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