Trichophyton mentagrophytes - a new genotype of zoophilic dermatophyte causes sexually transmitted infections.

BACKGROUND: A new genotype of the zoophilic fungal species Trichophyton (T.) mentagrophytes was recently described in two studies. It was isolated from three patients who had visited Southeast Asia and one patient who had visited Egypt. In contrast to these studies, we have observed a number of cases with the dimensions of an epidemic outbreak. PATIENTS AND METHODS: At the University Hospital Charité Berlin, 43 patients, mostly suffering from highly inflammatory, painful and persistent infections of the pubogenital region were observed between January 2016 and July 2017. Mycological examination was performed with fungal culture and sequencing of the ITS (internal transcribed spacer) region of the ribosomal DNA. Three additional genomic regions were spot-checked. RESULTS: In 37 of the cases, a new genotype of T. mentagrophytes (referred to here as T. mentagrophytes VII) was isolated as the etiological agent, and sequencing revealed identical sequences for all isolates. Most of the infected patients had no history of travel, and only two patients reported contact with animals. CONCLUSIONS: The new genotype clustered phylogenetically among the strains of the zoophilic species T. mentagrophytes with four different DNA markers. While human-to-human transmission of zoophilic dermatophytes is rare, transmission via sexual contact seemed to be quite effective here.

Detection of azole susceptibility patterns in clinical yeast strains isolated from 1998 to 2008.

4,860 clinical yeast isolates (25 genera, 47 species) were tested in parallel to fluconazole, itraconazole, ketoconazole, and voriconazole. After re-evaluation of all species according to their current valid taxonomic denominations, the range of the top four of the dermatology, gynaecology and paediatrics associated species from superficial infections was similar to those isolated from other wards with mainly systemic/invasive infections. Candida albicans (44.7%) was the most frequent pathogen followed by C. glabrata, C. tropicalis, and C. parapsilosis. The MIC-assessment revealed for the ten-year test period an overall azole-susceptibility of about 75%, and ~80% for their associated ICUs. The overall susceptibility of the isolates from systemic and superficial infections to the four azoles was 79% and 80% respectively, and demonstrates a high in vitro activity. When two test periods (1998-2001 and 2002-2008) were compared by characteristic MIC values and multi-azole resistance, no significant increase could be detected in azole susceptibility/resistance over the two periods, respectively, over the total investigation period of ten years. This holds true when the characteristic MIC values were compared with those from different azole susceptibility studies from similar time periods and from different investigators around the world (1991 to 2010). With a new method, susceptibility pattern analysis for fungi, detailed information of multi-resistant microorganism populations could be obtained, and different characteristic resistance patterns in clinical yeast species detected. Although at a relatively low level, multi-resistance was seen in individual species populations demonstrating resistance to two (6.7%), three (4.4%), or all four (4%) azoles tested. A level of 4% and 2% fourfold parallel resistance was also determined in Candia spp. and non-Candida spp. derived of blood culture isolates.

Reactive oxygen species and the bacteriostatic and bactericidal effects of isoconazole nitrate.

Bacterial superinfections often occur in dermatomycoses, resulting in greatly inflamed or eczematous skin. The objective of this study was to evaluate the antibacterial efficacy of isoconazole nitrate (ISN), a broad-spectrum antimicrobial imidazole, commonly used to treat dermatomycoses. Several gram-positive bacteria minimal inhibitory concentrations (MICs) for ISN (ISN solution or ISN-containing creams: Travogen or corticosteroid-containing Travocort) and ampicillin were obtained using the broth-dilution method. Speed of onset of the bactericidal effect was determined with bacterial killing curves. Reactive oxygen species (ROS) were visualised by staining cells with singlet oxygen detector stain. Compared with ampicillin MICs, ISN MICs for Bacillus cereus, Staphylococcus haemolyticus and Staphylococcus hominis were lower and ISN MICs for Corynebacterium tuberculostearicum and Streptococcus salivarius were similar. Incubation with ISN led to a 50% kill rate for Staphylococcus aureus and methicillin-resistant strains (MRSA). Post-ISN incubation, 36% (30 min) and 90% (60 min) of S. aureus cells were positive for ROS. Isoconazole nitrate has a broad bacteriostatic and bactericidal action, also against a MRSA strain that was not reduced by the corticosteroid in the Travocort cream. Data suggest that the antibacterial effect of ISN may be ROS dependent. An antifungal agent with robust antibacterial activity can provide a therapeutic advantage in treating dermatomycoses with suspected bacterial superinfections.

Misdiagnosed zoophile tinea faciei and tinea corporis effectively treated with isoconazole nitrate and diflucortolone valerate combination therapy.

There have been few published reports on the human transmission of Trichophyton mentagrophytes, a zoophilic fungus frequently occurring in pets. Here we report on 2 girls, living with a pet dwarf rabbit, who presented with inflammatory skin lesions positive for T. mentagrophytes and subsequently diagnosed as zoophile tinea faciei and tinea corporis. The patients were successfully treated with systemic terbinafine and 2-week therapy with Travocort cream containing isoconazole nitrate 1% and diflucortolone valerate 0.1%.

Effective treatment of tinea corporis due to Trichophyton mentagrophytes with combined isoconazole nitrate and diflucortolone valerate therapy.

Trichophyton mentagrophytes is the dermatophyte species most commonly reported in cases of guinea pig-associated dermatophytosis (or guinea pig fungus) a condition that more often affects children than adults. In this case, a 13-year-old girl with recent direct contact with guinea pigs presented with a previously undertreated inflammatory skin lesion on the left side of her upper body, which was positive both for Trichophyton mentagrophytes and Staphylococcus epidermidis. The condition was subsequently diagnosed as tinea corporis due to Trichophyton mentagrophytes with concomitant bacterial infection and effectively treated with 2 weeks of twice-daily application of Travocort cream containing isoconazole nitrate 1% and diflucortolone valerate 0.1%. Visible improvement in the lesion was apparent after only 1 week of treatment.

Trichophyton mentagrophytes cause underestimated contagious zoophilic fungal infection.

Trichophytia infection, paraphrased cuddly toy mycosis, occurs primarily in prepubertal children, occasionally in infants and adults. The presented case shows the highly contagious infection of four family members with Trichophyton mentagrophytes. Effective treatment requires detailed diagnostic: identifying the dermatophyte, finding the infection source, treating the infection carriers. Tinea must be treated systemically and topically because of infectivity and ignitability. Systemic terbinafine or fluconazole treatment and topical fixed combination isoconazole nitrate/diflucortolone valerate are recommended.

Epidemiology and changes in patient-related factors from 1997 to 2009 in clinical yeast isolates related to dermatology, gynaecology, and paediatrics.

From 1997 to 2009, 1,862 dermatology, gynaecology, and paediatrics (DGP) associated clinical yeast isolates were analysed for species occurrence, specimen origin and type, (multi-) resistance pattern, and testing period. The top seven of the isolated DGP-associated species remained the same as compared to total medical wards, with Candida albicans (45%) as most frequent pathogen. However, the DGP wards and DGP ICUs showed species-specific profiles; that is, the species distribution is clinic-specific similar and however differs in their percentage from ward to ward. By applying the "one fungus one name" principle, respectively, the appropriate current taxonomic species denominations, it has been shown that no trend to emerging species from 1998 to 2008 could be detected. In particular the frequently isolated non-Candida albicans species isolated in the DGP departments have already been detected in or before 1997. As yeasts are part of the cutaneous microbiota and play an important role as opportunistic pathogens for superficial infections, proper identification of the isolates according to the new nomenclature deems to be essential for specific and calculated antifungal therapy for yeast-like DGP-related infectious agents.

Diagnostic PCR of dermatophytes--an overview.

The prevalence of onychomycosis is increasing steadily, sevenfold alone in the US within the last twenty years. An important aspect in this development is the demographic development of the human population of the industrial countries like Germany. A fast and accurate laboratory diagnosis is essential for successful treatment because 50% of the cases are misdiagnosed when relying on the clinical appearance only. The current diagnosis of dermatophytosis, based on direct microscopy and culture of the clinical specimen, is problematic given the lacking specificity of the former and the length of time needed for the latter. Molecular techniques can help to solve these problems. In recent years, a number of in-house PCR assays have been developed to identify dermatophytes directly from clinical specimens. Based on the "Mikrobiologisch-infektiologischen Qualitätsstandards (MIQ) für Nukleinsäure-Amplifikationstechniken" and the MIQE guideline (Minimum Information for Publication of Quantitative Real-Time PCR Experiments) 11 studies are reviewed which were published between 2007 and 2010. The present article evaluates the quality of the PCR assays regarding false positive and false negative results due to contamination, PCR format, statistical analysis, and diagnostic performance of the studies. It shows that we are only at the beginning of providing high quality PCR diagnosis of dermatophytes.

Susceptibility screening of hyphae-forming fungi with a new, easy, and fast inoculum preparation method.

In vitro susceptibility testing of clinically important fungi becomes more and more essential due to the rising number of fungal infections in patients with impaired immune system. Existing standardized microbroth dilution methods for in vitro testing of molds (CLSI, EUCAST) are not intended for routine testing. These methods are very time-consuming and dependent on sporulating of hyphomycetes. In this multicentre study, a new (independent of sporulation) inoculum preparation method (containing a mixture of vegetative cells, hyphae, and conidia) was evaluated. Minimal inhibitory concentrations (MIC) of amphotericin B, posaconazole, and voriconazole of 180 molds were determined with two different culture media (YST and RPMI 1640) according to the DIN (Deutsches Institut für Normung) microdilution assay. 24 and 48 h MIC of quality control strains, tested per each test run, prepared with the new inoculum method were in the range of DIN. YST and RPMI 1640 media showed similar MIC distributions for all molds tested. MIC readings at 48 versus 24 h yield 1 log(2) higher MIC values and more than 90 % of the MICs read at 24 and 48 h were within ± 2 log(2) dilution. MIC end point reading (log(2 MIC-RPMI 1640)-log(2 MIC-YST)) of both media demonstrated a tendency to slightly lower MICs with RPMI 1640 medium. This study reports the results of a new, time-saving, and easy-to-perform method for inoculum preparation for routine susceptibility testing that can be applied for all types of spore-/non-spore and hyphae-forming fungi.

Pharmacokinetics and penetration of moxifloxacin into infected diabetic foot tissue in a large diabetic patient cohort.

OBJECTIVES: Physiological changes occurring in patients with diabetes may affect the pharmacokinetics and penetration of antimicrobial agents into peripheral tissue. We examined the pharmacokinetics and the penetration of moxifloxacin into perinecrotic tissue of diabetic foot lesions in patients with diabetic foot infections (DFI). PATIENTS AND METHODS: Adult patients suffering from type 2 diabetes mellitus and hospitalized for DFI (Texas classification of at least B2) were treated with 400 mg moxifloxacin intravenously (IV) or orally (PO) once daily. The pharmacokinetics of moxifloxacin and its concentration 3 h after administration in samples of perinecrotic tissue resected from infected diabetic foot wounds were determined at steady state (days 4-8). RESULTS: A total of 53 patients with diabetes mellitus type 2 (mean age 69.4 ± 10.8 years) were included in the study, of whom 28 received PO and 25 IV moxifloxacin therapy for a median of 8 days. In the PO and IV subgroups, the mean maximum observed plasma concentration (C (max)) in plasma was 2.69 and 4.77 mg/l at a median of 2 [time to reach C (max) (T (max)) range 1.0-8.0 h] and 1 h after administration, respectively. A mean area under the plasma concentration-time curve from time 0 until the last quantifiable plasma concentration (AUC(0-24 h)) of 29.36 mg h/l (PO) and 27.09 mg h/l (IV) was achieved. Mean moxifloxacin concentrations in perinecrotic tissue of infected diabetic foot wounds following PO or IV administration were 1.79 ± 0.82 and 2.20 ± 1.54 µg/g, thus exceeding the MIC(90) (minimum inhibitory concentration required to inhibit growth of 90% of organisms) for Staphylococcus aureus (0.25 mg/l) by seven- and eightfold and the MIC(90) for Escherichia coli (0.06 mg/l) by 29-fold and 36-fold, respectively. The mean tissue-to-plasma ratios of moxifloxacin concentration 3 h after administration were 1.01 ± 0.57 (PO) and 1.09 ± 0.69 (IV). Significant differences between the routes of administration were observed for T (max) and C (max) (P < 0.01), but not for other clinically relevant parameters (AUC(0-24); moxifloxacin DFI tissue concentration). CONCLUSIONS: The plasma concentration-time curve of moxifloxacin in diabetic patients is similar to that of healthy volunteers. We also observed a good penetration of moxifloxacin into inflamed DFI tissue which taken together with the possibility of sequential IV/PO therapy suggest that moxifloxacin 400 mg once daily is a therapeutic option in the treatment of DFI caused by susceptible organisms.

Epidemiological trends in skin mycoses worldwide.

Fungal infections of the skin and nails are a common global problem. The high prevalence of superficial mycotic infections shows that 20-25% of the world's population has skin mycoses, making these one of the most frequent forms of infection. Pathogens responsible for skin mycoses are primarily anthropophilic and zoophilic dermatophytes from the genera Trichophyton (T.), Microsporum (M.) and Epidermophyton (E.). There appears to be considerable inter- and intra-continental variability in the global incidence of these fungal infections. Trichophyton rubrum, T. interdigitale (mentagrophytes var. interdigitale), M. canis, M. audouinii, T. tonsurans and T. verrucosum are the most common, but the attack rates and incidence of specific mycoses can vary widely. Local socio-economic conditions and cultural practices can also influence the prevalence of a particular infection in a given area. For example, tinea pedis (athlete's foot) is more prevalent in developed countries than in emerging economies and is likely to be caused by the anthropophilic germ T. rubrum. In poorer countries, scalp infections (tinea capitis) caused by T. soudanense or M. audouinii are more prevalent. This review summarises current epidemiological trends for fungal infections and focuses on dermatomycosis of glabrous skin on different continents.