JITT Beta Lactams Flashcards
What do beta lactams do?
They inhibit transpeptidases and carboxypeptidases (PBPs!), thereby killing bacteria as they try to grow and divide
What does transpeptidase do? Carboxypeptidase?
Cleaves D-ala to D-ala in the NAM sections of the peptidoglycan, Releases ATP
What are the main kinds of beta lactams?
Penicillins, beta-lactamase inhibitors, cephalosporins, monobactams, carbepenems
What are penicillin binding proteins?
PBPs are transpeptidases and carboxypeptidases - targets of beta-lactams!
What are the 3 determinants of antibiotic activity?
- Can it get to its target (permeability)?
- Can it bind to its target (affinity)?
- Will it be destroyed first (stability)?
How do gram + and gram - bacteria try to decrease permeability?
Gram +: thick peptidoglycan layer; Gram -: small peptidoglycan layer w/ porin (porin size is very important to permeability; it’s harder for many beta lactams to get into gram negs than gram positives)
How do beta-lactamases differ in gram positives vs gram negatives?
Gram +: release beta-lactamases into the environment (hoping to kill antibiotic before it gets to the cell wall); gram -: more like an ambush - concentrated in the periplasmic space (more efficient)
What are the key beta-lacatamase examples?
Penicillin ashes, cephalosporin ashes, extended-spectrum beta-lactamases, ampC beta-lactams she’s, carbepenemases
What makes MRSA resistant?
PBP-2a
What antibiotics can you use in MRSA?
Non-beta-lactams like linezolid, vancomycin, daptomycin
How is s. Pneumoniae developing resistance and to what?
Acquires alterations in its PBPs, resulting in resistance to penicillins (and in rare cases cephalosporins)
What are the basics of pharmacology in beta-lactams?
Short half-lives (often have to dose every 4-6h), excellent penetration into bodily fluids (sometimes CSF), most are renally excreted (so they require dose adjustment in renally impaired patients)
What are general side effects of beta lactams?
seizures, diarrhea, C. Difficile colitis, renal toxicity (particularly interstitial nephritis), immune-mediated cytopenias
What can you use if patient has penicillin allergy?
Aztreonam
What are rare cross-reactive beta lactams if patient has allergy to penicillin?
Cephalosporins and carbepenams
What is penicillin G? How is it active?
Acts against: gram positive cocci, streptococci, enterococcus, staphylococci (note: many staph and strep are now penicillin-resistant); treatment of choice for syphilis, n. Meningitidis, strep pyogenes, dental infections, IUD infections
What are the different common penicillins and how are they given?
Penicillin G: IV; Benzathine penicillin: IM; Penicillin G procaine: IM; Penicillin VK: oral
How can anti-staphylococcal penicillins fight beta-lactamases?
Bulky side chain - steric hindrance - BUT they can’t enter gram-negatives
What are the anti-staphylococcal penicillins?
Don’t “NOD” off now! Nafcillin, oxacillin, dicloxacillin; NOTE they undergo biliary excretion (negligible renal clearance)
What are amino-penicillins?
Penicillins w/ -NH3 group, can get through porins giving them better GNR coverage (strep and enterococci); have to add beta-lactamase inhibitor to some b/c it will prevent the antibiotic from being killed in the periplasmic space
What are common amino-penicillins and what are added to them?
Ampicillin, amoxicillin; ampicillin-sulbactam, amoxicillin-clavulanate
What are the side effects of beta-lactamase inhibitors?
GI (diarrhea, vomiting, pain)! Amoxicillin has better absorption than ampicillin b/c it has an -OH that makes it stable in stomach acid
What are anti-pseudo only penicillins?
Piperacillin-tazobactam (aka Zosyn) - broad spectrum of action, beta-lactamase inhibitor, given for HAI and VAP; NOT treatment of choice for bacteria w/ AmpCs
What are beta lactams?
Antibiotics that inhibit the bacterial cell wall; bactericidal; the beta lactam nucleus must be intact for the antibiotic to be active; side chains give different pharmacodynamic properties
What are first generation cephalosporins?
Cephalexin (PO), cefezolin (IV); used in Gram +s, streptococci, staphylococci, Gram -s (E coli, klebsiella, proteus); particularly helpful for skin and soft tissue infections or in the OR as perioperative prophylaxis to prevent surgical site infections
What should you NOT use first generation cephalosporins for?
Enterococci, MRSA, resistant GNs, gut anaerobes (aka bacteroides)
What are the differences between cephalosporins?
Cephalosporin nucleus can be modified in many places, yielding different drugs
What are 2nd gen cephalosporins?
Increased GN activity, decreased GP activity; Cefuroxime - h influenza epidemic, community acquired respiratory tract infections; cefoxitin, cefotetan: increased anaerobic coverage and against beta-lactams she bacteroides - used in gut and pelvic surgery
What are 3rd gen cephalosporins?
Better GN coverage, great for pneumococcus that is resistant to penicillin; ceftriaxone and cefotaxime have excellent CNS penetration and are frequently used to treat meningitis (Ax in the Head); used to treat gonorrhea
What are 4th gen cephalosporins?
Broadest cephalosporin; used for gram positives and gram negatives (including pseudomonas), excellent CNS penetration; Cefepime
What are 5th gen cephalosporins?
Ceftaroline - very new, similar to non-pseudomonas 3rd gen cephalosporins, increased affinity for PBP2a (MRSA), not currently used without ID consult
What is aztreonam?
Used for GN infections in severely PCN allergic patients
What is carbepenemases?
SUPER BROAD SPECTRUM - gram positive (but not MRSA), gram-negative (even if ESBL or ampC); excellent CNS penetration
When should you not use carbapenem?
MRSA, E. Fascism, listeria, stenotrophomonas, burkholderia
What is the key side effect of carbepenams?
May cause seizures in high doses/cases of renal insufficiency
What are the key beta-lactamases?
TEM-1 and TEM-2
What are the organisms w/ ampC beta-lactamases?
SPACE organisms (Serratus, pseudomonas indole, acinetobacter, vitro cater, enterobacter)
What is vancomycin?
Glycopeptide antibiotic (NOT a beta-lactam); only active against gram-positive bacteria (like MRSA) - use in MRSA, resistant s. Pneumonia do, enterococci, listeria, bacillus, clostridium species
How does vancomycin work?
Binds to the terminus and prevents PBPs from cross-linking the cell walls
How should vancomycin be given for C. difficile?
Orally or rectally
What is Redman syndrome?
If vancomycin runs in quickly, then histamine is released (face gets red, patient is itchy) - may have renal toxicity
What is the relevant pharmacology of vancomycin?
> 90% eliminated by kidney (so has to be dose adjusted for those w/ renal insufficiency); dosed by weight; have to monitor trough levels to ensure adequate serum concentrations and prevent toxicity
