Anti-Fungal Compounds Eukaryotic pathogens –Similar cell structure and function Many fungi are opportunistic –Fungal infections on the rise Most have detoxification systems

Fungal infections (mycoses) may be: –Cutaneous Dermatophytic –Subcutaneous –Systemic

Antifungal Disruption of Cell Membrane many target membrane sterols (ergosterol) Polyenes –Produced by Streptomyces –Toxicity is a serious issue –Amphotericin B Used for systemic mycoses –Nystatin Effective topical treatment for cutaneous and subcutaneous mycoses

Azoles –Synthetic drugs –Fluconazole & Ketoconazole –Used to treat systemic mycoses, dermatophytic infections, cutaneous mycoses

Anti-fungal Inhibition of Cell Wall Synthesis Inhibition of β-glucan results in incomplete cell wall Echinocandins –Caspofungin –used against many opportunistic mycoses Candida, Aspergillus and Pneumocystis

Anti-fungal Inhibition of Nucleic Acids Work on specific enzymes not in mammalian cells Fluorocytocine –Synthetic drug –Cytosine analog interferes with RNA synthesis –Serious toxicity issues –Used to treat systemic yeast infections

Other Anti-fungals Griseofulvin –Given orally; reaches target site through sweat –Inhibits cell division Tolnaftate –Used for athlete's foot; action unknown

Nitroimidazoles –Metronidazole Effective against Trichomonas and Girardia Effective against anaerobic bacteria Activated by anaerobic metabolism Alters DNA Side effect – black, hairy tongue Causes birth defects; passed in breast milk Anti-protozoan Inhibition of Nucleic Acids

Nifurtimox –Effective against Trypanosoma –Interferes with electron transport –Mild gastrointestinal upset Anti-protozoan Inhibition of Necessary Metabolites

Quinine and Quinolines –Isolated from a Peruvian tree; replaced with synthetic versions –Exact mechanism of action unknown- inhibits protozoan metabolism –Chloroquine & mefloquine Malaria treatment Other Anti-protozoan Drugs

Niclosamide –Prevents ATP generation Tapeworms Praziquantel –Causes tetanic contractions Flukes Ivermectin –Paralyzes worm Intestinal roundworms and tissue nematodes Anti-helminthic Drugs

Available antiviral drugs effective specific type of virus –None eliminate latent viruses –Attachment –Un-coating –Nucleic acid synthesis –Protein synthesis –Maturation –Release Anti-viral Drugs

Nucleoside/nucleotide analogs –Results in an increased mutation rate Azidothymidine (AZT) –HIV Ribavirin –Flu, respiratory syncytial virus, hepatitis Acyclovir –Reduces frequency and severity of herpes outbreaks –Herpes viruses Anti-viral Inhibition of Nucleic Acids

Indinavir –Protease inhibitor- inhibit viral assembly/release HIV Amantadine –Inhibit viral un-coating Flu Zanamivar –Neuraminidase inhibitor- inhibit viral attachment Flu Anti-viral Inhibition of Viral Proteins

Mutations lead to resistance Resistance is transferred between cells –Resistance genes are often on plasmids or transposons Multi-drug-resistant pathogens Cross resistance Anti-microbial Resistance

Mechanisms of antibiotic resistance 1. Drug inactivating enzymes 2.Decreased uptake of the drug 3.Alteration of target molecule 4. Increased elimination of the drug 5. Protecting the target

Misuse selects for resistant mutants –Using outdated, weakened antibiotics –Using antibiotics for inappropriate conditions –Use of antibiotics in animal feed –Failure to complete the prescribed regimen

Slowing emergence and spread of resistance –Responsibilities of healthcare workers Increase efforts to prescribe antibiotics for specific organisms Educate patients on proper use of antibiotics Synergism –Responsibilities of patients Follow instructions carefully Complete prescribed course of treatment