Diagnosis and management of Aspergillus diseases: executive summary of the 2017 ESCMID-ECMM-ERS guideline.

The European Society for Clinical Microbiology and Infectious Diseases, the European Confederation of Medical Mycology and the European Respiratory Society Joint Clinical Guidelines focus on diagnosis and management of aspergillosis. Of the numerous recommendations, a few are summarized here. Chest computed tomography as well as bronchoscopy with bronchoalveolar lavage (BAL) in patients with suspicion of pulmonary invasive aspergillosis (IA) are strongly recommended. For diagnosis, direct microscopy, preferably using optical brighteners, histopathology and culture are strongly recommended. Serum and BAL galactomannan measures are recommended as markers for the diagnosis of IA. PCR should be considered in conjunction with other diagnostic tests. Pathogen identification to species complex level is strongly recommended for all clinically relevant Aspergillus isolates; antifungal susceptibility testing should be performed in patients with invasive disease in regions with resistance found in contemporary surveillance programmes. Isavuconazole and voriconazole are the preferred agents for first-line treatment of pulmonary IA, whereas liposomal amphotericin B is moderately supported. Combinations of antifungals as primary treatment options are not recommended. Therapeutic drug monitoring is strongly recommended for patients receiving posaconazole suspension or any form of voriconazole for IA treatment, and in refractory disease, where a personalized approach considering reversal of predisposing factors, switching drug class and surgical intervention is also strongly recommended. Primary prophylaxis with posaconazole is strongly recommended in patients with acute myelogenous leukaemia or myelodysplastic syndrome receiving induction chemotherapy. Secondary prophylaxis is strongly recommended in high-risk patients. We strongly recommend treatment duration based on clinical improvement, degree of immunosuppression and response on imaging.

Neonatal candidiasis: analysis of epidemiology, drug susceptibility, and molecular typing of causative isolates.

A prospective observational study of invasive candidiasis was conducted in the neonatal intensive care unit of Aristotle University in Hippokration Hospital between 1994 and 2000. During this period, 59 neonates developed invasive candidiasis (58 cases of candidemia and 1 case of peritonitis), resulting in an overall incidence of 1.28% that showed a decreasing trend over the study period. Eleven (18.6%) cases developed within the first week of life and the others within a mean (+/-SEM) of 13.4+/-1.7 days after birth. The three most frequent causative species were Candida albicans (65.5%), Candida parapsilosis (15.5%), and Candida tropicalis (7%). C. albicans was the predominant species between 1994 and 1998, whereas, non-albicans Candida spp., particularly C. parapsilosis, were the most frequent species during the period 1999-2000 (P<0.001). While the overall mortality due to candidemia was 29% (17 of 59 cases), mortality associated with C. albicans and C. parapsilosis was 39.5% and 11.1%, respectively (P=0.032), and that observed in the 1999-2000 period was 0% (P=0.011). Virtually all isolates were susceptible to amphotericin B, flucytosine, fluconazole, and itraconazole, and no increases in minimal inhibitory concentrations were observed during these years. With the exception of a limited cluster of cases due to genotypically identical isolates, no clonal relation of C. albicans isolates was found. Moreover, no clonal persistence of C. albicans and no decrease in antifungal drug susceptibility occurred over the 6-year study period. Non-albicans Candida spp., mostly C. parapsilosis, have emerged as important pathogens in neonatal intensive care units, with infected patients having better outcomes as compared to patients infected with C. albicans.

Antifungal activities of posaconazole and granulocyte-macrophage colony-stimulating factor ex vivo and in mice with disseminated infection due to Scedosporium prolificans.

Invasive infection due to Scedosporium prolificans is characterized by drug resistance and a high rate of mortality. The effects of posaconazole (POS), an investigational antifungal triazole, murine granulocyte-macrophage colony-stimulating factor (GM-CSF), and their combination against S. prolificans were evaluated ex vivo and in a newly developed murine model of disseminated infection due to this organism. When POS was combined with polymorphonuclear leukocytes from untreated or GM-CSF-treated mice (P < 0.01) ex vivo, it had increased activity in terms of the percentage of hyphal damage. Immunocompetent BALB/c mice were infected with 4 x 10(4) conidia of S. prolificans via the lateral tail vein. At 24 h postinfection the mice were treated with GM-CSF (5 microg/kg of body weight/day subcutaneously), POS (50 mg/kg/day by gavage), both agents, or saline only. Half of the brain, lung, liver, and kidney from each animal were cultured; and the other half of each organ was processed for histopathology. The mean survival times were 7.0 +/- 0.3 days for the controls, 7.4 +/- 0.4 days for POS-treated mice, 8.0 +/- 0.3 days for GM-CSF-treated mice (P = 0.08 compared with the results for the controls), and 7.3 +/- 0.3 days for POS-GM-CSF-treated mice. Fungal burdens (determined as the numbers of CFU per gram of tissue) were found in descending orders of magnitude in the kidneys, brains, livers, and lungs. The burdens were significantly reduced in the brains of GM-CSF-treated mice (P < 0.05) and the livers of POS-treated mice (P < 0.05). The numbers of lesions in the organs closely corresponded to the fungal burdens. GM-CSF tended to prolong survival (P = 0.08 compared with the results for the controls). While the combination of POS and GM-CSF showed enhanced activity ex vivo, it did not increase the activities of the two agents against this highly refractory filamentous fungus in mice.

Comparison of efficacy and safety of teicoplanin and vancomycin in children with antineoplastic therapy-associated febrile neutropenia and gram-positive bacteremia.

To compare their efficacy and safety, teicoplanin and vancomycin were randomly administered to 32 children for 52 gram-positive bacteremias during malignancy-associated neutropenia (<1000/microl). Patients mainly suffered from hematological malignancies. Twenty-five episodes were treated with teicoplanin (10 mg x kg(-1) x d(-1)) and 21 with vancomycin (40 mg x kg(-1) x d(-1)) plus ceftazidime and netilmicin. Six episodes were treated with teicoplanin because of previous "red man" reaction to vancomycin. Staphylococci (12% Staphylococcus aureus) were isolated from 50 episodes and viridans streptococci from 2. Defervescence on 3rd-4th day occurred in 29/31 (93.5%) teicoplanin-treated and 18/21 (85.7%) vancomycin-treated episodes. All 12 teicoplanin-treated and 13/13 vancomycin-treated episodes with repeat blood cultures on 3rd-4th day showed microbiological response. Two teicoplanin-treated and 3 vancomycin-treated patients required antifungals. Mild renal insufficiency appeared in 5 vancomycin-treated patients that was corrected without drug discontinuation. While both glycopeptides exhibit equal clinical and microbiological efficacy, teicoplanin is less likely to induce allergic reactions or nephrotoxicity in children.

Multifocal osteoarthritis due to Candida albicans in a neonate: serum level monitoring of liposomal amphotericin B and literature review.

A 32-week neonate weighing 2,300 g at birth with fungemia due to Candida albicans subsequently developed multifocal osteoarthritis of the lower extremities due to the same organism during therapy with amphotericin B (0.5 mg/kg/day) and flucytosine (100 mg/kg/day) to which the isolates were susceptible. Liposomal amphotericin B (3.5 mg/kg/day) was substituted for conventional amphotericin B and complete clinical and radiologic recovery as well as sterilization of affected joints were achieved with a 38-day-course (144.5 mg/kg total). Adequate drug concentrations in serum and synovial fluid were attained with liposomal amphotericin B. Nine neonates (< or = 28 days of age) with bone and/or joint infections due to Candida spp. had previously been reported in the English-language literature. To our knowledge, the present case is the first reported cure with liposomal amphotericin B. Previous cases are reviewed and the potential role of liposomal amphotericin B in this serious neonatal infection is discussed.