Invasive aspergillosis a complication severe respiratory viral infections (influenza and COVID-19)

Invasive aspergillosis is a life-threatening complication in patients with severe influenza and COVID-19 in intensive care units. Risk factors for the invasive aspergillosis development are transitory immunosuppression associated with severe influenza and COVID-19, as well as the use of glucocorticosteroids and immunosuppressive therapy. In the presence of risk factors, suspected clinical and radiological signs of invasive aspergillosis, bronchoscopy and examination of material from the lower respiratory tract are necessary: test for galactomannan, microscopy with white calcofluor staining and inoculation on Sabouraud agar medium. Voriconazole or are recommended as first-line treatment for invasive aspergillosis in patients with severe influenza and COVID-19. Amphotericin B Liposomal, Amphotericin B Lipid Complex, and Caspofungin are the alternative options for the invasive aspergillosis treatment. Combination therapy is possible. It is necessary to control the underlying disease with eliminate or reduce the severity of risk factors.

Nadir Etken Bir Maya: Üçüncü Basamak Üniversite Hastanesinde İzlenen Rhodotorula mucilaginosa Enfeksiyonu Olguları

Rhodotorula species are yeasts that are common in the environment,but are not frequently encountered as an infectious agent in humans. Rhodotorula mucilaginosa, Rhodotorula glutinis and Rhodotorula minuta are the species that cause disease in humans. Although its isolation from mucosa is doubtful in terms of the presence of true infection, it is more frequently encountered in daily practice due to the increasing number of invasive procedures, immune system deficiencies caused by immunosuppressive drugs and diseases. R.mucilaginosa growth isolated from various clinical samples between 2000 and 2018 in a tertiary university hospital was presented in this case report. The first case was an 82-year-old man with chronic lung disease, hypertension, congestive heart failure and acute leukemia causing severe immunosuppression. Use of broad spectrum antibiotics, history of immunosuppressive therapy, presence of jugular catheter were the risk factors in this patient. R.mucilaginosa was isolated from blood culture while the patient was receiving fluconazole treatment for Candida albicans grown in urine culture and the patient died before starting the treatment. The second case was a 34-year-old female patient with congenital heart disease. Discharge was observed at the intracardiac defibrillator site of the patient, a temporary pacemaker was inserted, and she used broad spectrum antibiotics for a long time. When the yeast growth was reported in the blood culture, caspofungin treatment was initiated. Although the treatment was switched to amphotericin B lipid complex after the culture result was reported as R.mucilaginosa, the patient died after 12 hours. The third case was a 70-year-old woman with hypertension, dementia, diabetes mellitus and rheumatoid arthritis admitted to the intensive care unit due to cerebrovascular accident. She received different immunosuppressive treatments and had invasive procedures. R.mucilaginosa was isolated from the blood culture taken from the patient’s catheter, and there was no growth in the blood culture obtained from the peripheral vein. Anidulafungin was started empirically, which was changed to amphotericin B lipid complex after the identification of the yeast. The patient died for various reasons 10 days after the antifungal treatment was stopped. Our last case was a 55-year-old woman with metastatic ovarian cancer and secondary ascites. Broad-spectrum multiple antibiotics were used and invasive procedures were performed. R.mucilaginosa and C.albicans were isolated from the urine of the patient who had a urinary catheter. No growth was detected from urine after changing the urinary catheter. Therefore, growths were evaluated as colonization, and fluconazole was administered for C.albicans due to the high risk of invasive infection. The patient was lost for different reasons. The development and diversity of the treatment methods lead to the emergence of some opportunistic infectious agents that were not observed previously. Rhodotorula species are one of the rare agents that have increased over the years. Rhodotorula species should be considered as the cause of an infection if no clinical response is obtained after echinocandin and/or fluconazole treatment in patients with long-term immunosuppression and invasive procedures. Data on clinical pictures, treatment responses, follow-up and treatment results of this rare yeast are still limited. This case series was presented to draw attention to the risk factors related to R.mucilaginosa infection/colonization, clinical characteristics of the patients, follow-up results and treatment options and to contribute to the literature.

Modeling Invasive Aspergillosis: How Close Are Predicted Antifungal Targets?

Animal model systems are a critical component of the process of discovery and development of new antifungal agents for treatment and prevention of invasive aspergillosis. The persistently neutropenic rabbit model of invasive pulmonary aspergillosis (IPA) has been a highly predictive system in identifying new antifungal agents for treatment and prevention of this frequently lethal infection. Since its initial development, the persistently neutropenic rabbit model of IPA has established a strong preclinical foundation for dosages, drug disposition, pharmacokinetics, safety, tolerability, and efficacy for deoxycholate amphotericin B, liposomal amphotericin B, amphotericin B lipid complex, amphotericin B colloidal dispersion, caspofungin, micafungin, anidulafungin, voriconazole, posaconazole, isavuconazole, and ibrexafungerp in treatment of patients with invasive aspergillosis. The findings of combination therapy with a mould-active triazole and an echinocandin in this rabbit model also predicted the outcome of the clinical trial for voriconazole plus anidulafungin for treatment of IPA. The plasma pharmacokinetic parameters and tissue disposition for most antifungal agents approximate those of humans in persistently neutropenic rabbits. Safety, particularly nephrotoxicity, has also been highly predictive in the rabbit model, as exemplified by the differential glomerular filtration rates observed in animals treated with deoxycholate amphotericin B, liposomal amphotericin B, amphotericin B lipid complex, and amphotericin B colloidal dispersion. A panel of validated outcome variables measures therapeutic outcome in the rabbit model: residual fungal burden, markers of organism-mediated pulmonary injury (lung weights and infarct scores), survival, and serum biomarkers. In selected antifungal studies, thoracic computerized tomography (CT) is also used with diagnostic imaging algorithms to measure therapeutic response of pulmonary infiltrates, which exhibit characteristic radiographic patterns, including nodules and halo signs. Further strengthening the predictive properties of the model, therapeutic response to successfully developed antifungal agents for treatment of IPA has been demonstrated over the past two decades by biomarkers of serum galactomannan and (1→3)-β-D-glucan with patterns of resolution, that closely mirror those documented responses in patients with IPA. The decision to move from laboratory to clinical trials should be predicated upon a portfolio of complementary and mutually validating preclinical laboratory animal models studies. Other model systems, including those in mice, rats, and guinea pigs, are also valuable tools in developing clinical protocols. Meticulous preclinical investigation of a candidate antifungal compound in a robust series of complementary laboratory animal models will optimize study design, de-risk clinical trials, and ensure tangible benefit to our most vulnerable immunocompromised patients with invasive aspergillosis.

Invasive Fungal Infection After Lung Transplantation: Epidemiology in the Setting of Antifungal Prophylaxis

Background Lung transplant recipients commonly develop invasive fungal infections (IFIs), but the most effective strategies to prevent IFIs following lung transplantation are not known. Methods We prospectively collected clinical data on all patients who underwent lung transplantation at a tertiary care academic hospital from January 2007–October 2014. Standard antifungal prophylaxis consisted of aerosolized amphotericin B lipid complex during the transplant hospitalization. For the first 180 days after transplant, we analyzed prevalence rates and timing of IFIs, risk factors for IFIs, and data from IFIs that broke through prophylaxis. Results In total, 156 of 815 lung transplant recipients developed IFIs (prevalence rate, 19.1 IFIs per 100 surgeries, 95% confidence interval [CI] 16.4–21.8%). The prevalence rate of invasive candidiasis (IC) was 11.4% (95% CI 9.2–13.6%), and the rate of non-Candida IFIs was 8.8% (95% CI 6.9–10.8%). First episodes of IC occurred a median of 31 days (interquartile range [IQR] 16–56 days) after transplant, while non-Candida IFIs occurred later, at a median of 86 days (IQR 40–121 days) after transplant. Of 169 IFI episodes, 121 (72%) occurred in the absence of recent antifungal prophylaxis; however, IC and non-Candida breakthrough IFIs were observed, most often representing failures of micafungin (n = 16) and aerosolized amphotericin B (n = 24) prophylaxis, respectively. Conclusions Lung transplant recipients at our hospital had high rates of IFIs, despite receiving prophylaxis with aerosolized amphotericin B lipid complex during the transplant hospitalization. These data suggest benefit in providing systemic antifungal prophylaxis targeting Candida for up to 90 days after transplant and extending mold-active prophylaxis for up to 180 days after surgery.