Tetracyclines and Glycylcyclines

Agents: doxycycline, minocycline, tetracycline, tigecycline (a glycylcycline)

Once considered broad-spectrum antibiotics, the relentless advance of bacterial resistance and the off-patent status of the drugs have reduced the use of tetracyclines to niche indications. They are useful (but not highly studied) alternatives for the treatment of common respiratory tract infections and drugs of choice for a variety of uncommon infections. Doxycycline is preferred in most situations over tetracycline and minocycline. This class may see a revival with the introduction of the glycylcyclines (starting with tigecycline), which evade most tetracycline resistance mechanisms and have a broad spectrum of activity.

Spectrum: Tetracycline/doxycycline/minocycline

Good: atypicals, rickettsia, spirochetes (e.g.,  B. burgdorferi,  H. pylori),  Plasmodium species  (malaria)

Moderate: staphylococci (including MRSA), S. pneumoniae

Poor : most GNRs, anaerobes, enterococci

Spectrum: Tigecycline

Good: atypicals, enterococci (including VRE), staphylococci (including MRSA), S. pneumoniae Acceptable: most GNRs, anaerobes

Poor : Pseudomonas, Proteus, Providencia

Adverse Effects

GI side effects (nausea, diarrhea) and photosensitivity are most common. Tigecycline, though an IV drug, can cause severe nausea, vomiting, and diarrhea. Tetracyclines can cause esophageal irritation,  and patients should take the drug with water,  while standing up if possible. Minocycline may cause dizziness and vertigo. All tetracyclines can cause discoloration of developing teeth and are contraindicated in pregnant women and children younger than 8 years old.

Important Facts

• Doxycycline and minocycline bioavailability is approximately 100%. Tigecycline is IV only.

 • Tetracyclines chelate cations, and their oral bioavailability is  decreased significantly when administered with calcium, iron, antacids, or multivitamins. Have patients separate these agents by at least 2 hours or take a week off from the supplements, if possible. Food decreases the absorption of tetracycline substantially, but of minocycline and doxycycline minimally.

• Doxycycline does not need to be adjusted in renal or hepatic dysfunction; tetracycline is eliminated renally and should not be used in cases of renal insufficiency (it can worsen renal dysfunction).

• Tigecycline has a very large volume of distribution, indicating that it distributes highly into many tissues. However, it is eliminated hepatically, achieves low urinary concentrations, and  should probably not be used for UTIs. Its extensive distribution also leads to low bloodstream concentrations, and it is not an ideal choice for treating primary bloodstream infections.

What they’re Good For

Uncomplicated respiratory tract infections: acute exacerbations of chronic bronchitis, sinusitis, com-munity-acquired pneumonia. They are the drugs of choice for many tick-borne diseases. Use as alter-native drugs for skin or soft-tissue infections,  syphilis, pelvic inflammatory disease (with cefoxitin). Use as an alternative to ciprofloxacin in bioterrorism scenarios (they are active against anthrax, plague, tularemia). Use for malaria prophylaxis and treatment. Tigecycline may have a role in the treatment of complicated polymicrobial infections, such as intra-abdominal infections and complicated skin and skin structure infections.

Don’t Forget!

Ask patients if they take mineral supplements (like calcium and iron) at home. Just because supple-ments are not on a patient’s medication profile does not mean they do not take them. A patient who washes down a tetracycline with a calcium supplement or even a glass of milk may completely negate an otherwise brilliant therapeutic plan.

References

Gallagher ,J.C. and MacDougall ,c. (2012). Antibiotics Simplified. Second Edition. Jones & Bartlett Learning, LLC.