The black-pigmented fungus Exophiala dermatitidis is considered to be a harmless colonizer of the airways of cystic fibrosis (CF) patients. The aim of this study was to establish the recovery rate of E. dermatitidis in respiratory specimens from CF patients, transplant recipients, and subjects with other respiratory disorders in Sweden. Second, we wished to determine if particular clinical traits were associated with E. dermatitidis colonization of the airways and the antifungal susceptibility profiles of Exophiala strains. Sputum and bronchoalveolar lavage samples (n ‫؍‬ 492) derived from 275 patients were investigated. E. dermatitidis was isolated in respiratory specimens from 19% (18/97) of the CF patients but in none of the other patient categories. All isolates were recovered after 6 to 25 days of incubation on erythritol-chloramphenicol agar (ECA) medium. Morphological and genetic analyses confirmed species identity. Pancreatic insufficiency was positively associated with the presence of E. dermatitidis in sputum samples (P ‫؍‬ 0.0198). Antifungal susceptibility tests demonstrated that voriconazole and posaconazole had the lowest MICs against E. dermatitidis. In conclusion, E. dermatitidis is a frequent colonizer of the respiratory tract in CF patients in Sweden and appears to be associated with more advanced disease. Whether E. dermatitidis is pathogenic remains to be elucidated.

Whereas patients with multiple myeloma (MM) have a well-documented susceptibility to infections, this has been less studied in other B-cell disorders, such as Waldenstrom's macroglobulinemia (WM) and monoclonal gammopathy of undetermined significance (MGUS). We investigated the humoral immunity to 24 different pathogens in elderly patients with MM (n ‫؍‬ 25), WM (n ‫؍‬ 16), and MGUS (n ‫؍‬ 18) and in age-matched controls (n ‫؍‬ 20). Antibody titers against pneumococci, staphylococcal alpha-toxin, tetanus and diphtheria toxoids, and varicella, mumps, and rubella viruses were most depressed in MM patients, next to lowest in WM and MGUS patients, and highest in the controls. In contrast, levels of antibodies specific for staphylococcal teichoic acid, Moraxella catarrhalis, candida, aspergillus, and measles virus were similarly decreased in MM and MGUS patients. Comparable titers in all study groups were seen against Haemophilus influenzae type b (Hib), borrelia, toxoplasma, and members of the herpesvirus family. Finally, a uniform lack of antibodies was noted against Streptococcus pyogenes, salmonella, yersinia, brucella, francisella, and herpes simplex virus type 2. To conclude, although MM patients displayed the most depressed humoral immunity, significantly decreased antibody levels were also evident in patients with WM and MGUS, particularly against Staphylococcus aureus, pneumococci, and varicella. Conversely, immunity was retained for Hib and certain herpesviruses in all study groups.Patients with malignancies and dysfunctions of the B-cell lineage have impaired immunity and an increased risk of contracting severe infections. This is well documented in the case of multiple myeloma (MM), while Waldenstrom's macroglobulinemia (WM) and monoclonal gammopathy of undetermined significance (MGUS) have been less studied in this respect. Despite the use of prophylactic antimicrobial agents, infections remain a leading cause of morbidity and mortality in MM patients (7,32). Bacterial infections predominate, in particular those caused by Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, and Escherichia coli (7,23,29). However, the introduction of autologous stem cell transplantation and novel therapeutic agents, e.g., thalidomide, bortezomib, and lenalidomide, has led to a shift in the spectrum of infections in MM patients such that viral and fungal infections are increasingly diagnosed (1, 29). The highest risk of infection occurs within the first months after diagnosis of MM (32), especially in patients with renal failure (7, 29). Augustson et al. showed that 45% of early deaths in MM (within 60 days of diagnosis) were due to infections, mainly pneumonia and sepsis (5).Information regarding which types of infections that tend to afflict patients with WM or MGUS is sparse. In a study of 217 WM patients, the second most frequent cause of death next to disease progression was infectious diseases (19% of deaths); again, sepsis and pneumonia predominated (15). An increased risk of bacteremia has prev...

Candida albicans is the most frequently isolated fungal species in hospital settings worldwide. However, non-albicans Candida species with decreased susceptibility to antifungals have emerged as an important cause of fungemia. The aims of this study were to determine the species distribution of fungi isolated from the blood samples of patients at a Swedish University Hospital and to define the in vitro susceptibilities of these isolates to nine antifungal agents. In total, 233 yeast isolates from 143 patients were included in this study. Antifungal susceptibility testing was performed using broth dilution Sensititre YeastOne panels, which comprised amphotericin B, 5-flucytosine, fluconazole, itraconazole, voriconazole, posaconazole, anidulafungin, micafungin, and caspofungin. The most common species in all age groups was C . albicans (n = 93, 65%), followed by C . glabrata (n = 27, 19%) and C . parapsilosis (n = 15, 10%). C . glabrata was mostly found in elderly individuals, while C . parapsilosis was found mainly in young children (p = 0.008). Antifungal resistance was low in the Candida species, except for reduced susceptibility to fluconazole among C . glabrata strains. C . albicans is the most frequent colonizer of Swedish patients. In general antifungal resistance is uncommon in Candida species. Nevertheless, reduced susceptibilities to fluconazole and echinocandins were found in C . glabrata and C . parapsilosis , respectively.

The aim of this study was to develop and validate a rapid and sensitive real-time PCR method for detection of all known species of dermatophytes, including identification of Trichophyton rubrum and Trichophyton interdigitale. Fungal DNA was extracted directly from clinical samples by using a pre-lysis step, followed by automated DNA extraction on the MagNA Pure Compact. In total, 202 clinical samples were examined by both conventional culture and by the new PCR method. In 103 (51%) of the samples fungal nucleic acid was detected by PCR, while only 79 (39%) were found to be positive by culture. Out of 103 PCR-positive clinical samples, 94 (91%) were identified as T. rubrum and eight (8%) as T. interdigitale. This real-time PCR is far more sensitive and 2-4 weeks faster than conventional culture for detection of dermatophytes present in clinical samples.

The performance of a new commercially available duplex PCR, which combines pan-dermatophyte PCR with a Trichophyton rubrum-specific PCR, was evaluated. This Dermatophyte PCR kit, which requires one day for laboratory diagnosis, was compared with the conventional methods of microscopy and culture that necessitate up to 4 weeks for final diagnosis of dermatophytosis. We studied 177 nail samples from patients with suspected onychomycosis by fluorescence microscopy (blankophore), cultures and the Dermatophyte PCR kit. More samples were positive by PCR (78/177, 44%) than by culture (59/177, 34%). T. rubrum was present in 95% of all culture-positive nail specimens, which was confirmed by PCR in 55/56 specimens. The positive predictive value, negative predictive value, specificity and sensitivity of the duplex PCR was 93%, 87%, 94% and 85%, respectively, when confirmed by positive culture, microscopy or both. Due to its sensitivity, specificity and rapidity, we conclude that this PCR is an attractive method for routine investigation of nail dermatophytosis in a clinical setting.

Novel antifungals are in high demand due to the challenges associated with resistant, persistent, and systemic fungal infections. Synthetic mimics of antimicrobial peptides are emerging as a promising class of compounds for antifungal treatment. In the current study, five synthetic cationic antimicrobial tripeptides were evaluated as antifungal therapeutics against 24 pathogenic strains of fungi. Three of the peptides displayed strong general antifungal properties at low micromolar inhibitory concentrations. The most promising peptide, compound 5, was selected and evaluated as an antifungal remedy for Candida albicans candidiasis in a human skin model and for the treatment of Trichophyton rubrum induced onychomycosis in an infected human nail model. Compound 5 was shown to display antifungal properties and a rapid mode of action superior to those of both the commercial comparators Loceryl and Lamisil. Compound 5 was also active against a clinical isolate of Candida albicans with acquired fluconazole resistance.

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Both pathogenic bacteria and fungi are developing resistance to common antimicrobial treatment at an alarming rate. To counteract this development, it is of essence to develop new classes of antimicrobial agents. One such class is antimicrobial peptides, most of which are derived from the innate immune system. In this study, a series of novel 2,5‐diketopiperazines were designed, synthesized, and evaluated for their antimicrobial abilities. The compounds were designed to probe the pharmacophore dictated for short linear mimics of antimicrobial cationic peptides, and as such, the compounds contain a range of cationic and hydrophobic functionalities. Several of the prepared compounds displayed high antimicrobial activities toward bacteria and also against human pathogenic fungi. Of particular interest was the high activity toward fungal strains with an inherent increased resistance toward conventional antifungal agents. The most effective compounds displayed inhibition of Candida glabrata and Candida krusei growth at concentrations between 4 and 8 μg/mL, which is comparable to commercial antifungal agents in use. Structure activity relationship studies revealed a similar dependence on cationic charge and the volume of the hydrophobic bulk as for linear cationic antimicrobial peptides. Finally, the hemolytic activity of selected compounds was evaluated, which revealed a potential to produce active compounds with attenuation of unwanted hemolysis. The findings highlight the potential of cyclic cationic amphiphilic peptidomimetics as a class of promising compounds for the treatment of infections caused by microorganisms with an increased resistance to conventional antimicrobial agents.