C.17

Question 1

Glycopeptides. Lipopeptides. Bacitracin. Mupirocin

Answer 1

1. Glycopeptides:
   Vancomycin,
   Teicoplanin,
   Oritavancin,
2. Polypeptides:
   Baritracin,
   Daptomycin,
   Fusidic acid,
3. Miscellaneous antibiotics:
   Mupirocin

Question 2

glycopeptides

Answer 2

MOA: binds D-ala-D-ala group→ preventing binding of PBP enzyme;
SEs: Nephrotoxicity (vancomycin - higher risk), Ototoxicity (Teicoplanin - mild hearing disturbances, tinnitus;
-Vancomycin - risk irreversible damage), Red man syndrome (Vancomycin - histamine release→flushing, blood pressure fall), Local irritation (pain, phlebitis at injection site), Neutropenia

Question 3

Vancomycin

Answer 3

Pharmacokinetics: bad absorption (p.o administration - local action in GI tract), wide distribution, short T1/2, excretion by kidneys, not removed by hemodialysis;
IND: parentrally (1h i.v. infusion 2x/day)→ sepsis or endocarditis caused by MRSA, in combination with aminoglycosides alternative for enterococcal endocarditis in patients with penicillin allergy, in combination with cefotaxime/ceftriaxone/rifampin for the treatment of meningitis caused by highly penicillin-resistant strain of pneumococcus, highly resistant Corynebacterium Jeikeium strain. Oral vancomycin→ treatment of enterocolitis caused by C.difficile (in this case metronidazole is preferred);
Drug interactions: combination with aminoglycosides can be dangerous and cause irreversible hearing damage)

Question 4

Teicoplanin

Answer 4

Pharmacokinetics: bad absorption
(administration p.o →local action in the GI tract), wide distribution (low cc. in liquor), high protein binding, long T1/2 (45-70min), excretion by kidneys, not removed by hemodialysis;
IND: same as vancomycin, systemic use i.v. or i.m. X1/day

Question 5

Oritavancin

Answer 5

IND: acute bacterial skin and skin structure infections caused by G(+) bacteria;
Pharmacokinetics: high protein binding, excreted by the kidneys, long T1/2

Question 6

Bacitracin

Answer 6

MOA: inhibits cell wall synthesis (by peptidoglycan subunit transfer);
Spectrum: all G(+) bacteria;
SEs: highly nephrotoxic;
Pharmacokinetics: administered ONLY topically (due to toxicity), no absorption from GI tract;
IND: wounds, surface lesions, irrigation of joint wounds, pleural cavity; Extra: polypeptide from Bacillus Subtilis

Question 7

Daptomycin

Answer 7

MOA: incorporated into the cell membrane →depolarizes it→ cell death;
Bactericidal;
Spectrum: active against polyresistant G(+) cocci;
SEs: myopathy, CK elevation; Extra: inactivated by surfactant (→ not to use in pneumonia!);
ROA: parentral;
IND: Severe skin & sofy tissue infections, S. aureus endocarditis

Question 8

Fusidic acid

Answer 8

MOA: Interferes with bacterial protein synthesis
(→ prevents translocation of the EF-G from the ribosome); Bactriostatic;
Pharmacokinetics: high protein binding, eye drops or p.o (↑BAp.o), T1/2=5-6h;
Spectrum: G(+) (besides enterococci), Clostridium and Corynebacterium;
SEs: systemic use can be hepatotoxic

Question 9

Mupirocin

Answer 9

IND: ONLY effective against G (+) and only locally, impetigo and secondary skin infections caused by S. aureus and S.pyogenes, also used for MRSA decolonization;
MOA: Specifically and reversibly binds bacterial tRNA synthetase→inhibition of bacterial protein and RNA synthesis;
Bacteriostatic at ↓cc but exerts bactericidal with prolonged exposure;
Pharmacokinetics: administered topically, p.o or i.v., high protein binding, metabolized and eliminated by kidneys, T1/2=20-40min, can be excreted in breast milk