Tetracycline is a broad-spectrum antibiotic used to treat bacterial infections.1 It is part of a family of antibiotics known as tetracyclines which include other drugs such as doxycycline and minocycline. Tetracyclines are used to treat various infections including those of the skin, genitals, intestine, respiratory tract, urinary tract and lymphatic system.2 They may only be used for difficult-to-treat infections due to their association with antibiotic resistance and teeth staining.
What is tetracycline?
Definition and history of tetracycline
Tetracyclines were first introduced in the 1940s after being discovered in a soil bacterium.3 They work by preventing bacteria from producing the proteins they need to grow and spread.4 Tetracyclines are used to treat common bacterial infections and, like all antibiotics, do not work on viral infections such as the common cold or flu. It is important to only take antibiotics when prescribed by a healthcare provider and to not miss any doses to avoid the development of antibiotic resistance.
How it is used in medicine?
As they are broad-spectrum, tetracycline antibiotics can be used to treat a range of different bacterial infections.1 However, they are usually given to those with a penicillin allergy or difficult-to-treat infections including:
- Rickettsial infections
- H pylori infections
- Parasite-caused infections such as rocky mountain spotted fever (RMSF), malaria, and Lyme disease
- Long-term skin conditions such as rosacea and acne vulgaris
- Sexually transmitted infections such as chlamydia trachomatis
Tetracyclines are usually given orally but, depending on the type and severity of the infection, they can also be applied topically to the skin or delivered intravenously (through a needle in the vein).
The most common side effect of tetracyclines in adults is stomach upset. In rarer cases, symptoms can include photosensitivity (sensitivity to the sun), causing a red rash or blistering; staining of teeth; and liver toxicity. Tetracycline should not be given to children under 12 and pregnant/breastfeeding women, unless the benefit outweighs the risk, due to the risk of teeth discolouration and inhibition of bone growth in foetuses.5,6 Tetracycline may interact with other medicines, including birth control and calcium supplements.1
Types of tetracycline
Tetracyclines are divided into 4 different types: naturally occurring, semi-synthetic, glycylcycline and ‘newer’.1
|Can be isolated from the natural source||Partly modified from the naturally-occuring||Further modified to overcome antibiotic resistance||The mostly recently approved modified drugs|
There is a range of different tetracyclines as some are more suited to treat certain infections than others. Due to bacteria becoming resistant to some tetracyclines, scientists have produced modified tetracyclines to try and overcome this problem. Tetracyclines may be sold in slightly different forms to those above or under specific brand names. For example, you may see tetracycline referred to as tetracycline hydrochloride or Achromycin V.
Effects of tetracycline on teeth
Tetracycline can bind to the teeth and cause permanent tooth discolouration, particularly in children under the age of 8 who are still developing their secondary teeth. Staining can affect both the enamel (thin outer covering of the tooth) and dentine (layer under enamel that protects the nerves) of the crown.8 Because tetracycline can cross the placenta, it can bind to the teeth and bones of the foetus causing discolouration in the primary and secondary teeth and potentially inhabit bone growth.9 There is no clear evidence that tetracycline causes enamel hypoplasia (tooth decay).
How tetracycline affects the colour of teeth
Tetracycline stains on the crowns of the teeth vary from a mild yellow hue to a more severe brown or grey hue as the teeth are exposed to oxygen and light over time.9,10 The roots can also appear black or green.
The mechanism of tetracycline staining
Tetracycline can bind to calcium in the body and form a tetracycline-calcium complex.6 If tetracycline is taken during calcification or mineralisation (build-up of calcium in teeth and bones), then the complex can be deposited in developing bones and teeth. The tooth calcification process begins during the fourth/fifth month in the uterus and continues until around 8 years old.9 If taken by pregnant or breastfeeding women, tetracycline can pass through the placenta or breastmilk and affect the foetus or child. However, it is thought that calcium in breast milk can bind to tetracycline and suppress its effects.
The different degrees of tetracycline staining
The degree of staining depends on the type of tetracycline, the dose, the number of courses and the timing of tooth development.10 Doxycycline has the lowest incidence of staining because it is less attracted to calcium compared to other tetracyclines. Minocycline, used to treat severe acne, has been seen to cause pigmentation of the teeth, nails, thyroid and bone. This is likely because it can pass through tissue and body fluids easily which is helped by its ability to dissolve in fatty substances.11 Staining can also increase over time, upon exposure to oxygen and light, from fluorescent yellow to brown.
Diagnosis of tetracycline staining
Tetracycline staining can be diagnosed by a dentist by examining the teeth and discussing the patient’s medical history. An X-ray or UV light can be used to identify the extent of the staining and rule out other potential causes.
Treatment of tetracycline staining
There are a selection of treatment options available to treat tetracycline staining depending on the severity including12
- Dental cleaning and polishing - Can help to remove surface stains but is typically not effective for treating tetracycline stains. Abrasive cleaning has proven to be effective for treating some adults because their teeth have already undergone calcification and there is a lack of free calcium in the enamel.13 If tetracycline binds to the calcium whilst a child’s teeth are calcifying, then permanent staining can occur on both the dentine and enamel of the crown
- Teeth whitening - Bleaching agent used to remove stains but can be ineffective, particularly in severe cases. Internal bleaching, involving root canal treatment, is an option but it is quite an aggressive approach in otherwise healthy teeth
- Dental bonding- Application of a tooth-coloured resin to the affected teeth to improve their appearance
- Crowns - Caps placed over teeth. Cave has been used to treat severe staining but involves the removal of a large amount of teeth tissue
- Veneers - Thin shells that are custom-made to fit over the front of the teeth. A minimal amount of tooth needs to be removed compared to crowns
Prevention of tetracycline staining
Awareness of the risks of tetracycline staining
Healthcare practitioners and patients should be aware of the risk of tetracycline so they can make an informed decision about treatment. In most adults, the risk of staining is minimal and, for difficult-to-treat infections, the benefit of tetracyclines outweighs the risk.
Limiting the use of tetracycline in children
If tetracycline use in a child is necessary, considerations include reducing the dose of the drug and avoiding use in critical periods of calcification.
Alternative antibiotics for pregnant women and children
There are other broad-spectrum antibiotics that are effective for treating bacterial infections in pregnant women and children. If no other treatments work, tetracyclines may be considered.
Complications of tetracycline staining
Tetracycline staining, particularly if it is severe, can have psychological and social effects on patients. These include low self-esteem, avoiding social situations and experiencing stigma.
Tetracyclines are a family of broad-spectrum antibiotics used for difficult-to-treat bacterial infections. There is a wide range of tetracyclines available and some are more suited to treating certain infections than others. Scientists continue to develop new tetracycline medicines because of problems with antibiotic resistance. Tetracyclines are not recommended for use in children under 8 and in pregnant women because they can cause permanent teeth discolouration in young children and foetuses. Tooth staining can range from a mild hue to a more severe brown hue and the extent of damage is dependent on the type of tetracycline, the dose and the age of the foetus/child when the medicine is taken. There are some treatment options available but the damage is permanent so it is important that healthcare practitioners and patients can make an informed decision about whether the benefit of tetracycline treatment outweighs the risk.
- Shutter MC, Akhondi H. Tetracycline. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 [cited 2023 May 7]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK549905/
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- Nelson ML, Levy SB. The history of the tetracyclines. Ann N Y Acad Sci. 2011 Dec;1241:17–32.
- PubChem. Tetracycline [Internet]. [cited 2023 May 8]. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/54675776
- Tetracycline antibitotics & Tetracycline side effects - Patient [Internet]. 2022 [cited 2023 May 7]. Available from: https://patient.info/medicine/tetracycline-tablets
- Virginia JMK PharmD, CACP, BCPS, CDE Clinical Assistant Professor, West Virginia University Family Medicine Clinical Pharmacist, Harpers Ferry Family Medicine Harpers Ferry, West Virginia Jon P Wietholter, PharmD, BCPS Clinical Assistant Professor, West Virginia University Internal Medicine Clinical Pharmacist, Cabell Huntington Hospital Huntington, West Virginia Vanessa T Kline, PharmD, BCPS Clinical Specialist, Winchester Medical Center Winchester, Virginia Jennifer Confer, PharmD, BCPS Clinical Assistant Professor, West Virginia University Critical Care Clinical Pharmacist, Cabell Huntington Hospital Huntington, West. Pediatric antibiotic use: a focused review of fluoroquinolones and tetracyclines [Internet]. [cited 2023 May 8]. Available from: https://www.uspharmacist.com/article/pediatric-antibiotic-use-a-focused-review-of-fluoroquinolones-and-tetracyclines
- Olson MW, Ruzin A, Feyfant E, Rush TS, O’Connell J, Bradford PA. Functional, biophysical, and structural bases for antibacterial activity of tigecycline. Antimicrob Agents Chemother [Internet]. 2006 Jun [cited 2023 May 8];50(6):2156–66. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1479133/
- How does the antibiotic tetracycline cause permanent staining of the teeth and who is at risk? [Internet]. [cited 2023 May 9]. Available from: https://www.ebmconsult.com/articles/tetracycline-stains-teeth-mechanism
- Demers P, Fraser D, Goldbloom RB, Haworth JC, LaRochelle J, MacLean R, et al. Effects of tetracyclines on skeletal growth and dentition. A report by the nutrition committee of the canadian paediatric society. Can Med Assoc J [Internet]. 1968 Nov 2 [cited 2023 May 8];99(17):849–54. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1945410/
- Sánchez AR, Rogers RS, Sheridan PJ. Tetracycline and other tetracycline-derivative staining of the teeth and oral cavity. Int J Dermatol. 2004 Oct;43(10):709–15.
- Bookstaver PB, Bland CM, Griffin B, Stover KR, Eiland LS, McLaughlin M. A review of antibiotic use in pregnancy. Pharmacotherapy [Internet]. 2015 Nov [cited 2023 May 8];35(11):1052–62. Available from: https://onlinelibrary.wiley.com/doi/10.1002/phar.1649
- Faus-Matoes V, Faus-Matoses I, Ruiz-Bell E, Faus-Llácer VJ. Severe tetracycline dental discoloration: Restoration with conventional feldspathic ceramic veneers. A clinical report. J Clin Exp Dent [Internet]. 2017 Nov 1 [cited 2023 May 9];9(11):e1379–82. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5741855/
- Yeung JCC, Lai JSM. Reversible tetracycline staining of adult dentition in the treatment of chronic blepharitis. Eye [Internet]. 2007 Nov [cited 2023 May 9];21(11):1440–1. Available from: https://www.nature.com/articles/6702957