P-1947. Aspergillus Susceptibility Trends in High-risk Hematologic Malignancy Patients with Pulmonary Infections

TL;DR

This study examines antifungal susceptibility trends in Aspergillus infections among high-risk hematologic cancer patients, highlighting growing resistance to certain drugs.

Contribution

The paper presents in-vitro susceptibility data for Aspergillus species in a high-risk patient cohort, revealing concerning resistance patterns to common antifungal agents.

Findings

All isolates were susceptible to posaconazole, but only 44% were susceptible to amphotericin B.

Resistance to voriconazole and isavuconazole was observed in 44% and 28% of isolates, respectively.

Higher amphotericin B MIC values were associated with patient mortality, though not statistically significant.

Abstract

Aspergillus causes invasive fungal infections (IFI) in immunocompromised patients. Our center primarily uses voriconazole for prophylaxis for Aspergillus. Susceptibility patterns shift with prophylaxis/environmental factors. We assessed in-vitro susceptibility of invasive Aspergillus in high-risk hematologic cancer patients.Clinical Characteristics and Outcomes of Patients with Aspergillus Infections (N = 25)In Vitro Susceptibility of Aspergillus Species Isolates to Antifungal Agents (N=25)

Clinical Characteristics and Outcomes of Patients with Aspergillus Infections (N = 25)

In Vitro Susceptibility of Aspergillus Species Isolates to Antifungal Agents (N=25)

We performed a single-center MedMined chart review of hematologic malignancy patients with Aspergillus IFI (Jan 2023-Mar 2025), evaluating clinical/lab data and describe susceptibility.Minimum Inhibitory Concentration (MIC) Summary for Aspergillus Species Across five Antifungal Agents

Minimum Inhibitory Concentration (MIC) Summary for Aspergillus Species Across five Antifungal Agents

This heatmap displays the susceptibility profiles of 11 Aspergillus species to five antifungal agents: Amphotericin B, Voriconazole, Itraconazole, Posaconazole, and Isavuconazole. MIC values are labeled within each cell using interpretative ranges (e.g., “≤0.06”, “1–≥4”) derived from in vitro susceptibility testing of clinical isolates. Background shading reflects the relative MIC intensity, where:Lighter shades indicate lower MIC values (greater fungal susceptibility)Darker shades indicate higher MIC values (reduced susceptibility or resistance)

Lighter shades indicate lower MIC values (greater fungal susceptibility)

Darker shades indicate higher MIC values (reduced susceptibility or resistance)

MIC values are expressed in µg/mL. Cells marked as “N/A” represent species-drug combinations for which no data were available. This representation helps visualize and compare antifungal susceptibility trends across different Aspergillus species.

144 culture-positive cases were reviewed, 23 patients with probable IFI and hematologic malignancy were included; two had multiple Aspergillus species, which were included. We excluded 100 cases with solid tumors and 19 without susceptibility testing/deemed colonized. The specimen sources were BAL, sputum, blood, and tissue. Most patients (72%) were not receiving prophylaxis; 28% were neutropenic (ANC < 500) at diagnosis. All had pulmonary IFIs; 56% had nodular pneumonia. Of 12 patients with BAL galactomannan, 75% were positive (median 5.77 index, range: 0.04-8.3). In this cohort, MIC values were deemed susceptible for posaconazole [S: < =0.25] in all isolates, while isavuconazole [S: 1] was at 18 (72%), voriconazole [S: 0.5] was at 14 (56%), and amphotericin B [S: 1] was at 11 (44%). Mann-Whitney U tests showed no significant MIC distribution differences between discharged/deceased patients for amphotericin B (U=7.00, p=0.096), isavuconazole (U=12.000, p=0.244), posaconazole (U=20.000, p=0.721), or voriconazole (U=8.000, p=0.111).

While all isolates showed low MICs and were deemed susceptible to posaconazole, a smaller proportion of isolates were considered susceptible to isavuconazole (72%), voriconazole (56%), and amphotericin B (44%). The death group tend to have higher amphotericin B MIC values (U=7.000, p=0.096). The increasing number of Aspergillus species with elevated MIC to voriconazole, isavuconazole, and amphotericin in this small high-risk patient sample is highly concerning. Further multi-center research is needed to validate these findings and identify antifungal resistance mechanisms in this population.

All Authors: No reported disclosures

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