6 categories of antibiotics that target bacteria and note host cells
#1) Cell Wall Biosynthesis (our cells don’t have a cell wall and we don’t have D amino acids) #2) Membrane Potential #3) Cell Membrane Disruption #4) Protein Synthesis #5) Nucleic Acid Biosynthesis #6) DNA Replication or Transcription
Lowest concentration that inhibits bacterial growth after 24 hrs in vitro
Suppression of bacterial growth continues even when antibiotic concentration is below MIC due to residual concentration in bacteria or in plasma.
2nd opportunistic infection after antibiotic therapy often due to loss of normal flora
What is the LADME process?
Liberation of drug -> Absorption of drug -> Distribution of drug to other tissues -> Metabolism of drug -> Excretion of drug
What is the one-compartment model?
Drugs rapidly equilibrate in a linear time course to all body tissues.
What is the two-compartment model?
Distribution phase: movement of drug into tissue compartment. Elimination phase: the predominant process.
Antibiotic that binds the least protein in plasma and is therefore the most active in plasma?
3 kinetic patterns of antibiotic action
1) Concentration-dependent killing of microbes 2) Time-dependent killing of microbes 3) Area of curve killing of microbes
What are the inhibitors of bacterial cell wall synthesis?
Beta lactams: penicillins, cephalosporins, monolactams and carbapenems. Note that all classes have the beta lactam ring (in red). Glycopeptides: vancomycin and telcoplanin.
How do beta lactam antibiotics work?
The look like D-Ala-D-Ala, COVALENTLY bind the bacterial transpeptidase enzyme and inhibit cell wall synthesis.
What are the penicillin binding proteins?
Though transpeptidase is the classic target, proteins required for bacterial shape, formation of septum and D-Ala carboxypeptidases are also targeted.
How have bacteria gained resistance to the beta lactam antibiotics?
1) Penicillinases and 2) Amidases
4 classes within the penicillin group of beta lactam antibiotics? What is each group tailored to?
Penicillin G & V (Gram +), Penicillinase-resistant penicillin, extended range penicillin (covers more gram -) and antipseudomonal penicillin (for pseudomonas)
Which penicillin can only be given IV or IM? Which can be given orally? Which has a longer half life?
Penicillin G is not acid stable and must be given IM or IV, it has a short half life (10-15 min). Penicillin V is modified to be acid stable and can be given orally and has a slightly longer half life.
How can you improve the half life of penicillin G given IM?
Combine it with procaine or benzathine (bases) that decrease penicillin solubility. This slows the release of penicillin from the injection site and prolongs the half life.
What organisms are penicillin V and G largely effective against?
Pneumococcus, streptococcus and peptococcus, gram + bacteria.
What drugs fall into the penicillinase-resistant penicillins of the beta lactam antibiotics? What organisms are these used to treat?
Nafcillin, cloxacillin, methicillin and oxacillin. These are used against Staph aureus and Staph epidermidis organisms that developed a penicillinase to open up the beta lactam ring. They are also useful against all microbes that normal penicillin clears.
How long is the half life of the penicillinase-resistant drug cloxacillin, the extended range penicillin amoxicillin?
~4 hours, it is orally available.
What drugs fall into the class of extended range penicillins of the beta lactam antibiotics? What microbes are these used to treat?
Ampicillin and amoxicillin. These are active against gram negative E. coli, P. mirabilis, H. influenzae, Salmonella, Shigella, Neisseria.
What drug falls into the class of anti-pseudomonal penicillins of the beta lactam antibiotics? What microbes is it used to treat?
Ticarcillin. It is used to treat Pseudomonas, Enterobacter, Proteus, H. influenzae and E. coli.
What drug is a ureidopenicillin derivative used to treat gram positive cocci, Pseudomonas and Klebsiella?
What is the half-life of ticarcillin?
It drops rapidly from time of administration and is almost eliminated at 6 hours because it is given IV.
The cephalosporins add increased diversity to the beta lactam class because you can substitute at what positions?
7 on beta lactam ring = change in bacterial spectrum. 3 on dihydrothiazine ring = change in pharmacokinetics.
How does bacterial coverage change as you move from the 1st to the 4th generation cephalosporins?
1st = increased gram + coverage. 4th = increased gram - coverage.
What drugs fall into the class of 1st generation cephalosporins of the beta lactam antibiotics? What microbes are they used to treat?
Cefazolin (IV/IM), cephalexin (oral), cephradine (oral, IV, IM), cefadroxil (oral). These are used for gram positive streptococci and staph aureus.
What 1st generation cephalosporin is often used prophylactically for surgery? What are the 2nd generation cephalosporins used for in surgical prophylaxis?
Cefazolin is used for normal flora, it has a longer half life of 2 hours than its counterparts. 2nd generations are used for prophylaxis against intestinal microbes.
What drugs fall into the class of 2nd generation cephalosporins of the beta lactam antibiotics? What microbes are they used to treat?
Cefotetan, cefoxitin (B. fragilis), cefuroximine, cefaclor (H. influenzae), locarbef. These are less active against gram + but more active against gram -. Also note that these drugs have some beta-lactamase resistance.
Which 2nd generation cephalosporin is able to penetrate the CNS?
What drugs fall into the class of 3rd generation cephalosporins of the beta lactam antibiotics? What microbes are they used to treat?
Ceftriaxone (N. meningitides w/ 8 hr half life), cefotaxime (highly resistant to gram - beta lactamases) ceftazidime and cefoperazone (last 2 good against drug-resistant pseudomonas). Ceftaroline has good gram + coverage and is used for MRSA. This class is good for Klebsiella, Enterobacter and Proteus.