Penicillins Flashcards
Are penicillins bactericidal or bacteriostatic?
- Penicillins, like all beta-lactam antibiotics are bactericidal, except against enterococcus spp, where they display bacteriostatic activity.
Natural penicillins spectrum of activity
excellent activity against non-beta-lactamase-producing gram-positive cocci and bacilli but very little activity against staphylococcus spp due to penicillinase production; active against gram-negative cocci; good activity against gram-positive anaerobes; other: treponema pallidum
Examples of natural penicillins
Ex. aqueous penicillin G, benzathine penicillin G, procaine penicillin G, penicillin VK
2. Pen G is still considered to be a potential drug of choice for the treatment of infections due to viridans and group streptococci, Neisseria meningitidis, corynebacterium diphtheriae, bacillus anthracis, clostridium perfringens, and tetani, and treponema pallidum
Penicillinase-resistant penicillins spectrum of activity
gram positive – MSSA (not active against MRSA) and not active against enterococcus spp; no activity against gram-negatives or anaerobes
1. These agents contain an acyl side chain that sterically inhibits the action of the penicillinase by preventing opening of the beta-lactam ring.
Examples of penicillinase-resistant penicillins
Ex. nafcillin, methicillin, oxacillin, and dicloxacillin
Aminopenicillins spectrum of activity
gram positive – ineffective against staphylococcus aureus, better acitivty than natural penicillins against enterococcus spp, excellent against listeria monocytogenes; better gram-negative activity than natural penicillins; activity similar to pen G regarding anaerobes
1. Have an additional amino group to the basic penicillin molecule to extend their activity against gram-negative aerobic bacilli.
2. Drug of choice for infections due to listeria monocytogenes and enterococcus spp.
Examples of aminopenicillins
Ex. ampicillin and amoxicillin
Carboxypenicillins spectrum of activity
weak activity against gram-positive; enhanced activity against gram-negative – 1st group of penicillins with activity against pseudomonas aeruginosa. NOT active against klebsiella spp or serratia spp.
1. Add a carboxyl group to the basic penicillin molecule. This caused it to lose gram-positive spectrum of activity.
Examples of carboxypenicillins
Ex. ticarcillin
Urediopenicillins spectrum of activity
gram positive – some activity against enterococcus spp, no activity against staphylococcus spp; improved gram-negative activity – pseudomonas aeruginosa (piperacillin is penicillin of choice for this); anaerobes – come activity against Bacteroides fragilis
1. Derived from ampicillin molecule with acyl side chain adaptations to allow for greater cell wall penetration and increased PBP affinity.
Examples of ureidopenicillins
Ex. piperacillin
Beta-lactamase inhibitor combinations spectrum of activity
gram positive – active against beta-lactamase producing strains of staphylococcus aureus (MSSA); gram-negative – not very active against pseudomonas aeruginosa, serratia marcescens, Citrobacter spp, indole-positive proteus spp, or Enterobacter spp; anaerobes – enhanced activity against beta-lactamase producing strains of Bacteroides fragilis and B. fragilis group (DOT) organisms.
1. Combo antibiotics containing a penicillin and a beta-lactamase inhibitor. Beta-lactamase inhibitor irreversibly binds to the catalytic site of the beta-lactamase enzyme, preventing the hydrolytic action on the penicillin. They enhance the antibacterial activity of penicillin against bacteria where the resistance is primarily mediated by beta-lactamase production.
Examples of beta-lactamase inhibitor combos
Ex. Amoxicillin/Clavulanate (Augmentin), ampicillin/sulbactam (Unasyn), ticarcillin/clavulanate (timentin), piperacillin/tazobactam (Zosyn).
Penicillin distribution
- Cerebrospinal fluid: all parenteral penicillins (not beta-lactamase inhibitors) will penetrate the cerebral spinal fluid when used at max doses in the presence of inflamed meninges. Pencillins are widely distributed into body tissues and fluid including pleural fluid, synovial fluid, bone, bile, placenta, and pericardial fluid. They do NOT penetrate the eye or prostate.
Which penicillins are NOT primarily eliminated by the kidneys?
- Not primarily eliminated by the kidney: nafcillin and oxacillin, which are eliminated primarily by the liver, and piperacillin which undergoes dual elimination.
What penicillins require dosage adjustments in renal insufficiency?
- Require dosage adjustments in renal insufficiency:
- pen G, pen V, ampicillin, ampicillin/sulbactam, amoxicillin, amoxicillin/clavulanic acid
- Probenecid blocks the tubular secretion of renally-eliminated penicillins and can increase their serum concentrations.
Which penicillins are removed during hemodialysis?
- Removed during hemodialysis: all except for nafcillin and oxacillin (don’t require supplemental dosing after hemodialysis procedure).
What penicillins should be used with caution in patients with congestive heart failure or renal failure due to the sodium load associated with administration of their parenteral formulations?
- Use these with caution because it can lead to electrolyte abnormalities and fluid retention: aqueous sodium pen G, nafcillin, carbenicillin, ticarcillin, piperacillin
Clinical uses of natural penicillins
- IV aqueous pen G is used for serious infection in hospitalized patients due to its rapid effect and high serum concentration. Oral pen VK achieves lower serum concentrations, so its use is limited to the treatment of mild-moderate infections such as pharyngitis or prophylaxis in some situations.
- THE drug of choice for treponema pallidum – syphilis.
Clinical uses of penicillinase-resistant penicillins
- Primary drug for the treatment of infections due to methicillin-susceptible staphylococcus aureus (MSSA). Ex. nafcillin
- Oral dicloxacillin for mild-moderate skin and soft tissue infections.
Clinical uses of aminopenicillins
- Parenteral ampicillin for treating enterococcal infections and listeria monocytogenes meningitis.
Clinical uses of carboxypenicillins and ureidopenicillins
- Useful for serious infections due to enhanced activity against gram-negative bacteria (especially hospital acquired infections).
- Piperacillin is the most active penicillin against pseudomonas aeruginosa.
Clinical uses of beta-lactamase inhibitor combos
- Amoxicillin-clavulanate (Augmentin PO) for treating otitis media, sinusitis, bronchitis, lower respiratory tract infections, and human or animal bites (dogmentin LOL).
- Due to expanded activity against gram-positive and gram-negative bacteria, used to treat polymicrobial infections such as intraabdominal infections, gynecological infections, diabetic foot infections.
- Ampicillin-sulbactam (Unasyn IV) for treating mixed aerobic/anaerobic infections.
- Piperacillin-tazobactam (Zosyn IV) for treating polymicrobial infections and other infections involving gram-negative bacteria (pseudomonas aeruginosa) such as hospital acquired infections.
What penicillins are most likely to cause interstitial nephritis?
immune-mediated damage to renal tubules where the penicillin acts as a hapten when bound to renal tubular cells most commonly associated with methicillin but can occur with nafcillin; initial manifestation may be eosinophiluria and an abrupt increase in serum creatinine!
Major AEs of penicillins
- Hypersensitivity reaction is the most frequently occurring side effect.
- Cross-allergenicity observed among natural and semisynthetic penicillins due to their common nucleus patients allergic to one penicillin should be considered allergic to ALL other members of the penicillin family and caution should be sued with some other beta-lactams.
- Neurologic: generalized seizures (not seen with nafcillin/oxacillin because not renally eliminated).
- Hematologic: leukopenia, neutropenia, or thrombocytopenia – usually in patients receiving long-term therapy.
- Gastrointestinal: transient increases in liver enzymes – oxacillin, nafcillin, piperacillin, and carbenicillin; diarrhea with amoxicillin-clavulanate; pseudomembranous colitis
- Phlebitis (nafcillin), hypokalemia (carbenicillin, ticaricillin), sodium overload and fluid retention (ticarcillin, piperacillin)
