-
Kidney International Jul 2024
Topics: Humans; Amphotericin B; Antifungal Agents
PubMed: 38906655
DOI: 10.1016/j.kint.2024.01.032 -
The Medical Letter on Drugs and... Jun 2024
Topics: Humans; Antifungal Agents; Candidiasis, Invasive; Echinocandins
PubMed: 38905526
DOI: 10.58347/tml.2024.1705d -
Future Microbiology Jun 2024The emergence of fungal pathogens and changes in the epidemiological landscape are prevalent issues in clinical mycology. Reports of resistance to antifungals have been... (Review)
Review
The emergence of fungal pathogens and changes in the epidemiological landscape are prevalent issues in clinical mycology. Reports of resistance to antifungals have been reported. This review aims to evaluate molecular and nonmolecular mechanisms related to antifungal resistance. Mutations in the genes and overexpression of the efflux pump ( and genes) were the most reported molecular mechanisms of resistance in clinical isolates, mainly related to Azoles. For echinocandins, a molecular mechanism described was mutation in the genes. Furthermore, nonmolecular virulence factors contributed to therapeutic failure, such as biofilm formation and selective pressure due to previous exposure to antifungals. Thus, there are many public health challenges in treating fungal infections.
PubMed: 38904325
DOI: 10.1080/17460913.2024.2342150 -
Future Microbiology Jun 2024Currently, we have limited armamentarium of antifungal agents against Mucorales. There is an urgent need to discover novel antifungal agents that are effective, safe...
Currently, we have limited armamentarium of antifungal agents against Mucorales. There is an urgent need to discover novel antifungal agents that are effective, safe and affordable. In this study, the anti-Mucorale action of native lactoferrin (LF) and its functional fragments CLF, RR6 and LFcin against three common Mucorale species are reported. The synergistic action of LF with antifungal agents like amphotericin B, isavuconazole and posaconazole was analyzed using checkerboard technique. All the three mucor species showed inhibition when treated with fragments. The checkerboard assay confirmed that native LF showed the best synergistic action against Mucorales in combination with Amphotericin B. These results highlight the potential therapeutic value of native LF against Mucorales.
PubMed: 38904282
DOI: 10.1080/17460913.2024.2352263 -
Cureus May 2024Opportunistic infections caused by various bacteria, viruses, fungi, or parasites can cause esophagitis. The fungus is often believed to be the thief behind this... (Review)
Review
Opportunistic infections caused by various bacteria, viruses, fungi, or parasites can cause esophagitis. The fungus is often believed to be the thief behind this disorder. This condition's distinctive signs include the process of inflammation and the development of esophageal ulcers. The underlying immunodeficiency condition in HIV/AIDS patients, especially those in the late stages of the disease, may lead to severe illness or even death if the lowered immune system can no longer combat common infections. These individuals are, therefore, more at risk of contracting diseases like Candidiasis since they already have weakened immune systems. Furthermore, bacteria and mycobacteria can cause esophagitis in the same way that viruses can. Tobacco use, alcohol drinking, and nutritional deficiency are three additional problems that can lead to an HIV esophagitis infection. Complaints of inability to swallow, suffocating feeling or discomfort behind the breastbone, and painful swallowing are the primary symptoms of the patients. White plaques or ulcers observed in the esophagus during an endoscopy can be biopsied for further examination. The presence of hyphae and inflammatory infiltrates in these samples confirms the diagnosis of HIV-associated esophagitis. Treatment involves the use of antifungal medications and addressing any underlying causes of esophagitis, which is linked to AIDS. For superficial to moderate infections, fluconazole is typically used first. If the disease is severe or recurs after treatment, intravenous amphotericin B may be necessary. Patients with recurring oral symptoms of HIV esophagitis might also need to take antifungal drugs as a preventative measure.
PubMed: 38903321
DOI: 10.7759/cureus.60788 -
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 -
PLoS Neglected Tropical Diseases Jun 2024In Southeast Asia, treatment is recommended for all patients with post-kala-azar dermal leishmaniasis (PKDL). Adherence to the first-line regimen, twelve weeks of... (Randomized Controlled Trial)
Randomized Controlled Trial
A phase II, non-comparative randomised trial of two treatments involving liposomal amphotericin B and miltefosine for post-kala-azar dermal leishmaniasis in India and Bangladesh.
BACKGROUND
In Southeast Asia, treatment is recommended for all patients with post-kala-azar dermal leishmaniasis (PKDL). Adherence to the first-line regimen, twelve weeks of miltefosine (MF), is low and ocular toxicity has been observed with this exposure period. We assessed the safety and efficacy of two shorter-course treatments: liposomal amphotericin B (LAmB) alone and combined with MF.
METHODOLOGY/PRINCIPAL FINDINGS
An open-label, phase II, randomized, parallel-arm, non-comparative trial was conducted in patients with parasitologically confirmed PKDL, 6 to ≤60 years. Patients were assigned to 20 mg/kg LAmB (total dose, in five injections over 15 days) alone or combined with allometric MF (3 weeks). The primary endpoint was definitive cure at 12 months, defined as complete resolution of papular and nodular lesions and >80% re-pigmentation of macular lesions. Definitive cure at 24 months was a secondary efficacy endpoint. 118/126 patients completed the trial. Definitive cure at 12 months was observed in 29% (18/63) patients receiving LAmB and 30% (19/63) receiving LAmB/MF (mITT), increasing to 58% and 66%, respectively, at 24 months. Most lesions had resolved/improved at 12 and 24 months for patients receiving LAmB (90%, 83%) and LAmB/MF (85%, 88%) by qualitative assessment. One death, unrelated to study drugs, was reported; no study drug-related serious adverse events were observed. The most frequent adverse drug reactions were MF-related vomiting and nausea, and LAmB-related hypokalaemia and infusion reactions. Most adverse events were mild; no ocular adverse events occurred.
CONCLUSIONS/SIGNIFICANCE
Both regimens are suitably safe and efficacious alternatives to long-course MF for PKDL in South Asia.
TRIAL REGISTRATION
CTRI/2017/04/008421.
Topics: Humans; Amphotericin B; Phosphorylcholine; Bangladesh; Male; Antiprotozoal Agents; Adult; Adolescent; Female; Middle Aged; Young Adult; Child; India; Leishmaniasis, Visceral; Treatment Outcome; Leishmaniasis, Cutaneous; Drug Therapy, Combination
PubMed: 38900786
DOI: 10.1371/journal.pntd.0012242 -
Chemistry & Biodiversity Jun 2024This study reports on the chemical composition and antileishmanial and anticandidal activities of volatile oils of Schinus molle dried leaves (SM), Cinnamomum cassia...
This study reports on the chemical composition and antileishmanial and anticandidal activities of volatile oils of Schinus molle dried leaves (SM), Cinnamomum cassia branch bark (CC) and their blends. Major constituents of SM were spathulenol (26.93%), β-caryophyllene (19.90%), and caryophyllene oxide (12.69%), whereas (E)-cinnamaldehyde (60.11%), cinnamyl acetate (20.90%) and cis-2-methoxycinnamic acid (10.37%) were predominant in CC. SM (IC50 = 21.45 µg/mL) and CC (IC50 = 23.27 µg/mL) displayed good activity against L. amazonensis promastigotes, besides having good or moderate activity against nine Candida strains, with Minimum Inhibitory Concentration (MIC) values ranging from 31.25 to 250 µg/mL. While the three SM and CC blends were not more active than the EOs tested individually, they exhibited remarkably high antileishmanial activity, with IC50 values ranging between 3.12 and 7.04 µg/mL, which is very similar to the IC50 of amphotericin B (positive control).
PubMed: 38899851
DOI: 10.1002/cbdv.202401076 -
Future Medicinal Chemistry Jun 2024Zinc salicylaldimines may act as multidrug agents. Three zinc salicylaldimines and respective ligands - were examined for antimicrobial/anticancer drug action and...
Zinc salicylaldimines may act as multidrug agents. Three zinc salicylaldimines and respective ligands - were examined for antimicrobial/anticancer drug action and was structurally analyzed (tetrahedral, triclinic). Against two fungi, inhibited with 12 mm (21 mm for amphotericin B). Among four bacteria, two ligands inhibited and (9-10 mm), but the complexes inhibited all bacteria with 10-14 mm (21-26 mm for ampicillin). The half-maximal inhibitory concentrations for the ligands, complexes and doxorubicin were 195.5-310.7, 22.18-70.05 and 9.66 μM against cancerous MCF-7 cells and 186.4-199.9, 14.95-18.87 and 36.42 μM against normal BHK cells. The complexation produced pronounced enhancement in the ligand antimicrobial/anticancer activities, despite these activities are moderate comparing with standards.
PubMed: 38899770
DOI: 10.1080/17568919.2024.2363672 -
Therapeutic Advances in Infectious... 2024Chronic pulmonary aspergillosis (CPA) is a challenging respiratory infection caused by the environmental fungus . CPA has a poor prognosis, with reported 1-year... (Review)
Review
Chronic pulmonary aspergillosis (CPA) is a challenging respiratory infection caused by the environmental fungus . CPA has a poor prognosis, with reported 1-year mortality rates ranging from 7% to 32% and 5-year mortality rates ranging from 38% to 52%. A comprehensive understanding of the pathogen, pathophysiology, risk factors, diagnosis, surgery, hemoptysis treatment, pharmacological therapy, and prognosis is essential to manage CPA effectively. In particular, drug resistance and cryptic species pose significant challenges. CPA lacks tissue invasion and has specific features such as aspergilloma. The most critical risk factor for the development of CPA is pulmonary cavitation. Diagnostic approaches vary by CPA subtype, with computed tomography (CT) imaging and IgG antibodies being key. Treatment strategies include surgery, hemoptysis management, and antifungal therapy. Surgery is the curative option. However, reported postoperative mortality rates range from 0% to 5% and complications range from 11% to 63%. Simple aspergilloma generally has a low postoperative mortality rate, making surgery the first choice. Hemoptysis, observed in 50% of CPA patients, is a significant symptom and can be life-threatening. Bronchial artery embolization achieves hemostasis in 64% to 100% of cases, but 50% experience recurrent hemoptysis. The efficacy of antifungal therapy for CPA varies, with itraconazole reported to be 43-76%, voriconazole 32-80%, posaconazole 44-61%, isavuconazole 82.7%, echinocandins 42-77%, and liposomal amphotericin B 52-73%. Combinatorial treatments such as bronchoscopic triazole administration, inhalation, or direct injection of amphotericin B at the site of infection also show efficacy. A treatment duration of more than 6 months is recommended, with better efficacy reported for periods of more than 1 year. In anticipation of improvements in CPA management, ongoing advances in basic and clinical research are expected to contribute to the future of CPA management.
PubMed: 38899061
DOI: 10.1177/20499361241253751