Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc. Chapter 85 Bacteriostatic Inhibitors of Protein Synthesis: Tetracyclines, Macrolides, and Others

Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.2 Tetracyclines   Four members of the tetracycline family available for systemic therapy   Tetracycline   Demeclocycline   Doxycycline   Minocycline

Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.3 Tetracyclines  Tetracyclines  Broad-spectrum antibiotics  Inhibit protein synthesis  Increasing bacterial resistance has emerged  Uses  Rickettsial disease  Chlamydia trachomatis  Brucellosis  Cholera

Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.4 Tetracyclines  Uses (cont’d)  Mycoplasma pneumoniae  Lyme disease  Anthrax  Helicobacter pylori  Acne  Peptic ulcer disease  Periodontal disease

Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.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

Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.6 Tetracyclines  Drug and food interaction  Absorption of tetracyclines decreased if given with: Milk products Milk products Calcium supplements Calcium supplements Iron supplements Iron supplements Magnesium-containing laxatives Magnesium-containing laxatives Most antacids Most antacids

Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.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

Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.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

Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.9 Other Macrolides  Clarithromycin (Biaxin)  Azithromycin (Zithromax)  Dirithromycin (Dynabac)  Troleandomycin (Tao)

Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.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

Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.11 Clindamycin (Cleocin)  Adverse effects  Antibiotic-associated pseudomembranous colitis Hepatic toxicity Hepatic toxicity Blood dyscrasias Blood dyscrasias Diarrhea Diarrhea Hypersensitivity reactions Hypersensitivity reactions

Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.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)  Active against multidrug-resistant gram-positive pathogens (eg, vancomycin-resistant enterococci (VRE), methicillin-resistant Staphylococcus aureus (MRSA)

Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.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

Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.14 Linezolid (Zyvox)  Most common side effects  Diarrhea  Nausea and vomiting  Headache  May also cause myelosuppression  Drug interaction with MAOIs

Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.15 Telithromycin  First representative of ketolides class of antibiotics  Use  Effective against strains of Streptococcus pneumoniae  Adverse effects  GI effects  Gray syndrome  Visual disturbances

Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.16 Dalfopristin/Quinupristin  First members of streptogramins (new class of antibiotics)  Inhibit bacterial protein synthesis  Principal indication – VRE  Adverse effects  Hepatotoxicity  Drug interactions  CYP3A4

Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.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

Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.18 Additional Drugs  Spectinomycin (Trobicin)  Tigecycline (Tygacil)  Retapamulin and mupirocin  Topical antibiotics indicated for impetigo  Mupirocin – also for MRSA in nostrils