Chapter 85

1. Chapter 85 Bacteriostatic Inhibitors of Protein Synthesis: Tetracyclines, Macrolides, and Others

2. Tetracyclines • Four members of the tetracycline family available for systemic therapy • Tetracycline • Demeclocycline • Doxycycline • Minocycline

3. Tetracyclines • Tetracyclines • Broad-spectrum antibiotics • Inhibit protein synthesis • Increasing bacterial resistance has emerged • Uses • Rickettsial disease • Chlamydia trachomatis • Brucellosis • Cholera

4. Tetracyclines • Uses (cont’d) • Mycoplasma pneumoniae • Lyme disease • Anthrax • Helicobacter pylori • Acne • Peptic ulcer disease • Periodontal disease

5. Tetracyclines • Absorption – chelation • Calcium supplements, milk products, iron supplements, magnesium-containing laxatives, and most antacids • Adverse effects • Gastrointestinal irritation • Effect on bone and teeth • Superinfection • Hepatotoxicity • Renal toxicity • Photosensitivity and other effects

6. Tetracyclines • Drug and food interaction • Absorption of tetracyclines decreased if given with: • Milk products • Calcium supplements • Iron supplements • Magnesium-containing laxatives • Most antacids

7. Macrolides (Erythromycin) • Broad-spectrum antibiotic • MOA – inhibition of protein synthesis • Usually bacteriostatic but can be bactericidal • Use if allergic to penicillin • Active against most gram-positive and some gram-negative bacteria

8. Macrolides (Erythromycin) • Therapeutic uses • Whooping cough, acute diphtheria, Corynebacterium diphtheriae, chlamydial infections, M. pneumoniae, group A Streptococcus pyogenes • Drug interactions • Adverse effects • Gastrointestinal • QT prolongation and sudden cardiac death • Superinfection

9. Other Macrolides • Clarithromycin (Biaxin) • Azithromycin (Zithromax) • Dirithromycin (Dynabac) • Troleandomycin (Tao)

10. Clindamycin (Cleocin) • Inhibits protein synthesis • Can induce severe antibiotic-associated pseudomembranous colitis (can be fatal) • Active against most anaerobic bacteria (gram-positive and gram-negative) • Indicated only for certain anaerobic infections located outside the CNS

11. Clindamycin (Cleocin) • Adverse effects • Antibiotic-associated pseudomembranous colitis • Hepatic toxicity • Blood dyscrasias • Diarrhea • Hypersensitivity reactions

12. Linezolid (Zyvox) • First member of a new class of antibiotics – oxazolidinones • Use • Active against multidrug-resistant gram-positive pathogens (eg,vancomycin-resistant enterococci (VRE), methicillin-resistant Staphylococcus aureus (MRSA)

13. Linezolid (Zyvox) • Bacteriostatic inhibitor of protein synthesis • Cross-resistance with other agents unlikely • Active against aerobic and facultative gram-positive bacteria • VRE and MRSA

14. Linezolid (Zyvox) • Most common side effects • Diarrhea • Nausea and vomiting • Headache • May also cause myelosuppression • Drug interaction with MAOIs

15. Telithromycin • First representative of ketolides class of antibiotics • Use • Effective against strains of Streptococcus pneumoniae • Adverse effects • GI effects • Gray syndrome • Visual disturbances

16. Dalfopristin/Quinupristin • First members of streptogramins (new class of antibiotics) • Inhibit bacterial protein synthesis • Principal indication – VRE • Adverse effects • Hepatotoxicity • Drug interactions • CYP3A4

17. Chloramphenicol (Chloromycetin) • Broad-spectrum antibiotic • Inhibits protein synthesis • Uses • Only for life-threatening infections for which safer drugs are ineffective or contraindicated • Adverse effects • Reversible bone marrow depression • Fatal aplastic anemia • Gray syndrome • GI effects • Peripheral neuropathy

18. Additional Drugs • Spectinomycin (Trobicin) • Tigecycline (Tygacil) • Retapamulin and mupirocin • Topical antibiotics indicated for impetigo • Mupirocin – also for MRSA in nostrils