Tetracycline Antibiotics Overview

Tetracycline

• Short-acting: Chlortetracycline, Oxytetracycline, Tetracycline
• Intermediate-acting: Demeclocycline, Methacycline
• Long-acting: Doxycycline (Vibramycin), Minocycline (Minocin)

Tetracycline Spectrum & Mechanism of Action

• Effective against rickettsiae, gram-positive and gram-negative bacteria, chlamydia
• Inhibits protein synthesis by binding to the 30S subunit of the bacterial ribosome, preventing the binding of aminoacyl tRNA to the mRNA ribosomal complex
• Bacteriostatic

Tetracycline Absorption

• Incomplete GI absorption: tetracycline (60-80%), doxycycline (95%), minocycline (100%)
• Dairy foods decrease absorption through chelation with calcium ions; also magnesium, iron, and aluminum (antacids)

Tetracycline Distribution

• Widely distributed in the body
• Bind in tissues undergoing calcification (teeth, bones) or tumors with high calcium content (gastric carcinoma)
• Cross the placenta and concentrate in fetal bones and teeth

Tetracycline Excretion

• Doxycycline and minocycline are largely excreted in feces, making them suitable for use in renal insufficiency

Tetracycline Resistance

• Efflux pump
• Enzymatic inactivation
• Prevention of binding to ribosomes

Tetracycline Therapeutic Uses

• Lyme disease
• Mycoplasma pneumonia
• Rocky Mountain spotted fever
• Acne
• Chlamydia
• Cholera

Tetracycline Adverse Effects

• GI discomfort: anorexia, epigastric pain, abdominal distention, nausea, vomiting, diarrhea, sore mouth, perianal irritation
• Hepatotoxicity
• Nephrotoxicity
• Teeth damage in neonates if doses are not adjusted
• Low capacity to glucuronidate antibiotic and underdeveloped renal function in neonates, leading to decreased excretion ability
• Poor feeding, cyanosis, and death in neonates

Aminoglycosides

• Streptomycin
• Gentamycin (Genticin, Gentamycin)
• Tobramycin
• Amikacin
• Kenamycin
• Netilmicin
• Neomycin (Cicatrin powder, Polyfax ointment)

Aminoglycosides Mechanism of Action

• Binds to the 30S ribosomal subunit, interfering with the assembly of the functional ribosomal apparatus or misreading of the genetic code
• Effective against aerobic gram-negative bacteria
• Bactericidal or bacteriostatic

Aminoglycosides Kinetics

• All are parenteral except neomycin
• Neomycin is only used topically to reduce intestinal bacteria

Aminoglycosides Resistance

• Decreased uptake
• Altered receptor
• Enzymatic modification

Aminoglycosides Therapeutic Uses

• Bacterial endocarditis (in combination with penicillin)
• Tuberculosis (in combination with Streptomycin)
• Tularemia (hunters skinning infected animals)
• Urinary tract infections (E. coli, Enterobacter)
• Pneumonia (Pseudomonas, E. coli, Klebsiella)
• Meningitis
• Peritonitis
• Serious infections with Enterobacteriaceae and other aerobic gram-negative bacilli

Aminoglycosides Adverse Effects

• Ototoxicity
• Nephrotoxicity
• Neuromuscular paralysis
• Contact dermatitis (neomycin topical)
• Monitor peak and trough plasma levels

Macrolides

• Erythromycin
• Azithromycin
• Clarithromycin
• Dirithromycin
• Troleandomycin
• Telithromycin

Macrolides Mechanism of Action

• Bind to the 50S subunit of the bacterial ribosome, inhibiting the translocation step of protein synthesis
• Bacteriostatic activity
• Achieve better intracellular concentrations with gram-positive bacteria
• Clarithromycin and Azithromycin are more effective against anaerobes

Macrolides Metabolism

• Inhibits the oxidation of other drugs through interaction with the cytochrome P-450 system.

Macrolides Resistance

• Inability of the organism to take up the antibiotic
• Decreased affinity of the binding site for the antibiotic
• Efflux pump

Macrolides Therapeutic Uses

• Mycoplasma pneumonia
• Syphilis (in penicillin-allergic patients)
• Chlamydia (alternative to tetracycline during pregnancy)
• Legionellosis pneumonia
• Corynebacterium diptheriae carriers (prevention)
• Ureaplasma urethritis
• Alternative to penicillin in allergic patients
• Clarithromycin (Klaricid) and Azithromycin (Azomax) are used for:
  • COPD and pneumonia
  • Pharyngitis and tonsillitis
  • Acute maxillary sinusitis
  • Lower respiratory tract infections

Macrolides Adverse Effects

• Epigastric distress: nausea, vomiting, pain, diarrhea
• Cholestatic jaundice
• Ototoxicity (high doses)

Chloramphenicol

Chloramphenicol Mechanism of Action

• Binds to the 50S ribosomal subunit, inhibiting the peptidyl transferase step of protein synthesis
• Bacteriostatic
• Broad spectrum

Chloramphenicol Kinetics

• Excretion depends on conversion in the liver to glucuronide, then excretion in the kidneys

Chloramphenicol Therapeutic Uses

• Severe odontogenic infections threatening orbital contents or the brain
• Typhoid fever (Salmonella)
• Refractory meningitis caused by H. influenzae, S. pneumoniae, N. meningitidis, rickettsia, brucella, and Bacteroides

Chloramphenicol Adverse Effects

• Anemias
  • Hemolytic (reversible and mild)
  • Aplastic
• Gray baby syndrome (especially in neonates)

Clindamycin

Clindamycin Mechanism of Action

• Binds to the 50S subunit of bacterial ribosomes, inhibiting protein synthesis
• Bacteriostatic, but bactericidal against susceptible organisms in vivo

Clindamycin Spectrum

• Similar to erythromycin
• Increased activity against gram-positive and gram-negative anaerobes, including Staphylococcus aureus

Clindamycin Therapeutic Uses

• Infections caused by Streptococcus, Staphylococcus, pneumococcus, and anaerobic organisms
• Purulent osteitis or other bone infections caused by anaerobes

Clindamycin Adverse Effects

• GI distress: diarrhea
• Pseudomembranous colitis caused by Clostridium difficile
• Superinfections

Streptogramins

• Quinupristin-dalfopristin