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

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

  2nd gen:Telavancin (Vibativ) and Oritavancin

  Isoniazid used to treat Mycobacterium tuberculosis

  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

  Rely on prevention (vaccination) rather than treatment for most




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 (Zovirax)

  also Valacyclovir, Famciclovir, Ganciclovir

  Respiratory syncytial virus (RSV) ribavirin

  Nucleoside reverse transcriptase inhibitors

  HIV- Azidothymidine (AZT)        

also Didanosine (ddI), Lamivudine (3T3), 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

  Biofilms mixed communities of different kinds of bacteria and other microbes

  Microbes cooperate and are less sensitive to anti-microbials

  Cause 80% of chronic infections

  Commonly found on medical devices inserted into the body        




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!