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International Journal of Molecular... Feb 2021In a previous article, we reported on the higher toxicity of silver(I) complexes of miconazole [Ag(MCZ)NO ()] and [Ag(MCZ)ClO ()] in HepG2 tumor cells compared to the...
In a previous article, we reported on the higher toxicity of silver(I) complexes of miconazole [Ag(MCZ)NO ()] and [Ag(MCZ)ClO ()] in HepG2 tumor cells compared to the corresponding salts of silver, miconazole and cisplatin. Here, we present the synthesis of two silver(I) complexes of miconazole containing two new counter ions in the form of Ag(MCZ)X (MCZ = 1-[2-(2,4-dichlorobenzyloxy)-2-(2,4-dichlorophenyl)ethyl]-1H-imidazole]; X = BF (), SbF ()). The novel silver(I) complexes were characterized by elemental analysis, H NMR, C NMR and infrared (IR) spectroscopy, electrospray ionization (ESI)-MS spectrometry and X-ray-crystallography. In the present study, the antimicrobial activity of all obtained silver(I) complexes of miconazole against six strains of Gram-positive bacteria, five strains of Gram-negative bacteria and yeasts was evaluated. The results were compared with those of a silver sulfadiazine drug, the corresponding silver salts and the free ligand. Silver(I) complexes exhibited significant activity against Gram-positive bacteria, which was much better than that of silver sulfadiazine and silver salts. The highest antimicrobial activity was observed for the complex containing the nitrate counter ion. All Ag(I) complexes of miconazole resulted in much better inhibition of yeast growth than silver sulfadiazine, silver salts and miconazole. Moreover, the synthesized silver(I) complexes showed good or moderate activity against Gram-negative bacteria compared to the free ligand.
Topics: Anti-Bacterial Agents; Antifungal Agents; Coordination Complexes; Gram-Negative Bacteria; Gram-Positive Bacteria; Miconazole; Silver; Yeasts
PubMed: 33546211
DOI: 10.3390/ijms22041510 -
Clinical Oral Investigations Nov 2022To identify the antifungal susceptibility profile of Candida spp. isolated from the human oral cavity was assessed with meta-analyses of observational studies that... (Meta-Analysis)
Meta-Analysis Review
AIM
To identify the antifungal susceptibility profile of Candida spp. isolated from the human oral cavity was assessed with meta-analyses of observational studies that collected samples from the oral cavity of human subjects.
MATERIAL AND METHODS
Isolated Candida albicans tested by E-test®; disk diffusion test; microdilution and macrodilution; Sensititre YeastOne; and/or FungiTest. Search strategies were conducted on the MEDLINE, Embase, CINAHL, Dentistry, and Oral Sciences, Central, Scopus, and LILACS databases, and gray literature sources. Articles were initially screened by title and then their abstracts. Articles that met the conditions for inclusion were read in full, followed by data extraction. A descriptive analysis was conducted of each study, and the data were tabulated. A first meta-analysis was conducted to assess the resistance of antifungals regardless of systemic comorbidities. An additional stratified analysis was conducted by systemic comorbidity groups for the outcome "resistance" to the antifungals.
RESULTS
When not grouping Candida albicans isolates by systemic conditions, the lowest resistance rates to the antifungals tested were observed for amphotericin B, nystatin, flucytosine, and caspofungin. In contrast, the highest resistance rates were observed for miconazole and econazole. There was a high degree of heterogeneity and low resistance in general in all analyses, except for the "several associated comorbidities" group, which had high resistance rates.
CONCLUSIONS
Clinical C. albicans isolates had low antifungal resistance.
CLINICAL RELEVANCE
The presence of concomitant systemic comorbidities appears to be an essential factor that should be considered when evaluating resistance to antifungals for oral isolates.
Topics: Humans; Antifungal Agents; Candida albicans; Candidiasis; Microbial Sensitivity Tests; Drug Resistance, Fungal; Mouth
PubMed: 36167858
DOI: 10.1007/s00784-022-04716-2 -
Materials (Basel, Switzerland) May 2023Oral candidiasis is an opportunistic infection that affects mainly individuals with weakened immune system. Devices used in the oral area to treat this condition include...
Oral candidiasis is an opportunistic infection that affects mainly individuals with weakened immune system. Devices used in the oral area to treat this condition include buccal films, which present advantages over both oral tablets and gels. Since candidiasis causes pain, burning, and itching, the purpose of this work was to develop buccal films loaded with both lidocaine (anesthetic) and miconazole nitrate (MN, antifungal) to treat this pathology topically. MN was loaded in microparticles based on different natural polymers, and then, these microparticles were loaded in hydroxypropyl methylcellulose-gelatin-based films containing lidocaine. All developed films showed adequate adhesiveness and thickness. DSC and XRD tests suggested that the drugs were in an amorphous state in the therapeutic systems. Microparticles based on chitosan-alginate showed the highest MN encapsulation. Among the films, those containing the mentioned microparticles presented the highest tensile strength and the lowest elongation at break, possibly due to the strong interactions between both polymers. These films allowed a fast release of lidocaine and a controlled release of MN. Due to the latter, these systems showed antifungal activity for 24 h. Therefore, the treatment of oropharyngeal candidiasis with these films could reduce the number of daily applications with respect to conventional treatments.
PubMed: 37176470
DOI: 10.3390/ma16093586 -
Frontiers in Pediatrics 2022The use of antimicrobial-impregnated peripherally inserted central catheters (PICCs) has been introduced in the last few years to neonatal units aiming to reduce central...
BACKGROUND
The use of antimicrobial-impregnated peripherally inserted central catheters (PICCs) has been introduced in the last few years to neonatal units aiming to reduce central line-associated bloodstream infection (CLABSI).
METHODS
This retrospective observational study aimed to compare the CLABSI rates and other catheter-related parameters including the insertion success rates and catheter-related complications in the antimicrobial-impregnated and conventional (ordinary) PICCs in NICU between 2017 and 2020.
RESULTS
Our dedicated PICC team including physicians and nurses inserted 1,242 conventional (PremiCath and NutriLine) and 791 antimicrobial-impregnated PICCs (PremiStar) over the study period from 2017 to 2020. Of those 1,242 conventional PICCs, 1,171 (94.3%) were 1 Fr single lumen and only 71 (5.7%) were 2 Fr double lumen. The mean ± SD [median (IQR)] for the birth weight in all babies who had a PICC line was 1,343.3 ± 686.75 [1,200 (900, 1,500)] g, while the mean ± SD for the gestational age was 29.6 ± 4.03 [29 (27, 31)] weeks. The mean ± SD [median (IQR)] age at the time of insertion for all catheters was 9.3 ± 21.47 [2 (1, 9)] days, while the mean ± SD [median (IQR)] dwell time was 15.7 ± 14.03 [12 (8, 17)] days. The overall success rate of the PICC insertion is 1,815/2,033 (89.3%), while the first attempt success rate is 1,290/2,033 (63.5%). The mean ± SD [median (IQR)] gestational age, birth weight, age at catheter insertion, and catheter dwell time were 28.8 ± 3.24 [29, (26, 31)] weeks, 1,192.1 ± 410.3 [1,150, (900, 1,450)] g, 6.3 ± 10.85 [2, (1, 8)] days, and 17.73 ± 17.532 [13, (9, 18)] days in the antimicrobial-impregnated catheter compared with 30.1 ± 4.39 [29, (27, 32)] weeks ( < 0.001), 1,439.5 ± 800.8 [1,240, (920, 1,520)] g ( < 0.001), 11.1 ± 25.9 [1, (1, 9)] days ( < 0.001), and 14.30 ± 10.964 [12, (8, 17)] days ( < 0.001), respectively, in the conventional PICCs. The use of the antimicrobial-impregnated catheter was not associated with any significant reduction in the CLABSI rate (per 1,000 days dwell time), either the overall [ = 0.11, risk ratio (RR) (95% CI): 0.60 (0.32, 1.13)] or the yearly CLABSI rates.
CONCLUSIONS
The use of miconazole and rifampicin-impregnated PICCs did not reduce the CLABSI rate in neonates compared with conventional PICCs. However, it has a higher overall rate of elective removal after completion of therapy and less extravasation/infiltration, occlusion, and phlebitis compared with the conventional PICCs. Further large RCTs are recommended to enrich the current paucity of evidence and to reduce the risk of bias. Neonatal PICCs impregnation by other antimicrobials is a recommendation for vascular access device manufacturers.
PubMed: 36507144
DOI: 10.3389/fped.2022.1012800 -
Current Medical Mycology Mar 2021, as a new characterized pathogenic yeast, has attracted remarkable attention in the recent decade due to its rapid global emergence and multidrug resistance traits....
BACKGROUND AND PURPOSE
, as a new characterized pathogenic yeast, has attracted remarkable attention in the recent decade due to its rapid global emergence and multidrug resistance traits. This unique species is able to cause nosocomial outbreaks and tolerate adverse conditions; however, it has been mostly misidentified by conventional methods.
CASE REPORT
This report aimed to describe the first fluconazole-resistant case of otitis in an immunocompetent patient in Iran. The isolate showed minimum inhibitory concentration of ≥ 32 μg/ml for fluconazole; however, the patient was treated with topical clotrimazole and miconazole with no recurrence.
CONCLUSION
This was the second strain of isolated from otitis in Iran which was fluconazole-resistant, unlike the first Iranian isolate.
PubMed: 34553098
DOI: 10.18502/cmm.7.1.6243 -
Journal of Veterinary Research Jun 2021Dermatophytosis is a common skin disease in cats and dogs caused by and fungi. Species identification and knowledge of their antifungal susceptibility are...
INTRODUCTION
Dermatophytosis is a common skin disease in cats and dogs caused by and fungi. Species identification and knowledge of their antifungal susceptibility are therapeutically and epidemiologically important. This study assessed the prevalence of feline and canine dermatophytosis in Iran, identified the aetiological agents molecularly and tested their antifungal susceptibility.
MATERIAL AND METHODS
A total of 308 companion animals (134 dogs and 174 cats) with skin lesions were examined from March 2015 to March 2018. Hair and skin samples were examined by microscopy with 20% KOH and cultured on Sabouraud dextrose agar with cycloheximide and chloramphenicol. Fungal isolates were confirmed by sequencing of the internal transcribed spacer (ITS) r-DNA region. The antifungal susceptibility of dermatophytes was tested by broth microdilution assay using standard drugs.
RESULTS
Dermatophytes were found in 130 (42.2%) samples, 62 of them feline and 68 canine. Based on sequencing of all strains, (78.5%, P<0.05), (10.7%), and (10.7%) were the dermatophytes isolated. The non-dermatophyte species was also isolated from two feline dermatomycosis cases. Dogs and cats younger than one year (61.5%) showed a statistically significantly higher prevalence of infection (P<0.05). Caspofungin produced the lowest geometric mean MIC at 0.0018 μg/mL, followed by ketoconazole, terbinafine, itraconazole, miconazole, griseofulvin, clotrimazole and fluconazole, in a 0.038-1.53 μg/mL range.
CONCLUSION
This is the first molecular study to identify the causes of pet dermatophytosis in north-western Iran. ITS-PCR was shown to be a useful and reliable method for the identification of closely related species of dermatophytes in clinical and epidemiological settings. The lowest MIC of caspofungin indicated that this drug was the most potent .
PubMed: 34250302
DOI: 10.2478/jvetres-2021-0020 -
BMC Infectious Diseases Jun 2021Vaginal candidiasis is frequent in women of reproductive age. Accurate identification Candida provides helpful information for successful therapy and epidemiology study;...
Prevalence, species distribution and antifungal susceptibility of Candida albicans causing vaginal discharge among symptomatic non-pregnant women of reproductive age at a tertiary care hospital, Vietnam.
BACKGROUND
Vaginal candidiasis is frequent in women of reproductive age. Accurate identification Candida provides helpful information for successful therapy and epidemiology study; however, there are very limited data from the Vietnam have been reported. This study was performed to determine the prevalence, species distribution of yeast causing vaginal discharge and antifungal susceptibility patterns of Candida albicans among symptomatic non-pregnant women of reproductive age.
METHODS
Vaginal discharge samples were collected from 462 women of reproductive age in Hanoi, Vietnam between Sep 2019 and Oct 2020. Vaginal swabs from these patients were examined by direct microscopic examination (10% KOH). CHROMagar™ Candida medium and Sabouraud dextrose agar supplemented with chloramphenicol (0.5 g/l) were used to isolate yeast, and species identification was performed using morphological tests and molecular tools (PCR and sequencing). Antifungal susceptibility testing was determined according to the Clinical and Laboratory Standards Institute guidelines (M27-A3 and M27-S4).
RESULTS
The prevalence of vaginal yeast colonization in non-pregnant women was 51.3% of 462 participants. Nine different yeast species were identified. Among these isolates, C. albicans (51.37%) was the most frequent, followed by C. parapsilosis (25.88%), C. glabrata (11.37%), C. tropicalis (4.31%), C. krusei (3.92%), C. africana (1.57%), Saccharomyces cerevisiae (0.78%), C. nivariensis (1 isolates, 0.39%), and C. lusitaniae (1 isolates, 0.39%), respectively. Among C. albicans, all 46 isolates were 100% susceptible to micafungin, caspofungin, and miconazole. The susceptibility rates to amphotericine B, 5-flucytosine, fluconazole, itraconazole and voriconazole were 95.65, 91.30, 91.30, 82.61 and 86.95%, respectively.
CONCLUSIONS
The prevalence of VVC among symptomatic non-pregnant women of reproductive age in Vietnam was higher than many parts of the world. The high frequency of non-albicans Candida species, which were often more resistant to antifungal agents, was a notable feature. Resistance rates of vaginal C. albicans isolates to antifungal agents was low. Our findings suggest that continued surveillance of changes in species distribution and susceptibility to antifungals should be routinely screened and treated.
Topics: Adolescent; Adult; Antifungal Agents; Candida; Candida albicans; Candidiasis, Vulvovaginal; Drug Resistance, Fungal; Female; Humans; Microbial Sensitivity Tests; Middle Aged; Prevalence; Tertiary Care Centers; Vaginal Discharge; Vietnam; Young Adult
PubMed: 34082699
DOI: 10.1186/s12879-021-06192-7 -
Antibiotics (Basel, Switzerland) Sep 2022Phylogenetically diverse fungal species are an increasing cause of severe disease and mortality. Identification of new targets and development of new fungicidal drugs...
Phylogenetically diverse fungal species are an increasing cause of severe disease and mortality. Identification of new targets and development of new fungicidal drugs are required to augment the effectiveness of current chemotherapy and counter increasing resistance in pathogens. Nitroalkenyl benzene derivatives are thiol oxidants and inhibitors of cysteine-based molecules, which show broad biological activity against microorganisms. Nitropropenyl benzodioxole (NPBD), one of the most active antimicrobial derivatives, shows high activity in MIC assays for phylogenetically diverse saprophytic, commensal and parasitic fungi. NPBD was fungicidal to all species except the dermatophytic fungi, with an activity profile comparable to that of Amphotericin B and Miconazole. NPBD showed differing patterns of dynamic kill rates under different growth conditions for and and was rapidly fungicidal for non-replicating vegetative forms and microconidia. It did not induce resistant or drug tolerant strains in major pathogens on long term exposure. A literature review highlights the complexity and interactivity of fungal tyrosine phosphate and redox signaling pathways, their differing metabolic effects in fungal species and identifies some targets for inhibition. A comparison of the metabolic activities of Amphotericin B, Miconazole and NPBD highlights the multiple cellular functions of these agents and the complementarity of many mechanisms. The activity profile of NPBD illustrates the functional diversity of fungal tyrosine phosphatases and thiol-based redox active molecules and contributes to the validation of tyrosine phosphatases and redox thiol molecules as related and complementary selective targets for antimicrobial drug development. NPBD is a selective antifungal agent with low oral toxicity which would be suitable for local treatment of skin and mucosal infections.
PubMed: 36139967
DOI: 10.3390/antibiotics11091188 -
Pharmaceutics Dec 2021Dapivirine (DPV) is a potent NNRTI used to prevent the sexual transmission of HIV. In a phase 1 trial (IPM 028), the concomitant use of a DPV vaginal ring and an...
Dapivirine (DPV) is a potent NNRTI used to prevent the sexual transmission of HIV. In a phase 1 trial (IPM 028), the concomitant use of a DPV vaginal ring and an antifungal miconazole (MIC) vaginal capsule was found to increase the systemic exposure to DPV in women, suggesting a potential for drug-drug interactions. This study's objective was to investigate the mechanism of DPV-MIC interactions using drug-metabolizing enzymes (DMEs; CYPs and UGTs) that are locally expressed in the female reproductive tract (FRT). In vitro studies were performed to evaluate the metabolism of DPV and its inhibition and induction potential with DMEs. In addition, the impact of MIC on DPV metabolism and the inhibitory potential of DPV with DMEs were studied. Our findings suggest that DPV is a substrate of CYP1A1 and CYP3A4 enzymes and that MIC significantly decreased the DPV metabolism by inhibiting these two enzymes. DPV demonstrated potent inhibition of CYP1A1 and moderate/weak inhibition of the six CYP and eight UGT enzymes evaluated. MIC showed potent/moderate inhibition of seven CYP enzymes and weak/no inhibition of eight UGT enzymes. The combination of DPV and MIC showed potent inhibition of seven CYP enzymes (1A1, 1A2, 1B1, 2B6, 2C8, 2C19, and 3A4) and four UGT enzymes (1A3, 1A6, 1A9, and 2B7). DPV was not an inducer of CYP1A2, CYP2B6, and CYP3A4 enzymes in primary human hepatocytes. Therefore, the increased systemic concentrations of DPV observed in IPM 028 were likely due to the reduced metabolism of DPV because of CYP1A1 and CYP3A4 enzymes inhibition by MIC in the FRT.
PubMed: 34959473
DOI: 10.3390/pharmaceutics13122193 -
ACS Omega Sep 2020The rising prevalence of multidrug-resistant hospital-acquired infections has increased the need for new antibacterial agents. In this study, a library of 1586...
The rising prevalence of multidrug-resistant hospital-acquired infections has increased the need for new antibacterial agents. In this study, a library of 1586 FDA-approved drugs was screened against , a representative of the complex. Three compounds were found to have previously undiscovered antibacterial properties against : antifungal Miconazole, anthelminthic Dichlorophen, and Bithionol. These three drugs were tested against a wide range of Gram-positive and Gram-negative bacteria and confirmed to have broad-spectrum antibacterial properties. Combinations of these three drugs were also tested against the same bacteria, and two novel combination therapies with synergistic effects were discovered. In the future, antibacterial properties of these three drugs and two combination therapies will be evaluated against pathogenic bacteria using an animal model.
PubMed: 32984715
DOI: 10.1021/acsomega.0c03211