Bacteriostatic Inhibitors of Protein Synthesis: Tetracyclines, Macrolides, and Others

Tetracyclines   Four members of the tetracycline family available for systemic therapy   Tetracycline   Demeclocycline   Doxycycline   Minocycline

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

Tetracyclines  Uses (cont’d)  Mycoplasma pneumoniae  Lyme disease  Anthrax  Helicobacter pylori  Acne  Peptic ulcer disease  Periodontal disease

Tetracyclines  Absorption: chelation  Calcium supplements, milk products, iron supplements, magnesium-containing laxatives, and most antacids  Adverse effects  Gastrointestinal irritation  Effects on bone and teeth  Superinfection  Hepatotoxicity  Renal toxicity  Photosensitivity and other effects

Tetracyclines  Summary of major precautions  Tetracycline and demeclocycline are eliminated primarily in urine and will accumulate in patients with kidney disease  Discoloration of deciduous and permanent teeth  Diarrhea may indicate a potentially life-threatening suprainfection of the bowel  High-dose IV therapy has been associated with severe liver damage

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

Macrolides (Erythromycin)  Broad-spectrum antibiotic  Mechanism of action (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

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

Other Macrolides  Clarithromycin (Biaxin)  Azithromycin (Zithromax)

Clindamycin (Cleocin)  Inhibits protein synthesis  Can induce severe Clostridium difficile– associated diarrhea (CDAD) (can be fatal)  Active against most anaerobic bacteria (gram-positive and gram-negative)  Indicated only for certain anaerobic infections located outside the central nervous system (CNS)

Clindamycin (Cleocin)  Adverse effects  Clostridium difficile–associated diarrhea (CDAD) Hepatic toxicity Blood dyscrasias Blood dyscrasias Diarrhea Diarrhea Hypersensitivity reactions Hypersensitivity reactions

Linezolid (Zyvox)  First member of a newer 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])

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

Linezolid (Zyvox)  Most common side effects  Diarrhea  Nausea and vomiting  Headache  May also cause myelosuppression  Drug interaction with monoamine oxidase inhibitors (MAOIs)

Telithromycin  First representative of ketolide class of antibiotics  Use  Effective against strains of Streptococcus pneumoniae  Adverse effects  GI effects  Gray syndrome  Visual disturbances

Dalfopristin/Quinupristin  First members of streptogramins (new class of antibiotics)  Inhibit bacterial protein synthesis  Principal indication: VRE  Adverse effects  Hepatotoxicity  Drug interactions  CYP3A4

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

Additional Drugs  Tigecycline (Tygacil)  Active against broad spectrum of bacteria  Associated with increased mortality  Retapamulin and mupirocin  Topical antibiotics indicated for impetigo  Mupirocin: also for MRSA in nostrils