scholarly journals Activities of voriconazole, itraconazole and amphotericin B in vitro against 590 moulds from 323 patients in the voriconazole Phase III clinical studies

2008 ◽  
Vol 61 (3) ◽  
pp. 616-620 ◽  
Author(s):  
A. Espinel-Ingroff ◽  
E. Johnson ◽  
H. Hockey ◽  
P. Troke
Keyword(s):  
Amphotericin B ◽  
Clinical Studies ◽  
Phase Iii

An update on cefepime and its future role in combination with novel β-lactamase inhibitors for MDR Enterobacterales and Pseudomonas aeruginosa

2020 ◽  
Author(s):  
Burcu Isler ◽  
Patrick Harris ◽  
Adam G Stewart ◽  
David L Paterson
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Clinical Studies ◽  
Bacterial Infections ◽  
Animal Studies ◽  
Wide Spectrum ◽  
Clinical Development ◽  
Phase Iii ◽  
Lactam Antibiotic ◽  
Tract Infections

Abstract Cefepime, a wide-spectrum β-lactam antibiotic, has been in use for the treatment of serious bacterial infections for almost 25 years. Since its clinical development, there has been a dramatic shift in its dosing, with 2 g every 8 hours being preferred for serious infections to optimize pharmacokinetic/pharmacodynamic considerations. The advent of ESBLs has become a threat to its ongoing use, although future coadministration with β-lactamase inhibitors (BLIs) under development is an area of intense study. There are currently four new cefepime/BLI combinations in clinical development. Cefepime/zidebactam is generally active against MBL-producing Enterobacterales and Pseudomonas aeruginosa, in vitro and in animal studies, and cefepime/taniborbactam has activity against KPC and OXA-48 producers. Cefepime/enmetazobactam and cefepime/tazobactam are potential carbapenem-sparing agents with activity against ESBLs. Cefepime/enmetazobactam has completed Phase III and cefepime/taniborbactam is in Phase III clinical studies, where they are being tested against carbapenems or piperacillin/tazobactam for the treatment of complicated urinary tract infections. While these combinations are promising, their role in the treatment of MDR Gram-negative infections can only be determined with further clinical studies.

scholarly journals In Vitro Activities of Isavuconazole and Other Antifungal Agents against Candida Bloodstream Isolates

2007 ◽  
Vol 51 (5) ◽  
pp. 1818-1821 ◽  
Author(s):  
H. Seifert ◽  
U. Aurbach ◽  
D. Stefanik ◽  
O. Cornely
Keyword(s):  
Amphotericin B ◽  
Antifungal Agents ◽  
Tertiary Care ◽  
Common Species ◽  
University Hospital ◽  
Phase Iii ◽  
Highly Active ◽  
Fluconazole Resistant ◽  
Resistant Strains

ABSTRACT Isavuconazole is the active component of the new azole antifungal agent BAL8557, which is entering phase III clinical development. This study was conducted to compare the in vitro activities of isavuconazole and five other antifungal agents against 296 Candida isolates that were recovered consecutively from blood cultures between 1995 and 2004 at a tertiary care university hospital. Microdilution testing was done in accordance with CLSI (formerly NCCLS) guideline M27-A2 in RPMI-1640 MOPS (morpholinepropanesulfonic acid) broth. The antifungal agents tested were amphotericin B, flucytosine, fluconazole, itraconazole, voriconazole, and isavuconazole. C. albicans was the most common species, representing 57.1% of all isolates. There was no trend found in favor of non-Candida albicans species over time. In terms of MIC50s, isavuconazole was more active (0.004 mg/liter) than amphotericin B (0.5 mg/liter), itraconazole (0.008 mg/liter), voriconazole (0.03 mg/liter), flucytosine (0.125 mg/liter), and fluconazole (8 mg/liter). For isavuconazole, MIC50s/MIC90s ranged from 000.2/0.004 mg/liter for C. albicans to 0.25/0.5 mg/liter for C. glabrata. Two percent of isolates (C. glabrata and C. krusei) were resistant to fluconazole; C. albicans strains resistant to fluconazole were not detected. There were only two isolates with MICs for isavuconazole that were >0.5 mg/liter: both were C. glabrata isolates, and the MICs were 2 and 4 mg/liter, respectively. In conclusion, isavuconazole is highly active against Candida bloodstream isolates, including fluconazole-resistant strains. It was more active than itraconazole and voriconazole against C. albicans and C. glabrata and appears to be a promising agent against systemic Candida infections.

scholarly journals THE CONCEPT AND MANAGEMENT OF WAJAUL MAFASIL IN UNANI MEDICINE

2021 ◽  
pp. 7-13
Author(s):  
ZEHRA ZAIDI
Keyword(s):  
Side Effects ◽  
Clinical Studies ◽  
Pharmacological Therapy ◽  
Phase Iii ◽  
Herbal Drugs ◽  
Effective Management ◽  
Unani Medicine ◽  
Herbal Medications ◽  
Classical Knowledge

More than 54 million Americans suffer from some form of arthritis and 23.7 million are limited in their usual activity, primarily due to pain. The study aims to highlight the concept of Arthralgia and the potential of its management in Unani Medicines. Osteoarthritis (OA) is a slowly progressive condition with a variable prognosis. In general, predicting the prognosis in patients with OA is difficult. However, pharmacological therapy can be associated with serious side effects and high costs. Therefore, alternative therapies have been under investigation. Herbal medications have shown the potential for safe and effective management of arthritis. The Unani Medicine is a rich source of classical knowledge on arthritis. OA has been mentioned as Wajaul Mafasil Balghami/Saudawi, and Unani Physicians has been treating this disease successfully with mostly single herbal drugs and their compound formulations for centuries. It has been revealed through animal, in vitro, and clinical studies that most of the single and compound Unani formulations are safe, without any side effects, and effective in OA, especially gout and rheumatoid arthritis. There is a need to conduct studies at Phase III level after analyzing 2nd Phase clinical studies of Unani medicine, so a promising safe, economic, and effective treatment can be provided to the ailing society for OA.

In vitro activity of BMS-181184 compared with those of fluconazole and amphotericin B against various candida spp.

1996 ◽  
Vol 40 (9) ◽  
pp. 2229-2231 ◽  
Author(s):  
H M Wardle ◽  
D Law ◽  
D W Denning
Keyword(s):  
High Resolution ◽  
Amphotericin B ◽  
Clinical Studies ◽  
Antifungal Agents ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Candida Spp ◽  
New Class ◽  
Microdilution Method

We compared the in vitro activity of BMS-181184, the first compound of a new class of antifungal agents, the pradimicins, with those of fluconazole and amphotericin B against 64 clinical isolates of Candida species. MICs were determined by a microdilution method with high resolution medium for BMS-181184 and fluconazole and antibiotic medium no. 3 with 2% glucose for amphotericin B. MICs of BMS-181184 for all yeasts were in the range of 0.78 to 12.5 micrograms/ml. BMS-181184 was active against isolates resistant to other antifungal agents, consistent with a novel mode of action. Minimum fungicidal concentrations for 16 isolates showed that BMS-181184 was fungicidal. Clinical studies are now required to confirm its activity.

scholarly journals Hepatitis D virus in 2021: virology, immunology and new treatment approaches for a difficult-to-treat disease

Gut ◽  
2021 ◽  
pp. gutjnl-2020-323888
Author(s):  
Stephan Urban ◽  
Christoph Neumann-Haefelin ◽  
Pietro Lampertico
Keyword(s):  
Hepatitis B ◽  
Hepatitis B Surface Antigen ◽  
Treatment Strategies ◽  
Phase Iii ◽  
Interferon Α ◽  
T Cell Epitopes ◽  
The European Union ◽  
Hepatitis D ◽  
Hepatitis D Virus

Approximately 5% of individuals infected with hepatitis B virus (HBV) are coinfected with hepatitis D virus (HDV). Chronic HBV/HDV coinfection is associated with an unfavourable outcome, with many patients developing liver cirrhosis, liver failure and eventually hepatocellular carcinoma within 5–10 years. The identification of the HBV/HDV receptor and the development of novel in vitro and animal infection models allowed a more detailed study of the HDV life cycle in recent years, facilitating the development of specific antiviral drugs. The characterisation of HDV-specific CD4+ and CD8+T cell epitopes in untreated and treated patients also permitted a more precise understanding of HDV immunobiology and possibly paves the way for immunotherapeutic strategies to support upcoming specific therapies targeting viral or host factors. Pegylated interferon-α has been used for treating HDV patients for the last 30 years with only limited sustained responses. Here we describe novel treatment options with regard to their mode of action and their clinical effectiveness. Of those, the entry-inhibitor bulevirtide (formerly known as myrcludex B) received conditional marketing authorisation in the European Union (EU) in 2020 (Hepcludex). One additional drug, the prenylation inhibitor lonafarnib, is currently under investigation in phase III clinical trials. Other treatment strategies aim at targeting hepatitis B surface antigen, including the nucleic acid polymer REP2139Ca. These recent advances in HDV virology, immunology and treatment are important steps to make HDV a less difficult-to-treat virus and will be discussed.

scholarly journals Invasive infections with Purpureocillium lilacinum: clinical characteristics and outcome of 101 cases from FungiScope® and the literature

2021 ◽  
Author(s):  
Rosanne Sprute ◽  
Jon Salmanton-García ◽  
Ertan Sal ◽  
Xhorxha Malaj ◽  
Zdeněk Ráčil ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Organ Transplant ◽  
Solid Organ ◽  
Intrinsic Resistance ◽  
Breakthrough Infection ◽  
Purpureocillium Lilacinum ◽  
Invasive Infections ◽  
Oncological Diseases ◽  
Overall Mortality

Abstract Objectives To provide a basis for clinical management decisions in Purpureocillium lilacinum infection. Methods Unpublished cases of invasive P. lilacinum infection from the FungiScope® registry and all cases reported in the literature were analysed. Results We identified 101 cases with invasive P. lilacinum infection. Main predisposing factors were haematological and oncological diseases in 31 cases (30.7%), steroid treatment in 27 cases (26.7%), solid organ transplant in 26 cases (25.7%), and diabetes mellitus in 19 cases (18.8%). The most prevalent infection sites were skin (n = 37/101, 36.6%) and lungs (n = 26/101, 25.7%). Dissemination occurred in 22 cases (21.8%). Pain and fever were the most frequent symptoms (n = 40/101, 39.6% and n = 34/101, 33.7%, respectively). Diagnosis was established by culture in 98 cases (97.0%). P. lilacinum caused breakthrough infection in 10 patients (9.9%). Clinical isolates were frequently resistant to amphotericin B, whereas posaconazole and voriconazole showed good in vitro activity. Susceptibility to echinocandins varied considerably. Systemic antifungal treatment was administered in 90 patients (89.1%). Frequently employed antifungals were voriconazole in 51 (56.7%) and itraconazole in 26 patients (28.9%). Amphotericin B treatment was significantly associated with high mortality rates (n = 13/33, 39.4%, P = <0.001). Overall mortality was 21.8% (n = 22/101) and death was attributed to P. lilacinum infection in 45.5% (n = 10/22). Conclusions P. lilacinum mainly presents as soft-tissue, pulmonary or disseminated infection in immunocompromised patients. Owing to intrinsic resistance, accurate species identification and susceptibility testing are vital. Outcome is better in patients treated with triazoles compared with amphotericin B formulations.

scholarly journals Polishing the Therapy of Onychomycosis Induced by Candida spp.: Amphotericin B–Loaded Nail Lacquer

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 784
Author(s):  
Aleph M. S. Souza ◽  
Renato C. A. Ribeiro ◽  
Gleyse K. L. O. Pinheiro ◽  
Francisco I. Pinheiro ◽  
Wógenes N. Oliveira ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Ex Vivo ◽  
Drug Loading ◽  
Drug Bioavailability ◽  
Candida Spp ◽  
Drying Time ◽  
Analytical Method Validation ◽  
Nail Lacquer ◽  
In Vitro Adhesion

Onychomycosis induced by Candida spp. has several limitations regarding its treatment. Nail lacquers display the potential to overcome these drawbacks by providing therapeutic compliance and increasing local drug bioavailability. Thus, this work aimed to produce a nail lacquer loaded with Amphotericin B (AmB) and evaluate its performance. The AmB-loaded nail lacquer was produced and preliminarily characterized. An AmB quantification method was developed. Stability, drug release, permeability and anti-Candida activity assays were conducted. The analytical method validation met the acceptance criteria. The drug loading efficiency was 100% (0.02 mg/g of total product), whereas the AmB stability was limited to ≅ 7 days (≅ 90% remaining). The nail lacquer displayed a drying time of 187 s, non-volatile content of around 20%w/w, water-resistance of approximately 2%w/w of weight loss and satisfactory in vitro adhesion. Moreover, the in vitro antifungal activity against different Candida spp. strains was confirmed. The AmB release and the ex vivo permeability studies revealed that AmB leaves the lacquer and permeates the nail matrix in 47.76 ± 0.07% over 24 h. In conclusion, AmB-loaded nail lacquer shows itself as a promising extemporaneous dosage form with remarkable anti-Candida activity related to onychomycosis.

scholarly journals Clinical impact of subclonal EGFR T790M mutations in advanced-stage EGFR-mutant non-small-cell lung cancers

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Tereza Vaclova ◽  
Ursula Grazini ◽  
Lewis Ward ◽  
Daniel O’Neill ◽  
Aleksandra Markovets ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Progression Free Survival ◽  
Small Cell ◽  
Phase Iii ◽  
Advanced Stage ◽  
Small Cell Lung ◽  
Nsclc Patients ◽  
The Impact ◽  
Egfr T790m

AbstractAdvanced non-small-cell lung cancer (NSCLC) patients with EGFR T790M-positive tumours benefit from osimertinib, an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). Here we show that the size of the EGFR T790M-positive clone impacts response to osimertinib. T790M subclonality, as assessed by a retrospective NGS analysis of 289 baseline plasma ctDNA samples from T790M‐positive advanced NSCLC patients from the AURA3 phase III trial, is associated with shorter progression-free survival (PFS), both in the osimertinib and the chemotherapy-treated patients. Both baseline and longitudinal ctDNA profiling indicate that the T790M subclonal tumours are enriched for PIK3CA alterations, which we demonstrate to confer resistance to osimertinib in vitro that can be partially reversed by PI3K pathway inhibitors. Overall, our results elucidate the impact of tumour heterogeneity on response to osimertinib in advanced stage NSCLC patients and could help define appropriate combination therapies in these patients.

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