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24 Cards in this Set
- Front
- Back
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Six General Characteristics of β-Lactam Antibiotics
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1. Inhibitors of cell wall synthesis
2. Forms of resistance include beta-lactamase enzymes, alteration in penicillin binding proteins, decreased permeability of outer cell membrane in gram-negative bacteria 3. Time-dependent bactericidal activity 4. Short half-life of less than 2 hours requiring frequent dosing to keep serum concentration above MIC 5. Renal elimination (except penicillinase-resistant penicillins) 6. Cross-allergenicity |
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Basic structure of penicillins
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- 5-membered thiazolidine ring
- Beta lactam ring - Attached acyl side chains *Manipulation of side chains has led to agents with different antibacterial spectrums, stability, and PK properties |
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Beta-Lactamase
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A bacterial enzyme that can hydrolytically attack the beta-lactam ring of some penicillins and render the penicillin inactive
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Penicillins mechanism of action
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Interfere with bacterial cell wall synthesis by binding and inhibiting penicillin-binding proteins on the cell walls of bacteria. PBPs are enzymes that regulate synthesis, assembly, maintenance of peptidoglycan.
--> Inhibition of PBPs by beta-lactam antibiotics leads to inhibition of final transpeptidation step in peptidoglycan synthesis, exposing a less osmotically stable cell membrane that leads to lysis/death. |
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Affect of penicillins on Enterococcus
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Unlike their bacteriocidal activity on other bacteria, penicillins display BACTERIOSTATIC activity on Enterococcus.
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3 Bacterial mechanisms of resistance to penicillin antibiotics
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1. Beta-lactamase enzyme
2. Alteration in structure of PBPs 3. Inability of antibiotic to reach PBP target due to poor penetration through outer membrane of bacteria (gram neg) |
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Beta-Lactamase Enzymes
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- Over 100 different enzymes ID'd
- May be plasmid-mediated or chromosomally-mediated - May be inducible or constitutive - Produced by many gram-negative bacteria, some gram positive (S. aureus), and some anaerobic (b. fragilis) bacteria. |
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Location of Beta-lactamase enzyme in gram negative bacteria
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Enzymes reside in the periplasmic space which puts them in a good position to cleave the cyclic amide bond of the beta-lactam ring on penicillins
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NATURAL PENICILLINS
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Penicillin G
Benzathine penicillin G Procaine penicillin G Penicillin VK Good activity against non-B-lactamase producing gram + cocci/bacilli (little activity against Staph species) Good activity against gram + anaerobes Some gram - activity |
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Location of Anaerobes
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Gram-Positive Cocci are ABOVE diaphragm (peptococcus, peptostreptococcus).
Gram-Positive Bacilli are BELOW diaphragm (clostridum spp. except dificile) |
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PENICILLIN G
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Drug of choice for treatment of syphilis infections, N. meningitidis, C. diphtheriae, B. anthracis, C. perfringes/tetani, viridans, Group Strep.
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AMINOPENICILLINS
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Ampicillin
Amoxicillin Addition of amino group to basic penicillin molecule for extended activity against gram-negative aerobic bacilli |
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CARBOXYPENICILLINS
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Ticarcillin
Addition of carboxy group to basic penicillin molecule for resistant gram-negative bacteria and increasing freuency of P. aeruginosa Weak against gram positive Enhanced against gram negative |
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UREIDOPENICILLINS
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Ampicillin molecule with acyl side chain adaptations --> Greater cell wall penetration and increased PBP affinity
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BETA LACTIMASE INHIBITOR COMBINATIONS
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Amoxicillin/Clavulanic Acid (augmentin)
Ampicillin/Sulbactam (unasyn) Piperacillin/Tazobactam (zosyn) |
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PENICILLIN PHARMACOLOGY
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- Time-dependent bactericidal activity
- Clinical efficacy correlates with Time ABOVE MIC - There is post antibiotic antibiotic effect (PAE) for Gram Positive - No significant post antibiotic effect (PAE) for Gram Negative |
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PENICILLIN ACTIVITY ON ENTEROCOCCUS SPECIES
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- Penicillins display BACTERIOSTATIC (instead of typical bactericidal) activity against ENTEROCOCCUS SPP.
- Bactericidal activity (synergy) can be achieved by adding AMINOGLYCOSIDE (gentamycin/streptomycin) to penicillins |
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ABSORPTION OF PENICILLINS
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- Many penicillins are degraded by gastric acid and unsuitable for oral administration --> given parenterally
- Orally available penicillins have variable absorption from the GI tract. - Concentrations achieved with oral dosing are lower than those achieved with parenteral dosing so oral should be used for mild to moderate infections. - Food delays rate/extent of absorption. |
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DISTRIBUTION OF PENICILLINS
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- Widely distributed into body tissues and fluids: pleural fluid, synovial fluid, bone, bile, placenta, and pericardial fluid.
- DO NOT penetrate eye or prostate - To get adequate concentrations of penicillins in the CSF it requires presence of inflamed meninges when high doses of parenteral penicillins are used. - Penicillin binding to serum proteins varies from 15% (aminopenicillins) to 97% for dicloxacillin |
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ELIMINATION OF PENICILLINS
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- Most eliminated by the kidneys, unchanged via glomerular filtration and secretion
- Nafcillin and oxacillin are eliminated primarily by liver - Piperacillin undergoes dual elimination |
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PROBENECID
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- Blocks tubular secretion of renally-eliminated penicillins and can increase their serum concentrations
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RENAL DIALYSIS
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- Most penicillins are removed during hemodialysis or peritoneal dialysis, requiring supplemental dosing after a hemodialysis procedure.
- NOT nafcillin & oxacillin because they are excreted by the liver |
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SODIUM LOAD
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- Some parenterally-administered penicillins (carboxy- and ureidopenicillins) contain Na+ in their parenteral preparation.
- Must be considered in patients with cardiac/renal dysfunction |
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SODIUM PER GRAM OF TICARCILLIN
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5.2 mEq per gram (the highest)
Next highest is carbenicillin, followed by sodium penicillin G, and finally piperacillin |
