First detection of TR46/Y121F/T289A and TR34/L98H alterations in Aspergillus fumigatus isolates from azole-naive patients in Denmark despite negative findings in the environment

Antimicrobial Agents and Chemotherapy

Volumn 58, Issue 9, 2014, Pages 5096-5101

  Astvad, K M T ^a   Jensen, R H ^a   Hassan, T M ^a   Mathiasen, E G ^a   Thomsen, G M ^b,e   Pedersen, U G ^c   Christensen, M ^c   Hilberg, O ^d   Arendrup, M C ^a  

^a STATENS SERUM INSTITUT   (Denmark)

^b LILLEBAELT HOSPITAL   (Denmark)

^c Rigshospitalet   (Denmark)

^d AARHUS UNIVERSITY HOSPITAL   (Denmark)

^e ODENSE UNIVERSITY HOSPITAL   (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

AGAR; CYTOCHROME P450; CYTOCHROME P450 51A; PYRROLE; UNCLASSIFIED DRUG; ANTIFUNGAL AGENT; FUNGAL PROTEIN; MICROSATELLITE DNA; PYRROLE DERIVATIVE;

ADULT; AGED; ANTIFUNGAL RESISTANCE; ANTIFUNGAL SUSCEPTIBILITY; ARTICLE; ASPERGILLUS FUMIGATUS; AUTUMN; BROTH DILUTION; CASE REPORT; CONTROLLED STUDY; CYSTIC FIBROSIS; DELAYED DIAGNOSIS; DENMARK; FEMALE; FUNGAL DETECTION; FUNGUS ISOLATION; FUNGUS TRANSMISSION; GENE MUTATION; GENOTYPE; HUMAN; LUNG TRANSPLANTATION; MALE; MUTATIONAL ANALYSIS; NONHUMAN; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; RHIZOMUCOR PUSILLUS; SEASONAL VARIATION; WILD TYPE; ASPERGILLOSIS; DRUG EFFECTS; ENVIRONMENT; GENETICS; MICROBIAL SENSITIVITY TEST; MIDDLE AGED; PROCEDURES;

ADULT; AGED; ANTIFUNGAL AGENTS; ASPERGILLOSIS; ASPERGILLUS FUMIGATUS; AZOLES; DENMARK; DRUG RESISTANCE, FUNGAL; ENVIRONMENT; FEMALE; FUNGAL PROTEINS; GENOTYPE; HUMANS; MALE; MICROBIAL SENSITIVITY TESTS; MICROSATELLITE REPEATS; MIDDLE AGED;

EID: 84906090466     PISSN: 00664804     EISSN: 10986596     Source Type: Journal    
DOI: 10.1128/AAC.02855-14     Document Type: Article

References (45)

1. Van Der Linden JWM, Warris A, Verweij PE. 2011. Aspergillus species intrinsically resistant to antifungal agents. Med. Mycol. 49(Suppl 1):S82-S89. http://dx.doi.org/10.3109/13693786.2010.499916.
2. Arendrup MC, Mavridou E, Mortensen KL, Snelders E, Frimodt-Møller N, Khan H, Melchers WJG, Verweij PE. 2010. Development of azole resistance in Aspergillus fumigatus during azole therapy associated with change in virulence. PLoS One 5:e10080. http://dx.doi.org/10.1371/journal.pone.0010080.
3. Camps SMT, van der Linden JWM, Li Y, Kuijper EJ, van Dissel JT, Verweij PE, Melchers WJ. 2012. Rapid induction of multiple resistance mechanisms in Aspergillus fumigatus during azole therapy: a case study and review of the literature. Antimicrob. Agents Chemother. 56:10-16. http://dx.doi.org/10.1128/ AAC.05088-11.
4. Howard SJ, Arendrup MC. 2011. Acquired antifungal drug resistance in Aspergillus fumigatus: epidemiology and detection. Med. Mycol. 49(Suppl 1):S90-S95. http://dx.doi.org/10.3109/13693786.2010.508469.
5. Vermeulen E, Lagrou K, Verweij PE. 2013. Azole resistance in Aspergillus fumigatus: a growing public health concern. Curr. Opin. Infect. Dis. 26:493-500. http://dx.doi.org/10.1097/QCO.0000000000000005.
6. Stensvold CR, Jørgensen LN, Arendrup MC. 2012. Azole-resistant invasive aspergillosis: relationship to agriculture. Curr. Fungal Infect. Rep. 6:178-191. http://dx.doi.org/10.1007/s12281-012-0097-7.
7. Snelders E, Camps SMT, Karawajczyk A, Schaftenaar G, Kema GHJ, van der Lee HA, Klaassen CH, Melchers WJG, Verweij PE. 2012. Triazole fungicides can induce cross-resistance to medical triazoles in Aspergillus fumigatus. PLoS One 7:e31801. http://dx.doi.org/10.1371/journal.pone.0031801.
8. Howard SJ, Cerar D, Anderson MJ, Albarrag A, Fisher MC, Pasqualotto AC, Laverdiere M, Arendrup MC, Perlin DS, Denning DW. 2009. Frequency and evolution of azole resistance in Aspergillus fumigatus associated with treatment failure. Emerg. Infect. Dis. 15:1068-1076. http://dx.doi.org/10.3201/eid1507.090043.
9. Mortensen KL, Jensen RH, Johansen HK, Skov M, Pressler T, Howard SJ, Leatherbarrow H, Mellado E, Arendrup MC. 2011. Aspergillus species and other molds in respiratory samples from patients with cystic fibrosis: a laboratory-based study with focus on Aspergillus fumigatus azole resistance. J. Clin. Microbiol. 49:2243-2251. http://dx.doi.org/10.1128/JCM.00213-11.
10. Mortensen KL, Mellado E, Lass-Flörl C, Rodriguez-Tudela JL, Johansen HK, Arendrup MC. 2010. Environmental study of azole-resistant Aspergillus fumigatus and other aspergilli in Austria, Denmark, and Spain. Antimicrob. Agents Chemother. 54:4545-4549. http://dx.doi.org/10.1128/AAC.00692-10.
11. Snelders E, van der Lee HAL, Kuijpers J, Rijs AJMM, Varga J, Samson RA, Mellado E, Donders ART, Melchers WJG, Verweij PE. 2008. Emergence of azole resistance in Aspergillus fumigatus and spread of a single resistance mechanism. PLoS Med. 5:e219. http://dx.doi.org/10.1371/journal.pmed.0050219.
12. Verweij PE, Mellado E, Melchers WJ. 2007. Multiple-triazole-resistant aspergillosis. N. Engl. J. Med. 356:1481-1483. http://dx.doi.org/10.1056/ NEJMc061720.
13. Vermeulen E, Maertens J, Schoemans H, Lagrou K. 2012. Azole-resistant Aspergillus fumigatus due to TR46/Y121F/T289A mutation emerging in Belgium, July 2012. Euro Surveill. 17:pii=20326. http://www.eurosurveillance.org/ViewArticle. aspx?ArticleId=20326.
14. Chowdhary A, Kathuria S, Randhawa HS, Gaur SN, Klaassen CH, Meis JF. 2012. Isolation of multiple-triazole-resistant Aspergillus fumigatus strains carrying the TR/L98H mutations in the cyp51A gene in India. J. Antimicrob. Chemother. 67:362-366. http://dx.doi.org/10.1093/jac/dkr443.
15. Snelders E, Karawajczyk A, Schaftenaar G, Verweij PE, Melchers WJ. 2010. Azole resistance profile of amino acid changes in Aspergillus fumigatus CYP51A based on protein homology modeling. Antimicrob. Agents Chemother. 54:2425-2430. http://dx.doi.org/10.1128/AAC.01599-09.
16. Seyedmousavi S, Hashemi SJ, Zibafar E, Zoll J, Hedayati MT, Mouton JW, Melchers WJG, Verweij PE. 2013. Azole-resistant Aspergillus fumigatus, Iran. Emerg. Infect. Dis. 19:832-834. http://dx.doi.org/10.3201/eid1905.130075.
17. Lockhart SR, Frade JP, Etienne KA, Pfaller MA, Diekema DJ, Balajee SA. 2011. Azole resistance in Aspergillus fumigatus isolates from the ARTEMIS global surveillance study is primarily due to the TR/L98H mutation in the cyp51A gene. Antimicrob. Agents Chemother. 55: 4465-4468. http://dx.doi.org/10.1128/AAC. 00185-11.
18. Mellado E, De La Camara R, Buendía B, Rodriguez-Tudela JL, Cuenca-Estrella M. 2013. Breakthrough pulmonary Aspergillus fumigatus infection with multiple triazole resistance in a Spanish patient with chronic myeloid leukemia. Rev. Iberoam. Micol. 30:64-68. http://dx.doi.org/10.1016/j.riam.2012. 09.002.
19. 34/L98H mutations in the cyp51A gene in India. PLoS One 7:e52871. http://dx.doi.org/10.1371/journal.pone.0052871.
20. van der Linden JW, Camps SM, Kampinga GA, Arends JP, Debets-Ossenkopp YJ, Haas PJ, Rijnders BJ, Kuijper EJ, van Tiel FH, Varga J, Karawajczyk A, Zoll J, Melchers WJ, Verweij PE. 2013. Aspergillosis due to voriconazole highly resistant Aspergillus fumigatus and recovery of genetically related resistant isolates from domiciles. Clin. Infect. Dis. 57:513-520. http://dx.doi.org/10. 1093/cid/cit320.
21. Rath PM, Buchheidt D, Spiess B, Arfanis E, Buer J, Steinmann J. 2012. First reported case of azole-resistant Aspergillus fumigatus due to the TR/L98H mutation in Germany. Antimicrob. Agents Chemother. 56:6060-6061. http://dx.doi.org/10.1128/AAC.01017-12.
22. Hamprecht A, Buchheidt D, Vehreschild JJ, Cornely OA, Spiess B, Plum G, Halbsguth TV, Kutsch N, Stippel D, Kahl P, Persigehl T, Steinbach A, Bos B, Hallek M, Vehreschild MJ. 2012. Azole-resistant invasive aspergillosis in a patient with acute myeloid leukaemia in Germany. Euro Surveill. 17:pii=20262. http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20262.
23. Bader O, Weig M, Reichard U, Lugert R, Kuhns M, Christner M, Held J, Peter S, Schumacher U, Buchheidt D, Tintelnot K, Groß U. 2013. cyp51A-based mechanisms of Aspergillus fumigatus azole drug resistance present in clinical samples from Germany. Antimicrob. Agents Chemother. 57:3513-3517. http://dx.doi.org/10.1128/AAC.00167-13.
24. Prigitano A, Venier V, Cogliati M, De Lorenzis G, Esposto MC, Tortorano AM; MykoLabNet-D Partners. 2014. Azole-resistant Aspergillus fumigatus in the environment of northern Italy, May 2011 to June 2012. Euro Surveill. 19:pii=20747. http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20747.
25. Chowdhary A, Sharma C, Kathuria S, Hagen F, Meis JF. 2014. Azole-resistant Aspergillus fumigatus with the environmental TR46/Y121F/T289A mutation in India. J. Antimicrob. Chemother. 69:555-557. http://dx.doi.org/10. 1093/jac/dkt397.
26. European Center for Disease Prevention and Control. 2013. Risk assessment on the impact of environmental usage of triazoles on the development and spread of resistance to medical triazoles in Aspergillus species. European Center for Disease Prevention and Control, Stockholm, Sweden. http://www.ecdc.europa.eu/en/ publications/-layouts/forms/Publication-DispForm.aspx?ID=823&List= 4f55ad51-4aed-4d32-b960-af70113dbb90.
27. De Hoog GS, Guarro J, Gene MJF. 2001. Atlas of clinical fungi, 2nd ed. ASM Press, Washington, DC.
28. Schwarz P, Lortholary O, Dromer F, Dannaoui E. 2007. Carbon assimilation profiles as a tool for identification of zygomycetes. J. Clin. Microbiol. 45:1433-1439. http://dx.doi.org/10.1128/JCM.02219-06. (Pubitemid 46762395)
29. Subcommittee on Antifungal Susceptibility Testing (AFST) of the ESCMID European Committee for Antimicrobial Susceptibility Testing (EUCAST). 2008. EUCAST technical note on the method for the determination of broth dilution minimum inhibitory concentrations of antifungal agents for conidia-forming moulds. Clin. Microbiol. Infect. 14: 982-984. http://dx.doi.org/10.1111/j.1469- 0691.2008.02086.x.
30. Espinel-Ingroff A. 2003. Evaluation of broth microdilution testing parameters and agar diffusion Etest procedure for testing susceptibilities of Aspergillus spp. to caspofungin acetate (MK-0991). J. Clin. Microbiol. 41:403-409. http://dx.doi.org/10.1128/JCM.41.1.403-409.2003. (Pubitemid 36098607)
31. Mellado E, Diaz-Guerra TM, Cuenca-Estrella M, Rodriguez-Tudela JL. 2001. Identification of two different 14-α sterol demethylase-related genes (cyp51A and cyp51B) in Aspergillus fumigatus and other Aspergillus species. J. Clin. Microbiol. 39:2431-2438. http://dx.doi.org/10.1128/JCM.39.7.2431-2438. 2001. (Pubitemid 32606215)
32. de Valk HA, Meis JF, Curfs IM, Muehlethaler K, Mouton JW, Klaassen CH. 2005. Use of a novel panel of nine short tandem repeats for exact and high-resolution fingerprinting of Aspergillus fumigatus isolates. J. Clin. Microbiol. 43:4112-4120. http://dx.doi.org/10.1128/JCM.43.8.4112-4120.2005. (Pubitemid 41129707)
33. van der Linden JW, Snelders E, Kampinga GA, Rijnders BJ, Mattsson E, Debets-Ossenkopp YJ, Kuijper EJ, Van Tiel FH, Melchers WJ, Verweij PE. 2011. Clinical implications of azole resistance in Aspergillus fumigatus, the Netherlands, 2007-2009. Emerg. Infect. Dis. 17:1846-1854. http://dx.doi.org/10. 3201/eid1710.110226.
34. Snelders E, Huis In 't Veld RA, Rijs AJ, Kema GH, Melchers WJ, Verweij PE. 2009. Possible environmental origin of resistance of Aspergillus fumigatus to medical triazoles. Appl. Environ. Microbiol. 75:4053-4057. http://dx.doi.org/10.1128/AEM.00231-09.
35. Walsh TJ, Anaissie EJ, Denning DW, Herbrecht R, Kontoyiannis DP, Marr KA, Morrison VA, Segal BH, Steinbach WJ, Stevens DA, van Burik JA, Wingard JR, Patterson TF; Infectious Diseases Society of America. 2008. Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin. Infect. Dis. 46:327-360. http://dx.doi.org/10.1086/525258. (Pubitemid 351265310)
36. Maertens J, Marchetti O, Herbrecht R, Cornely OA, Flückiger U, Frêre P, Gachot B, Heinz WJ, Lass-Flörl C, Ribaud P, Thiebaut A, Cordonnier C; Third European Conference on Infections in Leukemia. 2011. European guidelines for antifungal management in leukemia and hematopoietic stem cell transplant recipients: summary of the ECIL 3-2009 update. Bone Marrow Transplant. 46:709-718. http://dx.doi.org/10.1038/bmt.2010.175.
37. Greene RE, Schlamm HT, Oestmann J-W, Stark P, Durand C, Lortholary O, Wingard JR, Herbrecht R, Ribaud P, Patterson TF, Troke PF, Denning DW, Bennett JE, de Pauw BE, Rubin RH. 2007. Imaging findings in acute invasive pulmonary aspergillosis: clinical significance of the halo sign. Clin. Infect. Dis. 44:373-379. http://dx.doi.org/10.1086/509917. (Pubitemid 46147619)
38. Lortholary O, Gangneux JP, Sitbon K, Lebeau B, de Monbrison F, Le Strat Y, Coignard B, Dromer F, Bretagne S; French Mycosis Study Group. 2011. Epidemiological trends in invasive aspergillosis in France: the SAIF network (2005-2007). Clin. Microbiol. Infect. 17:1882-1889. http://dx.doi.org/10.1111/j. 1469-0691.2011.03548.x.
39. Upton A, Kirby KA, Carpenter P, Boeckh M, Marr KA. 2007. Invasive aspergillosis following hematopoietic cell transplantation: outcomes and prognostic factors associated with mortality. Clin. Infect. Dis. 44:531-540. http://dx.doi.org/10.1086/510592. (Pubitemid 46233255)
40. Nivoix Y, Velten M, Letscher-Bru V, Moghaddam A, Natarajan-Amé S, Fohrer C, Lioure B, Bilger K, Lutun P, Marcellin L, Launoy A, Freys G, Bergerat JP, Herbrecht R. 2008. Factors associated with overall and attributable mortality in invasive aspergillosis. Clin. Infect. Dis. 47:1176-1184. http://dx.doi.org/10.1086/592255.
41. Pagano L, Caira M, Candoni A, Offidani M, Martino B, Specchia G, Pastore D, Stanzani M, Cattaneo C, Fanci R, Caramatti C, Rossini F, Luppi M, Potenza L, Ferrara F, Mitra ME, Fadda RM, Invernizzi R, Aloisi T, Picardi M, Bonini A, Vacca A, Chierichini A, Melillo L, de Waure C, Fianchi L, Riva M, Leone G, Aversa F, Nosari A. 2010. Invasive aspergillosis in patients with acute myeloid leukemia: a SEIFEM-2008 registry study. Haematologica 95:644-650. http://dx.doi.org/10.3324/haematol.2009.012054.
42. Perkhofer S, Lass-Flörl C, Hell M, Russ G, Krause R, Hönigl M, Geltner C, Auberger J, Gastl G, Mitterbauer M, Willinger B, Knöbl P, Resch G, Waldner R, Makrai A, Hartmann G, Girschikofsky M, Greil R. 2010. The Nationwide Austrian Aspergillus Registry: a prospective data collection on epidemiology, therapy and outcome of invasive mould infections in immunocompromised and/or immunosuppressed patients. Int. J. Antimicrob. Agents 36:531-536. http://dx.doi.org/10.1016/j.ijantimicag.2010.08.010.
43. van Leer-Buter C, Takes RP, Hebeda KM, Melchers WJ, Verweij PE. 2007. Aspergillosis - and a misleading sensitivity result. Lancet 370:102. http://dx.doi.org/10.1016/S0140-6736(07)61055-1.
44. Clinical and Laboratory Standards Institute. 2008. Reference method for broth dilution antifungal susceptibility testing of yeasts, 3rd ed. Approved standard CLSI M27-A3. Clinical and Laboratory Standards Institute, Wayne, PA.
45. De Pauw B, Walsh TJ, Donnelly JP, Stevens DA, Edwards JE, Calandra T, Pappas PG, Maertens J, Lortholary O, Kauffman CA, Denning DW, Patterson TF, Maschmeyer G, Bille J, Dismukes WE, Herbrecht R, Hope WW, Kibbler CC, Kullberg BJ, Marr KA, Muñoz P, Odds FC, Perfect JR, Restrepo A, Ruhnke M, Segal BH, Sobel JD, Sorrell TC, Viscoli C, Wingard JR, Zaoutis T, Bennett JE; European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group; National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. 2008. 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) C. Clin. Infect. Dis. 46:1813-1821. http://dx.doi.org/10.1086/588660.