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Journal of Fungi (Basel, Switzerland) Oct 2018This review focuses on aspects of antimycotic therapy specific to veterinary medicine. In the first part, drug availability, limited mostly by economic consideration but... (Review)
Review
This review focuses on aspects of antimycotic therapy specific to veterinary medicine. In the first part, drug availability, limited mostly by economic consideration but also by clinical applicability and specific adverse effects, is described for polyenes, 5 fluorocytosine, azoles, echinocandins and terbinafine. In the second part, current knowledge and experience in the treatment of selected fungal infections are overviewed. These mycoses include disseminated mold infections in small animals (dogs and cats) and avian species, upper respiratory tract infections of small animals (sino-nasal and sino-orbital aspergillosis) and horses (guttural pouch mycosis), eumycetoma, infections caused by dimorphic fungi, (blastomycosis, histoplasmosis, coccidioidomycosis, paracoccidioidomycosis and sporothrichosis) and by yeasts and yeast-like microorganism ( spp. and ).
PubMed: 30380772
DOI: 10.3390/jof4040120 -
Mycopathologia Apr 2023Malassezia pachydermatis is part of the normal skin microbiota of various animal species but under certain circumstances becomes an opportunistic pathogen producing...
Malassezia pachydermatis is part of the normal skin microbiota of various animal species but under certain circumstances becomes an opportunistic pathogen producing otitis and dermatitis. Commonly these Malassezia diseases are effectively treated using azoles. However, some cases of treatment failure have been reported. Alterations in the ERG11 gene have been associated with in vitro azole resistance in M. pachydermatis. In the present study, in vitro antifungal susceptibility of 89 different strains of M. pachydermatis isolated from different animal species and health status was studied. The susceptibility to fluconazole (FLZ), itraconazole (ITZ), ketoconazole and amphotericin B was tested by a disk diffusion method and 17 strains were also subjected to an ITZ E-test. Mueller-Hinton supplemented with 2% glucose and methylene blue was used as culture medium in both susceptibility assays. Multilocus sequence typing was performed in 30 selected strains using D1D2, ITS, CHS2 and β-tubulin genes. Also, ERG11 gene was sequenced. The four antifungals tested were highly effective against most of the strains. Only two strains showed no inhibition zone to antifungals and a strain showed an increased MIC to ITZ. The study of the ERG11 sequences revealed a high diversity of DNA sequences and a total of 23 amino acid substitutions, from which only two have been previously described. Also, three deleterious substitutions (A302T, G459D and G461D) previously associated with azole resistance in this yeast were recovered. A correlation between certain genotypes and ERG11 mutations was observed. Some of the ERG11 mutations recovered were correlated with a reduced susceptibility to azoles.
Topics: Animals; Antifungal Agents; Azoles; Malassezia; Ketoconazole; Itraconazole; Microbial Sensitivity Tests; Drug Resistance, Fungal
PubMed: 36495417
DOI: 10.1007/s11046-022-00696-9 -
Polish Journal of Veterinary Sciences Jun 2023Yeast infections such as otitis externa and seborrheic dermatitis in dogs and cats are frequently associated with secondary infection. It is part of the normal...
Yeast infections such as otitis externa and seborrheic dermatitis in dogs and cats are frequently associated with secondary infection. It is part of the normal cutaneous microflora of most warm-blooded vertebrates, however, under certain conditions, it can become a causative agent of infection that needs to be treated pharmacologically. Azole derivatives are the drugs of the first choice. An interesting trend in developing resistance is the use of natural substances, which include manuka honey with confirmed antimicrobial properties. The main intention of this research was to evaluate the mutual effect of manuka honey in combination with four conventional azole antifungals - clotrimazole, fluconazole, itraconazole, and miconazole - on 14 isolates obtained from dogs and 1 reference strain. A slightly modified M27-A3 method (CLSI 2008) and the checkerboard test (Nikolić et al. 2017) were used for this purpose. Our results show an additive effect of all 4 antifungals with manuka honey concurrent use. Based on the determined values of fractional inhibitory concentration index (FICI - 0.74±0.03 when manuka honey combined with clotrimazole, 0.96±0.08 with fluconazole, 1.0±0 with miconazole and 1.16±0.26 with itraconazole), it was found in all cases that the effect of substances used is more pronounced in mutual combination than when used separately.
Topics: Animals; Cats; Dogs; Antifungal Agents; Fluconazole; Itraconazole; Miconazole; Clotrimazole; Cat Diseases; Honey; Dog Diseases; Azoles
PubMed: 37389413
DOI: 10.24425/pjvs.2023.145037 -
The Journal of Veterinary Medical... Mar 2023Canine Malassezia dermatitis and otitis externa are generally treated by antifungal drugs. However, multi-drug-resistant strains of Malassezia pachydermatis have been...
Canine Malassezia dermatitis and otitis externa are generally treated by antifungal drugs. However, multi-drug-resistant strains of Malassezia pachydermatis have been reported worldwide. Given the presence of these multi-drug-resistant strains, it is unclear which antifungal agent is the most effective for canine Malassezia dermatitis and canine otitis. In this study, we attempted to determine the most effective drug against azole-resistant M. pachydermatis. Susceptibility to azoles and terbinafine (TBF) was assessed using a modified broth microdilution method. In all tested isolates, the minimum inhibitory concentration at 90% of organisms (MIC) were 16 to >32 μg/mL for the azoles, and 2 μg/mL for TBF. All of the strains that showed low susceptibility to both itraconazole and miconazole were also relatively susceptible to TBF.
Topics: Animals; Dogs; Azoles; Terbinafine; Malassezia; Japan; Antifungal Agents; Microbial Sensitivity Tests; Dermatitis; Dog Diseases
PubMed: 36724970
DOI: 10.1292/jvms.22-0358 -
Methods in Molecular Biology (Clifton,... 2023Galleria mellonella larva has been widely exploited as an infection model for bacteria and fungi. Our laboratory uses this insect as a model for fungal infection caused...
Galleria mellonella larva has been widely exploited as an infection model for bacteria and fungi. Our laboratory uses this insect as a model for fungal infection caused by the genus Malassezia, in particular, systemic infections caused by Malassezia furfur and Malassezia pachydermatis, which are poorly understood. Here, we describe the G. mellonella larva inoculation process with M. furfur and M. pachydermatis and the posterior assessment of the establishment and dissemination of the infection in the larvae. This assessment was done through the evaluation of larval survival, melanization, fungal burden, hemocytes populations, and histological changes. This methodology allows for the identification of virulence patterns between Malassezia species and the impact of inoculum concentration and temperature.
Topics: Animals; Malassezia; Moths; Mycoses; Larva; Reference Standards
PubMed: 37145273
DOI: 10.1007/978-1-0716-3199-7_2 -
Medical Mycology Feb 2020Malassezia pachydermatis, a lipophilic and aerobic yeast, is a causative agent of Malassezia dermatitis, a common skin mycosis in dogs and cats. This fungus is also...
Malassezia pachydermatis, a lipophilic and aerobic yeast, is a causative agent of Malassezia dermatitis, a common skin mycosis in dogs and cats. This fungus is also responsible for zoonotic fungal infections in human neonates. Ravuconazole (RVZ) is an antifungal azole compound and the active metabolite of fosravuconazole, which was approved for use in humans in Japan in 2018. In the present study, in vitro RVZ susceptibility and multi-azole resistance of 13 clinical M. pachydermatis strains was investigated using the modified Clinical and Laboratory Standards Institute M27-A3 test. The minimum inhibitory concentrations (MICs) for the 13 isolates ranged from 0.094 to >32 mg/L for itraconazole (ITZ) and from 0.5 to >32 mg/l for RVZ. Similarly, MICs for ITZ- or RVZ-resistant strains (MICs >32 mg/l) were also >32 mg/l for clotrimazole (CTZ), >32 mg/l for miconazole (MCZ), and 0.25 to >32 mg/L for voriconazole (VRZ). BLAST analysis using the NCBI database showed that ERG11 cDNA of the RVZ-resistant strain encoded Gly at codon 461 and Asp in cytochrome p450 encoded by M. pachydermatis ERG11 mRNA. This work is the first report to describe that an RVZ-resistant M. pachydermatis strain contains ERG11 mutations. The affinity of the protein encoded by ERG11 for RVZ may differ from that of ITZ. Therefore, RVZ has considerable therapeutic potential for treating ITZ-resistant canine Malassezia dermatitis. However, RVZ-resistant strains already exist in canine Malassezia dermatitis in Japan.
Topics: Animals; Antifungal Agents; Azoles; Dermatomycoses; Dog Diseases; Dogs; Drug Resistance, Multiple, Fungal; Itraconazole; Japan; Malassezia; Microbial Sensitivity Tests; Thiazoles; Triazoles
PubMed: 31329927
DOI: 10.1093/mmy/myz037 -
Journal of Fungi (Basel, Switzerland) Nov 2022The yeast , an opportunistic pathogen that inhabits the skin of various domestic and wild animals, is capable of producing a biofilm that plays an important role in...
The yeast , an opportunistic pathogen that inhabits the skin of various domestic and wild animals, is capable of producing a biofilm that plays an important role in antifungal resistance. The aim of this research study was to find the intensity of biofilm production by strains isolated from the ear canal of healthy dogs, and to determine the susceptibility of planktonic, adhered and biofilm-forming cells to three azole antifungals-itraco-nazole, voriconazole and posaconazole-that are most commonly used to treat infections. Out of 52 isolates, 43 strains (82.7%) were biofilm producers with varying levels of intensity. For planktonic cells, the minimum inhibitory concentration (MIC) range was 0.125-2 µg/mL for itraconazole, 0.03-1 µg/mL for voriconazole and 0.03-0.25 µg/mL for posaconazole. Only two isolates (4.7%) were resistant to itraconazole, one strain (2.3%) to voriconazole and none to posaconazole. For adhered cells and the mature biofilm, the following MIC ranges were found: 0.25-16 µg/mL and 4-16 µg/mL for itraconazole, 0.125-8 µg/mL and 0.25-26 µg/mL for voriconazole, and 0.03-4 µg/mL and 0.25-16 µg/mL for posaconazole, respectively. The least resistance for adhered cells was observed for posaconazole (55.8%), followed by voriconazole (62.8%) and itraconazole (88.4%). The mature biofilm of showed 100% resistance to itraconazole, 95.3% to posaconazole and 83.7% to voriconazole. The results of this study show that higher concentrations of commonly used antifungal agents are needed to control infections caused by biofilm-forming strains of .
PubMed: 36422031
DOI: 10.3390/jof8111209 -
Medical Mycology Jul 2019Malassezia pachydermatis and Malassezia furfur are lipophilic yeasts of the cutaneous microbiome, although these organisms are occasionally responsible for serious...
Malassezia pachydermatis and Malassezia furfur are lipophilic yeasts of the cutaneous microbiome, although these organisms are occasionally responsible for serious invasive infections in neonates. Since phagocytosis is an important mechanism mediating the adaptive immune response, here we evaluated the phagocytosis capacity and production of nitric oxide and cytokine by macrophages after challenged with M. furfur CBS-1878 and M. pachydermatis CBS-1696. The phagocytic indexes was determined using RAW 264.7 cultivated or not with M. furfur or M. pachydermatis in the concentrations of 5:1 or 2:1 (yeasts:macrophages ratio) for 6 h, 24 h, and 48 h following the challenges. Evaluation of nitric oxide and pro- and anti-inflammatory cytokines (interleukin [IL]-2, IL-4, IL-6, IL-10, IL-17A, interferon (IFN)-γ and tumor necrosis factor [TNF]-α) by Griess method and flow cytometry, respectively, were performed in the different intervals by collecting the cell culture supernatant. Results showed a higher phagocytic index in the 5:1 ratio in 24 h for both species. Malassezia pachydermatis-infected macrophages had superior phagocytic indexes than M. furfur-infected macrophages. Phagocytosis evaluation at 48 h showed significant microorganisms proliferation and macrophages death, particularly in macrophages infected with M. pachydermatis, suggesting yeast evasion mechanism. Significant variations in the nitric oxide production were observed in macrophages infected with both species. Levels of TNF-α and IL-4 cytokines have increased in M. furfur and M. pachydermatis macrophage-infected cultures, respectively. The low microbicidal activity and the presence of pro- and anti-inflammatory cytokines reinforce the dichotomous character of the relation of these yeasts with the host, acting as a commensal in the cutaneous microbiome or causing infection.
PubMed: 30388249
DOI: 10.1093/mmy/myy104 -
Journal of Fungi (Basel, Switzerland) Jun 2020is a yeast inhabiting the skin and ear canals in healthy dogs. In the presence of various predisposing conditions it can cause otitis and dermatitis, which are treated... (Review)
Review
is a yeast inhabiting the skin and ear canals in healthy dogs. In the presence of various predisposing conditions it can cause otitis and dermatitis, which are treated with multiple antifungal agents, mainly azole derivatives. This manuscript aims to review the available evidence regarding the occurrence of resistance phenomena in this organism. Various findings support the capacity of for developing resistance. These include some reports of treatment failure in dogs, the reduced antifungal activity found against yeast isolates sampled from dogs with exposure to antifungal drugs and strains exposed to antifungal agents in vitro, and the description of resistance mechanisms. At the same time, the data reviewed may suggest that the development of resistance is a rare eventuality in canine practice. For example, only three publications describe confirmed cases of treatment failure due to antifungal resistance, and most claims of resistance made by past studies are based on interpretive breakpoints that lack sound support from the clinical perspective. However, it is possible that resistant cases are underreported in literature, perhaps due to the difficulty of obtaining a laboratory confirmation given that a standard procedure for susceptibility testing of is still unavailable. These considerations highlight the need for maintaining surveillance for the possible emergence of clinically relevant resistance, hopefully through a shared strategy put in place by the scientific community.
PubMed: 32630397
DOI: 10.3390/jof6020093 -
The Pediatric Infectious Disease Journal May 2020Malassezia pachydermatis is a rare cause of systemic infection in infants. (Review)
Review
BACKGROUND
Malassezia pachydermatis is a rare cause of systemic infection in infants.
METHODS
A total of 4 cases of M. pachydermatis fungemia that occurred in our neonatal intensive care unit over a 21-month period were reviewed, as well as 27 cases reported in the literature since 1988.
RESULTS
The patients were preterm with multiple complications and had birth weights ranging from 490 to 810 g and gestational age between 23 and 26 weeks. All patients had received prophylactic fluconazole, broad-spectrum antibiotics and parenteral lipid supplements before fungemia onset, which occurred between the age of 7 and 28 days. Symptoms were nonspecific and thrombocytopenia was the primary laboratory finding. All patients received intravenous antifungal treatment and recovered from their infection. The 27 cases from review of the literature also indicated that the infected infants were extremely low birth weight (77.8%), with multiple underlying diseases (94.7%), receiving lipid-supplementation (100%) from a central vascular catheter. Most infants received antifungal treatment (73.1%) and catheter removal (73.1%) as the management.
CONCLUSIONS
M. pachydermatis is a pathogenic agent that causes late onset sepsis in critically ill low birth weight infants with generally good outcomes. Targeted antifungal treatment as well as catheter removal appear to be key factors for infection management.
Topics: Antifungal Agents; Birth Weight; Case-Control Studies; Cross Infection; Dermatomycoses; Female; Fungemia; Gestational Age; Humans; Infant; Infant, Low Birth Weight; Infant, Newborn; Intensive Care Units, Neonatal; Malassezia; Male; Retrospective Studies; Sepsis
PubMed: 32118859
DOI: 10.1097/INF.0000000000002591