“A Chameleon in CT”

Invasive pulmonary aspergillosis poses a major threat, especially to immunocompromised individuals such as tumor patients. The mortality rate is over 60%, and diagnosis and treatment of the fungal infection are often difficult. An expert presented new findings and gave practical advice for the care of these patients.

When dealing with invasive aspergillosis (IA), there are patient groups whose risk is high enough to make a prophylactic approach worthwhile. This is mainly the case in patients with acute myeloid leukemia (AML), explained Prof. Dr. Oliver A. Cornely, CECAD Institute for Translational Research, Center for Clinical Trials, Clinical Infectiology/European Center for Medical Mycology, University of Cologne (D) [1]. These may receive prophylaxis with posaconazole to reduce the breakthrough infection rate. In a 2007 study led by Prof. Cornely, this was achieved from 8% to 2% vs. Flucanozole/Itraconazole. Survival also improved with posaconazole in this study [2] (Fig. 1).

However, when dealing with patients who have ALL instead of AML, for example, prophylaxis is not possible due to various drug interactions with the chemotherapeutic agents. So if a patient presents with a diagnosed leukemia who is at high risk, a so-called baseline CT of the thorax can already be performed. If structural changes or even infiltrates are found there, it is clear that special attention must be paid to these individuals, because one must expect a rate of aspergillosis twice as high here compared to the patients in whom the lungs present themselves inconspicuously and without pathology.

Aspergillosis on CT can present “like a chameleon,” Prof. Cornely explained: the forms can range from small (round) infiltrates to air crescent signs to large-scale infiltrates. In high-risk patients, any infiltrate leads directly to bronchoscopy, BAL (box), and laboratory (galactomannan test). “We want these lab tests so we also have mycological evidence of the fungal infection.”

Therapy options

Three options are available for antifugal treatment when invasive aspergillosis is suspected:

• Isavuconazole
• Liposomal amphotericin B
• Voriconazole

For about 20 years, voriconazole has been the standard of care for invasive aspergillosis in high-risk patients. Nevertheless, the active ingredient also brings disadvantages, as Prof. Cornely pointed out: you have to do therapeutic drug monitoring (TDM), at least once a week. The target reference range is between 1 and 5.5 mg/l. Failure to bring the patient into this range continues to threaten a poor course of aspergillosis. However, if the target range is exceeded, liver elevations or other toxicities can be expected. Increased light sensitivity or “color vision” (yellow or violet cast) is also frequently reported by patients in such cases.

Isavuconazole was compared in one study against voriconazole in a group of patients with underlying hematologic disease. Here, there were no differences in survival over a 3-month period. For the most part, both agents performed similarly in safety, but isavuconazole proved beneficial in skin lesions (33.5% ISA vs. 42.5% VOR, p=0.037), visual disturbances (15.2% vs. 26.6%, p=0.002), and liver elevations (8.9% vs. 16.2%, p=0.016). “The skin changes in particular were often thought to be infections in the past, but they might actually be toxicity to the azoles.” In addition, TDM is not required for isavuconazole and is not recommended according to European guidelines.

New risk groups: COVID-19 and IAPA

In Prof. Cornely’s Cologne Center for Clinical Studies, invasive aspergillosis was detected in 5 of the first 19 ventilated COVID-19 patients in 2020 [3]. Concerned that the then novel viral infection with pulmonary involvement might pave the way for IA, patients were specifically screened. “If we had not looked specifically for aspergillosis in this group, we would not have found it and would have treated it too late or perhaps never,” the expert explained.

The causative pathogen in COVID-19-associated IA is primarily (close to 70%) A. fumigatus, with A. niger, A. flavus, and A. terreus occurring far less frequently (<10% each). “In such cases, if an Aspergillus is detected microscopically, it can be assumed to be treatable with both azoles and liposomal amphotericin B.”

A disease that is likely to become more common than COVID-19-associated pulmonary aspergillosis in the future is influenza-associated pulmonary aspergillosis (IAPA). In patients requiring intensive care with respiratory failure on the floor of influenza, the incidence of IAPA was 25%, Prof. Cornely said, referring to a Dutch study. Most of these (71%) were identified in the first 38 hours, and mortality was relatively high at 53%.

Sources:

1. Cornely OA: Lecture “Invasive Aspergillus infections” in the context of the symposium “Aspergillus-associated diseases in pneumology”. 63rd Congress of the German Society for Pneumology and Respiratory Medicine e.V. in Düsseldorf, March 30, 2023.
2. Cornely OA, Maertens J, Winston DJ, et al: Posaconazole vs fluconazole or itraconazole prophylaxis in patients with neutropenia. N Engl J Med 2007; 356: 348-359; doi: 10.1056/NEJMoa061094.
3. Koehler P, Cornely OA, Böttiger BW, et al: COVID-19 associated pulmonary aspergillosis. Mycoses 2020; 63: 528-534; doi: 10.1111/myc.13096.

InFo PNEUMOLOGIE & ALLERGOLOGIE 2023; 5(2): 38–39