Patterns of Susceptibility of Aspergillus Isolates Recovered from Patients Enrolled in the Transplant-Associated Infection Surveillance Network

Abstract

We analyzed antifungal susceptibilities of 274 clinical Aspergillus isolates from transplant recipients with proven or probable invasive aspergillosis collected as part of the Transplant-Associated Infection Surveillance Network (TRANSNET) and examined the relationship between MIC and mortality at 6 or 12 weeks. Antifungal susceptibility testing was performed by the Clinical and Laboratory Standards Institute (CLSI) M38-A2 broth dilution method for amphotericin B (AMB), itraconazole (ITR), voriconazole (VOR), posaconazole (POS), and ravuconazole (RAV). The isolate collection included 181Aspergillus fumigatus, 28 Aspergillus niger, 27 Aspergillus flavus, 22 Aspergillus terreus, seven Aspergillus versicolor, five Aspergillus calidoustus, and two Aspergillus nidulans isolates and two isolates identified as Aspergillus spp. Triazole susceptibilities were <4 g/ml for most isolates (POS, 97.6%; ITR, 96.3%; VOR, 95.9%; RAV, 93.5%). The triazoles were not active against the five A. calidoustus isolates, for which MICs were >4 g/ml. AMB inhibited 93.3% of isolates at an MIC of <1 g/ml. The exception was A. terreus, for which 15 (68%) of 22 isolates had MICs of >1 g/ml. One of 181 isolates of A. fumigatus showed resistance (MIC > 4 g/ml) to two of three azoles tested. Although there appeared to be a correlation of higher VOR MICs with increased mortality at 6 weeks, the relationship was not statistically significant (R 2 ‫؍‬ 0.61; P ‫؍‬ 0.065). Significant relationships of in vitro MIC to all-cause mortality at 6 and 12 weeks for VOR or AMB were not found.

Aerial Prevalence of Aspergillus calidoustus Isolates in and around a Tertiary Care Hospital in Kuwait and Assessment of Their Pathogenicity

“…These observations suggest that A. calidoustus conidia remain dormant and may be able to cause significant tissue invasion/ destruction only in the presence of severe and sustained immunosuppression. This is consistent with successful animal models of experimental invasive aspergillosis by Aspergillus fumigatus which have been achieved by frequent administration of at least two agents to obtain and maintain profound and persistent immunosuppression mimicking human invasive aspergillosis (9)(10)(11)(12).…”

Comparison of the Broth Microdilution Methods of the European Committee on Antimicrobial Susceptibility Testing and the Clinical and Laboratory Standards Institute for Testing Itraconazole, Posaconazole, and Voriconazole against Aspergillus Isolates

“…to itraconazole, posaconazole, and voriconazole as determined by both methods. The MIC results for each agent were typical of those for each species of Aspergillus (1,9,17,19,22,28).…”

“…Each of these agents has good in vitro and in vivo activity against most species of Aspergillus (1,9,12,16,17,22,29). Although resistance (R) to triazoles is uncommon, increased R has been noted in several regions of the world since 1999 (11,12,23,25,27,28).…”

Identification by Molecular Methods and Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry and Antifungal Susceptibility Profiles of Clinically Significant Rare Aspergillus Species in a Referral Chest Hospital in Delhi, India

“…Similarly, the population-based FILPOP survey to investigate the epidemiology and antifungal resistance in Spanish clinical strains of filamentous fungi from deep-tissue samples, blood cultures, and respiratory samples reported that 12% of the isolates were cryptic Aspergillus species (9). The most notable findings in both studies were that the cryptic species had high in vitro MICs to multiple antifungal drugs, including azoles and amphotericin B (9,10). Both azoles and amphotericin B antifungals are agents of choice to treat Aspergillus infections; thus, high MICs to these agents pose a serious therapeutic challenge.…”