Antibiotics

When was antibiotics introduced

• Introduced in 1930s, revolutionized medicine

What do antibiotics do

• Reduced certain infections but have not eradicated and probably never will

What is a post antibiotic era

Where the drugs we have are no longer effective

What is the goal of antimicrobial chemotherapy

• Drug destroys the infective agent without harming the patient

What must a drug be able to do

• Be easy to administer and able reach the infectious agent

• Remain in the body as long as needed be safely and easily broken down and excreted

What is the ideal antimicrobial

• Toxic to microbe but not host

• -cidal rather than -static

• Potent at low concentrations

• Long lasting in body

• Hard to develop resistance to

• Gets to site of infection

• Not stupid expensive

• Does not harm patients (harm for antifungals and antiprotozoals)

What is an antibiotic

• Common metabolic products of bacteria and fungi

  • micro biochemical warfare

  • kill competing microbes

What is antibiotics derived from

• Bacteria in the genera streptomyces and bacillus (mostly)

• Molds in the genera penicillium and cephalosporium

What is the Kirby-Bauer techique

• Surface of agar plate is spread with bacteria

• Small discs containing antibiotic are placed on the plate

What is the zone inhibition

• Surrounding the discs is measured and compared with a standard for each drug

What is less effective for the kirby-bauer technique

• Anaerobic, fastidious, or slow-growing bacteria

What are tube dilution tests

• More sensitive and quantitative

• Antimicrobial is diluted serially in tubes of broth

• Each tube is inocculated with a small uniform sample

What is minimum inhibiotory concentration (MIC)

The smallest concentration of drug that visbily inhibits growth

What are MIC Limitations

• The inability of the drug to diffuse into the body compartment (brain,joints, skin)

• Resistant microbes in the infection

• An infection caused by more than one pathogen (mixed) some of which are resistant to the drug

What should be taken in consideration before prescribing an antibiotic

• Preexisting conditions

• History. of allergy to a certain class of drugs

• Underlying liver or kidney disease

• Infants,the elderly and pregnant women

• Intake of other drugs

• Genetic or metabolic abnormalities

• Site of infection,route of administration and cost

What are the mechanisms of drug actions (5)

1. Inhibition of cell wall synthesis

2. Inhibition of nucleic acid structure and function

3. Inhibition of protein synthesis

4. Interference with cell membrane structure and function

5. inhibition of folic acid synthesis

What are the 4 cell wall inhibitors

• Pencillin

• Cephalosporins

• Bacitracin

• Vancomycin

What is Penicillin

• Cell wall inhibitors

• Gram+cocci: some gram

• Every generation is more broad but less potent

• Some carry enzymes to combat resistance

What drugs target protein synthesis

• Tetracyclins

• Macrolides

• Clindamycin

What are tetracyclins

• Protein synthesis, broad spectrum

What are macrolides

• Protein synthesis

• Broad spectrum

• predominantly-static

What are clindamycin

• Protein synthesis

• treats penicillin-resistant staph

What does Sulfas do

• Folic acid synthesis

• UTI,protozoals

What is fluroquinolones

• Nucleic acid synthesism

• cipro,levoquin-gram +

What is Rifampin

• Inhibits transcription

• Limited spectrum

• Gram + bacilli and cocci

What is Polymyxins

• Cell membrane permeability

• Treat drug-resistant organims

• Gram +

How does bacteria in biofilms behave differently

• Often unaffected by antimicrobials

• Antibiotics often cannon penetrate

• Bacteria in biofilms express a different phenotype and have different antibiotic susceptibility

What are biofilm treatment strategies

• Interrupt quorum sensing

• Adding DNAse to anitbiotics aids penetration

• Impregnating devices with antibiotics prior to implantation

What is a main drug that has shown success

• Daptomycin

What antibioitcs cause biofilm to form a higher rate than normal

• Beta lactams

• Thiopeptides

• Typically a problem of improper dosage

What is drug resistance

• An adaptive response in which microorganism begin to tolerate an amount of drug that would normally be inhibitory

• Survival of the fittest

How does drug resistance develop e

1. Spontaneous mutations in critical genes

2. Acquisition of entire new genes or sets of genes via horizontal transfer

What is persisters

• Slowing or stopping of metabolism so that the microbe can’t be harmed by the antibiotic

What is RNA interference

• Small pieces of RNA that regulate genes

• Used to shut down the metabolism of pathogens

What is bacteriophage therapy

• Either whole phage or phage enzymes

• Eastern european countries use bacteriophages as medicine

• Biophage-PA used to treat ear infections

• Incorporating bacteriophages into wound dressings

• Advantages to bacteriophage in their narrow specificity

What are the adverse effect

• 5% of all persons taking an antimicrobial drug will experience an adverse side effect

What organs could drugs adversely affect

• Liver

• Kidneys

• GI tract

• Cardiovascular system

• Nervous system

• Resipiratory tract

• Skin

• Bones and teeth

What is biota/normal flora

• Normal microbial colonists

• Normally consist of harmless or beneficial bacteria

• Broad-spectrum antimicrobials destroy healthy biota along with pathogens

What is superinfection

• Microbes that were once small in number overgrow when competitive pressure is eliminated by killing normal flora

• ex: yeast infections

What is urinary tract infection caused by E.coli

• Superinfection

• Lactobacilli in the female vagina are killed by the broad-spectrum cephalosporin used to treat TI

What is Antibiotic-associated colitis

• Oral therapy with tetracyclines,clindamycin, and broad spectrum pencillins kill normal biota of colon

• Overgrowth of Clostridium difficle invades the intestinal lining and release toxins that cause diarrhea, fever, and abdominal pain