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Antifungal agents slideshare

Antifungal agents slideshare

antifungal agents slideshare

The increased use of antibacterial and antifungal agents in recent years has resulted in the development of resistance to these drugs. The significant clinical implication of resistance has led to heightened interest in the study of antimicrobial resistance from different angles.

Areas addressed include mechanisms underlying this resistance, improved methods to detect resistance when it occurs, alternate options for the treatment of infections caused by resistant organisms, and strategies to prevent and control the emergence and spread of resistance.

In this review, the mode of action of antifungals and their mechanisms of resistance are discussed. Additionally, an attempt is made to discuss the correlation between fungal and bacterial resistance.

Antifungals can be grouped into three classes based on their site of action: azoles, which inhibit the synthesis of ergosterol the main fungal sterol ; polyenes, which interact with fungal membrane sterols physicochemically; and 5-fluorocytosine, which inhibits macromolecular synthesis.

Many different types of mechanisms contribute to the development of resistance to antifungals. These mechanisms include alteration in drug target, alteration in sterol biosynthesis, reduction in the intercellular concentration of target enzyme, and overexpression of the antifungal drug target.

Although the comparison between the mechanisms of resistance to antifungals and antibacterials is necessarily limited by several factors defined in the review, a correlation between the two exists. For example, modification of enzymes which serve as targets for antimicrobial action and the involvement of membrane pumps in the extrusion of drugs are well characterized in both the eukaryotic and prokaryotic cells.

The past decade has witnessed a significant increase in the prevalence of resistance to antibacterial and antifungal agents. Resistance to antimicrobial agents has important implications for morbidity, mortality and health care costs in U. Hence, substantial attention has been focused on developing a more detailed understanding of the mechanisms of antimicrobial resistance, improved methods to detect resistance when it occurs, new antimicrobial options for the treatment of infections caused by resistant organisms, and methods to prevent the emergence and spread of resistance in the first place.

Most of this attention has been devoted to the study of antibiotic resistance in bacteria for several reasons: i bacterial infections are responsible for the bulk of community-acquired and nosocomial infections; ii the large and expanding number of antibacterial classes offers a more diverse range of resistance mechanisms to study; and iii the ability to move bacterial resistance determinants into standard well-characterized bacterial strains facilitates the detailed study of molecular mechanisms of resistance in bacterial species.

The study of resistance to antifungal agents has lagged behind that of antibacterial resistance for several reasons. Perhaps most importantly, fungal diseases were not recognized as important pathogens until relatively recently 2 For example, the annual death rate due to candidiasis was steady between and about Sincethis rate increased significantly in association with several changes in medical practice, including more widespread use of therapies that depress the immune system, the frequent and often indiscriminate use of broad-spectrum antibacterial agents, the common use of indwelling intravenous devices, and the advent of chronic immunosuppressive viral infections such as AIDS.

These developments and the associated increase in fungal infections 5 intensified the search for new, safer, and more efficacious agents to combat serious fungal infections. For nearly 30 years, amphotericin B Fig. The approval of the imidazoles and the triazoles in late s and early s were major advances in our ability to safely and effectively treat local and systemic fungal infections. The high safety profile of triazoles, in particular fluconazole Fig.

Fluconazole has been used to treat in excess of 16 million patients, including overAIDS patients, in the United States alone since the launch of this drug a. Concomitant with this widespread use, there have been increasing reports of antifungal resistance The clinical impact of antifungal resistance has been recently reviewed Also, three excellent reviews concentrating on various aspects of antifungal resistance including clinical implications have been published recently 2786 Therefore, the clinical impact of resistance is not covered in this review.

Antifungal Drugs - PowerPoint PPT Presentation

Instead, our goal is to focus on the molecular mechanisms of antifungal resistance.Amphotericin B, an effective but relatively toxic drug, has long been the mainstay of antifungal therapy for invasive and serious mycoses.

However, newer potent and less toxic triazoles and echinocandins are now often recommended as first-line drugs for many invasive fungal infections. These drugs have markedly changed the approach to antifungal therapy, sometimes even allowing oral treatment of chronic mycoses. See also Overview of Fungal Infections. Some Adverse Effects. Conventional formulation: Acute infusion reactions, neuropathy, gastrointestinal GI upset, renal failure, anemia, thrombophlebitis, hearing loss, rash, hypokalemia, hypomagnesemia.

Candidiasisincluding candidemia. Mucosal and systemic candidiasis. Cryptococcal meningitis. Candidiasis systemic. Pancytopenia due to bone marrow toxicity, neuropathy, nausea, vomiting, hepatic and renal injury, colitis. Nausea, vomiting, hepatitis, QT shortening with no evidence of cardiac risk, infusion-related reactions. Histoplasmosisblastomycosiscoccidioidomycosissporotrichosis.

Hepatitis, GI upset, rash, headache, dizziness, hypokalemia, hypertension, edema, QT prolongation, heart failure. Histoplasmosisblastomycosisaspergillosis. Amphotericin B has been the mainstay of antifungal therapy for invasive and serious mycoses, but other antifungals eg, fluconazolevoriconazoleposaconazolethe echinocandins are now considered first-line drugs for many of these infections.

Although amphotericin B does not have good cerebrospinal fluid penetration, it is still effective for certain mycoses such as cryptococcal meningitis. For acute, life-threatening mycoses, amphotericin B deoxycholate may be started at 0.

It is usually given over 2 to 3 hours, although more rapid infusions over 20 to 60 minutes can be used in selected patients. However, more rapid infusions usually have no advantage.

Many patients experience chills, fever, nausea, vomiting, anorexia, headache, and, occasionally, hypotension during and for several hours after an infusion. Amphotericin B may also cause chemical thrombophlebitis when given via peripheral veins; a central venous catheter may be preferable. Pretreatment with acetaminophen or nonsteroidal anti-inflammatory drugs is often used; if these drugs are ineffective, hydrocortisone 25 to 50 mg or diphenhydramine 25 mg is sometimes added to the infusion or given as a separate IV bolus.

Often, hydrocortisone can be tapered and omitted during extended therapy. Severe chills and rigors can be relieved or prevented by meperidine 50 to 75 mg IV. Several lipid vehicles reduce the toxicity of amphotericin B particularly nephrotoxicity and infusion-related symptoms.

Two preparations are available:. Lipid formulations are preferred over conventional amphotericin B because they cause fewer infusion-related symptoms and less nephrotoxicity. Renal impairment is the major toxic risk of amphotericin B therapy. Amphotericin B is unique among nephrotoxic antimicrobial drugs because it is not eliminated appreciably via the kidneys and does not accumulate as renal failure worsens.

Acute nephrotoxicity can be reduced by aggressive IV hydration with saline before amphotericin B infusion; at least 1 L of normal saline should be given before amphotericin infusion. Mild to moderate renal function abnormalities induced by amphotericin B usually resolve gradually after therapy is completed. Amphotericin B also frequently suppresses bone marrow function, manifested primarily by anemia. Hepatotoxicity or other untoward effects are unusual. Azoles block the synthesis of ergosterol, an important component of the fungal cell membrane.

They can be given orally to treat chronic mycoses. The first such oral drug, ketoconazolehas been supplanted by more effective, less toxic triazole derivatives, such as fluconazoleisavuconazole, itraconazoleposaconazoleand voriconazole. Drug interactions can occur with all azoles but are less likely with fluconazole.

Antifungal Drugs

The drug interactions mentioned below are not intended as a complete listing; clinicians should refer to a specific drug interaction reference before using azole antifungal drugs. Drug interactions are common with azole antifungals; review all concurrent drug use before prescribing them.Micallef, S. Aliyu, R. Santos, N. Brown, D. Rosembert, D. Antifungal stewardship aims to promote the optimal use of antifungals through the careful selection of agents based on patient profile, target organism, toxicity, costs and the likelihood of emergence and spread of resistance.

We report on an observational prospective 12 month study conducted by an antifungal stewardship team targeting the use of echinocandins caspofungin and micafunginvoriconazole and liposomal amphotericin B in a tertiary referral hospital in the UK. One-hundred-and-seventy-three patients were reviewed on occasions.

Clinical advice was given and implemented during review of 45 Except for voriconazole, nearly half of all treatments reviewed were stopped or changed. Using a multidisciplinary team, antifungal stewardship can achieve significant improvements in patient management and it may reduce costs.

Antifungal stewardship refers to a systematic programme that promotes the optimal use of antifungals through the careful selection of agents based on patient profile, target organism, toxicity, costs and the likelihood of emergence and spread of resistance.

Antifungals have become an essential part of modern healthcare due to the increased incidence of invasive fungal infections linked to immunosuppression and the widespread use of invasive devices.

antifungal agents slideshare

In this study, we describe the clinical value and possible impacts on costs of a recently introduced antifungal stewardship programme ASP targeting patients receiving high-cost antifungals specifically liposomal amphotericin B, voriconazole, caspofungin and micafungin at our centre. In Julyan ASP was launched for all adult inpatients receiving high-cost antifungals liposomal amphotericin B, voriconazole, caspofungin and micafungin. An antifungal stewardship team comprising a consultant microbiologist and an antimicrobial pharmacist was formed for the purpose of delivering this programme.

The antimicrobial pharmacist C.

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Patients who were on therapy but had been discharged prior to review were nevertheless reviewed when possible. Data collected included patient demographics, indication for antifungal, primary diagnosis, antifungal, significant clinical results and types of interventions.

Mortality was calculated at day 28 and 3 months after the initial visit. Candidaemia was defined as the isolation of Candida from blood cultures and invasive Candida disease as the isolation of Candida from a normally sterile site. Identification and susceptibility testing of Candida spp.Micallef, S.

Aliyu, R. Santos, N. Brown, D. Rosembert, D. Antifungal stewardship aims to promote the optimal use of antifungals through the careful selection of agents based on patient profile, target organism, toxicity, costs and the likelihood of emergence and spread of resistance.

We report on an observational prospective 12 month study conducted by an antifungal stewardship team targeting the use of echinocandins caspofungin and micafunginvoriconazole and liposomal amphotericin B in a tertiary referral hospital in the UK. One-hundred-and-seventy-three patients were reviewed on occasions. Clinical advice was given and implemented during review of 45 Except for voriconazole, nearly half of all treatments reviewed were stopped or changed.

Using a multidisciplinary team, antifungal stewardship can achieve significant improvements in patient management and it may reduce costs. Antifungal stewardship refers to a systematic programme that promotes the optimal use of antifungals through the careful selection of agents based on patient profile, target organism, toxicity, costs and the likelihood of emergence and spread of resistance.

Antifungals have become an essential part of modern healthcare due to the increased incidence of invasive fungal infections linked to immunosuppression and the widespread use of invasive devices. In this study, we describe the clinical value and possible impacts on costs of a recently introduced antifungal stewardship programme ASP targeting patients receiving high-cost antifungals specifically liposomal amphotericin B, voriconazole, caspofungin and micafungin at our centre.

In Julyan ASP was launched for all adult inpatients receiving high-cost antifungals liposomal amphotericin B, voriconazole, caspofungin and micafungin. An antifungal stewardship team comprising a consultant microbiologist and an antimicrobial pharmacist was formed for the purpose of delivering this programme.

The antimicrobial pharmacist C. Patients who were on therapy but had been discharged prior to review were nevertheless reviewed when possible. Data collected included patient demographics, indication for antifungal, primary diagnosis, antifungal, significant clinical results and types of interventions.

Mortality was calculated at day 28 and 3 months after the initial visit. Candidaemia was defined as the isolation of Candida from blood cultures and invasive Candida disease as the isolation of Candida from a normally sterile site. Identification and susceptibility testing of Candida spp. Serum and bronchoalveolar lavage galactomannan bioassay Bio-Rad, Hemel Hempstead, UK was available for use throughout the study.

It was available for routine use by the haematology team but could also be used by the transplant team after discussion with one of the microbiology consultants D. The Trust's antifungal prescribing policy was to use micafungin as the first-line echinocandin and this was used principally for invasive infections due to Candida spp.

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Voriconazole was the standard therapy for invasive aspergillosis. This policy did not change in the years reviewed. Clinical: diagnostic and therapeutic advice was provided e.

Financial: included switching patients to a cheaper agent or stopping therapy and returning unused stock when therapy was stopped or switched. Total costs for the high-cost antifungals were compared for the year preceding implementation of the ASP 1 July —30 June with the year of implementation.Copy embed code:. Automatically changes to Flash or non-Flash embed. WordPress Embed Customize Embed. URL: Copy. Al- Ameen college of pharmacy.

Pharmacology-Antifungal drugs MADE EASY!

This binding results in the formation of pores in the membrane that increase permeability to proteins and monovalent ions especially K and divalent cationseventually leading to cell death.

Polyenes attach with higher affinity to ergosterol containing membranes than that of cholesterol containing ones. It is lipid constitutents the cell membrane same cholesterol in the animal cell. CNS: headache,periperal neuropathy,malaise 2. V: hypotension,hypertension,tachycardia 3. I: nausae,vomiting,diarrhoea Uses: for treatment of a variety of systemic fungal infection,such as blastomycosis,coccidioidomycasis.

Nystatain: Nystatain - The first polyene entered the clinic without systemic absorption. PowerPoint Presentation: After adsorption to the membrane interface topthe antibiotics self-associate in a pore structure bottomwhen the surface concentration is higher than a critical value. Antimetabolites : Antimetabolites - This class has only one example, flucytosine or 5-fluorocytosine 5-FC.

Although ineffective against tumors it was later found to have antifungal activity PowerPoint Presentation: Mechanism: Flucytosine is converted to 5-FU,which is an antimetabolites that inhibits thymidylate synthetase and thus DNA synthesis.

PowerPoint Presentation: Uses -Systemic fungi,mainly candida,and cryptococcus. Azloes : Azloes They are the group of synthetic antimycotic agents with broad spectrum of activity. Superior drug for systemic infections. N 3 of imidazole and N 4 of triazole binds to P iron. The most active ones have two or three aromatic rings, at least one of them is substituted with halogens or other nonpolar groups 2,4-dichlorophenyl or 2,4-difluorophenyl.

Antifungal Agents - PowerPoint PPT Presentation

The most active azoles have flourine in the structure. Ring substitution at other positions makes the azole inactive. The big nonpolar part resembles the steroid molecule in binding to the enzyme. Squalene is cidal to sensitive organisms. Block and John. Follow us on:. Go to Application. US Copy embed code:.

Automatically changes to Flash or non-Flash embed. WordPress Embed Customize Embed. URL: Copy. Presentation Description No description available. By: afzaye month s ago. Songco, Marjorie Ann R. Tagupa, Gerald Bong G. Nephrotoxicity may occur when given in high doses. Hypokalemia might occur. Hydration before infusion may reduce risk of neprotoxicity Monitor potassium levels closely and report signs of hypokalemia Drug is potentially ototoxic. C: PO, —U q.

When treating infanmts,swab medications on oral mucosa. Highly selective inhibitor of fungal cytochrome P- Used to treat cryptococcal meningitis in AIDS clients and oropharyngeal and systemic candidiasis. Discontinue drug if lesions progress,and notify prescriber. Uses and Considerations: Effective against various systemic fungal infections, particularly blastomycosis and histoplasmosis. Take with food to avoid GI discomfort. Also for vaginal fungal infections. Fungal resistance occurs if the drug is given alone.

Use cautiously in breast-feeding patients. Because drug is bound to plasma protein, use cautiously with other highly protein-bound drugs, and assess patient for toxicity when used together Alert: Because of risk of concurrent pulmonary infections, monitor patient closely during therapy. Follow us on:.

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View by Category Toggle navigation. Products Sold on our sister site CrystalGraphics. Title: Antifungal Drugs. Description: In fungi: ergosterol in membranes: higher affinity than. Impair synthesis of ergosterol; inhibit sterol 14 a-demethylase of cyt. Tags: antifungal drugs ergosterol in keratin libido vivo.

Latest Highest Rated. Even those susceptible to others but where the disease rapidly progressive, in Immunocompromized or involves CNS. Na entry Depolarization Voltage-dep. Do not use alone, but in combination with AmB cryptococcal meningitis Bone marrow toxicity pancytopenia -reversible 15 The Azoles Imidazoles and Triazoles Triazoles newer with fewer side effects Impair synthesis of ergosterol inhibit sterol 14 a-demethylase of cyt.

antifungal agents slideshare

Acumulation of precursors which inhibit growth. Mammalian cells can incorporate already formed cholesterol fungi have to synthesize Adverse effects due to inhibition of mammalian steroid synthesis Drug interactions due to inbibition of cyt.

antifungal agents slideshare

P enzymes. P enzymes Adverse effects - Nausea, anorexia, vomiting - Endocrine menstrual abnormalities, gynecomastia, azoospermia, decreased libido and potency - Hypertension and fluid retention - Hepatitis rare-fatal - Drug Interactions inhibition of cyt.

P Therapeutic Use coccidiomycosis, histoplasmosis if not severely ill or immunocompromized.

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Oral, esophageal, mucocutaneous candidiasis 17 Triazoles Itraconazole Varied absorption. Metabolized by cyt P Has less endocrine effects but occur at high doses Less hepatitis Histoplasmosis and blastomycosis Many drug interactions due to inhibition of cyt PA4 Fluconazole Completely absorbed and better tolerated Renal excretion Less endocrine effects Penetrates well into CSF Cryptococcal, coccidial meningitis.

Toxicity headache, neuro hepatotoxicity, photo-sensitivity, carcinogenic. Topical Antifungals For stratum corneum, mucosa, cornea by dermatophytes Candida. Not for subcutaneous, nail or hair infections.

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