Monitoring and use of antimycotic (micafungin) for systemic use provided by the pharmacy of Marsala Hospital, Italy

Micafungin is an antimycotic drug and represents an important addition to the available therapies for the treatment of systemic fungal infections. Micafungin is used: in the treatment of invasive candidiasis, oesophageal and prophylaxis of <em>Candida</em> infections. It inhibits, in a non-competitive way, the synthesis of 1,3-β-D-glucan, a component of fungal cell wall and is rapidly distributed into the tissues. It has a high-rate respectful bond with plasma protein, which is independent from the concentration of the drug. It is metabolized through the liver, being not subject to intense metabolic transformations until the excretion. There is no evidence of systemic accumulation after repeated use. The steady-state is reached in 4-5 days. Medical records examined at the pharmacy of Marsala Hospital highlight that, from 01/06/2014 to 01/08/2014, in this hospital 12 vials were used by the hospitalized patients in the Department of Intensive Care: 8 patients between 75 and 83 years old had a body weight (BW) higher than 40 kg; 3 patients between 40 and 60 years of age had a BW higher than 40 kg, and one 17 year-old patient had a BW of 40 kg. Two patients needed a dose increase, while for the other 10 patients the first dose resulted sufficient. Mycamine<sup>®</sup> was used for the treatment of hypovolemic post-operative shock. The most recorded adverse reactions were anemia, hypokalemia, hypomagnesemia, phlebitis, nausea, liver problems. Given the different weight of the subjects, the dosage was different.

Download Full-text

Gingerol Derivatives as 14α-demethylase Inhibitors: Design and Development of Natural, Safe Antifungals for Immune-compromised Patients

Letters in Drug Design & Discovery ◽

10.2174/1570180816666191025105752 ◽

2020 ◽

Vol 17 (7) ◽

pp. 918-928

Author(s):

Sweta Sharma ◽

Arpita Yadav

Keyword(s):

Cell Membranes ◽

Fungal Infections ◽

Dynamics Simulation ◽

Stable Complex ◽

Active Site Residues ◽

Design And Development ◽

Triazole Derivative ◽

Fungal Cell ◽

Term Administration ◽

Compromised Patients

Background: : Currently, clinically used drugs for internal fungal infections have severe side effects. Patients suffering from severe fungal infections and those at a constant risk of developing such infections require long-term administration of safe antifungals. Objective: : This work deals with the design and development of safe, non-toxic antifungals derived from natural compounds for immune-compromised patients, such as HIV patients, who are at a constant risk of developing internal fungal infections. Methods: : Molecular modeling, docking and molecular dynamics simulation studies were performed on the main constituents of ginger and their derivatives to study their capability to inhibit 14α- demethylase enzyme. Results: : Ergosterol is the key component of the fungal cell membrane for its integrity and rigidity, synthesized from lanosterol catalyzed by 14α-demethylase enzyme. In our studies, it is determined that 6-gingerol, 6-paradol, 6-shogaol and their imidazole and triazole derivatives can inhibit the synthesis of ergosterol thus weakening the fungal cell membranes. The triazole derivative of 6-gingerol forms enhanced binding interactions with the active site residues of 14α-demethylase, carries an affinity for catalytically required cofactor heme and forms a stable complex with time without the probability of premature expulsion. Thus, this compound inhibits the formation of ergosterol leading to weakened fungal cell membranes and eventually death of fungal cells. Conclusion: : The triazole derivative of 6-gingerol is recommended as a lead compound for the development of non-toxic antifungals.

Download Full-text

Small-head metal on metal total hip arthroplasty is associated with a high rate of complication and reoperation at mid-term follow-up

SAGE Open Medicine ◽

10.1177/20503121211014707 ◽

2021 ◽

Vol 9 ◽

pp. 205031212110147

Author(s):

Nobuhiko Sumiyoshi ◽

Kazuhiro Oinuma ◽

Yoko Miura

Keyword(s):

Total Hip Arthroplasty ◽

Hip Arthroplasty ◽

Adverse Reactions ◽

Small Diameter ◽

High Rate ◽

Metal Debris ◽

Total Hip ◽

Metal On Metal ◽

Small Head

Background: Adverse reactions to metal debris are significant complications after metal-on-metal total hip arthroplasty. Recently, late appearances of adverse reactions to metal debris and subsequent need for reoperations have been reported with small-diameter head metal-on-metal devices. We retrospectively investigated mid-term clinical outcomes of small-head metal-on-metal total hip arthroplasty. Methods: We reviewed 159 hips in 139 patients who had a small-head metal-on-metal total hip arthroplasty (M2a Taper; Biomet, Warsaw, IN) with a minimum 5-year follow-up and documented postoperative complications. Results: Focal osteolysis in either the femur or acetabulum was observed in 12 hips (7.5%, 44 months after surgery on average), with pseudotumor observed in 8 hips (5%, 120 months after surgery on average). Four hips (2.5%) had dislocations (84 months after surgery on average) and six hips (3.8%, 122 months after surgery on average) underwent reoperation. Conclusion: Small-head metal-on-metal total hip arthroplasty is associated with a high degree of complications at mid-term follow-up period. Considering this, we discourage the use of metal-on-metal total hip arthroplasty regardless of head size.

Download Full-text

Spatial Distribution of a Porphyrin-Based Photosensitizer Reveals Mechanism of Photodynamic Inactivation of Candida albicans

Frontiers in Medicine ◽

10.3389/fmed.2021.641244 ◽

2021 ◽

Vol 8 ◽

Author(s):

Thomas Voit ◽

Fabian Cieplik ◽

Johannes Regensburger ◽

Karl-Anton Hiller ◽

Anita Gollmer ◽

...

Keyword(s):

Cell Wall ◽

Candida Albicans ◽

Fungal Infections ◽

Cell Envelope ◽

Antimicrobial Photodynamic Therapy ◽

Fungal Cell ◽

Before And After ◽

Antifungal Action ◽

Complete Cell ◽

Further Development

The antimicrobial photodynamic therapy (aPDT) is a promising approach for the control of microbial and especially fungal infections such as mucosal mycosis. TMPyP [5,10,15, 20-tetrakis(1-methylpyridinium-4-yl)-porphyrin tetra p-toluenesulfonate] is an effective photosensitizer (PS) that is commonly used in aPDT. The aim of this study was to examine the localization of TMPyP in Candida albicans before and after irradiation with visible light to get information about the cellular mechanism of antifungal action of the photodynamic process using this PS. Immediately after incubation of C. albicans with TMPyP, fluorescence microscopy revealed an accumulation of the PS in the cell envelope. After irradiation with blue light the complete cell showed red fluorescence, which indicates, that aPDT is leading to a damage in the cell wall with following influx of PS into the cytosol. Incubation of C. albicans with Wheat Germ Agglutinin (WGA) could confirm the cell wall as primary binding site of TMPyP. The finding that the porphyrin accumulates in the fungal cell wall and does not enter the interior of the cell before irradiation makes it unlikely that resistances can emerge upon aPDT. The results of this study may help in further development and modification of PS in order to increase efficacy against fungal infections such as those caused by C. albicans.

Download Full-text

Candida Coinfection among Patients with Pulmonary tuberculosis in the World; A Systematic Review and Meta-analysis of Cross-Sectional Studies

10.21203/rs.2.14804/v1 ◽

2019 ◽

Author(s):

Mehran Ghazalibina ◽

Ali Shakerimoghaddam ◽

Azad Khaledi

Keyword(s):

Systematic Review ◽

Pulmonary Tuberculosis ◽

Fungal Infections ◽

Secondary Infection ◽

Meta Analysis ◽

High Rate ◽

Candida Spp ◽

Cross Sectional ◽

Cross Sectional Studies ◽

Early Diagnose

Abstract Background Diagnosis of fungal co-infections in patients with pulmonary tuberculosis has critical importance. In this review, we aimed to determine the prevalence of candida coinfection in patients with pulmonary tuberculosis.Methods The present systematic review of cross-sectional studies was conducted based on the Preferred Reporting Items for Systematic reviews and Meta-analysis (PRISMA) Protocol. Studies published online in English from January 2001 to March 2019 were assessed. Literature search was performed in Web of Science, MEDLINE/PubMed, and Scopus databases using keywords combinations of “pulmonary fungal”, “pulmonary coinfection”, OR “pulmonary mycosis”, “pulmonary fungal infections/agents”, OR “polymicrobial infection”, OR “secondary infection”, OR “mixed infections”, “pulmonary candidiasis”, “fungi coinfection”, “fungal co-colonization”, AND “pulmonary tuberculosis”, OR “pulmonary TB”. Data was analyzed using Comprehensive Meta-Analysis software. Heterogeneity between studies was evaluated by Cochran's Q, and I 2 tests.Results The pooled global prevalence of candida coinfection among patients with pulmonary tuberculosis was 25.7% (95% CI: 23.7-27.9). C. albicans was the most prevalent Candida spp. with a pooled prevalence of 65.8% (95% CI: 54.3-75.7). Risk factors of candida coinfection included smoking, diabetes, advanced age, and low body mass index.Conclusion The present review showed the high rate of candida coinfection among patients suffering from pulmonary tuberculosis. Adequate measures are necessary to early diagnose and treat these infections.

Download Full-text

Rapid determination of binding parameters of chitin binding domains using chitin-coated quartz crystal microbalance sensor chips

The Analyst ◽

10.1039/c8an01453a ◽

2018 ◽

Vol 143 (21) ◽

pp. 5255-5263 ◽

Cited By ~ 2

Author(s):

Stephan Vogt ◽

Marco Kelkenberg ◽

Tanja Nöll ◽

Benedikt Steinhoff ◽

Holger Schönherr ◽

...

Keyword(s):

Cell Walls ◽

Quartz Crystal ◽

Fungal Infections ◽

Rapid Determination ◽

Binding Parameters ◽

Fungal Cell ◽

Binding Domains ◽

Quartz Crystal Microbalance Sensor ◽

Fungal Cell Walls

Chitin present in fungal cell walls has been considered as a diagnostic polymer for the detection of fungal infections.

Download Full-text

ESTIMATION OF POSSIBILITY OF APPLICATION OF TIGERASE® (DORNASE ALFA) DRUG ON THE RESULTS OF A MULTICENTER SCIENTIFIC PROGRAM OF POST-MARKETING USE OF THE DRUG

PEDIATRIA Journal named after G N SPERANSKY ◽

10.24110/0031-403x-2021-100-3-218-226 ◽

2021 ◽

Vol 100 (3) ◽

pp. 218-226

Author(s):

E.I. Kondratyeva ◽

◽

V.V. Shadrina ◽

E.G. Furman ◽

A.Yu. Voronkova ◽

...

Keyword(s):

Medical Records ◽

Adverse Reactions ◽

Clinical Manifestations ◽

Scientific Program ◽

Bronchial Secretion ◽

Patient Complaints ◽

Clinical Observations ◽

Number Of Patients ◽

Gender And Age ◽

Post Marketing

The aim of the program was to study the tolerability of Tigerase® in patients with cystic fibrosis (CF) of all ages in rutine clinical practice. Study design: retrospective open uncontrolled comparative multicenter solid. Materials and methods of research: retrospective data of clinical observations were collected from medical records of patients with CF on the use of Tigerase®. Results: therapy with Tigerase® was well tolerated by 668 (93,4%) of 715 patients included in the study. In 47 (6,6%) patients, 127 adverse reactions (ADRs) associated with the use of Tigerase® were recorded. ADRs from the respiratory system were the most common. Of these, 24 (3,4%) were coughing and 10 (1,4%) had increased viscosity of bronchial secretion. Among all patients included in the study, the proportion of patients in whom ADRs were registered based on clinical manifestations (3,9%) did not differ statistically significantly from the proportion of patients in whom ADRs were recorded based on complaints only (2,8%) (p=0,30). The distribution of ADRs by the source of registration and place of residence of patients did not depend on their gender and age. Registration of ADRs in different regions of the country differed statistically significantly both in frequency and in the source of detection (p<0,001). ADRs were not recorded in several regions, and the largest number of ADRs were registered in patients living in Moscow, and most of them were based only on patient complaints. 22 patients (47% of the number of patients with ADR) had medical commissions for ADR, and only in 8 (17% of the number of patients with ADR) of them had expertise of specialists with experience in the treatment of patients with CF. In 29 patients (62% of the number of patients with ADR), the development of ADR did not require cessation of the Tigerase® therapy. Conclusion: in the majority of CF patients (93,4%) tolerated the Tigerase® therapy well.

Download Full-text

Molecular Modeling Study for the Evaluation of Natural Compounds as Potential Lanosterol 14α-demethylase Inhibitors

Letters in Drug Design & Discovery ◽

10.2174/1570180818666211027114007 ◽

2021 ◽

Vol 18 ◽

Author(s):

Nidhi Rani ◽

Randhir Singh ◽

Praveen Kumar

Keyword(s):

Molecular Docking ◽

Molecular Modeling ◽

Fungal Infections ◽

Docking Study ◽

Natural Compounds ◽

Docking Studies ◽

Prosthetic Group ◽

Fungal Cell ◽

Adme Profile ◽

Target Enzyme

Background: Candida albicans is one of the most important causes of fatal fungal infections. Ergosterol, the main sterol in the fungal cell membrane, is the resultant product of Lanosterol in the presence of the enzyme Lanosterolα-demethylase (Cytochrome P450DM). This enzyme is the target enzyme of azole antifungal agents. Aim: To evaluate the antifungal potency of some of the natural compounds via molecular modeling and Absorption, Distribution, Metabolism and Excretion (ADME) study. Method: The study involved the selection and modeling of the target enzyme, followed by the refinement of the model using molecular dynamic simulation. The modelled structure of the enzyme was validated using the Ramachandran plot and Sequence determination technique. A series of natural compounds was evaluated for cytochrome P450 inhibitory activity using molecular docking studies. The structures of compounds were prepared using a Chem sketch, and molecular docking was performed using Molergo Virtual Docker (MVD) program. Results: The docking study indicated that all the natural compounds have interactivity with protein residue of 14α-demethylase, and the heme prosthetic group and water molecules are present at the active site. The data were also correlated with the synthetic compounds that were experimentally inactive against the fungus and had a low docking score. The compounds with a high dock score were further screened for Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) profile, and it was predicted that these compounds can be used as lead with a good ADME profile and low toxicity. Conclusion: The natural compound, i.e., curcumin, can easily be used further for lead optimization.

Download Full-text

Profile of blood donors who presented adverse reactions to the donation

Revista Brasileira de Enfermagem ◽

10.1590/0034-7167-2018-0305 ◽

2019 ◽

Vol 72 (1) ◽

pp. 81-87

Author(s):

Melissa Orlandi Honório Locks ◽

Nádia Chiodelli Salum ◽

Beatriz Steingreber de Barros ◽

Eliane Matos ◽

Jane Cristina Anders ◽

...

Keyword(s):

Blood Donors ◽

Adverse Reactions ◽

Descriptive Statistics ◽

High Rate ◽

Total Blood ◽

Cross Sectional ◽

Level Of Education ◽

Sociodemographic Profile ◽

Care Practices ◽

Complete Average

ABSTRACT Objective: identify the adverse reactions presented by blood donors and outline their sociodemographic profile. Method: a quantitative, cross-sectional retrospective study of 780 records of blood donors from a public hemocenter in the southern region of Brazil, from December 2015 to January 2016. For the analysis the descriptive statistics was used. Results: it was identified that throughout 12 months, the total blood donors corresponded to 27,300 people, in which 780 developed at least one reaction. They were characterized by female and recurrent donors, single, with a complete average level of education, ranging from 16 to 30 years, who triggered between 1 and 3 reactions. Mild reactions were more frequent, followed by moderate and severe reactions. Conclusion: There is a high rate of adverse reactions from donors emphasizing the need for changes in hemotherapy care practices.

Download Full-text

Effect of Infusion Rate on Amphotericin B-Associated Febrile Reactions

Drug Intelligence & Clinical Pharmacy ◽

10.1177/106002808802201005 ◽

1988 ◽

Vol 22 (10) ◽

pp. 769-772 ◽

Cited By ~ 26

Author(s):

John D. Cleary ◽

Daniel Weisdorf ◽

Courtney V. Fletcher

Keyword(s):

Bone Marrow ◽

Amphotericin B ◽

Bone Marrow Transplant ◽

Cardiac Disease ◽

Infusion Rate ◽

Adverse Reactions ◽

Fungal Infections ◽

Marrow Transplant ◽

Transplant Recipients ◽

Axillary Temperature

Our objective was to prospectively study febrile and chill reactions associated with two amphotericin B (AB) infusion rates, slow (2-hour) versus rapid (45 minute). Seventeen consenting bone marrow transplant recipients in whom AB was to be initiated for documented or suspected fungal infections were recruited. After standardized premedication, patients received eight daily AB infusions (0.5 mg/kg/d, concentration 0.25 mg/ml). Rate was assigned using a randomized, crossover pair design. Axillary temperature, chills, and meperidine dose required to resolve chills were monitored for each infusion. For the first pair of infusions, fever (defined as a rise of 1 °C) occurred frequently, in 12 of 17 (70.5 percent) and 13 of 17 patients (76.4 percent), with a mean rise of 1.7 °C (range 1.1–3.7) and 1.7 °C (1.1–3.5) degrees for the 45-minute and 2-hour infusions, respectively (p > 0.10). Chills were observed in 15 of 17 (88.2 percent) and 14 of 17 (82.3 percent) recipients of the 45-minute and 2-hour infusions, respectively. The time of onset (p > 0.10) and the duration of chills (p = 0.08) were similar for both infusion rates. Meperidine requirements for rapid and slow infusions were similar as well (p = 0.12). These data suggest that for patients free of preexisting renal and cardiac disease, rapid AB infusions are well tolerated and produce adverse reactions (fever and chills) similar in nature and severity to slower infusions.

Download Full-text

Targeting adhesion in fungal pathogen Candida albicans

Future Medicinal Chemistry ◽

10.4155/fmc-2020-0052 ◽

2020 ◽

Author(s):

Harlei Martin ◽

Kevin Kavanagh ◽

Trinidad Velasco-Torrijos

Keyword(s):

Candida Albicans ◽

Fungal Infections ◽

Initial Step ◽

Infection Process ◽

Host Cells ◽

Fungal Cell ◽

Receptor Interactions ◽

Genes Encoding ◽

Invasive Infections ◽

Wall Components

Fungal infections with increasing resistance to conventional therapies are a growing concern. Candida albicans is a major opportunistic yeast responsible for mucosal and invasive infections. Targeting the initial step of the infection process (i.e., C. albicans adhesion to the host cell) is a promising strategy. A wide variety of molecules can interfere with adhesion processes via an assortment of mechanisms. Herein, we focus on how small molecules disrupt biosynthesis of fungal cell wall components and membrane structure, prevent the localization of GPI-anchor proteins, inhibit production of enzymes involved in adhesion, downregulate genes encoding adhesins and competitively inhibit receptor interactions. As a result, adhesion of C. albicans to host cells is reduced, paving the way to new classes of antifungal agents.

Download Full-text