Chapter 12


Antimicrobial Drugs



Antibacterial Drugs (Antibiotics)

   Most are produced by bacteria and fungi that normally reside in the soil

  ex. Streptomyces, Bacillus, Penicillium, and Cephalosporium

   Most exhibit selective toxicity - cause greater harm to microorganism than to human host

   May be broad-spectrum or narrow-spectrum



Mechanisms of Action: Inhibit Cell Wall Synthesis

   Beta-lactam drugs

  inhibit formation of peptide bridges between adjacent strands of peptidoglycan

  bactericidal against a variety of gram-positive and gram-negative bacteria

  Generally mild and well tolerated; biggest problems are allergic reactions and resistance           

  Penicillins and cephalosporins

  2nd & 3rd gen: Ampicillin, Carbenicillin, and Amoxicillin more broad spectrum

  For resistance: Cloxacillin, Nafcillin, Mezlocillin, Azlocillin, Methicillin, Clavamox (Augmentin), and Zosyn

  1st and 2nd gen: Cephalothin, Cefazolin, Cefaclor, Cefonicid

  For resistance: Cephalexin (Keflex), Cefotaxime, Ceftriaxone (Rocephin), Cefpirome, Cefepime more broad spectrum, Ceftobiprole 

  Carbapenems are new class of beta-lactam drugs

  Ex. Doripenem, Imipenem, Aztreonam

  reserved for use in hospitals when other drugs arent working

   Glycopeptide antibiotics

  Vancomycin narrow spectrum antibiotic used to treat resistant, life-threatening Staphlococcus infections

  2nd gen:Telavancin (Vibativ) and Oritavancin

   Bacitracin narrow spectrum antibiotic used topically because of toxicity

  component of Neosporin




Mechanisms of Action: Inhibit Protein Synthesis

   Target prokaryotic ribosome subunits to block translation

   Bactericidal or bacteriostatic against a variety of gram-positive and gram-negative bacteria

   Aminoglycosides and tetracyclines target the 30S subunit

  Ex. Streptomycin, Gentamicin, Tobramycin, Doxycycline

  Glycylcyclines (Tygacil) for resistance

  biggest problem with tetracyclines is GI disruption

   Macrolides and Chloramphenicol target the 50S subunit

  1st & 2nd gen: Erythromycin, Azithromycin, Clarithromycin, Clindamycin

  Ketolides (Telithromycin - Ketek) for resistance

  Chloramphenicol is used as a last resort because of its toxicity to human cells

   Synercid targets 50S subunit in resistant bacteria

  used for resistant Staphlococcus and Enterococcus species

   Linezolid (Zyvox) inhibits protein synthesis initiation

  used for resistant Staphlococcus and Enterococcus




Mechanisms of Action: Inhibit Nucleic Acid Synthesis

   Target enzymes required for replication and transcription  

   Bactericidal against gram-positive and gram-negative bacteria     

   Floroquinolones and rifamycins

  2nd, 3rd, 4th gen: Ciprofloxacin, Ofloxacin, Levofloxacin (Levaquin), and Trovafloxacin

  Rifampin and Xifaxan are examples of rifamycins




Mechanisms of Action: Inhibit Folic Acid Synthesis

   Block the enzyme that makes folic acid

   Bacteriostatic against gram-positive and gram-negative bacteria

   Sulfonamides and trimethoprim

  Ex. Sulfisoxazole, Sulfamethoxazole, Septra, and Bactrim




Mechanisms of Action: Inhibit Cell Membrane

   Bind to bacterial cell membrane and alters permeability

   Also bind eukaryotic membranes so toxic to human cells

   Polymyxins B and E and Daptomycin




Antiviral Drugs

   Viruses are difficult to target because they rely on the host cell machinery for  their replication

   Viruses completely unaffected by antibiotics




Mechanisms of Action:  Inhibit Viral Entry

   Block binding of virus to host cell and prevent fusion

   HIV Fuzeon

   Influenza A and B viruses - Relenza and Tamiflu




Mechanisms of Action:  Inhibit Nucleic Acid Synthesis

   Nucleoside analogs - mimic the structure of nucleotides and incorporate into DNA to cause termination

  Herpesviruses Acyclovir, Valacyclovir, Famciclovir, Ganciclovir

  Respiratory syncytial virus (RSV) ribavirin

   Nucleoside reverse transcriptase inhibitors

  HIV- Azidothymidine (AZT), Didanosine (ddI), Lamivudine (3T3)     

  also Zalcitabine (ddC), stavudine (d4T)

   Non-nucleoside reverse transcriptase inhibitors

  bind directly to reverse transcriptase and inhibit its activity

  HIV Nevirapine, Efavirenz, and Delavirdine            




Mechanisms of Action:  Inhibit Assembly and Release

   Target enzymes necessary for the production and release of virus

   HIV - protease inhibitors

  Indinavir, Saquinavir

  used in combination with nucleotide analogs and reverse transcriptase inhibitors




Antiviral Drugs : Interferon

   Glycoprotein produced by human cells in response to virus infection

   Used clinically to treat chronic Hepatitis C infections and cancers




Antimicrobial Resistance

   Microbes can become resistant to drugs due to spontaneous mutations during DNA replication or by gene transfer between species   




Mechanisms of Drug Resistance

   Beta-lactamases bacterial enzymes that inactivate the beta-lactam ring of penicillins and cephalosporins

  methicillin-resistant Staphylococcus aureus (MRSA)

  Penicillinase-producing Neisseria gonorrhoea (PPNG)           

   Multidrug-resistant (MDR) pumps actively transport drugs out of cells

  Staphylococcus, Streptococcus, Pseudomonas, and E.coli

   Alterations in binding proteins in cell wall

  Vancomycin-resistant enterococci (VRE)

  Penicillin-resistant Streptococcus pneumoniae





Kirby-Bauer Technique

   Agar diffusion test used to measure antibiotic sensitivity




Negative Effects of Antimicrobial Drugs

   Toxicity to Organs

  Antimicrobial drugs can adversely affect any organ system in the body (liver, kidney, GI tract, cardiovascular system, nervous system, etc.)

  Minimum inhibitory concentration (MIC) smallest concentration of drug that visibly inhibits bacterial growth

  sensitive and quantitative tube dilution tests that determine the smallest effective dose

  Therapeutic index (TI) - ratio of the dose of the drug that is toxic to humans as compared to its MIC

  larger number better                                                                                   

   Allergic responses to drugs

  especially penicillins and sulfonamides

  Can cause hives or anaphylaxis


   Disruption of the normal resident flora         

  broad spectrum antibiotics kill beneficial organisms, allowing pathogenic organisms to overgrow and cause infection

  yeast infection, thrush, antibiotic-associated colitis

  Probiotics and prebiotics can be given to improve the intestinal flora





Dont Forget Self-directed Study for Antifungal and Antiparasitic Drugs!