Micro - Cell Wall Synthesis Inhibitors Flashcards
Penicillin G, V mech:
Penicillin G (IV/IM); Penicillin V (oral) Bind penicillin-binding proteins (transpeptidases). Block transpeptidase cross-linking of peptidoglycan. Activate autolytic enzymes
Penicillin uses:
Mostly used for gram + organisms (S. pneumo, S. pyogenes, Actinomyces). Also used for N. meningitidis and T. pallidum.
Bactericidal for gram+ cocci, gram+ rods, gram - cocci, and spirochetes
Penicillinase sensitive
Penicillin tox:
Hypersensitivity reactions, hemolytic anemia
Penicillin resistance:
Penicillinase in bacteria (a type of beta-lactamase) cleaves beta-lactam ring.
Penicillinase can be induced by presence of beta-lactam ring.
Ampicillin, Amoxicillin (Aminopenicillins) mech:
Same as penicillin, but wider spectrum: Binds penicillin-binding proteins (transpeptidases)
Block transpeptidase cross-linking of peptidoglycan.
Combine with Clavulanic acid to protect against beta-lactamase
Aminopenicillin mnemonic:
AMinoPenicillins are AMPed-up penicillin.
AmOxicillin has greater Oral bioavailability than ampicillin. Food doesn’t interfere with Amox
Aminopenicillin uses:
Extended spectrum penicillin - Haemophilus influenzae, E. Coli, Listeria monocytogenes, Proteus mirabilis, Salmonella, Shigella, enterococci, Moraxella catarrhalis, Enterococcus faecalis
Ampicillin/Amoxicillin HELPSS ME kill enterococci
Aminopenicillin tox:
Hypersensitivity reactions; rash (1-28 days, not hypersensitivity rxn –> if used for pts with mono)
Pseudomembranous colitis
Superinfections
Aminopenicillin MOR:
Penicillinase in bacteria (type of beta-lactamase) cleaves beta-lactam ring.
Penicillinase-resistant Penicillins:
Oxacillin, Nafcillin, Dicloxacillin, Methicillin (not used clinically)
Penicillinase-resistant Penicillins mech:
Same as penicillin: Binds PBP (transpeptidases). Blocks transpeptidase cross-linking of peptidoglycan. Activates autolytic enzymes.
Narrow spectrum
Penicillinase-resistant because bulky R group blocks access of beta-lactamase to beta-lactam ring
Penicillinase-resistant Penicillins uses:
S. aureus (except MRSA; resistant because of altered penicillin-binding protein target site)
“Use naf for staph”
Penicillinase-resistant Penicillins tox:
Hypersensitivity rxns, interstitial nephritis (Type IV hypersensitivity)
Anti-Pseudomonals:
Ticarcillin, Piperacillin, Carbenicillin
Anti-Pseudomonal mech:
Same as penicillin: Binds PBPs (transpeptidases) and blocks transpeptidase cross-linking of peptidoglycan. Activates autolytic enzymes.
Extended Spectrum
Anti-Pseudomonal uses:
Pseudomonas spp. and gram - rods (Klebsiella); susceptible to penicillinase; use with beta-lactamase inhibitors
Anti-Pseudomonal tox:
Hypersensitivity rxns
Ticarcillin: prolonged bleeding time; excess Na+ in dosage form may be problem for CHF or renal failure
Beta-Lactamase Inhibitors:
CAST
Clavulanic Acid, Sulbactam, Tazobactam
Beta-Lactamase Inhibitors: uses
Often added to penicillin antibiotics to protect the antibiotic from destruction by beta-lactamase (penicillinase).
Themselves have weak antibacterial activity
Not good inhibitors of inducible beta-lactamases (gram - rods)
Penicillins do not penetrate well into:
Eye, prostate, BBB
In meningitis, BBB is disrupted –> penicillins pass into CSF
Cephalosporins mech:
Beta-lactam drugs that inhibit cell wall synthesis but are LESS SUSCEPTIBLE to penicillnases.
Bactericidal.
Cephalosporins: Organisms not covered
Organisms typically not covered are LAME: Listeria, Atypicals (Chlamydia, Mycoplasma), MRSA, and Enterococci
Exception: ceftaroline covers MRSA
Cephalosporins 1st generation:
Cefazolin, Cephalexin
Gram+ cocci, Proteus mirabilis, E. coli, Klebsiella pneumoniae
1st gen: PEcK
Cefazolin: main use
1st gen cephalosporin - used prior to surgery to prevent S. aureus wound infections
Cephalosporins 2nd generation:
Cefoxitin, Cefaclor, Cefuroxime, Cefprozil
Gram+ cocci, Haemophilus influenzae, Enterobacter aerogenes, Neisseria spp., Proteus mirabilis, E. coli, Klebsiella pneumoniae, Serratia marcescens
2nd gen: HEN PEcKS
Cephalosporins 3rd generation:
Ceftriaxone, Cefotaxime, Ceftazidime, Cefixime
Serious gram - infections resistant to other beta-lactams (Serratia, Pseudomonas, Hib, Neisseria)
Ceftriaxone: main uses
meningitis and gonorrhea (single IM), disseminated Lyme dx
Ceftazidime: main uses
Pseudomonas
Cephalosporins 4th generation:
Cefepime
Increased activity against Pseudomonas and gram+ organisms
Cephalosporins 5th generation:
Ceftaroline
Broad gram+ and gram - organism coverage, including MRSA, does not cover Pseudomonas
Cephalosporins tox:
Hypersensitivity reactions (no skin tests!), Vitamin K deficiency (kill off vit-K producing bacteria in gut).
Low cross-reactivity with penicillins.
Autoimmune hemolytic anemia.
Increased nephrotoxicity of aminoglycosides.
Alcohol intolerance –> Disulfuram like reaction (buildup of acetaldehyde)
Cefaclor tox:
most commonly associated with serum sickness
Aztreonam: mech
A monobactam; resistant to beta-lactamases.
Prevents peptidoglycan cross-linking by binding to penicillin-binding protein 3. Synergistic with aminoglycosides. No cross-allergenicity with penicillins.
Aztreonam: uses
Gram negative rods only - no activity against gram + or anaerobes. For penicillin-allergic pts and those with renal insufficiency who cannot tolerate aminoglycosides.
Aztreonam: tox
Usually nontoxic; occasional GI upset
Carbapenems:
Imipenem, meropenem, ertapenem, doripenem
Carbapenem mech:
Disrupt bacterial cell wall synthesis. Good permeability with gram - and high affinity for PBP
Beta-lactamase resistant
Imipenem: mech
Broad-spectrum, Beta-lactamase-resistant carbapenem. Always administered with Cilastatin (inhibitor of renal dehydropeptidase I) to decrease inactivation of drug in renal tubules
With imipenem, “the kill is lastin’ with cilastatin.”
Carbapenems: uses
Gram+ cocci, gram - rods, and anaerobes.
Wide spectrum, but significant side effects limit use to life-threatening infections or after other drugs have failed.
Meropenem has a decreased risk of seizures and is stable to dehydropeptidase I.
Carbapenems: tox
GI distress, skin rash, and CNS toxicity (seizures) at high plasma levels
Allergies: those allergic to penicillin should be considered allergic to carbapenems
Vancomycin: mech
IV, except when treating C. Diff (oral)
Inhibits cell wall peptidoglycan formation by binding D-ala D-ala portion of cell wall precursors.
Bactericidal.
Vancomycin: uses
Gram + only - serious, multidrug resistant organisms, including MRSA, enterococci, and C. diff
Penetrates CSF
Vancomycin: tox
Well tolerated in general - but NOT trouble free. Nephrotoxicity, Ototoxicity, Thrombophlebitis, diffuse flushing - red man syndrome (can largely prevent by pretreatment with antihistamines and slow infusion rate)
Vancomycin: MOR
Occurs in bacteria via amino acid modification of D-ala D-ala to D-ala D-lac.
“Pay back 2 D-alas (dollars) for VANdalizing (vancomycin).”
