Tetracyclines

Tetracyclines are a class of antibiotics that may be used to treat infections caused by susceptible microorganisms such as gram positive and gram negative bacteria, chlamydiae, mycoplasma, protozoans, or rickettsiae.

They were discovered in the 1940s and the first tetracyclines were obtained or derived from Streptomyces bacteria.

Tetracyclines inhibit protein synthesis in the microbial RNA (an important molecule that acts as a messenger for DNA). They are primarily bacteriostatic which means that they prevent bacteria from multiplying but don't necessarily kill them.

Although tetracyclines are still widely used in human and veterinary medicine, the emergence of bacterial resistance has limited their effectiveness and is of major concern.

What are tetracyclines used for?

Tetracyclines are used widely in both human and veterinary medicine; for example, tetracyclines have been used:

• For the prevention of malaria
• For the treatment of moderate-to-severe acne or rosacea
• To treat anthrax
• To treat infections of the eye, gastrointestinal tract, genitourinary tract, gums, respiratory tract, and skin
• To treat infections caused by lice, mites, or ticks (such as Rocky Mountain spotted fever, typhus fever)
• To treat infections caused by Campylobacter, Chlamydiae, Yersinia pestis (plague), Vibrio cholerae (cholera) and other atypical organisms
• To treat respiratory tract infections caused by Mycoplasma pneumoniae
• As a growth promoter in animals.

Because many strains of microorganisms are now resistant to some tetracyclines, culture and susceptibility testing is recommended before beginning treatment.

Doxycycline is a tetracycline that may be considered when penicillin is contraindicated.

What are the differences between tetracyclines?

Although tetracyclines all work in the same way, there are differences between them.

Doxycycline is the most widely prescribed tetracycline because it has the advantage of once or twice daily dosing, availability as both an oral and an IV preparation, and it may be taken with food without significant disruption to its absorption. Eravacycline is the first fully synthetic fluorocycline tetracycline antibacterial that may be used to treat resistant pathogens in complicated intraabdominal infections. Omadacycline is available in oral and IV formulations and is effective against strains with bacterial ribosomal protection proteins or tetracycline-specific efflux pumps which are traditionally resistant to tetracyclines. Conversely, sarecycline (used to treat inflammatory acne) has a narrow spectrum of activity (mainly against Cutinebacterium acnes) and is less likely to cause disruption to the gastrointestinal microbiome. 

Are tetracyclines safe?

Tetracyclines are considered safe when used at the recommended dosages for the recommended duration of time. However, tetracyclines have been associated with serious side effects, such as:

• Tooth discoloration (yellow-gray-brown) and bony growth retardation when given during tooth or bone development (last half of pregnancy, infancy, and during childhood up until the age of 8 years)
• Clostridium difficile associated diarrhea (CDAD). CDAD ranges in severity from mild diarrhea to fatal colitis and has been associated with nearly all antibacterial agents, not just tetracyclines
• Intracranial hypertension (increased pressure within the brain) has been associated with tetracycline use. Symptoms include a headache; double, blurred, or loss of vision. Women of childbearing age who are overweight or who have a history of intracranial hypertension are most at risk. Coadministration of isotretinoin increases the risk and is contraindicated
• Toxicity to a developing fetus (tetracyclines can slow skeletal development). Tetracyclines should only be used in pregnancy if the benefits outweigh the risk
• Drug Rash with Eosinophilia and Systemic Symptoms (DRESS). Symptoms include widespread rash, fever, and swollen lymph nodes, and is potentially fatal. Discontinue the tetracycline immediately.

For a complete list of severe side effects, please refer to the individual drug monographs.

What are the side effects of tetracyclines?

The following are some of the side effects that have been reported with tetracyclines:

• Gastrointestinal effects such as acid reflux, diarrhea, nausea, vomiting, stomach cramps, or loss of appetite
• A headache
• An increase in some laboratory values (such as blood urea nitrogen [BUN]) particularly in people with impaired renal function. This does not appear to happen with doxycycline
• Photosensitivity reactions (such as an exaggerated sunburn reaction). Rarely occurs with minocycline
• Pigmentation or discoloration of the skin and mucous membranes (minocycline only)
• Skin rash or itching
• Sore mouth or tongue
• Vaginal itching or discharge.

Demeclocycline has also been associated with increased thirst, increased frequency of urination and unusual tiredness. Minocycline has been associated with dizziness, light-headedness, and unsteadiness. Tetracyclines may also cause darkening or discoloration of the tongue but this is usually temporary.

Sarecycline is less likely to cause gastrointestinal side effects such as acid reflux, diarrhea, nausea, vomiting, stomach cramps, or loss of appetite, because it has a narrow spectrum of activity and is unlikely to disrupt the gastrointestinal microbiota.

For a complete list of side effects, please refer to the individual drug monographs.