B&B Beta Lactams Flashcards by Erina McKinney

Penicillin consists

Beta Lactam Ring
Thiazolidine Ring (only found in penicillin)

How well did you know this?

Not at all

Perfectly

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)

How well did you know this?

Not at all

Perfectly

Carbapenems

Imipenem, Meropenem, Ertapenem, Doripenem

How well did you know this?

Not at all

Perfectly

Carbapenems are

Beta-lactams (not penicillins b/c not attached to thiazoladine ring)
Resistant to cleavage by most beta-lactamase

How well did you know this?

Not at all

Perfectly

Extended Spectrum Beta Lactamase (ESBL)

Plasmid-mediated bacterial enzymes
Confer resistance to most beta-lactam antibiotics:
-Penicillin
-Cephalosporins
-Aztreonam

How well did you know this?

Not at all

Perfectly

Where are extended spectrum beta lactamase (ESBL) enzymes found?

Gram-negative bacteria

How well did you know this?

Not at all

Perfectly

Gram-negative bacteria

Pseudomonas
Klebsiella
E. Coli
Enterobacter
Salmonella
Serratia
Shigella

How well did you know this?

Not at all

Perfectly

Carbapenems

Impenem, Meropenem, Etrapenem, Doripenem

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

First commercially available Carbapenem

Imipenem
Metabolized in kidneys
-Loss of antibacterial effect
-Nephrotoxic metabolites
Proximal tubule enzyme: dehydropeptidase I
Given with cilastatin (enzyme inhibitor)

How well did you know this?

Not at all

Perfectly

Carbapenem S/E

N/V/D

Skin rash

How well did you know this?

Not at all

Perfectly

Carbapenem S/E with high doses or renal failure

Neurotoxicity

Seizures due to inhibition of GABA receptors
Lower risk with Meropenem

How well did you know this?

Not at all

Perfectly

Aztreonam

Monobactum: Beta-lactum ring not fused to another ring

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

Aztreonam is administered

IV (hospitalized patients)

How well did you know this?

Not at all

Perfectly

Aztreonam is synergistic with

aminoglycosides

How well did you know this?

Not at all

Perfectly

Does Aztreonam cross-react with penicillin allergies?

No. Can be used safely with penicillin allergy.

How well did you know this?

Not at all

Perfectly

Cephalosporin

Similar structure to penicillin but not attached to thiazolidine

How well did you know this?

Not at all

Perfectly

Cephalosporins are divided into

1st through 4th generations

How well did you know this?

Not at all

Perfectly

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