Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2015 May 8:6:428.
doi: 10.3389/fmicb.2015.00428. eCollection 2015.

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

Anuradha Chowdhary  1 , Cheshta Sharma  1 , Shallu Kathuria  1 , Ferry Hagen  2 , Jacques F Meis  3
Affiliations

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

Anuradha Chowdhary et al. Front Microbiol. .

Abstract

Aspergillus fumigatus causes varied clinical syndromes ranging from colonization to deep infections. The mainstay of therapy of Aspergillus diseases is triazoles but several studies globally highlighted variable prevalence of triazole resistance, which hampers the management of aspergillosis. We studied the prevalence of resistance in clinical A. fumigatus isolates during 4 years in a referral Chest Hospital in Delhi, India and reviewed the scenario in Asia and the Middle East. Aspergillus species (n = 2117) were screened with selective plates for azole resistance. The isolates included 45.4% A. flavus, followed by 32.4% A. fumigatus, 15.6% Aspergillus species and 6.6% A. terreus. Azole resistance was found in only 12 (1.7%) A. fumigatus isolates. These triazole resistant A. fumigatus (TRAF) isolates were subjected to (a) calmodulin and β tubulin gene sequencing (b) in vitro antifungal susceptibility testing against triazoles using CLSI M38-A2 (c) sequencing of cyp51A gene and real-time PCR assay for detection of mutations and (d) microsatellite typing of the resistant isolates. TRAF harbored TR34/L98H mutation in 10 (83.3%) isolates with a pan-azole resistant phenotype. Among the remaining two TRAF isolates, one had G54E and the other had three non-synonymous point mutations. The majority of patients were diagnosed as invasive aspergillosis followed by allergic bronchopulmonary aspergillosis and chronic pulmonary aspergillosis. The Indian TR34/L98H isolates had a unique genotype and were distinct from the Chinese, Middle East, and European TR34/L98H strains. This resistance mechanism has been linked to the use of fungicide azoles in agricultural practices in Europe as it has been mainly reported from azole naïve patients. Reports published from Asia demonstrate the same environmental resistance mechanism in A. fumigatus isolates from two highly populated countries in Asia, i.e., China and India and also from the neighboring Middle East.

Keywords: Asia; G54E; India; TR34/L98H; microsatellite typing; triazole resistant A. fumigatus.

PubMed Disclaimer

Figures

FIGURE 1
FIGURE 1
Genotypicrelationship of Indian Aspergillus fumigatus isolates (clinical resistant, n = 14; clinical susceptible, n = 3; environmental resistant, n = 3; environmental susceptible, n = 6) with isolates from Asia including China (clinical resistant, n = 8), Middle East including Iran (environmental resistant, n = 5; environmental susceptible, n = 4), and Kuwait (clinical resistant, n = 2; clinical susceptible, n = 2; environmental resistant, n = 8; environmental susceptible, n = 2), and Europe including France (clinical resistant, n = 1), Germany (clinical resistant, n = 7; clinical susceptible, n = 1), the Netherlands (clinical resistant, n = 2; environmental susceptible, n = 3), and Australia (clinical resistant, n = 2; clinical susceptible, n = 2). The dendrogram is based on a categorical analysis of nine microsatellite markers in combination with Unweighted Pair Group Method with arithmetic mean clustering. The scale bar indicates the percentage identity. The isolates VPCI 343/P/11/1, VPCI 343/P/11/2, and VPCI 245/P/12-1, VPCI 245/P/12-2 were serial isolates from two individual patients, respectively.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Abdolrasoulia A., Rhodes J., Beale M. A., Hagen F., Rogers T. R., Chowdhary A., et al. (2015). Genomic context of azole-resistance mutations in Aspergillus fumigatus using whole-genome sequencing. mBio 6 (in press). - PMC - PubMed
    1. Agarwal R., Chakrabarti A., Shah A., Gupta D., Meis J. F., Guleria R., et al. (2013). Allergic bronchopulmonary aspergillosis: review of literature and proposal of new diagnostic and classification criteria. Clin. Exp. Allergy 43 850–873 10.1111/cea.12141 - DOI - PubMed
    1. Ahmad S., Joseph L., Hagen F., Meis J. F., Khan Z. (2015). Concomitant occurrence of itraconazole-resistant and -susceptible strains of Aspergillus fumigatus in routine cultures. J. Antimicrob. Chemother. 70 412–415 10.1093/jac/dku410 - DOI - PubMed
    1. Ahmad S., Khan Z., Hagen F., Meis J. F. (2014). Occurrence of triazole-resistant Aspergillus fumigatus with TR34/L98H mutations in outdoor and hospital environment in Kuwait. Environ. Res. 133 20–26 10.1016/j.envres.2014.05.009 - DOI - PubMed
    1. Alastruey-Izquierdo A., Mellado E., Peláez T., Pemán J., Zapico S., Alvarez M., et al. (2013). Population-based survey of filamentous fungi and antifungal resistance in Spain (FILPOP Study). Antimicrob. Agents Chemother. 57 3380–3387 10.1128/AAC.00383-13 - DOI - PMC - PubMed

LinkOut - more resources