Cell Wall Agents Flashcards
Bacterial cell wall action
Bacteriacidal
Agents kill when cell walls are synthesizing
Fosfomycin
Inhibits Maureen monomer synthesis
Effective against gram negative in urinary tract infections
E. coli, Klebsiella, Serratia
Enters via g6p or glycerophosphate transporter
Vancomycin
Gram positive
MRSA
Bind D-Ala-D-Ala of murine monomer unit, inhibiting peptidoglycan polymerization
Resistance via D-Ala-D-Lactate
Not absorbed orally, only used orally for C. diff
Rapid IV infusion leads to red mans syndrome (histamine, IgE)
Monitor troughs
Timer dependent killing
Beta lactams
Inhibits transpeptidase that mediates cross linking
Organisms that lack peptidoglycan cell walls are inherently resistant (mycobacteria, protozoa)
Most active in logarithmic phase
Beta lactam resistance
Production of beta lactamases
Encoded on DNA plasmids
Beta lactamase inhibitors often added to prevent beta lactamase catalyze degradation of penicillin
Cephalosporins and carbapenems steric hinderance prevents beta lactamase degradation but ESBL and carbapenemases have emerged
Beta lactam resistance
Alterations in or acquisition of Penicillin binding proteins
MRSA has altered PBP = inherent resistance to beta lactams except ceftaroline
Intracellular bacterial generally resistant (mammalian cells lack beta lactam uptake mechanisms)
Beta lactamase inhibitors
Clavulanic acid
Sulbactam
Tazobactam
Beta lactam side effects
Seizures: GABA antagonists, esp Ipienem
Most renally cleared, except Ceftriaxone
Lipophilic and highly bound to plasma protein, can displace bilirubin from albumin binding to sites in neonates, CONTRAINDICATED
Penicillin G and V
Narrow spectrum beta lactamase susceptible
Not staph infections
Used for strep and syphillis, gram + anaerobes
T. Palladium very effective, pregnant women undergo desensitization protocols
Aminopenicillins
Ampicillin (PO, IV) and Amoxicillin (PO)
Penicillinase sensitive
Stable in acid
Amino group increases penetration through gram -
Neisseria, Escherichia, Haemophilus, enterococci, listeria, H pylori, Klebsiella
Amoxicillin for S pneumoniae
Penicillinase resistant penicillins
Oxacillin, nafcillin (gram +), cloxacillin, methicillin
Bulky substitutes prevent breakdown by wimpy beta lactamase but also limit spectrum
For confirmed staphylococcal infection
Antipseudomonal penicillins
Ticarcillin, piperacillin
Piperacillin has broadest spectrum of penicillins
Ticarcillin, only available with clavulanate, significant amounts of Na
Klebsiella, Pseudomonas, Enterobacter, Bacteroides
Resistance to Penicillins
Inactivation of antibiotic by beta lactamase
Modification of target PBP (basis of MRSA and penicillin resistance in pneumococci and enterococci, resistant organisms produce PBP with low affinity for beta lactam Abx)
Impaired penetration of drug to target PBP (only in gram - due to cell wall)
Abx efflux (gram -)
Cephalosporins
Similar mechanism to penicillins
Not active against LAME
Listeria
Atypical pathogens in pneumonia (mycoplasma and chlamydophilia)
MRSA
Enterococci
Susceptible to ESBLs but not to most wimpy beta lactamases
First generation cephalosporins
Cephalexin (PO) and Cefazolin (IV)
Gram +, some gram - (PEcK: proteus, E. coli, Klebsiella)
Don’t let LEXicon FAZe you, 1st gen only one with PH
2nd generation cephalosporin
Cefprozil, Cefoxitin, Cefuroxime, Cefaclor
Gram + and HENPEcK (Haemophilus, Enterobacter, Neisseria, Proteus, E. coli, Klebsiella
3rd gen cephalosporin
Cefdinir (PO), Ceftriaxone (IV, IM and not cleared renally), Ceftazidime (IV), Cefotaxime
Community acquired PNA, gonorrhea, meningitis
Ceftazidime:Pseudomonas
4th gen cephalosporin
Broad spectrum including pseudomonas
Resistant to many beta lactamases
Febrile neutropenia, diabetic foot, HCAP/VAP, decubiti
5th gen cephalosporin
Ceftaroline
IV only
Ceftriaxone that also covers MRSA
Acute bacterial skin infections and community acquired PNAs
Carbapenems
Injectable only
Imipenem/Cilastatin, Ertapenem, Doripenem, Meropenem
ESBL gram -, Pseudomonas, Acinetobacter, anaerobes
Cilastatin added to imipenem to prevent deactivation by dipeptidase in renal brush border cells (low urinary concentrations)
Seizures (esp imipenem)
Aztreonam
Monobactam: safe even in severe beta lactam allergy (except Ceftazidime)
Similar to amino glycosides aerobic gram - including Pseudomonas
Cell wall agents and special populations
Allergy to beta lactam: type 1 to penicillin, cephalosporin, or carbapenem, avoid other classes; other type switch to different class
Neonates: Ceftriaxone may displace bilirubin, no supplemental IV Ca + Ceftriaxone
Pregnancy: beta lactams, vancomycin generally safe
