Tetracyclines, Macrolies, & Other Protein Synthesis Inhibitors
Name the 5 macrolide antibiotics and describe their MOA.
(a) 1. erythromycin; 2. azithromycin; 3. clarithromycin; 4. telithromycin; 5. fidaxomycin (b) MOA: bind to 50S ribosomal subunit; bacteriostatic
Name the 4 tetracycline antibiotics and describe their MOA.
(a) 1. tetracycline; 2. doxycycline; 3. minocycline; 4. tigecycline (b) MOA: binds to 30S ribosomal subunit; bacteriostatic; resistance
Chloramphenicol
(a) MOA: binds to 50S ribosomal subunit; bacteriostatic (b) Indications: wide spectrum, but mainly backup (e.g., for severe infections by Salmonella species; for treatment of pneumococcal and meningococcal meningitis in beta-lactam sensitive individuals); NO activity against Chlamydia species; bactericidal for highly susceptible strains of Haemophilus influenzae, Neisseria meningitidis, and Bacteroides (c) ADRs: dose-related aplastic anemia; gray baby syndrome (d) Pharmacokinetics: oral, IV; hepatic clearance; short half-life; commonly used as a topical agent to avoid toxicities (e) Resistance: plasma-mediated acetyltransferases that inactivate the drug
Clindamycin
(a) Subclass: Lincosamide (b) MOA: bind to 50S ribosomal subunit; bacteriostatic (c) Indications: skin, soft tissue, and anaerobic infections; main use is in the treatment of severe infections caused by certain anaerobes, such as Bacteroides; back-up drug against gram-positive cocci (MRSA); recommended for prophylaxis of endocarditis in valvular disease patients allergic to penicillin; active against Pneumocystis joriveci; used in combination with pyrimethamine for AIDS-related toxoplasmosis (d) ADRs: GI upsets; C. difficile pseudomembranous colitis (e) Pharmacokinetics: oral, IV; hepatic clearance
Tetracycline, Doxycycline, Minocycline, Tigecycline
(a) Subclass: Tetracyclines (b) MOA: binds to 30S ribosomal subunit; bacteriostatic; tigecycline has broadest spectrum and resistance is least common (c) Primary Indications: infections due to Chlamydiae, Mycoplasma, Rickettsiae, vibrios, spirochetes, and H. pylori (d) Secondary Indications: alternative to macrolides in the initial treatment community acquired pneumonia (doxycycline); alternative drugs for treatment of syphilis, respiratory infections, leptospirosis, and treatment of acne (e) ADRs: GI upsets, deposition in developing bones and teeth, photosensitivity, superinfection (life-threatening enterocolitis); contraindicated in pregnancy (f) Pharmacokinetics: Oral, IV; renal & biliary clearance; doxycycline mainly in GI elimination and long half-life; oral absorption impaired by foods and multivalent cations
Eyrthromycin, Azithromycin, Clarithromycin, Telithromycin, Fidaxomicin
(a) Subclass: macrolides (b) MOA: bind to 50S ribosomal subunit; bacteriostatic; least resistance to telithromycin (c) Indications: community-acquired pneumonia, Pertussis, Corynebacteria, and Chlamydial infections (d) ADRs: GI upsets, hepatic dysfunction, QT elongation; CYP450 inhibition (with the exception of azithromycin). (e) Pharmacokinetics: Oral; IV for erythromycin, azithromycin; hepatic clearance; azithromycin long half-life (>40h)
Linezolid
(a) Subclass: oxazolidinone (b) MOA: binds to 23S RNA of 50S subunit; bacteriostatic (c) Indications: activity includes MRSA, PRSP, and VRE strains; also active against L. monocytogenes and corynebacteria (d) ADRs: dose-related anemia, neuropathy, optic neuritis; serotonin syndrome with SSRIs (e) Pharmacokinetics: oral, IV; hepatic clearance
Quinupristin-dalfopristin
(a) Subclass: streptogramins (b) MOA: binds to 50S ribosomal subunit; bactericidal (c) Indications: staphylococcal infections (MRSA & VRSA); vancomycin-resistant E. faecium (not E. faecalis b/c of efflux pump resistance) (d) ADRs: infusion-related arthralgia and myalgia; CYP450 (3A4) inhibition (e) Pharmacokinetics: IV; renal clearance
Tigecycline
Antimicrobial activity if tigecycline includes gram-positive cocci resistant to methicillin (MRSA) and vancomycin (VRE), beta-lactamase-producing gram-negative bacteria, anaerobes, chlamydiae, and mycobacteria
Erythromycin
Effective in the treatment of infections caused by M pnuemoniae, Corynebacterium, Campylobacter jejuni, Chlamydia trachomatis, Chlamydophila pneumoniae, Legionella Pneumophila, Ureaplasma urealyticum, and Bordetella pertussis; drug also has activity against gram-positive cocci (but not MRSA or PRSP).
Demeclocycline
Inhibits the actions fo antidiuretic hormone (ADH) and is used in the management of patients with ADH secreting tumors
Telithromycin
Ketolide antibiotic structurally related to macrolides with same MOA; less bacterial resistance; used in community acquired pneumonia and multidrug resistant organisms; ADRs—hepatic dysfunction, prolongation of QTc interval, inhibition of CYP3A4
Fidaxomicin
Narrow spectrum macrolide; selectively active against gram-positive aerobes and anaerobes; as effective as vancomycin for treatment of C difficile colitis
Clarithromycin
Similar to azithromycin but greater activity against species of Chlamydia, Mycobacterium avium complex, and Toxoplasma gondii; used as prophylaxis against and treatment of M avium complex and as a component of drug regimens for ulcers caused by H pylori.
Azithromycin
Similar to erithromycin but more active against H influenzae, Moraxella catarrhalis, and Neisseria; due to its long half-life, single dose effective in treatment of urogenital infections caused by C trachomatis and a 4-day course treatment is effective in community-acquired pneumonia
Doxycycline
Treatment for Lyme disease; Prevention of Malaria; Treatment of Amebiasis; alternative to macrolides in the initial treatment community acquired pneumonia
Minocycline
Treatment for meningococcal carrier state
Tetracycline
Treatment of gastrintestinal ulcers
