Skip directly to search Skip directly to A to Z list Skip directly to page options Skip directly to site content

Volume 15, Number 7—July 2009

Research

Frequency and Evolution of Azole Resistance in Aspergillus fumigatus Associated with Treatment Failure1

Susan J. Howard, Dasa Cerar, Michael J. Anderson, Ahmed Albarrag, Matthew C. Fisher, Alessandro C. Pasqualotto, Michel Laverdiere, Maiken C. Arendrup, David S. Perlin, and David W. DenningComments to Author 
Author affiliations: Regional Mycology Laboratory, Manchester, UK (S.J. Howard, D.W. Denning); University of Manchester, Manchester Academic Health Science Centre, Manchester (S.J. Howard, M.J. Anderson, A. Albarrag, D.W. Denning); University Medical Centre, Ljubljana, Slovenia (D. Cerar); Imperial College, London, UK (M.C. Fisher); Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil (A.C. Pasqualotto); Hôpital Maisonneuve-Rosemont, Montreal, Québec, Canada (M. Laverdiere); Statens Serum Institut, Copenhagen, Denmark (M.C. Ardendrup); Public Health Research Institute, Newark, NJ, USA (D.S. Perlin)

Main Article

Table 2

Clinical information for 17 patients with azole resistant Aspergillus fumigatus infections*

Patient no. Age, y/sex City No. isolates Aspergillus disease Other diseases, y Daily dose, duration Serum azole levels, mg/L† Outcome Survival
1
50/F
Cambridge, UK
1
CCPA with aspergilloma
Breast cancer, 1990; M. malmoense pulmonary tuberculosis, 1999 and 2005
Vori 200–400 mg, 18 mo
ND
Clinical and radiological failure
Alive
2
21/F
Copenhagen, Denmark
1
ABPA
CF, concomitant bacterial colonization with Staphylococcus aureus and Achromobacter
Itra 200 mg, 14 mo (plus previous courses)
ND
Unknown
Alive
3
40/F
Manchester, UK
2‡
CCPA with aspergilloma, then CFPA
Pulmonary TB with residual bilateral UL scarring and LUL cavity, 1986; smoke inhalation, 1989
Itra 400 mg, 90 mo
15.0–26.0§
Clinical failure
Died
4
72/M
Manchester, UK
3
CCPA with aspergilloma
COPD, squamous cell carcinoma with LUL segmentectomy, 1992
Itra 400 mg, >2 mo
2.9–11.3
No improvement
Died
5
43/M
Montreal, Quebec, Canada
2
Cerebral aspergillosis, Nov 1998
AML-M2, 1997; RUL lobectomy, 1997; AlloHSCT, 1998; GVHD
Itra 400 mg, 4 mo
ND
Regression of cerebral abscess, then IPA with respiratory failure
Died
6
60/M
Manchester, UK
2
CCPA with aspergilloma
COPD, M. szulgai pulmonary infection, 2003; celiac disease
Itra 200–400 mg, 1 mo
<0.8 (200 mg),
5.3–7.7 (400 mg)
Clinical failure
Died
7
77/M
Manchester, UK
1
Acute invasive pulmonary
COPD,
possible bronchiectasis
Itra 600–400 mg, 1 mo; vori 400 mg, 12 d
17.0–21.0 (itra)
No improvement; switched to vori, developed toxicity
Died, without
IPA
8
46/F
Northampton, UK
2
ABPA
Bronchiectasis, asthma, 
AVR, hypermobility syndrome, M. xenopi pulmonary infection, 2007
Itra 200–400 mg, 9 mo
0.0–5.2
Initial improvement, then failure
Alive
9
46/M
Liverpool, UK
12
CCPA with bilateral aspergillomas, CFPA
Pulmonary sarcoidosis, 1988
Itra 200–400 mg, 30 mo
0.9–10.3
Clinical failure
Died
10
41/F
Manchester, UK
2
Aspergillus bronchitis
Bronchiectasis, onychomycosis, 2007; α-1-antitrypsin deficiency
Itra 400 mg pulse, 3 mo
ND
Itra resistance identified, so treated with posa
Alive
11
62/F
Manchester, UK
2
CCPA with aspergilloma
RUL pneumonia, 2002
Itra 400 mg, 1.5 mo
20.0–>25.6
No improvement
Alive
12
29/F
Manchester, UK (Malawi origin)
1
CCPA with 2 aspergillomas
Pulmonary TB, 1995; HIV positive, HAART
Itra 400 mg, 18 mo
2.5–8.4
Improvement then progression
Alive
13
64/M
Preston, UK
4
CCPA with aspergilloma
COPD, bronchiectasis, M. avium pulmonary infection, 2002 and 2006
Itra 600 mg, 10 mo
2.6–4.5
Progression
Alive
14
42/M
Birkenhead, UK
1
CCPA with LUL aspergilloma
Sarcoidosis, COPD, celiac disease; aspergilloma removed as part of left lung transplant, 2007¶
Itra 400 mg, 11 mo
13.8–17.8
Unchanged, switched to vori
Unknown
15
68/F
Wirral, UK
1
Sputum isolate
Cardiac transplant for congestive cardiomyopathy, 1999; chronic cough; 2007; polymyalgia rheumatica, hiatal hernia, oesophagitis
Not documented
NA
Not assessable
Alive
16
12/F
Liverpool, UK
1
Sputum isolate
Unknown
Unknown
Unknown
Unknown
Unknown
17 43/M Manchester, UK 1 Sputum isolate Unknown Unknown Unknown Unknown Unknown

*CCPA , chronic cavitary pulmonary aspergillosis; M., Mycobacterium; vori, voriconazole; ND, not determined; ABPA, allergic bronchopulmonary aspergillosis; CF, cystic fibrosis; itra, itraconazole; CFPA, chronic fibrosing pulmonary aspergillosis; TB, tuberculosis; UL, upper lobe; LUL, left upper lobe; COPD, chronic obstructive pulmonary disease; AML, acute myeloid leukemia; RUL, right upper lobe; AlloHSCT, allogeneic haematopoietic stem cell transplant; GVHD, graft versus host disease; IPA, invasive pulmonary aspergillosis; AVR, aortic valve replacement; posa, posaconazole; HAART, highly active antiretroviral therapy.
†Determined by bioassay (target range 5–15 mg/L).
‡Plus aspergilloma isolates studied, taken at autopsy.
§Received a generic formulation of itra, resulting in lower concentrations (i.e., 4.6 mg/L) and then probably was noncompliant at end of treatment period.
¶Successfully completed with vori treatment.

Main Article

1These data were presented in part at the 2nd Advances Against Aspergillosis meeting, February 22–26, 2006, Athens, Greece; and 46th Interscience Conference on Antimicrobial Agents and Chemotherapy, September 27–30, 2006, San Francisco, CA, USA.

TOP