Exam IV: Antibotics I Flashcards
Natural Products
Central nucleus: lactam ring= natural product
Penicillin- produced by the fungus penicillium chrysogenum
Tetracycline - produced by streptomyces genus
Semi-Synthetic Drugs
Semi synthetic products are based off of the lactam ring nuclei of natural products
Ampicillin and amoxicillin are semi-synthetic- penicillin class Most cephalosporins are semi-synthetic Doxycycline is semi-synthetic- tetracycline class
Semi-synthetic products have been modified chemically to:
Improve the efficacy of the natural product
Reduce its side effects
Prevent developing resistance
Expand the range of bacteria covered
Synthetic Products
Sulfa drugs, quinolones
General Principles of Antibiotics
- Inhibit bacteria without harming human host
- Should penetrate body tissues in order to reach bacteria
Oral absorption
Crosses the blood brain barrier
GI infections are treated well with drugs that are not orally absorbed
Drugs to treat meningitis must cross the blood brain barrier
Drugs used to treat systemic infection for instance pneumonia the drug must be orally absorbed through the GI tract - Empiric Treatment- give patient the standard treatment for their specific complaint; example ear infection = amoxicillin; when patient is very sick in the hospital, must get a culture to figure out which bacteria to treat/drug to use, but in the meantime treat empirically
Antimicrobial Spectrum
Narrow spectrum: drug only covers one class of bacteria; sometimes preferred because they target a specific pathogen without disturbing normal flora
Broad spectrum: effective against a range of pathogens; sometimes preferred for initial use when causative pathogen is not known
Intermediate spectrum: sometimes called extended spectrum drugs
Adding of a side chain: a narrow spectrum drug is modified by adding a side chain the new compound will be effective against more bacteria
The new drug can be an extended spectrum antibiotic
Treating Patient in Hospital: Before vs. After Culture
When treating patient in hospital empirically, you want to start them on a broad spectrum antibiotic to cover everything until cultures come back because don’t know what the bacteria is yet
Culture comes back: take off broad spectrum and put them on narrow spectrum because they target the specific pathogen WITHOUT disturbing the normal flora because clostridum difficle can take over and that is very hard to treat
Bacteriostatic
Bacteriostatic: slows down growth of bacteria; depends on the patient’s immune system to work with the antibiotic; if immunocompromised this won’t work and need bactericidal
if bacteria develops resistance, this type of antibiotic only slows it down/kills bacteria that are not resistant but the resistant bacteria is left and can infect more people and the antibiotic that was used to treat it initially does not work
Sulfonamides block synthesis of folic acid a co-factor for enzyme that synthesize DNA and amino acids
Tetracycline is bacteriostatic because it reversibly inhibits bacterial protein synthesis
Bactericidal
Bactericidal: kills the bacteria
Actions induce lethal changes in microbial metabolism or block activity for microbial viability
Example penicillins prevent the formation of the bacterial cell wall = necessary for survival of the bacteria
Streptomycin irreversibly inhibit protein synthesis
Cancer patient on chemotherapy- their immune system is gone so need bactericidal
Bacteriostatic and Bactericidal Drugs
Bacteriostatic: sulfonamides, tetracyclines, chloramphenicol, erythromycin, ethambutol, clindamycin, and linezolid (SLEET CC)
Bactericidal: penicillin, aminoglycoside, polypeptides, rifampicin, isoniazid, cephalosporins, ciprofloxacin, and metronidazole (MAP PRICC)
Rules of Antibiotics
- It must be able to reach the infection
- Should not cause development of resistance
- Cause few side effects
- Given orally or IV without too much protein binding
- Should be soluble in body fluids
- Able to reach concentrations that kill bacteria
Classification of Antimicrobial Drugs
Classified on the basis of their site and mechanism of action and sub-classified on their chemical structure
Sites of Action:
1. Cell wall synthesis inhibitors: beta lactam antibiotics; carbapenems, cephalosporins, monobactams, pencillins, bacitracin, fosfomycin, vancomycin
- Metabolic and nucleic acid inhibitors
a. Inhibitors of folate synthesis: sulfonamides, trimethoprim
b. DNA gyrase inhibitors: fluoroquinolones
c. RNA polymerase inhibitors: rifampin
Inhibitors of Protein Synthesis
Site of Action: 50S subunit = chloramphenicol, erythromycin, clindamycin, and oxaloidinones
Site of Action: 30S subunit = aminoglycosides, tetracyclines, streptomycin, and amikacin
Inhibitors of Cell Membrane
Cell Membrane: polymyxins
Inhibit Cell Wall Synthesis and Repair
Penicillins, cephalosporins, vancomycin, bacitracin, monobactams, fosfomycin, and cycloserine
DNA + RNA Inhibition
Inhibit replication, transcription, and gyrase = quinolones (Cipro)
Inhibit RNA polymerase = rifampin
Inhibition of Folic Acid Synthesis
Inhibit folic acid metabolism = sulfonamides and trimethoprim
Minimal Inhibitory Concentration (MIC)
The lowest concentration of a drug that inhibits bacterial growth
A particular bacteria can be classified as susceptible or resistant to a particular drug
In general the peak serum concentration of a drug should be 4 to 10 times greater than the MIC in order for a pathogen to be susceptible
Pathogens with intermediate sensitivity may respond to treatment with maximal doses of an antimicrobial agent
The lower the MIC of an antibiotic the better coverage it has against a bacteria
Example: 2 different antibiotics against a bacteria
Antibiotic 1 MIC 10mcg/ml
Antibiotic 2 MIC 5mcg/ml
Antibiotic 2 has the better coverage
Broth Dilution Test
Tubes are inoculated with equal numbers of bacteria
Serially diluted concentrations of antibiotic
The MIC is identified as the lowest antibiotic concentration that prevents visible growth of bacteria
The MIC is 8 micrograms/ml
Remember the peak serum concentration of the antibiotic should be 4 to 10 times greater than the MIC in order for the pathogen to be susceptible
Kirby Bauer Test
The antibiotic disks are placed on an agar plate seeded with the organism
The plates are incubated to allow them to grow
The zone diameter for each antibiotic is compared with standard values for each particular antibiotic
The organism is determined to be susceptible intermediate or resistant
Unfortunately, just because it works on an agar plate/test tube doesn’t mean it will work on your patient (95% of the time it does)
Concentration and Time Dependent Effects
CDKR= concentration-dependent killing rate
Some aminoglycosides and fluroquinolones exhibit a CDKR against a large group of gram negative bacteria
Pseudomonas and enterobacter
Beta lactam antibiotics will not show the same curve against the above gram negative bacteria
Different areas of the US have different strains of bacteria that are common and how the bacteria react to certain drugs
Some bacteria in Cali are resistant to a certain drug, but in Erie the bacteria are killed with that same drug
