L27 Protein Synthesis Inhibitors Flashcards
What is the mechanism of action of Clindamycin?
Protein synthesis inhibition via exclusive binding to the 50S ribosomal subunit
Clindamycin is ___ (static/cidal).
Bacteriostatic
What are the mechanisms of resistance to Clindamycin?
- Altered target sites (altered 50S, encoded by erm gene)
- Efflux pump (encoded by mef gene)
- Drug inactivation
Discuss the spectrum of activity of Clindamycin broadly.
- Gram-positive aerobes
- Anaerobes
- Other bacteria
What is the most important Gram positive bacteria Clindamycin has activity against?
MSSA, MRSA
Also: PSSP, group/viridans strep
What is the most important anaerobic bacteria Clindamycin has activity against?
Bacteroides species
Also: Peptostreptococcus, Actinomyces, Propionibacterium, Prevotella, Fusobacterium, Clostridium (not C. diff)
What other bacteria does Clindamcyin have activity against?
Pneumocystis carinii, Toxoplasmosis gondii, Malaria
Discuss the absorption, distribution, and elimination of Clindamycin.
- Rapid and complete absorption (IV and PO)
- Distribution: good, includes bone, minimal CSF
- Elimination: hepatic, not removed during dialysis
What are the clinical uses for Clindamycin?
- Anaerobic infections (NOT CNS)
- SSTI (penicillin allergic patients, MRSA)
- Alternative for C. perfringens, PCP, Toxo, malaria, bacterial vaginosis
What are the most important adverse effects of Clindamcyin?
C. difficile colitis
Also: GI, rare hepatotoxicity, rare allergy, rare neutropenia and thrombocytopenia
What are the three macrolides?
- Erythromycin
- Clarithromycin
- Azithromycin
What is the mechanism of action of macrolides?
Protein synthesis inhibition via exclusive binding to the 50S ribosomal subunit (same as Clindamycin)
Macrolides are ___-dependent and ___ (cidal/static).
Time (E/C); Concentration (A); static, but can be cidal at higher concetrations against susceptible organisms
What are the mechanisms of resistance to Macrolides?
- Altered target sites (altered 50S, encoded by erm gene)
2. Efflux pump (encoded by mef gene)
Discuss the spectrum of activity of Macrolides broadly.
- Gram-positive aerobes (C>E>A)
- Gram-negative aerobes (A>C>E)
- Anaerobes
- Atypical bacteria
- Other bacteria
What are the most important Gram positive bacteria Macrolides have activity against?
MSSA
Other: PSSP, group/viridans strep, Bacillus, Corynebacterium
What are the most important Gram negative bacteria Macrolides have activity against? What does it NOT have activity against?
H. influenzae (not E), M. catarrhalis, Neisseria (none highlighted)
NO Enterobacteriaceae activity
What are the most important anaerobic bacteria Macrolides have activity against?
ADAs
What are the most important atypical bacteria Macrolides have activity against?
Legionella pneumophila
Also: Chlamydophila/Chlamydia, Mycoplasma
What are the most important other bacteria Macrolides have activity against?
MAC (A/C), M. chelonae, H. pylori, Bordetella, Brucella, Pasteurella (none highlighted)
Discuss the absorption, distribution, and elimination of Macrlodies.
Absorption: variable - food may decrease (E), acid stable (C, A)
Distribution: extensive (C, A better), minimal CSF
Elimination: bile (E), kidney (C)
What are the clinical uses for Macrolides?
- Respiratory tract infections
- Uncomplicated skin infections
- STDS (A)*
- MAC (A/C)*
- Alternative for PCN allergic patients (GAS, bacterial endocarditis prophylaxis, syphilis/gonorrhea, RF prophylaxis)
What are the most important adverse effects of Macrolides?
Prolonged QTC
Also: GI, cholestatic hepatitis, thrombophlebitis, tinnitus/deafness
What are the important drug interactions with Macrolides?
E and C are inhibitors CYP450 (increase concentrations of drugs metabolized by these)
