The Glucatell (1r3)-b-D-glucan (BG) detection assay (Associates of Cape Cod) was studied as a diagnostic adjunct for invasive fungal infections (IFIs). On the basis of findings from a preliminary study of 30 candidemic subjects and 30 healthy adults, a serum BG level of у60 pg/mL was chosen as the cutoff. Testing was performed with serial serum samples obtained from 283 subjects with acute myeloid leukemia or myelodysplastic syndrome who were receiving antifungal prophylaxis. At least 1 serum sample was positive for BG at a median of 10 days before the clinical diagnosis in 100% of subjects with a proven or probable IFI. IFIs included candidiasis, fusariosis, trichosporonosis, and aspergillosis. Absence of a positive BG finding had a 100% negative predictive value, and the specificity of the test was 90% for a single positive test result and у96% for у2 sequential positive results. The Glucatell serum BG detection assay is highly sensitive and specific as a diagnostic adjunct for IFI.The mortality rate for invasive fungal infections in neutropenic subjects is 50% for subjects with Candida infection [1,2] and may approach 100% for those with invasive aspergillosis [3,4], fusariosis [5], or trichosporonosis [6]. Early diagnosis of invasive fungal infection in neutropenic subjects has the potential to increase antifungal therapeutic response, but meaningful diagnostic tests have proven to be elusive. Histopathologic demonstration of organisms in tissue specimens or growth of fungal agents in culture media is still the

Nineteen cases of suspected Crimean-Congo hemorrhagic fever reported from Turkey.

(1-->3)-beta-d-glucan is a well known cell wall constituent of fungal isolates that can be detected by assays in vivo and in vitro. Previous studies have shown that different fungal isolates may show different levels of reactivity with an assay for beta glucan. In this study we evaluated the in vitro reactivity of 127 clinical fungal isolates belonging to 40 different genera, with the Glucatell assay. The majority of the fungal isolates released high levels of beta glucan. Beta glucan test reactivity appears to be species-specific and this may reflect the beta glucan content of the organism.

The effects of protein binding on the activities of caspofungin, anidulafungin, and micafungin were evaluated against Candida and Aspergillus species. Adding human serum sharply increased the MICs of micafungin and anidulafungin and modestly affected the MIC of caspofungin. The increase in MICs does not appear consistent with the rate of protein binding for the three compounds.The echinocandins are a new class of lipopeptide antifungal agents that act by inhibiting the synthesis of (1,3)-␤-D-glucan. Compounds of this class are relatively highly protein bound, with rates of 96% reported for caspofungin (5), 99.8% for micafungin (15), and ϳ99% for anidulafungin (Eraxis package insert; Pfizer). Protein binding may change the in vitro and in vivo activities of antimicrobial agents (17). The available data on the effects of protein binding on the antifungal activities of echinocandins are limited to reports of increased MICs for anidulafungin when tested against Candida albicans (Eraxis package insert; Pfizer), of increased MICs for micafungin when tested against Candida spp. and Aspergillus fumigatus (4, 16), of no effect on caspofungin MICs for one isolate of C. albicans (2), and of a potentiation of the effect of caspofungin versus A. fumigatus (3). As none of these reports have provided comparative data and the total number of isolates evaluated has been small, we now report the effect of 50% human serum on the activities of the echinocandins against a collection of Candida and Aspergillus isolates.A total of 16 Candida isolates and 8 Aspergillus isolates were tested. The isolates included were C. albicans (two isolates), C. parapsilosis (five isolates), C. krusei (three isolates), C. glabrata (two isolates), C. tropicalis (two isolates), C. lusitaniae (two isolates), A. fumigatus (four isolates), A. flavus (two isolates), A. terreus (one isolate), and A. niger (one isolate). The two quality control isolates specified in the Clinical and Laboratory Standards Institute (CLSI) M27-A2 procedure (10), ATCC 6258 (C. krusei) and ATCC 22019 (C. parapsilosis), were included in each set of the test and the results compared with published control limits (1).Caspofungin, micafungin, and anidulafungin were supplied by their respective manufacturers. Stock solutions were prepared by dissolving the compounds in dimethyl sulfoxide (anidulafungin) or water (caspofungin and micafungin). Following the principles of CLSI M27-A2, serial dilutions at twice the desired final concentration were prepared in doublestrength test medium (RPMI 1640 medium buffered with 0.165 M morpholinepropanesulfonic acid [MOPS] to pH 7.0). Test trays were prepared in advance by dispensing 100 l of serially diluted drug into 96-well microdilution plates and freezing the plates at Ϫ70°C. All three compounds were tested over a 20-fold dilution range from 64 to 0.00012 g/ml.The MICs of test drugs with Candida species and Aspergillus species were determined using the broth microdilution variants of CLSI M27-A2 and CLSI M38-A (9), respectively. Testing was per...

Despite notable scientific and medical advances, broader political, socioeconomic and behavioural factors continue to undercut the response to the COVID-19 pandemic1,2. Here we convened, as part of this Delphi study, a diverse, multidisciplinary panel of 386 academic, health, non-governmental organization, government and other experts in COVID-19 response from 112 countries and territories to recommend specific actions to end this persistent global threat to public health. The panel developed a set of 41 consensus statements and 57 recommendations to governments, health systems, industry and other key stakeholders across six domains: communication; health systems; vaccination; prevention; treatment and care; and inequities. In the wake of nearly three years of fragmented global and national responses, it is instructive to note that three of the highest-ranked recommendations call for the adoption of whole-of-society and whole-of-government approaches1, while maintaining proven prevention measures using a vaccines-plus approach2 that employs a range of public health and financial support measures to complement vaccination. Other recommendations with at least 99% combined agreement advise governments and other stakeholders to improve communication, rebuild public trust and engage communities3 in the management of pandemic responses. The findings of the study, which have been further endorsed by 184 organizations globally, include points of unanimous agreement, as well as six recommendations with >5% disagreement, that provide health and social policy actions to address inadequacies in the pandemic response and help to bring this public health threat to an end.

In this study, we evaluated the in vitro activity of anidulafungin against selected mold isolates. Anidulafungin showed promising activity against Bipolaris spicifera, Exophiala jeanselmei, Fonsecaea pedrosoi, Madurella mycetomatis, Penicillium marneffei, Phialophora verrucosa, Pseudallescheria boydii, Sporothrix schenckii, and Wangiella dermatitidis.The incidence of invasive fungal infections has increased in the past two decades. Candida species and Aspergillus species are the most common etiologic agents causing invasive fungal infections. Although rare overall, Fusarium species are the second most common mold isolate after Aspergillus species (14,15). Some other less common filamentous fungi, like Penicillium, Bipolaris, Pseudallescheria, and Scedosporium species, have also been emerging as causative agents of opportunistic infections in immunocompromised patients (7,14,24,26,31).Amphotericin B has been historically accepted as the "gold standard" for the treatment of most fungal infections, although it is known to have poor outcomes in immunocompromised patients with severe mold infections (13). Alternative therapeutic agents, like new azoles and echinocandins, are under clinical evaluation (18). The relatively recent approvals of caspofungin for aspergillosis and voriconazole for aspergillosis, fusariosis, and scedosporidiasis have revolutionized the field of antifungal therapy (2, 4, 5, 8-11, 19, 29, 30).Anidulafungin is an echinocandin with excellent in vivo and in vitro activities against Candida spp. and Aspergillus spp. (17, 20-23, 27, 28). The in vitro activity of anidulafungin against less common but clinically emerging filamentous fungi has been evaluated in a limited number of studies (6,22,25). We sought to evaluate its in vitro activity against selected mold isolates in comparison with the activities of voriconazole and amphotericin B.A collection of 74 clinical mold isolates (Table 1) were tested. Isolates were obtained from the Department of Pathology, University of Texas, Medical Branch, Galveston. All isolates were stored at Ϫ80°C, and each isolate was subcultured on potato dextrose agar slants (Becton, Dickinson and Company, Sparks, Md.) at least twice to ensure purity and viability. The quality control strains were Candida parapsilosis ATCC 22019 and Candida krusei ATCC 6258.Anidulafungin (Vicuron Pharmaceuticals, Inc., King of Prussia, Pa.), voriconazole (Pfizer Pharmaceutical Group, New York, N.Y.), and amphotericin B (Bristol-Myers Squibb, Wallingford, Conn.) were dissolved in 100% dimethyl sulfoxide (Fisher Chemicals, Fair Lawn, N.J.) and then were further diluted (1:50) in 2ϫ RPMI 1640 medium (Sigma Chemical Company, St. Louis, Mo.) buffered to pH 7.0 with 0.165 M morpholinepropanesulfonic acid (MOPS) buffer according to the recommendations of National Committee for Clinical Laboratory Standards (NCCLS) approved standard M38-A (16) to yield two times the final strength required for the test. Amphotericin B was diluted 1:50 with 2ϫ antibiotic medium 3 (AM3; BBL, Cockeysville, Md.) buf...

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The in vitro interactions of anidulafungin with itraconazole, voriconazole, and amphotericin B were evaluated by using the checkerboard method. For Aspergillus spp., anidulafungin with amphotericin B showed indifference for 16/26 isolates, while anidulafungin with either azole showed a synergy trend for 18/26 isolates. All drug combinations showed indifference for 7/7 Fusarium sp. isolates.Invasive fungal infections due to molds are becoming more prevalent in immunocompromised patients (21). Among the invasive mold infections, Aspergillus spp. and Fusarium spp. are particularly challenging to manage, due to aggressive courses and high mortality (11,20).Since 1959, amphotericin B deoxycholate (AMBD) had been considered the "gold standard" for the treatment of fungal infections. However, due to high failure rates and significant toxicity (6), other agents are being explored today both singly and in combination therapy. Among the azoles, itraconazole (ITR) continues to show some promise against Aspergillus spp. (3). Voriconazole (VOR), a novel azole (11), is perhaps the current "gold standard" for the treatment of invasive aspergillosis, although success rates are still less than optimal (5, 8). The echinocandins (caspofungin, anidulafungin [ANID], and micafungin) inhibit 1,3-␤-D-glucan synthesis and have in vitro and in vivo activity against Candida and Aspergillus spp. (4,16,17). In the clinical setting, caspofungin appears to be at least as effective as AMBD for salvage therapy of invasive aspergillosis compared to historical controls (13).Due to the high mortality and lack of an ideal drug for these diseases, combination therapy has been an attractive possibility that has recently received much attention in medical mycology. Early studies have shown in vitro and in vivo advantages of several combinations. Arikan et al. (2) showed additive to synergistic effects of caspofungin with AMBD in vitro against Aspergillus and Fusarium spp. In a guinea pig model, colony counts of Aspergillus spp. and the number of culture-positive tissues were reduced after treatment with VOR and caspofungin compared with either of the agents alone (10). Similarly, Petraitis et al. showed that the combination of micafungin and ravuconazole in a rabbit model had synergistic effects against invasive aspergillosis (18).The purpose of this study was to evaluate the in vitro interactions of ITR, VOR, and AMBD with ANID against Aspergillus spp. and Fusarium spp. as preliminary work to support further in vivo and clinical research on these combinations.Isolates. Twenty-six clinical isolates of Aspergillus spp. and seven clinical isolates of Fusarium spp. were used. The species distribution was as follows: eight isolates of Aspergillus flavus,