High prevalence of clinical and environmental triazole-resistant Aspergillus fumigatus in Iran: is it a challenging issue?

Abstract

Triazole antifungal agents are the mainstay of aspergillosis treatment. As highlighted in numerous studies, the global increase in the prevalence of triazole resistance could hamper the management of aspergillosis. In the present three-year study, 513 samples (213 clinical and 300 environmental samples) from 10 provinces of Iran were processed and screened in terms of azole resistance (4 and 1 mg l À1 of itraconazole and voriconazole, respectively), using selective plates. Overall, 150 A. fumigatus isolates (71 clinical and 79 environmental isolates) were detected. The isolates were confirmed by partial sequencing of the b-tubulin gene. Afterwards, in vitro antifungal susceptibility tests against triazole agents were performed, based on the Clinical and Laboratory Standards Institute (CLSI) M38-A2 document. The CYP51A gene was sequenced in order to detect mutations. The MIC of itraconazole against 10 (6.6 %) strains, including clinical (n=3, 4.2 %) and environmental (n=7, 8.8 %) strains, was higher than the breakpoint and epidemiological cut-off value. Based on the findings, the prevalence of azole-resistant A. fumigatus in Iran has increased remarkablyfrom 3.3 % to 6.6 % in comparison with earlier epidemiological research. Among resistant isolates, TR 34 /L98H mutations in the CYP51A gene were the most prevalent (n=8, 80 %), whereas other point mutations (F46Y, G54W, Y121F, G138C, M172V, F219C, M220I, D255E, T289F, G432C and G448S mutations) were not detected. Although the number of patients affected by azole-resistant A. fumigatus isolates was limited, strict supervision of clinical azole-resistant A. fumigatus isolates and persistent environmental screening of azole resistance are vital to the development of approaches for the management of azole resistance in human pathogenic fungi.

Osteomyelitis and lung abscess due to Aspergillus fumigatus in a chronic granulomatous disease patient

“…New generation of azoles and echinocandins might be useful in this regard. However, based on a recent report from Iran, the number of azole-resistant A. fumigatus strains against itraconazole increased significantly from 3% to 6% [16]. Some studies indicated that mutations might confer resistance to individual azoles, rather than to the whole class [17].…”

Use of cell surface protein typing for genotyping of azole‐resistant and ‐susceptible Aspergillus fumigatus isolates in Iran

“…In addition, 29 environmental isolates were collected from soil and leaves of gardens surrounding hospitals and from indoor air of hospital wards. The isolates were identified by partial sequencing of the β‐tubulin gene . Antifungal susceptibility testing was performed according to Clinical and Laboratory Standards Institute guidelines (M38‐A2, 2008) .…”

“…The latter disorder is associated with immunocompromising conditions, that is, neutropenia, hematopoietic stem cell transplantation (HSCT), solid organ transplantation (SOT) and chemotherapy . Although triazole antifungal drugs (voriconazole and posaconazole) are currently the first‐line therapy in the management and prophylaxis of aspergillosis, surveillance studies and case series suggest a global presence of clinical and environmental azole‐resistant A. fumigatus isolates in Africa, Australia, Asia, Europe, Latin‐America, the Middle East and United States . Azole‐resistance may develop either in patients who are treated with long‐term azole therapy or in the environment through the exposure of the fungus to azole fungicides used in agriculture .…”

“…Azole‐resistance may develop either in patients who are treated with long‐term azole therapy or in the environment through the exposure of the fungus to azole fungicides used in agriculture . Since 2013, the prevalence of azole‐resistant A. fumigatus isolates has increased from 3.3 % to 6.6 % in Iran . Molecular typing methods have been used to study nosocomial outbreaks, understanding genetic diversity, relationships between clinical and environmental isolates, and patterns of either colonisation or invasion .…”

Invasive Pulmonary Aspergillosis in Patients with Non-Decompensated Liver Cirrhosis: A Case Report

“…Subsequently, molecular tests were performed for accurate identification of Aspergillus fumigatus. Briefly, DNA was extracted from the colony using homogenization by glass beads followed by phenol-chloroform purification, as described previously (5,6). Polymerase chain reaction (PCR) amplification of the β-tubulin gene was performed using the primers B2a (5'-GGTAACCAAATCGGTGCTTTC-3') and B2b ('5-ACCCTCAGTGTAGTGACCCTTGGC-3') with cycles of five minutes at 94°C for primary denaturation, followed by 35 cycles at 94°C (60 seconds), 58°C (30 seconds), and 72°C (80 seconds), with a final seven-minutes extension step at 72°C.…”