Clinical Bacteriology LEC Lesson 2 Part 5: Action of Chemotherapeutic Agents Definition of Terms

Chemotherapeutic agents

Chemical substances which when taken orally or parenterally destroys microorganisms, without injury to the body cells

Antibiotics

Chemical substances produced by microorganisms which has the capacity to inhibit the growth of bacteria and even kill the bacteria and other microorganisms in dilute solution

or

Substances produced by microorganisms or to similar substances produced wholly or partially by chemical synthesis, which in low concentrations, inhibit the growth of other microorganisms

Spectrum

Refers to a compound's range of antimicrobial activity

Broad Spectrum

Indicates a wide variety of microorganisms affected, including usually both Gram (+) and (-) bacteria

chloramphenicol, tetracycline and derivatives ampicillin, rifampin, kanamycin, gentamicin, tobramycin, sulfonamides

Examples of Broad Spectrum

Narrow Spectrum

Affects only a few organism

B-lactams

Glyccopeptides

ANTIMICROBIAL CLASS that targets CELL WALL (CW)

penicillin, ampicillin, mezlocillin, piperacillin, cefazolin, cefotetan, ceftriaxone, ceftazidime, aztreonam, imipenem

B-lactams examples

vancomycin, bacitracin

Glyccopeptides examples

B-lactams Mechanism of Action and Spectrum

Mechanism of Action: nhibit CW synthesis by binding enzymes involved in peptidoglycan production (i.e., penicillin-binding proteins (pbps))

Spectrum: Both Gram (+) & (-) bacteria

Glycopeptides Mechanism of Action and Spectrum

Mechanism of Action: Inhibit CW synthesis by interacting with precursors. & disrupting their incorporation into the growing CW recycling of certain metabolites required for maintaining peptidoglycan synthesis

Spectrum: Gram (+) bacteria only

Polymyxins

ANTIMICROBIAL CLASS that targets CELL MEMBRANE (CM)

polymyxin B, colistin

Polymyxins examples

Polymyxins Mechanism of Action and Spectrum

Mechanism of Action: Disruption of CM resulting in leakage of macromolecules & ions essential for cell survival

Spectrum: Gram (-) bacteria, poor activity against Gram (+) bacteria

Aminoglycosides

Macrolide-lincosamide-streptogramin (MLS) group

Chloramphenocol

Tetracycline

ANTIMICROBIAL CLASS that targets PROTEIN SYNTHESIS (PS)

gentamicin, tobramycin, amikacin, netilmicin, streptomycin, kanamycin

Aminoglycosides

erythromycin, azithromycin, clarithromycin, clindamycin

Macrolide-lincosamide-streptogramin (MLS) group

Aminoglycosides Mechanism of Action and Spectrum

Mechanism of Action: Inhibit bacterial PS by binding to protein reception on the organism's 305 ribosomal subunit

Spectrum: Gram (+) & (-) bacteria; not anaerobic bacteria

Macrolide-lincosamide-streptogramin (MLS) group Mechanism of Action and Spectrum

Mechanism of Action: Inhibit PS by binding to receptors on the bacterial 505 ribosomal subunit & subsequent disruption of the growing peptide chain

Spectrum: Most Gram (+) bacteria; some Gram (-) bacteria

Tetracycline Mechanism of Action and Spectrum

Mechanism of Action: Inhibit PS by binding to 305 ribosomal subunit so that the incoming trna-amino acid complexes cannot bind to the ribosome, thus halting the peptide chain elongation

Spectrum: Gram (+) & (-) bacteria; several intracellular pathogens

Fluoroquinolones

Metronidazole

Rifampin

ANTIMICROBIAL CLASS that targets DNA AND RNA SYNTHESIS

ciprofloxacin, ofloxacin, norfloxacin

examples of quinolones/Fluoroquinolones (quinolones)

Fluoroquinolones (quinolones) Mechanism of Action and Spectrum

Mechanism of Action: Bind to & interfere with DNA gyrase enzymes involved in the regulation of bacterial DNA supercoiling, a process essential for DNA replication & transcription

Spectrum: Gram (+) & (-) bacteria

Metronidazole Mechanism of Action and Spectrum

Mechanism of Action: Exact mechanism is uncertain but is believed to involve direct interactions between the activated drug & DNA that results in breakage of DNA strands

Spectrum: Gram (-) & certain general of Gram (+) anaerobic bacteria

Rifampin Mechanism of Action and Spectrum

Mechanism of Action: Binds to the enzyme DNA dependent RNA polymerase & inhibits synthesis of RNA

Spectrum: Gram (+) & certain Gram (-) bacteria

Sulfonamides

Trimethoprim

Nitrofurantoin

ANTIMICROBIAL CLASS that targets OTHER METABOLIC PROCESSES

Sulfonamides Mechanism of Action and Spectrum

Mechanism of Action: Bind to one of the enzymes, dihydroplaroate synthase & disrupt folic acid pathway

Spectrum: Gram (+) & certain Gram (-) bacteria

Trimethoprim Mechanism of Action and Spectrum

Mechanism of Action: Targets the folic acid pathway by binding to dihydrofolate reductase

Spectrum: Gram (+) & certain Gram (-) bacteria

Nitrofurantoin Mechanism of Action and Spectrum

Mechanism of Action: Mechanism is not completely known; may have several targets involved in bacterial protein & enzyme synthesis, may also directly damage DNA

Spectrum: Gram (+) & (-) bacteria

Hypersensitivity or Allergy

Signs of hypersensitivity are variable in different persons but include skin rashes, joint pains, anaphylactic shock, urticaria, pruritus, etc.

Toxicity

Aplastic anemia induced by chloramphenicol

Deafness and vertigo due to streptomycin

Dental defects in tetracycline administration in young children and infants

Toxicity to liver in INH, rifampin therapy

superinfections

Antimicrobial drugs affect not only the infecting organisms but also the susceptible members of the normal microbial flora of the body. An imbalance is thus created with the outgrowth of drug-resistant indigenous bacteria or fungi that are normally kept in kept by the drug sensitive members of the flora. This leads to what is termed as "__________."

Oral antimicrobial drugs may suppress the normal intestinal flora with the overgrowth of resistant staphylococcal causing enterocolitis

Candida albicans

Suppression of normal vaginal flora may lead to the overgrowth of fungus particularly ____________ causing vaginitis

Resistance

means that a drug is no longer effective in suppressing the growth and multiplication of bacteria. Bacteria vary in their ability to develop resistance to gives drug.

The occurrence of ______ is related to the frequency with which antibiotics are used.

Resistant strains

occur in greatest proportion in hospital populations and it is well established that resistant strains appear most commonly in persona undergoing prolonged antimicrobial therapy as in TB

True

Resistant variants are produced in experimental animals treated with subcurative amounts of chemotherapeutic agents-this shows that adequate dosage is very important. True or False?

Poem

Roses are red

Dyes might be blue

I can't stand alone

I must be with you