B&B Beta Lactams Flashcards
Penicillin consists
Beta Lactam Ring Thiazolidine Ring (only found in penicillin)
Carbapenems, Aztreonam, Cephalosporins
Beta Lactam Antibiotics
Have similar MOA to penicillin
Bind transpeptidases (penicillin-binding proteins)
Prevents peptidoglycan crosslinking
Autolysis
Usually bacteriocidal
Potentially susceptible to beta lactamase enzymes (because contain beta lactamase ring)
Carbapenems
Imipenem, Meropenem, Ertapenem, Doripenem
Carbapenems are
Beta-lactams (not penicillins b/c not attached to thiazoladine ring)
Resistant to cleavage by most beta-lactamase
Extended Spectrum Beta Lactamase (ESBL)
Plasmid-mediated bacterial enzymes Confer resistance to most beta-lactam antibiotics: -Penicillin -Cephalosporins -Aztreonam
Where are extended spectrum beta lactamase (ESBL) enzymes found?
Gram-negative bacteria
Gram-negative bacteria
Pseudomonas Klebsiella E. Coli Enterobacter Salmonella Serratia Shigella
Carbapenems
Impenem, Meropenem, Etrapenem, Doripenem
What is the drug of choice for ESBL bacteria?
Carbapenems Broad spectrum: -Gram (+) -Gram (-) including pseudomonas, enterobacter -Anaerobes including B. fragilis Used in hospitalized patients
First commercially available Carbapenem
Imipenem Metabolized in kidneys -Loss of antibacterial effect -Nephrotoxic metabolites Proximal tubule enzyme: dehydropeptidase I Given with cilastatin (enzyme inhibitor)
Carbapenem S/E
N/V/D
Skin rash
Carbapenem S/E with high doses or renal failure
Neurotoxicity
- Seizures due to inhibition of GABA receptors
- Lower risk with Meropenem
Aztreonam
Monobactum: Beta-lactum ring not fused to another ring
Aztreonam MOA
Binds only to penicillin-binding protein 3 (PBP-3) -Found in gram (-) bacteria -Prevents cross-linking of peptidoglycan -Bactericidal Limited susceptibility to beta-lactamase -Some resistance in ESBL bacteria Only active against gram (-) bacteria -Does not bind PBP of gram (+) bacteria -No activity against gram (+) or anaerobes -Active against pseudomonas
Aztreonam is administered
IV (hospitalized patients)
Aztreonam is synergistic with
aminoglycosides
Does Aztreonam cross-react with penicillin allergies?
No. Can be used safely with penicillin allergy.
Cephalosporin
Similar structure to penicillin but not attached to thiazolidine
Cephalosporins are divided into
1st through 4th generations
1st generation Cephalosporins
Mostly gram positive coverage
Successive generations of Cephalosporins
Gradually increased gram (-) coverage
1st Generation Cephalosporins
Cefazolin, Cephalexin
1st Generation Cephalosporins (Cefazolin and Cephalexin) were developed to treat
S. Aureus resistance to penicillin
1st Generation Cephalosporins (Cefazolin and Cephalexin) covers
Many gram (+) including S. Aureus (but not MRSA
- Stable against. S. Aureus beta lactamase
- Does not cover enterococcus or listeria
- Susceptible to gram (-) beta lactamases
Main uses of 1st Generation Cephalosporins
Surgical wound (skin) infections Cefazolin give pre-op for prevention
2nd Generation Cephalosporins
Cefuroxime, Cefutoxin, Cefotetan
- Developed to treat amoxicillin-resistant infections
- Increased affinity for gram (-) PBPs
- More resistant to beta lactamase
- Increased gram (-)
- Increased anaerobic coverage (B. fragilis)
Gram (-)
H. influenza, Enterobacter, Proteus
E. Coli, Klebsiella, Serratia, N. gonorrhea
Cefuroxime (oral)
2nd generation Cephalosporin
- Otitis media (S. pneumonia, H. flu)
- UTI in kids (E. coli, no fluoroquinolones)
Cefoxitin/Cefotetan (IV)
2nd generation Cephalosporin
PID (covers Neisseria, also give doxycycline for chlamydia)
Pre-op in kids with appendicitis
-E. Coli
-Covers gram negatives and some anaerobes
-Usually given with metronizadole
3rd Generation Cephalosporins
Ceftriaxone
Cefotaxime
Ceftazidime
3rd Generation Cephalosporins have
Broad gram (-) coverage
- more resistance to beta lactamase enzymes
- more gram (-) PBP affinity
Ceftriaxone, Cefotaxime
3rd Generation Cephalosporins
Do not cover pseudomonas well
Ceftazidime
3rd Generation Cephalosporins
Covers pseudomonas
-Used in hospitalized patients with gram (-) infections
-Sepsis/pneumonia
3rd Generation Cephalosporins (Ceftriaxone, Cefotaxime, Ceftazidime): Most achieve good
CSF penetration (meningitis)
Ceftriaxone
3rd Generation Cephalosporin Commonly used in N. gonorrhea Commonly used in meningitis -Active against S. pneumonia, N. meningitis -Good CSF penetration
4th Generation Cephalosporin
Cefepime Broad spectrum (>3rd generation drugs) -MSSA -Many gram (+)'s -Many gram (-)'s including pseudomonas Resistant to some ESBL Hospitalized patients with gram (-) infections
Sensitivity to beta-lactamase is based on
side chain
Most sensitive to beta-lactamase
Penicillins
Exception: Antistaphylococcal penicillins can resist staph penicillinase
Which Cephalosporin Generation is most resistant to beta-lactamase?
4th Generation
Aztreonam is very resistant to beta-lactamase but
is resistant to gram (-) only
Most resistant to beta-lactamase
Carbapenems most resistant to beta-lactamase so drug of choice in setting of ESBL bacteria
What resistance mechanisms do bacteria use against Cephalosporins?
Modified penicillin binding proteins (PBPs)
Altered cell permeability
Beta lactamase
Cephalosporins Adverse Effects
Same hypersensitivity reactions as penicillin
Cephalosporins have some allergic cross-reactivity with
Penicillin
Cephalosporins Adverse Reactions: Vitamin K Deficiency
Vitamin K1 from diet
Vitamin K2 from GI bacteria
Antibiotics reduce bacterial vitamin K production
Result: Increased INR and potential bleeding
Problem for patients on Warfarin
May be caused by any antibiotic
What is a cause of bleeding that is unique to Cephalosporins?
Hypoprothrombinemia (reduced clotting factor levels)
Cefotetan and Cefazolin have NMTT side chains that inhibit epoxide reductase (similar to Warfarin)
-decrease in hepatic synthesis of clotting factors
-may prolong PT/INR
-Reversible with Vitamin K
-mostly reported in malnourished patients
Cephalosporins can cause nephrotoxicity when combined with
aminoglycosides (well known cause of nephrotoxicity)
What can occur when alcohol is consumed with Cephalosporin?
Disulfuram reaction
Alcohol consumption with cephalosporins
Warmth, flushing, sweating
Inhibition of acetaldehyde dehydrogenase
Accumulation of acetaldehyde occurs with certain side chain structures
Only occurs with Cefoperazone, Cefamandole, and Cefotetan
Ethanol Metabolism
Ethanol is metabolized to acetaldehyde by alcohol dehydrogenase
Acetaldehyde is metabolized to acetate by aldehyde dehydrogenase
Cephalosporins inhibit aldehyde dehydrogenase
Increased levels of acetaldehyde makes alcoholics sick and not want to drink
