Needles in a haystack: Extremely rare invasive fungal infections reported in FungiScopeⓇ-Global Registry for Emerging Fungal Infections.

OBJECTIVES: Emerging invasive fungal infections (IFI) have become a notable challenge. Apart from the more frequently described fusariosis, lomentosporiosis, mucormycosis, scedosporiosis, and certain dematiaceae or yeasts, little is known about extremely rare IFI. METHODS: Extremely rare IFI collected in the FungiScopeⓇ registry were grouped as Dematiaceae, Hypocreales, Saccharomycetales, Eurotiales, Dermatomycetes, Agaricales, and Mucorales. RESULTS: Between 2003 and June 2019, 186 extremely rare IFI were documented in FungiScopeⓇ. Dematiaceae (35.5%), Hypocreales (23.1%), Mucorales (11.8%), and Saccharomycetales (11.3%) caused most IFI. Most patients had an underlying malignancy (38.7%) with acute leukemia accounting for 50% of cancers. Dissemination was observed in 26.9% of the patients. Complete or partial clinical response rate was 68.3%, being highest in Eurotiales (82.4%) and in Agaricales (80.0%). Overall mortality rate was 29.3%, ranging from 11.8% in Eurotiales to 50.0% in Mucorales. CONCLUSIONS: Physicians are confronted with a complex variety of fungal pathogens, for which treatment recommendations are lacking and successful outcome might be incidental. Through an international consortium of physicians and scientists, these cases of extremely rare IFI can be collected to further investigate their epidemiology and eventually identify effective treatment regimens.

Treatment of resistant influenza virus infection in a hospitalized patient with cystic fibrosis with DAS181, a host-directed antiviral.

We report a cystic fibrosis patient infected with influenza 2009H1N1 who had persistent viral shedding and clinical deterioration despite prolonged treatment with oseltamivir and zanamivir. The patient was diagnosed with H275Y neuraminidase inhibitor resistant influenza during treatment, thus was treated for 10 days with DAS181, an investigational host-directed inhaled sialidase fusion protein. Viral clearance occurred after 5 days of therapy and the patient became eligible for lung transplantation. Although the patient succumbed prior to receiving a transplant, this case exemplifies the potential utility of a host-directed approach against influenza which has potential to become resistant to neuraminidase inhibitors.

Screening for Acinetobacter baumannii colonization by use of sponges.

There is currently no consensus method for the active screening of Acinetobacter baumannii. The use of swabs to culture nostrils, pharynx, and skin surface of various anatomical sites is known to yield less-than-optimal sensitivity. In the present study, we sought to determine whether the use of sterile sponges to sample large areas of the skin would improve the sensitivity of the detection of A. baumannii colonization. Forty-six patients known to be colonized with A. baumannii, defined by a positive clinical culture for this organism as defined by resistance to more than two classes of antimicrobials, participated in the study. The screening sites included the forehead, nostrils, buccal mucosa, axilla, antecubital fossa, groin, and toe webs with separate rayon swabs and the forehead, upper arm, and thigh with separate sponges. Modified Leeds Acinetobacter medium (mLAM) agar plates that contained vancomycin and either aztreonam or ceftazidime were used as the selective medium. An enrichment culture grown overnight substantially increased the sensitivity for most sites. The sensitivity ranged between 69.6 and 82.6% for individual sponge sites and 21.7 to 52.2% for individual swab sites when mLAM plates with ceftazidime were inoculated after a 24-h enrichment period. The sponge and swab sites with the best sensitivity were the leg and the buccal mucosa, respectively (82.6% and 52.2%; P = 0.003). The combined sensitivity for the upper arm and leg with a sponge was 89.1%. The novel screening method using sterile sponges was easy to perform and achieved excellent sensitivity for the detection of A. baumannii colonization.

Intrapulmonary disposition of amphotericin B after aerosolized delivery of amphotericin B lipid complex (Abelcet; ABLC) in lung transplant recipients.

BACKGROUND: Inhaled amphotericin preparations have been used for prophylaxis against invasive aspergillosis in lung transplant recipients. However, no published data exist regarding the pharmacokinetic profile of amphotericin B lipid complex in lung transplant recipients. METHODS: We prospectively determined the concentrations of amphotericin B in the epithelial lining fluid (ELF) and plasma after aerosolized nebulization (AeroEclipse), of amphotericin B lipid complex at 1 mg/kg every 24 hr for 4 days in 35 lung transplant recipients. One brochoalveolar lavage sample and a simultaneous blood sample were collected at various time points after the fourth dose from each subject. High-performance liquid chromatography and high-performance liquid chromatography-MS-MS were used to measure amphotericin B. RESULTS: Concentrations of amphotericin B in ELF (median, 25-75 IQR) were at 4 hr (n=5) 7.20 µg/mL (1.3-17.6), 24 hr (n=6) 8.26 µg/mL (3.9-82.7), 48 hr (n=5) 2.15 µg/mL (1.4-5.5), 72 hr (n=4) 1.25 µg/mL (0.75-5.5), 96 hr (n=6) 0.86 µg/mL (0.55-1.4), 120 hr (n=4) 1.04 µg/mL (0.44-1.6), 144 hr (n=1), 4.25 µg/mL, 168 hr (n=3) 1.14 µg/mL, and 192 hr (n=1) 1 µg/mL. The plasma concentration of the drug remained below 0.08 µg/mL at all time points. During the study, the side effects noted included wheezing, coughing, and 12% decline in forced expiratory volume in 1 sec. CONCLUSIONS: We conclude that administration through aerosolized nebulization of amphotericin B lipid complex every 24 hr for 4 days in lung transplant recipients achieved amphotericin B concentrations in ELF above minimum inhibitory concentration of the Aspergillus nearly at 168 hr after the last inhaled dose and is well tolerated.