Skip to main content
Top
Published in: Antimicrobial Resistance & Infection Control 1/2020

01-12-2020 | Itraconazole | Research

Screening for triazole resistance in clinically significant Aspergillus species; report from Pakistan

Authors: Safia Moin, Joveria Farooqi, Kauser Jabeen, Sidra Laiq, Afia Zafar

Published in: Antimicrobial Resistance & Infection Control | Issue 1/2020

Login to get access

Abstract

Background

Burden of aspergillosis is reported to be significant from developing countries including those in South Asia. The estimated burden in Pakistan is also high on the background of tuberculosis and chronic lung diseases. There is concern for management of aspergillosis with the emergence of azole resistant Aspergillus species in neighbouring countries in Central and South Asia.
Hence the aim of this study was to screen significant Aspergillus species isolates at the Microbiology Section of Aga Khan Clinical Laboratories, Pakistan, for triazole resistance.

Methods

A descriptive cross-sectional study, conducted at the Aga Khan University Laboratories, Karachi, from September 2016–May 2019. One hundred and fourteen, clinically significant Aspergillus isolates [A. fumigatus (38; 33.3%), A. flavus (64; 56.1%), A. niger (9; 7.9%) A. terreus (3; 2.6%)] were included. The clinical spectrum ranged from invasive aspergillosis (IA) (n = 25; 21.9%), chronic pulmonary aspergillosis (CPA) (n = 58; 50.9%), allergic bronchopulmonary aspergillosis (ABPA) (n = 4; 3.5%), severe asthma with fungal sensitization (SAFS) (n = 4; 3.5%), saprophytic tracheobronchial aspergillosis (n = 23; 20.2%). Screening for triazole resistance was performed by antifungal agar screening method. The minimum inhibitory concentration (MIC) of 41 representative isolates were tested and interpreted according to the Clinical and Laboratory Standards Institute broth microdilution method.

Results

All the isolates were triazole-susceptible on agar screening. MICs of three azole antifungals for 41 tested isolates were found to be ≤1 ml/L; all isolates tested were categorized as triazole-susceptible, including 4 isolates from patients previously on triazole therapy for more than 2 weeks. The minimum inhibitory concentration required to inhibit the growth of 90% organisms (MIC90) of itraconazole, voriconazole and posaconazole of the representative Aspergillus isolates was 1 mg/L, 1 mg/L and 0.5 mg/L, respectively.

Conclusion

Triazole resistance could not be detected amongst clinical Aspergillus isolates from the South of Pakistan. However, environmental strains remain to be tested for a holistic assessment of the situation. This study will set precedence for future periodic antifungal resistance surveillance in our region on Aspergillus isolates.
Literature
1.
go back to reference C. LF. Susceptibility testing in Aspergillus species complex. Clin Microbiol Infect. 2014;20(s6):49–53. C. LF. Susceptibility testing in Aspergillus species complex. Clin Microbiol Infect. 2014;20(s6):49–53.
2.
go back to reference Xu HLL, Huang WJ, Wang LX, Li WF, Yuan WF. Invasive pulmonary aspergillosis in patients with chronic obstructive pulmonary disease: a case control study from China. Clin Microbiol Infect. 2012;18(4):403–8.CrossRef Xu HLL, Huang WJ, Wang LX, Li WF, Yuan WF. Invasive pulmonary aspergillosis in patients with chronic obstructive pulmonary disease: a case control study from China. Clin Microbiol Infect. 2012;18(4):403–8.CrossRef
3.
go back to reference Chakrabarti A. Burden of invasive fungal infections in developing countries. MYCOSES; 2015. Chakrabarti A. Burden of invasive fungal infections in developing countries. MYCOSES; 2015.
4.
go back to reference Jabeen K, Farooqi J, Mirza S, Denning D, Zafar A. Serious fungal infections in Pakistan. Eur J Clin Microbiol Infect Dis. 2017;36(6):949–56. Jabeen K, Farooqi J, Mirza S, Denning D, Zafar A. Serious fungal infections in Pakistan. Eur J Clin Microbiol Infect Dis. 2017;36(6):949–56.
5.
go back to reference Immaculata Xess SM, Jain N, jee UB. Prevalence of Aspergillus spp.in clinical samples isoalted in an Indian Tertiary care Hopsital. Ind J Med Sci. 2004;58:12. Immaculata Xess SM, Jain N, jee UB. Prevalence of Aspergillus spp.in clinical samples isoalted in an Indian Tertiary care Hopsital. Ind J Med Sci. 2004;58:12.
6.
go back to reference MI NI, Jabeen K, Farooqi J. Clinical features and outcome of Chronic Pulmonary Aspergillosis: experience from a high tuberculosis burden country. Medical Mycology,ISHAM. 2018;56:S1–S159 2018:PP1.044. MI NI, Jabeen K, Farooqi J. Clinical features and outcome of Chronic Pulmonary Aspergillosis: experience from a high tuberculosis burden country. Medical Mycology,ISHAM. 2018;56:S1–S159 2018:PP1.044.
7.
go back to reference Shivaprakash MGE, Chakrabarti A, Mouton JW, Meis JF. In vitro susceptibility of 188 clinical and environmental isolates of Aspergillus flavus for the new triazole isavuconazole and seven other antifungal drugs. Mycoses. 2011;54(5):e583–e9.CrossRef Shivaprakash MGE, Chakrabarti A, Mouton JW, Meis JF. In vitro susceptibility of 188 clinical and environmental isolates of Aspergillus flavus for the new triazole isavuconazole and seven other antifungal drugs. Mycoses. 2011;54(5):e583–e9.CrossRef
8.
go back to reference Anuradha Chowdhary CS, Kathuria S, Hagen F, Meis JF. Prevalence and mechanism of triazole resistance in Aspergillus fumigatus in a referral chest hospital in Delhi, India and an update of the situation in Asia. Front Microbiol. 2015;6:428.PubMedPubMedCentral Anuradha Chowdhary CS, Kathuria S, Hagen F, Meis JF. Prevalence and mechanism of triazole resistance in Aspergillus fumigatus in a referral chest hospital in Delhi, India and an update of the situation in Asia. Front Microbiol. 2015;6:428.PubMedPubMedCentral
9.
go back to reference Denning DWPS, Lass-Florl C, Fraczek MG, Kirwan M, Gore R, et al. High-frequency triazole resistance found in nonculturable Aspergillus fumigatus from lungs of patients with chronic fungal disease. Clin Infect Dis. 2011;52(9):1123–9.CrossRef Denning DWPS, Lass-Florl C, Fraczek MG, Kirwan M, Gore R, et al. High-frequency triazole resistance found in nonculturable Aspergillus fumigatus from lungs of patients with chronic fungal disease. Clin Infect Dis. 2011;52(9):1123–9.CrossRef
10.
go back to reference Verweij PECA, Melchers WJ, Meis JF. Azole resistance in Aspergillus fumigatus: can we retain the clinical use of mold-active antifungal azoles? Clin Infect Dis. 2015;civ885. Verweij PECA, Melchers WJ, Meis JF. Azole resistance in Aspergillus fumigatus: can we retain the clinical use of mold-active antifungal azoles? Clin Infect Dis. 2015;civ885.
11.
go back to reference Schelenz SBR, Barton RC, Cleverley JR, Lucas SB, Kibbler CC, et al. British Society for Medical Mycology best practice recommendations for the diagnosis of serious fungal diseases. Lancet Infect Dis. 2015;15(4):461–74.CrossRef Schelenz SBR, Barton RC, Cleverley JR, Lucas SB, Kibbler CC, et al. British Society for Medical Mycology best practice recommendations for the diagnosis of serious fungal diseases. Lancet Infect Dis. 2015;15(4):461–74.CrossRef
12.
go back to reference Fabio Silvio Taccone A-MVA, Bulpa P, on behalf of the AspICU Study Investigators, et al. Epidemiology of invasive aspergillosis in critically ill patients: clinical presentation, underlying conditions, and outcomes. Taccone et al Critical Care. 2015;19:7.CrossRef Fabio Silvio Taccone A-MVA, Bulpa P, on behalf of the AspICU Study Investigators, et al. Epidemiology of invasive aspergillosis in critically ill patients: clinical presentation, underlying conditions, and outcomes. Taccone et al Critical Care. 2015;19:7.CrossRef
13.
go back to reference Radek Dutkiewicz CAH. Aspergillus infections in the critically ill. Proc Am Thorac Soc. 2010;7:204–9.CrossRef Radek Dutkiewicz CAH. Aspergillus infections in the critically ill. Proc Am Thorac Soc. 2010;7:204–9.CrossRef
14.
go back to reference Stijn I, Blot FST, Van den Abeele A-M, the AspICU Study Investigators, et al. A Clinical Algorithm to Diagnose Invasive Pulmonary Aspergillosis in Critically Ill Patients. Am J Respir Crit Care Med. 2012;186(Iss. 1):56–64. Stijn I, Blot FST, Van den Abeele A-M, the AspICU Study Investigators, et al. A Clinical Algorithm to Diagnose Invasive Pulmonary Aspergillosis in Critically Ill Patients. Am J Respir Crit Care Med. 2012;186(Iss. 1):56–64.
16.
go back to reference AE WTJ, Denning DW, Herbrecht R, Kontoyiannis DP, Marr KA, et al. Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis. 2008;46(3):327–60.CrossRef AE WTJ, Denning DW, Herbrecht R, Kontoyiannis DP, Marr KA, et al. Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis. 2008;46(3):327–60.CrossRef
17.
go back to reference De Pauw BWT, 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):1813–21.CrossRef De Pauw BWT, 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):1813–21.CrossRef
18.
go back to reference De Hoog GGJ, Gene J, Figueras M. Atlas of clinical fungi, Centraalbureau voor Schimmelcultures Universitat Rovira i Virgili; 2000. De Hoog GGJ, Gene J, Figueras M. Atlas of clinical fungi, Centraalbureau voor Schimmelcultures Universitat Rovira i Virgili; 2000.
19.
go back to reference Clinical, Institute LS. Reference Method for Broth Dilution Antifungal Susceptibility Testing of Filamentous Fungi: Approved Standard. CLSI document M38-A2 2008. Clinical, Institute LS. Reference Method for Broth Dilution Antifungal Susceptibility Testing of Filamentous Fungi: Approved Standard. CLSI document M38-A2 2008.
20.
go back to reference Mortensen KLME, Lass-Flörl C, Rodriguez-Tudela JL, Johansen HK, Arendrup MC. Environmental study of azole-resistant Aspergillus fumigatus and other aspergilli in Austria, Denmark, and Spain. Int J Antimicrob Agents. 2010;54(11):4545–9.CrossRef Mortensen KLME, Lass-Flörl C, Rodriguez-Tudela JL, Johansen HK, Arendrup MC. Environmental study of azole-resistant Aspergillus fumigatus and other aspergilli in Austria, Denmark, and Spain. Int J Antimicrob Agents. 2010;54(11):4545–9.CrossRef
21.
go back to reference Iqbal N IM, Zubairi A, Jabeen K, Awan S, J. Clinical Manifestations and Outcomes of Pulmonary Aspergillosis ; Experience from Pakistan". BMJ resp research manuscript ID is bmjresp. 2016;K 2016–000155.R1. Iqbal N IM, Zubairi A, Jabeen K, Awan S, J. Clinical Manifestations and Outcomes of Pulmonary Aspergillosis ; Experience from Pakistan". BMJ resp research manuscript ID is bmjresp. 2016;K 2016–000155.R1.
24.
go back to reference Masato Tashiro KI. A Katsuji Hirano et al. correlation between Triazole treatment history and susceptibility in clinically isolated Aspergillus fumigatus. Antimicrobial Agents and Chemotherapy September. 2012;56(9):4870–5.CrossRef Masato Tashiro KI. A Katsuji Hirano et al. correlation between Triazole treatment history and susceptibility in clinically isolated Aspergillus fumigatus. Antimicrobial Agents and Chemotherapy September. 2012;56(9):4870–5.CrossRef
25.
go back to reference Musang Liu RZ, Zhang L, et al. Multiple cyp51A-Based Mechanisms Identified in Azole-Resistant Isolates of Aspergillus fumigatus from China. Antimicrob Agents Chemother. 2015;59:7. Musang Liu RZ, Zhang L, et al. Multiple cyp51A-Based Mechanisms Identified in Azole-Resistant Isolates of Aspergillus fumigatus from China. Antimicrob Agents Chemother. 2015;59:7.
26.
go back to reference Anuradha Chowdhary SK, Meis JF, et al. Clonal Expansion and Emergence of Environmental Multiple-Triazole-Resistant Aspergillus fumigatus Strains Carrying the TR34/L98H Mutations in the cyp51A Gene in India. PloS one. 2012;7(Issue 12):e52871.CrossRef Anuradha Chowdhary SK, Meis JF, et al. Clonal Expansion and Emergence of Environmental Multiple-Triazole-Resistant Aspergillus fumigatus Strains Carrying the TR34/L98H Mutations in the cyp51A Gene in India. PloS one. 2012;7(Issue 12):e52871.CrossRef
27.
go back to reference Mojtaba Nabili TS, Moazeni M, et al. High prevalence of clinical and environmental triazole-resistant Aspergillus fumigatus in Iran: is it a challenging issue? J Med Microbiol. 2016;65:468–75.CrossRef Mojtaba Nabili TS, Moazeni M, et al. High prevalence of clinical and environmental triazole-resistant Aspergillus fumigatus in Iran: is it a challenging issue? J Med Microbiol. 2016;65:468–75.CrossRef
28.
go back to reference Jacques F, Meis AC, Johanna L, Rhodes M, Fisher C, Paul E. Verweij. Clinical implications of globally emerging azole resistance in Aspergillus fumigatus. Phil Trans R Soc. 2016;B 371:20150460. Jacques F, Meis AC, Johanna L, Rhodes M, Fisher C, Paul E. Verweij. Clinical implications of globally emerging azole resistance in Aspergillus fumigatus. Phil Trans R Soc. 2016;B 371:20150460.
29.
go back to reference Sonia Kumari Shishodia STJS. Resistance mechanism and proteins in Aspergillus species against antifungal agents. Mycology. 2019;10(3):151–65.CrossRef Sonia Kumari Shishodia STJS. Resistance mechanism and proteins in Aspergillus species against antifungal agents. Mycology. 2019;10(3):151–65.CrossRef
30.
go back to reference Shivaprakash M, Rudramurthy RAP, Chakrabarti A, Mouton JW, Meis JF. Invasive Aspergillosis by Aspergillus flavus: Epidemiology, Diagnosis, Antifungal Resistance, and Management. J Fungi. 2019;5:55.CrossRef Shivaprakash M, Rudramurthy RAP, Chakrabarti A, Mouton JW, Meis JF. Invasive Aspergillosis by Aspergillus flavus: Epidemiology, Diagnosis, Antifungal Resistance, and Management. J Fungi. 2019;5:55.CrossRef
31.
go back to reference DJD MAP, Ghannoum MA, et al. Wild-type MIC distribution and epidemiological cutoff values for Aspergillus fumigatus and three Triazoles as determined by the clinical and laboratory standards institute broth microdilution methods. J Clin Microbiol. 2009;47(10):3142–6.CrossRef DJD MAP, Ghannoum MA, et al. Wild-type MIC distribution and epidemiological cutoff values for Aspergillus fumigatus and three Triazoles as determined by the clinical and laboratory standards institute broth microdilution methods. J Clin Microbiol. 2009;47(10):3142–6.CrossRef
32.
go back to reference Maria Khan AI, Zaman G, Gardezi A, Lalani FK. Pattern of antifungal susceptibility in pathogenic molds by microdilution method at a tertiary care hospital. Ann Med Health Sci Res. 2018;8:82–6. Maria Khan AI, Zaman G, Gardezi A, Lalani FK. Pattern of antifungal susceptibility in pathogenic molds by microdilution method at a tertiary care hospital. Ann Med Health Sci Res. 2018;8:82–6.
Metadata
Title
Screening for triazole resistance in clinically significant Aspergillus species; report from Pakistan
Authors
Safia Moin
Joveria Farooqi
Kauser Jabeen
Sidra Laiq
Afia Zafar
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Antimicrobial Resistance & Infection Control / Issue 1/2020
Electronic ISSN: 2047-2994
DOI
https://doi.org/10.1186/s13756-020-00731-8

Other articles of this Issue 1/2020

Antimicrobial Resistance & Infection Control 1/2020 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.