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Journal de Mycologie Medicale Jun 2024Histoplasma capsulatum is the etiological agent of histoplasmosis, the most common endemic pulmonary mycosis. Itraconazole (ITZ) is the choice for mild disease and a...
INTRODUCTION
Histoplasma capsulatum is the etiological agent of histoplasmosis, the most common endemic pulmonary mycosis. Itraconazole (ITZ) is the choice for mild disease and a step-down therapy in severe and disseminated clinical presentations. Drug encapsulation into nanoparticles (NPs) is an alternative to improve drug solubility and bioavailability, reducing undesirable interactions and drug degradation and reaching the specific therapeutic target with lower doses.
OBJECTIVE
evaluate the antifungal and immunomodulatory effect of ITZ encapsulated into poly(lactic-co-glycolic acid) (PLGA) NPs, administrated orally and intraperitoneally in an in vivo histoplasmosis model.
RESULTS
After intranasal infection and treatment of animals with encapsulated ITZ by intraperitoneal and oral route, fungal burden control, biodistribution, immune response, and histopathology were evaluated. The results showed that the intraperitoneal administered and encapsulated ITZ has an effective antifungal effect, significantly reducing the Colony-Forming-Units (CFU) after the first doses and controlling the infection dissemination, with a higher concentration in the liver, spleen, and lung compared to the oral treatment. In addition, it produced a substantial immunomodulatory effect on pro- and anti-inflammatory cytokines and immune cell infiltrates confirmed by histopathology.
CONCLUSIONS
Overall, results suggest a synergistic effect of the encapsulated drug and the immunomodulatory effect contributing to infection control, preventing their dissemination.
PubMed: 38908332
DOI: 10.1016/j.mycmed.2024.101494 -
Medicina 2024
Topics: Humans; Bronchitis; Tracheitis; Aspergillosis; Male; Aspergillus; Middle Aged; Female
PubMed: 38907982
DOI: No ID Found -
The Medical Letter on Drugs and... Jun 2024
Topics: Humans; Antifungal Agents; Candidiasis, Invasive; Echinocandins
PubMed: 38905526
DOI: 10.58347/tml.2024.1705d -
International Ophthalmology Jun 2024This study aimed to evaluate how the SARS-CoV-2 pandemic and associated lockdown measures influenced microbial keratitis in Taiwan by comparing demographic data,...
PURPOSE
This study aimed to evaluate how the SARS-CoV-2 pandemic and associated lockdown measures influenced microbial keratitis in Taiwan by comparing demographic data, predisposing factors, pathogen profiles, and treatment outcomes in 2019 and 2020.
METHODS
Data from patients diagnosed with microbial keratitis at National Chung Kung University Hospital between January 2019 and December 2020 were examined, focusing on patient demographics, predisposing factors, isolated pathogens, antibiotic usage, and clinical progress.
RESULTS
No significant differences were found in patient sex, laterality, or average age between the two years. Predisposing factors, such as contact lens use and chronic ocular/systemic disorders, remained unchanged. While fungal isolates slightly increased during the lockdown, bacterial isolates remained consistent. Medical treatment effectiveness, treatment strategies, and antibiotic susceptibility for common bacteria showed no significant alterations.
CONCLUSION
Despite the challenges posed by the SARS-CoV-2 pandemic and lockdown measures, this study revealed minimal changes in microbial keratitis trends in Taiwan. This highlights the importance of maintaining access to medical care during crises and offers insights into potential treatment strategies for patients facing difficulties in receiving timely care. Further research should investigate the pandemic's impact on healthcare access and patient outcomes in various populations and regions.
Topics: Humans; COVID-19; Taiwan; Male; Female; Middle Aged; Adult; SARS-CoV-2; Eye Infections, Bacterial; Aged; Keratitis; Retrospective Studies; Pandemics; Quarantine; Anti-Bacterial Agents; Young Adult; Eye Infections, Fungal
PubMed: 38904686
DOI: 10.1007/s10792-024-03200-y -
Przeglad Epidemiologiczny Jun 2024Infectious skin diseases constitute a significant public health problem. Despite the systematic development of many modern diagnostic and therapeutic tools, they still...
Infectious skin diseases constitute a significant public health problem. Despite the systematic development of many modern diagnostic and therapeutic tools, they still pose a serious challenge for clinicians. Due to their prevalence and mild course in most cases, they are often marginalized, which can delay their diagnosis and treatment initiation. Such an approach in more clinically advanced cases can have serious consequences, sometimes leading to tragic outcomes. This work presents a series of four cases of common infectious skin diseases with an unusually atypical clinical picture: the history of a 49-year-old female patient with recurrent erysipelas of the right lower leg co-occurring with a SARS-CoV-2 infection, a 75-year-old male patient with a generalized form of herpes zoster, a 38-year-old female patient with a complicated severe course of head lice, and a 34-year-old male patient with a severe form of post-steroid mycosis. In each of these cases, difficulties in making the correct diagnosis were highlighted, even though they represent some of the most common bacterial, viral, parasitic, and fungal dermatoses. The paper discusses the risk factors for these diseases, the pathophysiology of their atypical course, the effects and challenges in the therapeutic approach conducted. Infectious skin dermatoses require aggressive treatment and should never be underestimated.
Topics: Humans; Male; Female; Middle Aged; Aged; Adult; COVID-19; Skin Diseases, Infectious; Herpes Zoster; SARS-CoV-2; Erysipelas
PubMed: 38904310
DOI: 10.32394/pe.77.47 -
Frontiers in Cellular and Infection... 2024species comprise a ubiquitous pathogenic fungal genus responsible for causing candidiasis. They are one of the primary causatives of several mucosal and systemic...
species comprise a ubiquitous pathogenic fungal genus responsible for causing candidiasis. They are one of the primary causatives of several mucosal and systemic infections in humans and can survive in various environments. In this study, we investigated the antifungal, anti-biofilm, and anti-hyphal effects of six -substituted phthalimides against three species. Of the derivatives, -butylphthalimide (NBP) was the most potent, with a minimum inhibitory concentration (MIC) of 100 µg/ml and which dose-dependently inhibited biofilm at sub-inhibitory concentrations (10-50 µg/ml) in both the fluconazole-resistant and fluconazole-sensitive and . NBP also effectively inhibited biofilm formation in other pathogens including uropathogenic , , , and , along with the polymicrobial biofilms of and . NBP markedly inhibited the hyphal formation and cell aggregation of and altered its colony morphology in a dose-dependent manner. Gene expression analysis showed that NBP significantly downregulated the expression of important hyphal- and biofilm-associated genes, i.e., , , and , upon treatment. NBP also exhibited mild toxicity at concentrations ranging from 2 to 20 µg/ml in a nematode model. Therefore, this study suggests that NBP has anti-biofilm and antifungal potential against various strains.
Topics: Biofilms; Antifungal Agents; Phthalimides; Microbial Sensitivity Tests; Candida albicans; Hyphae; Candida; Candidiasis; Animals; Humans; Candida parapsilosis; Fungal Proteins; Fluconazole
PubMed: 38903941
DOI: 10.3389/fcimb.2024.1414618 -
Frontiers in Veterinary Science 2024Fungal diseases are frequently associated with elevated mortality rates in elasmobranchs. Currently, there is a notable absence of scientifically validated therapeutic...
Updates on antifungal pharmacotherapy in elasmobranchs: pharmacokinetics of 4 mg/kg voriconazole after IM and IV administration in undulate skates () maintained under human care.
INTRODUCTION
Fungal diseases are frequently associated with elevated mortality rates in elasmobranchs. Currently, there is a notable absence of scientifically validated therapeutic medications that can ensure both effectiveness and safety when administered to this group of animals. The empirical prescription of azole antifungal agents, particularly voriconazole, has been posited as a potentially efficacious treatment approach for addressing most common mycoses in sharks and rays. However, there are still no published pharmacokinetic studies supporting its use in elasmobranchs and there is a lack of scientific base for its utilization in elasmobranchs.
METHODS
For this study, voriconazole was administered intravenously (IV) and intramuscularly (IM), at a single dose of 4 mg/kg to six adult undulate skates (). A washout period of 8 weeks was left between each route of administration. Blood samples were collected both before and at ten predetermined intervals after each dosing (0.25, 0.5, 1, 1.5, 2, 4, 8, 12, 24, and 36 h after drug administration). Plasma concentrations were quantified using a validated high-performance liquid chromatography method, and pharmacokinetic (PK) data was analyzed through non-compartmental methods.
RESULTS
The mean extrapolated concentration at 0 h (C) after IV administration was 27.19 ± 7.15 μg/mL and the mean peak plasma concentrations (C) ± SEM after IM administration resulted 2.98 ± 0.28 μg/mL at a mean time to maximum concentration (T ) of 1.33 ± 0.17 h. Terminal half-lives were calculated and resulted 11.18 ± 1.32 h for IV injections and 9.59 ± 1.38 h for IM injections. The area under the curve extrapolated to infinity was determined as 58.14 ± 2.79 h·μg/ml following IV injections and 37.60 ± 6.67 h·μg/ml following IM injections. The IM-administered voriconazole exhibited a mean absolute bioavailability of 64.67 ± 11.47%.
DISCUSSION
These discoveries provide backing for the possible application of voriconazole through the intramuscular route in undulate skates and support using lower dosage regimens compared to those required for oral administration, emphasizing the importance of conducting further pharmacokinetic studies with antifungals in elasmobranchs.
PubMed: 38903684
DOI: 10.3389/fvets.2024.1376851 -
Annals of Clinical Microbiology and... Jun 2024Chromoblastomycosis (CBM), a chronic fungal infection affecting the skin and subcutaneous tissues, is predominantly caused by dematiaceous fungi in tropical and...
Chromoblastomycosis (CBM), a chronic fungal infection affecting the skin and subcutaneous tissues, is predominantly caused by dematiaceous fungi in tropical and subtropical areas. Characteristically, CBM presents as plaques and nodules, often leading to scarring post-healing. Besides traditional diagnostic methods such as fungal microscopy, culture, and histopathology, dermatoscopy and reflectance confocal microscopy can aid in diagnosis. The treatment of CBM is an extended and protracted process. Imiquimod, acting as an immune response modifier, boosts the host's immune response against CBM, and controls scar hyperplasia, thereby reducing the treatment duration. We present a case of CBM in Guangdong with characteristic reflectance confocal microscopy manifestations, effectively managed through a combination of itraconazole, terbinafine, and imiquimod, shedding light on novel strategies for managing this challenging condition.
Topics: Chromoblastomycosis; Imiquimod; Humans; Antifungal Agents; Itraconazole; Terbinafine; Male; Treatment Outcome; Microscopy, Confocal; Skin; Middle Aged
PubMed: 38902740
DOI: 10.1186/s12941-024-00718-y -
Nature Communications Jun 2024During pulmonary mucormycosis, inhaled sporangiospores adhere to, germinate, and invade airway epithelial cells to establish infection. We provide evidence that HIF1α...
During pulmonary mucormycosis, inhaled sporangiospores adhere to, germinate, and invade airway epithelial cells to establish infection. We provide evidence that HIF1α plays dual roles in airway epithelial cells during Mucorales infection. We observed an increase in HIF1α protein accumulation and increased expression of many known HIF1α-responsive genes during in vitro infection, indicating that HIF1α signaling is activated by Mucorales infection. Inhibition of HIF1α signaling led to a substantial decrease in the ability of R. delemar to invade cultured airway epithelial cells. Transcriptome analysis revealed that R. delemar infection induces the expression of many pro-inflammatory genes whose expression was significantly reduced by HIF1α inhibition. Importantly, pharmacological inhibition of HIF1α increased survival in a mouse model of pulmonary mucormycosis without reducing fungal burden. These results suggest that HIF1α plays two opposing roles during mucormycosis: one that facilitates the ability of Mucorales to invade the host cells and one that facilitates the ability of the host to mount an innate immune response.
Topics: Mucormycosis; Animals; Hypoxia-Inducible Factor 1, alpha Subunit; Mucorales; Humans; Epithelial Cells; Mice; Signal Transduction; Mice, Inbred C57BL; Disease Models, Animal; Lung; Female; Gene Expression Profiling
PubMed: 38902255
DOI: 10.1038/s41467-024-49637-8 -
The British Journal of General Practice... Jun 2024Vulvovaginal Candidiasis (VVC) is a fungal infection causing inflammation of the vagina and/or the vulva. Symptoms include itching, irritation, and discharge. VVC... (Comparative Study)
Comparative Study Review
BACKGROUND
Vulvovaginal Candidiasis (VVC) is a fungal infection causing inflammation of the vagina and/or the vulva. Symptoms include itching, irritation, and discharge. VVC presents commonly across primary care and, despite its mild symptoms, carries psychological burden and has a significant impact on women's quality of life. UK guidelines support treatment via oral or topical azole antifungal agents. Recent evidence attests to the superiority of novel non-azole antifungals. Thus, rigorous financial assessment of both antifungals is necessary for optimal VVC treatment allocation in UK primary care.
AIM
To evaluate the cost-effectiveness of ibrexafungerp against the gold standard fluconazole as first-line treatment of VVC within the NHS.
METHOD
A systematic review on the efficacy of ibrexafungerp and fluconazole in acute VVC was conducted. Cost-effectiveness analysis was initiated using health outcome data from the DOVE trial, a Phase 2 RCT. Costs in pound sterling were ascertained in monetary units, and effectiveness determined as reduced need for follow-up medication.
RESULTS
An incremental cost-effectiveness ratio of £2185.74 was determined. This suggests oral ibrexafungerp being largely more costly yet slightly more effective than fluconazole, and thus has unfavourable net benefit. Two sensitivity analyses were conducted considering follow-up medication combination and market price, which provided confidence in the calculated cost-effectiveness ratio.
CONCLUSION
This analysis highlights fluconazole's cost-effectiveness in current UK guidelines and favourability.
Topics: Humans; Fluconazole; Female; Cost-Benefit Analysis; Candidiasis, Vulvovaginal; Antifungal Agents; Administration, Oral; United Kingdom; Amphotericin B; State Medicine; Primary Health Care; Acute Disease; Treatment Outcome; Cost-Effectiveness Analysis; Glycosides; Triterpenes
PubMed: 38902100
DOI: 10.3399/bjgp24X738189