartlett MS, Ghan MA, Lancaster MV, Pfaller MA, Rex JH, Rinaldiand MG, Walsh JJ. Evaluation of possible correlations between antifungal susceptibilities of filamentous fungi invitro and fungal treatment outcomes in animal infection models. AntiMicrob Agents Chemoter 1998;42(2):282-8.
Dehghan P. DNA typing of A. flavus isolated from referral patients which identified by conventional methods and introducing a suitable and definite way of diagnosis of these organisms. PhD thesis. School of Public Health Tehran University of Medical Science 2007.
Beman Jebali A. Extraction of aflatoxin from aflatoxigenic aspergilli and production of antibody against it for diagnostic kit in future. PhD thesis. School of Public Health Tehran University of Medical Science 2009.
Clinical and Laboratory Standards Insititute. Reference method for broth dilution antifungal susceptibility testing of Yeast; informational supplement, M27-A3. Clinical and Laboratory Standards Institute,Wayne ,PA 2007.
Clinical and Laboratory Standards Institute. Reference method for broth dilution antifungal susceptibility testing of filamentous fungi; approved standard, M38A2. Clinical and Laboratory Standards Institute, Wayne, PA 2008.
Gomez-Lopez A, Garcia-Effron G, Mellado E, Monzon A, Rodriguez-Tudela JL, Cuenca-Estrella M. In Vitro activities of three licensed antifungal agents against Spanish clinical isolates of Aspergillus species. Antimicrob Agents Chemoter 2003; 47(10): 3085-8.
Dannaoui E, Meletiadis J, Tortorano AM, Symoens F, Nolard N, Viviani MA, Piens MA, Lebeau B, Verweij PE, Grillot R, EBGA Network. Susceptibility testing of sequential isolates of A. fumigatus recovered from treated patients. J Med Microbiol 2004;53(Pt2): 129-34
Warris A, Weemaes C, Verweij P. Multidrug Resistance in Aspergillus fumigatus. NEJM 2002; 347: 2173-4.
Manavathu EK, Cutright JL, Loebenberg D, ChandrasekarPH .A comparative study of the in vitro susceptibilities of clinical and laboratory-selected resistant isolates of Aspergillus spp. To amphotericin B, itraconazole, voriconazole and posaconazol, SCH56592. J Antimicrob Chemother 2000;46(2): 229-34.
Arikan S, Sanjac B, AlP S, Hascelik G, Mcnicholast P. Comparative in vitro activities of Posaconazole, voriconazole, itraconazole and amphotericin B against Aspergillus and Rhizopous and synergy testing for Rhizopus. Med Mycol 2008;46: 567-73.
Lass–Flörl C, Griff k, Petzer A, Gastl G, Bonatti H, Freund M. Epidemiology and outcome of infections due to Aspergillus terreus: 10-year single centre experience. BJH 2005;131(2):201-7.
Mosquera J, Denning DW. Azole cross-resistance in Aspergillus fumigatus. Antimicrob Agents Chemother 2002;46(2):556-7.
Steinbach WJ, Benjamin Dk, P KD, Perfect JR, LionakisMS, Torres HA, Jafri H, Walsh TJ Marr KA. Infections due to Aspergillus terreus: a multicenter respective analysis of 83 cases. Clin Infect Dis 2004; 39(2): 192-198.
Walter J, Sobattka I, Rogiers X, Broering D, Fischer L. Invasive aspergillosis caused by Aspergillus terreus in a living donor liver transplant recipient successfully treated by caspofungin. Mycoses 2011; 54: 220-2.
Zakeri M, Hashemi SJ, Zaini F, Daie R, Zibafar E. In Vitro susceptibility of Aspergillus spp. isolated from cutaneous and viseral lesions to antifungal drugs. TUMJ 2011;69(2):83-91.
Kartsonis NA, Saah AJ, Joy-Lipka C, Taylor AF, Sable CA. Salvage therapy with Caspofungin for invasive aspergillosis. Results from the Caspofungin compassionate use study. J Infect 2005; 50(3): 196-205.
Alcezar-Fuoli L, Rodriguez-Tudela JL, Mellado E. Antifungal drug resistance in molds. Clin Microbiol Factors 2008; 2(1): 36-42.
Arikan S, Lozanochiu M, Paetznick V, Rex JH. In Vitro susceptibility testing methods for caspofungin against Aspergillus and Fusarium isolates. Antimicrob Agents Chemother 2001; 45(1): 327-30.
Espinel-Ingroff A. Evaluation of Broth microdilution testing parameters and agar diffusion E-test procedure for testing susceptibilities of Aspergillus spp. to Caspofungin acetate (MK-0991). J Clin Microbiol 2003;41(1):403-9.
Eschertzhuber S, Velik-Salchner C, Hoermann C, HoeferD, Lass-Flörl C. Caspofungin-resistant A. flavus after heart transplantation and mechanical circulatory support: a casereport. Transpl Infect Dis 2008; 10: 190-192.
Moore CB, Sayers N, Mosquera J, Slaven J, Denning DW. Antifungal drug resistance in Aspergillus. JINF 2000;41:203-20.
Messer Sh, Jones R, Flitsche T. International surveillance of Candida spp. and Aspergillus spp. report from the SENTRY antimicrobial Surveillance Program (2003). J Clin Microb 2006;44(50):1782-7.
Kumar R, Shrivastava S, Chakraborti A. Comparison of Broth dilution and disc diffusion method for the antifungal susceptibility testing of Aspergillus flavus. Am J Biomed Sci 2010;2(21):202-8.
Badiee P, Alborzi A, Moeini M, Haddadi P, Farshad Sh, Japoni A, Ziyaeyan M. Antifungal Susceptibility of the Aspergillus Species by Etest and CLSI Reference Methods. Arch Iran Med. 2012; 15(7): 429-32
Espinel-Ingroff A, Johnson E, Hockey H, Troke P. Activities of voriconazole, itraconazole and amphotericin B in-vitro against 590 molds from 323 patients in the voriconazole phase III Clinical studies. Antimicrob Agents Chemother 2008;61(3):616-20.
Lass-Flörl, Kofler CG, Hermans J, Kreczy A, Dierich MP. In Vitro testing of susceptibility to amphotericin B is a reliable predictor of clinical outcome in invasive aspergillosis. J Antimicrob Chemother 1998;42(4):497-502.
Lionakis MS, Lewis RE, Torres HA, Albert ND, Raad I, Kontoyiannis DP. Increased frequency of non- Fumigatus Aspergillus spp. in amphotericin B or triazole pre exposed cancer patients with positive cultures for Aspergilli. J Diagn Microbiol Infect Dis 2005; 52(10): 15- 20.
Baddley J, Marr K, Andos R, Andes DR, Walsh TJ,Kauffman CA, Kontoyiannis DP, Ito JI, Arunmozli- Balajee S, Pappas PG, Moser SA. Patterns of susceptibility of Aspergillus isolates recovered from patients enrolled in the transplant-associated infection surveillance network. J Clin Microb 2009; 47(10): 3271-5.
Meletiadis J, Antachopoulos C, Stergiopoulou T,Pournaras S, Roilides E, Walsh T. Differential fungicidalactivities of AMB and voriconazole against Aspergillus spp. determined by Micro Broth methodology. AntimicrobAgents Chemoter 2007; 51(9): 3329-37.
Sabatelli F, Patel R, Mann PA, Mendrick CA, Norris CC, Hare R, Leobenberg D, Black TA, Mcnicholas PM. InVitro activities of posaconazole, fluconazole, itraconazole, voriconazole and amphotericin B against a large collection of clinically important molds and yeast. Antimicrob Agents Chemother 2006; 509(6): 2009-15.
Cahill, KM, EL Mofty AM, Kawaguchi TP. Primary cutaneous aspergillosis. Arch Dermatol 1967; 96: 545-6.
Oakley K, Moore C, Denning DW. Comparision of In Vitro activity of liposomal nystatin against Aspergillus spp. with those of nystatin, amphotericin B, deoxycholate, AB Colloidal Dispersion, liposomal AMB, AMB lipid complex and itraconazole. Antimicrob Agents Chemother 1999;43:1264-6.
Carlile JR, Millet RE, Cho CT, Vats TS. Primary cutaneous aspergillosis in leukemic child. Arch Dermatol 1978;114(1):78-80.
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.