Cell Wall and Membrane Active Antibiotics Flashcards
Classic penicillins
Drugs
Clinical use
Adverse effects
Classical penicillins: Drugs: - Penicillin G (benzylpenicillin) - IV: crystalline penicillin G - IM: procaine penicillin G, benzathine penicillin G - Oral penicillin V
Clinical use:
- Gram-positive aerobes (especially S. pyogenes, S. pneumoniae, Actinomyces)
- Gram-negative cocci (especially Neisseria meningitidis)
- Spirochetes (especially Treponema pallidum)
Adverse effects:
- Hemolytic anemia, seizures
Anti Staphylococcal Penicillins
Drugs Special characteristics Clinical use Adverse effects Development of resistance
Anti-staphylococcal penicillins: Drugs (oral or IV): - Nafcillin - Dicloxacillin - Oxacillin - Methicillin
Special characteristics:
- Intrinsically beta-lactamase resistant through the addition of bulky side chains (e.g., isoxazolyl)
Clinical use:
- Gram-positive aerobes, especially S. aureus (non-MRSA)
Adverse effects:
- Interstitial nephritis
Development of resistance:
- Due to alteration of binding site of penicillin-binding proteins → reduced affinity → pathogen is not bound or inactivated by β-lactam (one of the main virulence factors in MRSA)
Aminopenicillins
Drugs
Clinical use
Adverse effects
Aminopenicillins:
Drugs:
- Oral or IV amoxicillin (possibly ± clavulanate)
- IV or IM ampicillin (possibly ± sulbactam)
- Structures are similar to penicillin, therefore are susceptible to beta-lactamase degradation.
Clinical use: - Wider spectrum of activity than penicillin - Some gram-positive aerobes and gram-negative bacilli - Aminopenicillin therapy HHEELPSSS H. pylori H. influenza E. coli Enterococci Listeria Proteus Salmonella Shigella Spirochetes
Adverse effects:
- Diarrhea
- Pseudomembranous colitis
- Drug-induced rash when treating patients with infectious mononucleosis
AmOxicillin is administered Orally, while amPicillin is administered via a Prick!
Ureidopenicillins
Drugs
Clinical use
Ureidopenicillins:
Drugs:
- IV piperacillin (+ tazobactam)
Clinical use:
- Gram-negative bacilli
- Especially Pseudomonas
- Also anaerobes, i.e., Bacteroides fragilis
- Gram-positive aerobes
Carboxypenicillins
Drugs
Clinical use
Carboxypenicillins: Drugs: - IV ticarcillin - IV carbenicillin - Intrinsically beta-lactamase resistant
Clinical use:
- Gram-negative bacilli, especially Pseudomonas
For antipseudomonals: A TICk kills Pseudomonas with a
PIPE bomb in a CAR. (ticarcillin, piperacillin, carbenicillin)
Carbapenems
Drugs
Clinical use
Adverse effects
Drugs:
- IV imipenem (+ cilastatin)
- IV meropenem
- IV ertapenem
- IV doripenem
Clinical use:
- Broad-spectrum antibiotics with intrinsic beta-lactamase resistance
- Gram-positive cocci
- Gram-negative bacilli
- Anaerobes
Adverse effects:
- Considered a “last resort” drug because of its significant adverse effects
- Secondary fungal infections
- Can lower seizure threshold (especially imipenem)
- Gastrointestinal upset
- Skin rash
- Thrombophlebitis
“I’m a pen” that crosses out all the bacteria
Monobactams
Drug
Clinical use
Adverse effects
Drug:
- IV aztreonam
Clinical use:
- Intrinsic beta-lactamase resistance
- Very effective against gram-negative bacilli only (the opposite of vancomycin), including nosocomial Pseudomonas
- Alternative for penicillin-allergic patients
- Alternative to aminoglycosides for patients with renal insufficiency
- Broad-spectrum coverage in combination with vancomycin or clindamycin
- Synergistic with aminoglycosides
Adverse effects:
- Gastrointestinal upset
1st Generation Cephalosporins
First generation cephalosporins:
Drugs:
- Oral –> cephalexin
- IV, IM –> cefazolin
Clinical use:
- Gram-positive cocci
- Proteus mirabilis
- E. coli
- Klebsiella
- Cefazolin is used to prevent surgical wound infections (perioperative prophylaxis)
First generation cephalosporins: PEcK
2nd Generation Cephalosporins
Second generation cephalosporins:
Drugs:
- Oral –> cefaclor, cefuroxime (axetil)
- IV –> cefoxitin, cefotetan, cefuroxime
Clinical use:
- Gram-positive cocci
- H. influenza
- Enterobacter
- Neisseria
- Proteus mirabilis
- E. coli
- Klebsiella
- Serratia
Second generation cephalosporins: HEN PEcKS
3rd Generation Cephalosporins
Third generation cephalosporins: Drugs: - Oral --> cefixime - IV --> ceftriaxone , cefotaxime, ceftazidime, cefoperazone - IM --> ceftriaxone
Clinical use:
- Severe gram-negative infections that are resistant to other beta-lactams (e.g., Enterobacteriaceae)
- Ceftazidime and cefoperazone are effective against Pseudomonas.
- Ceftriaxone (good CNS penetration) is used in disseminated Lyme’s disease, meningitis, gonorrhea, and for perioperative prophylaxis against wound infection
4th Generation Cephalosporins
Fourth generation cephalosporins:
Drugs:
- IV cefepime
Clinical use:
- Gram-negative bacteria (including Pseudomonas)
↑ Activity against gram-positive bacteria (particularly Staphylococcus)
- Severe life-threatening infections (including nosocomial)
- Sepsis
- Pneumonia
- Severe urinary or biliary tract infections
- Intra-abdominal infections (including peritonitis)
5th Generation Cephalosporins
Fifth generation cephalosporins:
Drugs:
- IV ceftaroline
Clinical use:
- Gram-positive bacteria (including MRSA!)
- Gram-negative bacteria (but not effective against Pseudomonas!)
- Complicated skin and soft tissue infections
- Cephalosporins can be LAME because they don’t act against Listeria, Atypical organisms (Chlamydia, Mycoplasma), MRSA , and Enterococci!
Adverse effects of cephalosporins
Adverse effects of cephalosporins:
- Cross-reactivity in patients with penicillin allergies
- Autoimmune hemolytic anemia
- Vitamin K deficiency → increased bleeding tendency
- Some cephalosporins may cause a disulfiram-like reaction when consumed with alcohol (flushing, tachycardia, hypotension).
- Can lower seizure threshold
- Increase the nephrotoxicity of aminoglycosides
Glycopeptides
Glycopeptides:
Drugs:
- Oral or IV vancomycin
Mechanism of action:
- Inhibits cell wall synthesis by binding the D-ala-D-ala portion of cell wall precursors, which are present only in gram-positive bacteria.
- Vancomycin is bactericidal.
CNS penetration:
- Only when meninges are inflamed
Route of elimination:
- Renal
Clinical use:
- Especially effective against multidrug-resistant organisms
- Broad-spectrum coverage against gram-positive bacteria only
- Methicillin-resistant Staphylococcus aureus (MRSA)
- S. epidermidis
- Enterococci
- Clostridium difficile
Adverse effects:
- Nephrotoxicity
- Ototoxicity/vestibular toxicity
- Rapid infusions are associated with anaphylactoid reactions (“red man syndrome” or “red neck syndrome”)
- Thrombophlebitis
- Neutropenia
Contraindications:
- Pregnancy (relative contraindication)
Lipopeptides
Drugs:
- Daptomycin
Mechanism of action:
- Incorporation of potassium ion-channels into the cell membrane of pathogens, leading to rapid membrane depolarization
→ Inhibition of intracellular synthesis of DNA, RNA, and proteins.
- Bactericidal
CNS penetration:
- Poor
Route of elimination:
- Renal
Clinical use:
- Gram-positive aerobes
- However, daptomycin only has limited efficacy against Enterococci.
- MRSA –> daptomycin should not be used in patients with MRSA pneumonia because it binds to pulmonary surfactant and gets inactivated by it.
- Vancomycin-resistant Enterococci (VRE)
Adverse effects:
- Reversible myopathy
- Rhabdomyolysis
- Allergic pneumonitis
