Exam 1 - Smith - Antimicrobials I Flashcards
Name some antimicrobials that affect the cell wall synthesis in bacteria.
Beta lactams
- Penicillins
- Cephalosporins
- Carbapenems
- Monobactams
Vancomycin
Bacitracin
All beta-lactam drugs are known for 3 things. Name them.
Require actively proliferating microorganisms
Are INACTIVE against organisms devoid of peptidoglycans
-Viruses, mycobacteria, and fungi
Are Type II Time-Dependent - Most effective is dosed to achieve serum concentrations for at least 50% of dosing interval
To be effective, beta-lactams must first do what?
Evade bacterial defenses
Penetrate outer cell layers
Protect beta-lactam ring structure
**Bind to transpeptidase enzymes (AKA Penicillin-binding protein (PBP)
What is transpeptidase?
Penicillin binding protein
If a penicillin binds transpeptidase, what happens?
Bacterial cell wall is unable to form, and the bacteria is killed (autolyse)
What are 2 natural penicillins?
Penicillin G - this is the only naturally occurring penicillin
Penicillin V (Penicillin VK)
Great against Gram (+), except S aureus, and are very susceptible to bacterial beta-lactamases
What are 2 aminopenicillins (extended spectrum penicillins)?
Ampicillin
Amoxicillin
- Can effect Gram (-)’s
- Still susceptible to beta-lactamases
**These drugs are often paired with beta-lactamase inhibitors
What are 4 penicillinase-resistant penicillins? (Anti-staphylococcal penicillins)
Methicillin
Nafcillin
Oxacillin
Dicloxacicillin
**Relatively resistant to beta-lactamases
USE NAF FOR STAPH - First line treatment of choice for staphylococcal endocarditis
What are the 3 anti-pseudonomal penicillins to know?
Aztreonam
Piperacillin
Ticarcillin
*Ticarcillin and then piperacillin have the broadest spectrums of activity
What drug has 5 generations and what is that based on?
Cephalosporins
Based on their activity profile
What is imipenem?
Broadest antibacterial available - It is a CARBAPENEM
What is the only true naturally occurring penicillin?
Penicillin G
Pen G. Tell me about it
NATURAL
- Narrow spec - good against G(+)
- *Rapidly hydrolysis by penicillinase enzymes (beta-lactamase enzymes)
- Administered IV or IM (intramuscularly) - Poor Oral bioavailability - stomach acids destroy the drug
Pen V. Tell me about it
Acid-stable - so can be taken orally
Similar to Pen G, but less effective
What is benzathine penicillin?
Drug of choice when prolonged, low conc req’d
Treatment for syphilis
Aminopenicillins are what?
Extended spec penicillins
- Better Gram (-) coverage than either Pen G or Pen V
- Extends to sensitive strains of G(-) bacteria (H. Influenzae) and enterics
- Still sensitive to beta-lactamases
- Used for Listeria, prophylaxis of infective endocarditis, and UTIs
What is usually administered with a beta-lactamase inhibitor?
Aminopenicillins
What are the 2 main aminopenicillins?
Ampicillin
Amoxicillin
*Amoxicillin has higher oral absorption, longer half-life, and less likely to cause adverse GI effects than ampicillin
Amoxicillin does what to renal tubular excretion of methotrexate?
Causes prolonged high serum levels of methotrexate
What is the drug-of-choice for standard prophylactic prevention of bacterial endocarditis when appropriate?
Amoxicillin
*An alternative, in case of allergy is: **Cephalexin - 1st generation cephalosporin
**IF a beta-lactam allergy: Use clindamycin, azithromycin (Z-Pak), or clarithromycin
Ampicillin. Tell me about it.
Amoxicillin is much better to use b/c the side effects and requirements are lessened
What is the drug of choice in patients unable to take oral penicillins?
Ampicillin (parenterally)
- Ampicillin causes diarrhea - pseudomembranous colitis (C diff overgrowth), rashes, hypersensitivity rxns
- Oral contraceptives are not as effective if ampicillin is taken, and it slows renal excretion
How does probenecid increase serum levels of most beta-lactam antibacterials?
Uric acid reducer
- Inhibits organic anion transporters
- Probenecid does not interact with nafcillin, oxacillin, and dicloxacillin since they are Lipophilic and undergo biliary excretion, not renal
What is the mnemonic to know?
USE NAF FOR STAPH
*Use nafcillin for S aureus infections
What are 4 drugs to know that are penicillinase-resistant penicillins?
Methicillin (discontinued in US)
Nafcillin
Oxacillin
Dicloxacillin
-These are the drugs of choice against S aureus and s epidermidis that are not MRSA
What is the drug of choice for serious S aureus infections?
Nafcillin
What should you know about oxacillin and dicloxacillin?
Activity and beta-lactamase resistance similar to methicillin, but ACID STABLE, so orally active, and reduced risk of interstitial nephritis
Name 3 anti-pseudo Oral penicillins.
Carboxypenicllins
Ureidopenicillins
Monobactams
-Used for serious bacteremia, pneumonias, burn victims, UTIs
What are 2 carboxypenicillins to know?
Indanyl carbenicillin
Ticarcillin
-This is more active than indanyl carbenicllin, and is an injectable agent against G(-) bacteria, esp P aeruginosa
What is the broadest spec of the antipseudomonal penicillins?
Piperacillin
What is a great drudge to use for pts with IgE-mediated penicillin allegory?
Aztreonam (IV)
Can cause c diff overgrowth
What are common side effects of penicillins?
Hypersensitivity
-10% of people are allergic to penicillins and these people are usually cross sensitive to all other beta-lactams, including cephalopsporins
Local effects
Lethargy, confusion
Superinfection risk
What is pseudomembranous colitis induced diarrhea?
Aminopenicillins (ampicillin), piperacillin, cephalosporins, and aztreonam
Cephalosporins have how many generations and based on what?
5
By antimicrobial activity
- Resistant to many older beta-lactamases
- Renally excreted
- Pts with history of anaphylaxis CANNOT take this**
_____________ have a cross allergy with penicillins of only ~5%.
Cephalosporins
**Pts with a history of anaphylaxis cannot take cephalosporins
1st generation cephalosporins - what drugs and what do they do?
Cephalexin
Cefazolin
-Active against G(+), some G(-) - Not good against enterococci, MRSA, and S epidermidis
2nd generation cephalosporins - what drugs and what do they do?
Cefaclor
Cefuroxime
Cefoxitin
-Increased activity against G(-) that’s 1st gen, but less active than the 3rd gen
3rd generation cephalosporins - what drugs and what do they do?
Cefdinir
Cefotaxime
Ceftaxidime
Ceftriaxone
-Less active than 1st gen against G(+) cocci, but much more active against G(-)’s like enterobacteriaceae
4th generation cephalosporin - what drug and what does it do used for?
Cefepime
-Good activity against G (+) and G (-); even more beta-lactamase resistance
5th generation cephalosporin - what drug and what does it do?
Ceftaroline
-Good activity against MRSA, G (+) and G (-)
Cephalosporins generations 1-3- as generations increase, so does what two things?
Gram (-) activity and beta-lactamase resistance
Also, spectrum gets broader
What is special about 4th and 5th generation cephalosporins?
Good with both Grams and good resistance to beta-lactamases
*5th gen is good against MRSA
**B/c 2,3,4,5 generations are more broad spec, superinfection is a risk
________ is used for prophylaxis prior to surgery, and its most active against S aureus and strep.
Cefazolin
What is cefaclor used to treat?
Oral sinusitis and otitis media caused by H influenzae
What is Cefoxitin used for?
Kill anaerobes and extended beta-lactamase resistance
What is Cefuroxime used for?
Can cross the blood brain barrier to reach CNS
What has the broadest spectrum of all the cephalosporins and are extremely effective against G(-) organisms?
3rd generation cephalosporins
-Useful for G(-) bacteremias
-Can cross the BBB
What 3rd gen cephalosporin is active against Pseudomonas aeruginosa?
Ceftazidime
What is the highest selling cephalosporin?
Cefdinir
What are the 1st line treatment options for strep throat?
Penicillin
Amoxicillin
What is Cefepime?
4th generation
- Used for Strep and methicillin-susceptible staph and P aeruginosa
- Poor anaerobic coverage
What is Ceftaroline?
5th gen cephalosporin
- Active against MRSA
- Used for community-acquired (CA) pneumonia and complicated skin infections
Go thru Cephalosporins:
1st Gen
2nd Gen
3rd Gen
4th Gen
5th Gen
1st - Cephalexin, Cefazolin
2nd - Cefaclor, Cefuroxime, Cefoxitin
3rd - Cefdinir, Cefotaxime, Ceftazidime, Ceftriaxone
4th - Cefepime
5th - Ceftaroline
Tell me about Carbapenems.
Imipenem (Primaxin namebrand)
BROADEST SPECTRUM COVERAGE AVAILABLE TO MAN (IV or IM)
Used for multi-drug resistant organisms
What two bugs are resistant to Carbapenems?
MRSA
Mycoplasma
T/F - Carbapenems are very stable in the presence of beta-lactamases, including penicillinase and cephalosporinase that are resistant to most beta-lactam antibiotics.
TRUE
What is an adverse effect of carbapenem use?
Renal clearance is critical - Renal insufficiencies will cause seizures
What is Imipenem coadministered with?
Cilistatin
- This protects the imipenem from being degraded by the renal enzyme dehydropeptidase 1
- Meropenem and ertapenem are not inactivated by the renal enzyme and don’t require cilistatin
What are the protectors that are sometimes coadministered with antibiotics?
Usually beta-lactamase inhibitors or help protect the drug from being degraded too quickly
