Antibiotics II: Cell Wall Inhibitors Flashcards
What are the Beta-Lactams?
▪ Broad group of antibiotics including the penicillins, cephalosporins and carbapenems
▪ All have a beta-lactam ring (4 membered lactam) with different side chains
▪ Cell wall inhibitors – target bacterial cell walls
▪ Only effective against actively growing
bacteria
▪ Bactericidal, time dependent
▪ Some cross allergenicity between groups – conflicting data (< 1% to 10%) *side chain similarity
What do Beta-Lactams bind to?
▪ Bind to penicillin binding proteins (PBPs) which prevent the crosslinking of the cell wall components (peptidoglycans)
▪ PBPs are a family of enzymes needed for cell wall synthesis
▪ The cell wall is protective for the bacteria
- Cell contents are hyperosmolar and therefore withOUT the cell wall the cells swell and the bacterial cell membrane lyses (b/c of osmotic diff b/t inside/outside)
▪ Binding to a PBP in the septum of dividing bacteria prevent the division and result in long filamentous bacteria that die
What are the Penicillins?
▪ Natural penicillins
▪ Penicillinase resistant penicillins
▪ Extended Spectrum Penicillins
- Aminopenicillins
- Antipseudomonal
What are the names of the Natural Penicillins?
▪ Penicillin G, Penicillin VK
What are the Natural Penicillins?
▪ Penicillin G-IV, IM
▪ Dosed in million units
- Eg. 4MU IV q4h
▪ Penicillin V Potassium - PO
- Dose in mg eg. 300mg PO q6h
▪ Adjust dosing in renal impairment
▪ Short half-life (〰30-60 minutes)
▪ Poor penetration across blood brain barrier-even with inflamed meninges
▪ Spectrum of Activity (narrow):
*- Mostly gram positive – ie. streptococci, enterococci, gram negative cocci and some anaerobes
- Staphylococci produce penicillinases and are resistant
What are the names of the Penicillinase Resistant Penicillins?
▪ Cloxacillin, oxacillin, methicillin
What are the Penicillinase Resistant Penicillins?
▪ Cloxacillin used clinically in Canada
▪ IV or PO
▪ Absorption decreased with food therefore separate out in time
▪ Hepatic metabolism – do not have to adjust for renal impairment
▪ Distributes widely in the body including bone, eyes and most body fluids
Spectrum of activity (narrow)
▪ Gram positives including staphylococcus (methicillin sensitive staphylococcus aureus-MSSA) and streptococci
▪ not enterococci, gram negatives and anaerobes
What are the names of the Aminopenicillins?
▪ Amoxicillin-PO (and IV available as combination with clavulanic acid)
▪ Ampicillin-IV or PO
What are the Aminopenicllins?
▪ Amoxicillin-PO (and IV available as combination with clavulanic acid)
▪ Ampicillin-IV or PO
▪ Half-life 1-2 hours
▪ Adjust in renal impairment
Spectrum of Activity:
- gram positives (not staphylococci) and some gram negatives
- Like penicillin but with better gram negative coverage
- When combined with beta-lactamase inhibitor (clavulanate, sulbactam) then broader coverage including staphylococci, most gram negative and anaerobes
What are the names of the Antipseudomonal?
▪ Piperacillin-IV
What are the Antipseudomonal?
▪ Piperacillin-IV
▪ No longer available alone- *just in combination with tazobactam (b/c too much resistant)
▪ Adjust dosing in renal impairment
▪ Short half-life approx. 1 hour
▪ Spectrum of Activity (broad): Developed to cover Pseudomonas Aeruginosa
- When combined with beta-lactamase inhibitor (tazobactam) then coverage includes most gram positive, most gram negative including pseudomonas and most anaerobes
- “big gun”
What are the names of the Cephalosporins?
▪ Derived from the mold Acremonium
▪ 5 generations
▪ Generations 1-3 are available in Canada
What are the Cephalosporins?
▪ Derived from the mold Acremonium
▪ 5 generations
▪ Generations 1-3 are available in Canada
▪ Similar mechanism of action to penicillins – bind to PBPs and inhibit cross linking of the peptidoglycans in the bacterial cell wall
▪ Bactericidal, time-dependent
*▪ Overall more stable against beta lactamases and therefore have broader spectrum of activity
What are the names of the 1st Generation Cephalosporins?
▪ Cephalexin – PO
▪ Cefazolin – IV
▪ Others include: cefadroxil, cephalothin, cephirin and cephradrine (don’t know these)
What are the 1st Generation Cephalosporins?
▪ Cephalexin – PO
▪ Cefazolin – IV
▪ Others include: cefadroxil, cephalothin, cephirin and cephradrine
▪ Distributes widely into most tissues and fluids – poor CSF penetration
▪ Short half-life – 30-80 minutes
▪ Renal excretion – adjust in renal impairment
Spectrum of activity:
- Good gram positive coverage both staphylococci and streptococci, not enterococci
- Some gram negative coverage (not pseudomonas) and some anaerobes
What are the names of the 2nd Generation Cephalosporins?
▪ Cefuroxime, cefaclor, cefprozil – PO
▪ Cefuroxime, cefoxitin, cefotetan – IV
What are the 2nd Generation Cephalosporins?
▪ Cefuroxime, cefaclor, cefprozil – PO
▪ Cefuroxime, cefoxitin, cefotetan – IV
▪ Renally cleared - adjust dosing in renal impairment
▪ Spectrum of activity
- In general cover what 1st generation covers with increased gram negative coverage (some respiratory organisms) and anaerobes including B. fragilis
What are the names of the 3rd Generation Cephalosporins?
▪ Ceftazidime, ceftriaxone – IV
▪ Cefixime – PO
▪ Others include: cefoperazone, cefotaxime, ceftizoxime, cefpodoxime, cefdinir,cefditoren,ceftibuten
What are the 3rd Generation Cephalosporins?
▪ Ceftazidime, ceftriaxone – IV
▪ Cefixime – PO
▪ Others include: cefoperazone, cefotaxime, ceftizoxime, cefpodoxime, cefdinir,cefditoren,ceftibuten
▪ Ceftriaxone does not need to be adjusted for renal impairment
▪ Distributes widely into most body tissues and fluids
Spectrum of Activity
- In general, better gram negative and anaerobic coverage and loses some of the gram positive coverage
- Ceftriaxone – has activity against most gram positive organisms (not MRSA or enterococcus)
- Ceftazidime - covers pseudomonas
What are the names of the 4th and 5th Cephalosporins?
▪ Cefepime and ceftaroline
What are the 4th and 5th Cephalosporins?
▪ Cefepime and ceftaroline
▪ Cefepime – gram positive, gram negative including pseudomonas, and anaerobes
▪ Ceftaroline – gram positive including MRSA, gram negatives and anaerobes
What are the Carbapenems?
▪ Similar mechanism of action to penicillins – bind to PBPs and inhibit cross linking of the peptidoglycans in the bacterial cell wall
▪ Bactericidal, time-dependent
▪ Resistant to most beta lactamases (not carbapenemases or metallo- beta lactamases) and therefore have broad spectrum of activity
▪ Thought to have less cross allergenicity to other beta lactams
What are the names of the Carbapenems?
▪ Meropenem, Ertapenem – IV
▪ Also Imipenem and Doripenem
What are the Carbapenems?
▪ Meropenem, Ertapenem – IV
▪ Also Imipenem and Doripenem
▪ Penetrate body tissues and fluids well including CSF
▪ Bactericidal – time dependent
▪ Ertapenem – long half life 4 hours which allows for once daily dosing
▪ Spectrum of activity (broad) cover most gram positive, gram negative and anaerobes (ertapenem does not cover pseudomonas)
What are the names of the Monobactams?
▪ Aztreonam IM, IV
What are the Monobactams?
▪ Aztreonam IM, IV
▪ Distributes widely into body tissues and CSF
▪ Adjust dose in renal impairment
▪ Spectrum of Activity: aerobic gram negative rods (including pseudomonas)
What are the adverse reactions of the Monobactams?
▪ Mostly gastrointestinal – nausea, vomiting
▪ Allergic reactions – rash, hives, anaphylaxis
What are the names of the Glycopeptide?
▪ Vancomycin – IV, PO
What are Glycopeptides?
▪ Vancomycin – IV, PO
▪ Inhibits cell wall synthesis through binding to d-alanine-d-alanine on the peptidoglycan terminus which prevents further elongation and cross-linking
▪ Distributes widely into tissue and fluids *except CSF
▪ PO vancomycin not absorbed from the GI tract – c.diff tx (have to give PO - severe diarrhea)
▪ Slowly bacteriocidal, AUC/MIC
▪ Spectrum of Activity (narrow): gram positives including MRSA and enterococci and clostridium difficile
What is Vancomycin?
▪ Levels routinely drawn for IV formulation to ensure dosing is in target range and to prevent toxicity
▪ Weight based dosing adjusted for renal function
▪ Large molecule – v. poor absorption from GI tract
What are the adverse effects of Vancomycin?
▪ Red man syndrome – infusion related reaction causing flushing (red at back of neck & top of shoulders)
- slow down rate
▪ Renal toxicity - if levels are really high
▪ Ototoxicity at very high levels
What are the names of the Cyclic Lipopeptide?
▪ Daptomycin IV
What are the Cyclic Lipopeptides?
▪ Daptomycin IV
▪ Binds to cell membrane which results in depolarization with potassium efflux
▪ Bacteriocidal
▪ Inactivated by pulmonary surfactant therefore cannot be used for pneumonia (*not for lung infections)
▪ Adjust dose for renal impairment
▪ Adverse reactions
▪ Rare cases of rhabdomyolysis, allergic pneumonitis
▪ Spectrum of Activity – similar to vancomycin
