The incidence and mortality of invasive pulmonary aspergillosis (IPA) are rising, particularly in critically ill patients and patients with severe chronic obstructive pulmonary disease (COPD). Noninvasive aspergillosis occurring in these patients requires special attention because of the possibility of developing subsequent IPA, given the poor health and worsened immune state of these patients. We compared the performance of the Platelia galactomannan (GM) enzyme immunoassay in the bronchoalveolar lavage fluid (BALF) and serum. The sensitivity, and specificity of BALF-GM were 85.4% and 62.4%, and those of serum-GM were 67.9% and 93.5% at the cutoff index of 0.5. As the cutoff index increased, the specificity of BALF-GM detection was increased with the detriment of sensitivity. The area under the ROC curves was 0.817 (95% CI: 0.718–0.916) for BALF-GM and 0.819 (95% CI: 0.712–0.926) for serum-GM. The optimal cutoff index was 1.19 for BALF-GM, and the sensitivity and specificity were 67.9% and 89.2%. The BALF-GM assay is more sensitive in detecting pulmonary aspergillosis than serum-GM assay and fungal cultures. However, BALF-GM assay has a high false-positive rate at the cutoff index of 0.5. Hence, the diagnostic cutoff index of the BALF-GM assay should be improved to avoid the overdiagnosis of pulmonary aspergillosis in clinic.

The diagnosis of invasive pulmonary aspergillosis (IPA) is still in challenge in clinical practice, particularly for those patients without an obvious neutropaenia. In this study, a well-validated qPCR method and Platelia galactomannan (GM) assay were compared for their diagnostic performance using paired samples of bronchoalveolar lavage (BAL) fluid and serum from predominantly non-neutropaenic patients. In the serum samples, qPCR showed a comparable performance with GM assay in terms of sensitivity and specificity. In the BAL samples, qPCR and GM assay both demonstrated a good sensitivity (90 vs. 90 %); however, the specificity of qPCR was higher than that of GM assay (92.5 vs. 68.8 %, P < 0.001) in these samples. A better sensitivity was obtained with BAL compared with serum samples for both GM assay (90 vs. 50 %) and qPCR (90 vs. 60 %). In conclusion, in non-neutropaenic patients, BAL appears to provide improved sensitivity for both GM and qPCR assays. BAL qPCR offers a better diagnostic value for IPA compared with BAL GM assay, significantly increasing the specificity without affecting the sensitivity.

Combinations of terbinafine or caspofungin with amphotericin B, posaconazole, or itraconazole were studied as potential treatments against 18 isolates of Mucor irregularis in vitro. Synergism of the combinations of terbinafine with amphotericin B, posaconazole, and itraconazole against 38.9, 33.3, and 44.4% of the strains studied was observed. In contrast, synergism of the combinations of caspofungin with amphotericin B, posaconazole, and itraconazole against 99.4, 66.7, and 99.4% of the strains studied was observed. Furthermore, no antagonism was observed.C utanous zygomycosis is a fungal infection caused mainly by members of the order Mucorales that affect the skin. The most frequently reported genus in the English literature is Rhizopus, followed by Lichtheimia spp. and Rhizomucor pusillus (1). Cutaneous zygomycosis caused by Mucor irregularis (formerly Rhizomucor variabilis) is an emerging disease in China that is characterized by progressive swelling, ulceration, and destruction of involved skin at exposed sites, especially the central face, and leads to severe disfigurement and even death if left untreated (2-4). Notably, it seemed that most of the patients infected with M. irregularis were immunocompetent (2-9).Amphotericin B is the most potent drug used for the treatment of M. irregularis infection, but the toxicity of amphotericin B limits its long-term clinical application. Posaconazole has been used primarily as salvage therapy, but at present, there is no strong published clinical evidence supporting its role as a single agent for the treatment of mucormycosis (10). Itraconazole has variable effectiveness against M. irregularis in vitro (11) but was proven to be effective against some M. irregularis infections (2, 5). Terbinafine is an allylamine antifungal agent used primarily to treat dermotropic infections and onychomycosis but has potential for use in adjunct therapy in combination with azoles, polyenes, or echinocandins in the management of severe drug-resistant or refractory mycosis (12). Besides, terbinafine could reach high concentrations in the stratum corneum and sebum because of its lipophilic nature (13), which provided the possibility that terbinafine can be used in combination therapies to treat cutaneous zygomycosis.To our knowledge, with the exception of some reported cases (7, 9), no susceptibility of M. irregularis to combinations of antifungal drugs in vitro has been reported. In the present study, the combinations of terbinafine or caspofungin with amphotericin B, posaconazole, or itraconazole were assessed against M. irregularis isolates in vitro.A total of 18 M. irregularis patient isolates preserved by the Research Center for Medical Mycology at Peking University were tested. Isolates were identified by both conventional morphological methods and the internal transcribed spacer sequence analysis method (11).Drug combinations were conducted by using a checkerboard method based on Clinical and Laboratory Standards Institute document M38-A2 (14) that provided the MICs of each agen...

Aims Multi‐species biofilms formed by fungi and bacteria are clinically common and confer the commensal micro‐organisms with protection against antimicrobial therapies. Previously, the plant alkaloid berberine was reported to show antimicrobial efficacy to eliminate bacterial and fungal biofilms. In this study, the combination of berberine and amphotericin B, an antifungal agent, was evaluated against dual‐species Candida albicans/Staphylococcus aureus biofilms. Methods and Results Combinatorial treatment by berberine and amphotericin B significantly reduced the biomass and viability of residing species in biofilms. Moreover, morphological examination revealed hyphal filamentation of C. albicans and coadhesion between C. albicans/S. aureus were considerably impaired by the treatment. These effects coincided with the reduced expression of cell surface components and quorum‐sensing‐related genes in both C. albicans and S. aureus. Additionally, in C. albicans, the core transcription factors for controlling biofilm formation together with a crucial component of dual‐species biofilms were also downregulated. Conclusions These results demonstrated synergistic effects of berberine and amphotericin B against C. albicans/S. aureus dual‐species biofilms. Significance and Impact of the Study This study confirms the potential of berberine and amphotericin B for treating the C. albicans/S. aureus biofilms related infections and reveals molecular basis for the efficacy of combinatorial treatment.