How Antibiotics Can Affect Achilles Tendinopathy In Athletes
These authors consider the risk-benefit ratio for using antibiotics in patients with Achilles tendinopathy, especially athletes.
Over the last several years, more people of all ages have been playing sports, which has led to an increasing number of sports injuries, including tendinopathies. Achilles tendinopathies have been problematic, especially in athletes participating in all type of sports. However, these injuries are not related to athletes alone as one-third of all Achilles tendon issues occur in non-athletes.1
The Achilles tendon is one of the more frequently injured tendons due to its “whipping action" during use. Many factors appear to be involved with this problem, including changes in training patterns, shoe gear, training surfaces and any type of speed work. These problems can lead to an overloading of the tendon, resulting in breakdown, inflammation and even rupture. There are many other factors that can lead to breakdown of the tendon as well. The one we have been concerned about most recently is antibiotic use.1
Tendons are unique in that they transmit forces of the muscle to the bone. A tendon has mechanical strength, flexibility and elasticity. The tensile strength of a tendon is related to its thickness and its collagen content. The stress on the tendon during athletic activity can be tremendous.1
Since the discovery of penicillin in 1928, researchers have developed countless new classes of antibiotics to treat a wider variety of infections. These different classes (i.e., penicillins, cephalosporins, aminoglycosides, macrolides, tetracyclines, fluoroquinolones, etc.) work in different ways. Penicillin and cephalosporins interact similarly by altering cell membranes. Fluoroquinolones work by inhibiting DNA gyrase, resulting in improper DNA synthesis. Many antibiotics work to inhibit ribosomal subunits, which is important for protein synthesis. Of these antibiotics, aminoglycoside and tetracyclines act to inhibit the 30th subunit (a section of the ribosome genetic code used in protein synthesis of the bacteria) while macrolides inhibit the 50th subunit.2–6
A Closer Look At The Research On Tendon Ruptures And Antibiotic Use
Physicians began noticing problems with Achilles tendinitis and rupture in the mid-1980s with people taking antibiotics. Fluoroquinolones was the first antibiotic group recognized as having a relationship to tendinopathies. The mechanism of tendon injuries is not well understood although we know quinolones exhibit an affinity for connective tissues. The hypothesis is that quinolones disturb the prolonged interaction between cells and matrix by chelating divalent ions, leading to breakdown. Studies have attributed 2 to 6 percent of all Achilles tendon ruptures to quinolones.7–9 The first reported case of quinolone-related Achilles tendinopathy was in New Zealand in 1983.10 Researchers have now shown fluoroquinolones triple the risk of tendon rupture and the risks increase with age as well.7–9
Over the years, there have been increased reports of tendon rupture and tendinitis with other antibiotics, such as tetracyclines, doxycycline and macrolides (i.e. azithromycin). The Food and Drug Administration (FDA) reports that approximately 0.25 percent of patients with Achilles tendon rupture have experienced this side effect with azithromycin including tendon rupture and a staggering 7 percent of those that experience tendonitis with tetracycline.9 Typically, in younger patients, these side effects are not as severe and they also recover better. However, in elderly patients, the side effects can be quite debilitating, leading to decreased function as well as increased morbidity. Fifty percent of those patients having tendinopathies due to antibiotic use are over the age of 60. These percentages may be smaller in comparison to fluoroquinolone use in patients with tendinopathies but the fact remains that tendon injury, including rupture, can occur with other antibiotics.8–11
The use of antibiotics can also create an inflammatory response. Through this response, there may be a buildup of toxic substances (for example, free radicals) that may damage tendon cells as well. Another proposed mechanism of inflammation is through the inhibition of metalloprotease, which is known to occur with the use of doxycycline. Despite the many different mechanisms theorized, there is no clear-cut answer and the mechanism of inflammation is most likely multifactorial. While researchers have not determined the mechanism behind the side effect, these injuries tend to occur in individuals who have previously overused or injured their tendons in the past. These patients may include athletes or the elderly.
Athletes are a high risk population for the use of antibiotics. This is especially the case for older athletes. The routine use of antibiotics has been associated with tendon injuries, cardiac arrhythmias, diarrhea, cartilage issues and decreased performance. Athletes use oral antibiotics two times more often than non-athletes . The theory is that sports physicians prescribe a higher rate of antibiotics in hopes of getting the athlete to return to activity as soon as possible. Furthermore, researchers have proven that concurrent corticosteroid use puts individuals at an increased risk.3–5,9–15
Case Study One: Addressing Achilles Tendinopathy In A Marathon Runner Using Azithromycin
A 60-year-old 25-time marathoner and 50-time triathlete reported to our office with a painful left Achilles tendon. The athlete had previously suffered from Haglund’s disease of the right heel but had never experienced any pain in his left foot or ankle. The pain started on a normal workout while the patient was on a six-mile run. The pain became so intense he had to stop halfway through the run and walk home. The patient had done
a half Ironman triathlon three weeks earlier and had developed a sinus infection, which his primary care physician treated with azithromycin. Approximately one week after finishing the antibiotics, he noticed a swelling in his left Achilles tendon measuring 3 cm in length by 1 cm above the tendon insertion.
Our diagnosis was Achilles tendinopathy secondary to antibiotic use. His treatment consisted of cross training, heel lifts, stretching and anti-inflammatories. The patient slowly went back to his normal training program over the next month.
Case Study Two: When Ciprofloxacin Contributes To Tendinopathy
A 63-year-old man with a history of taking ciprofloxacin for four months for a urinary tract infection presented to the clinic for treatment of Achilles pain on the right side. He noted the pain had increased since he started taking the medication.
With a diagnosis of antibiotic-induced tendinopathy, the patient received a treatment that controlled the symptoms. Over time, the patient developed concomitant plantar fasciitis and a plantar fibroma with Achilles equinus on the ipsilateral limb. This also required ongoing treatment.
The risk/benefit ratio is something to consider with every drug, particularly antibiotics. Antibiotics certainly have a relationship to tendinopathies and this is a pertinent consideration for the physician when prescribing them.
The concern we have is that tendinitis and tendinopathies have been under-reported in patients with antibiotic use and researchers are currently only looking at Achilles tendon ruptures in this patient population. We also contend that one can extrapolate that all antibiotics may play a role in tendinopathies and further study may be required for this particular issue. We hope these case studies have brought to light the importance of being aware of antibiotic use and the possibility for Achilles tendinopathies, especially in athletes and those over the age of 60.
Dr. Mozena is in private practice at the Town Center Foot Clinic in Portland, Ore. He is a Fellow of the American College of Foot and Ankle Surgeons, and is board certified in foot and ankle surgery. He is a Clinical Assistant Professor of Surgery at the Western University of Health Sciences.
Dr. Jones is in private practice at the Town Center Foot Clinic in Portland, Ore. He is board certified in foot surgery. He is a Clinical Assistant Professor of Surgery at the Western University of Health Sciences.
Dr. Mehndiratta is currently a resident in family medicine with Central Washington Family Medical in Yakima, Wash.
1. Maffulli N, Sharma P, Luscombe KL. Achilles tendinopathy: aetiology and management. J R Society Med. 2004; 97(10):472–476.
2. Clardy J, Fischbach MA, Currie CR. The natural history of antibiotics. Current Biology. 2009; 19(11):R437–41.
3. Fayock K, Voltz M, Sandella B, et al. Antibiotic precautions in athletes. Sports Health. 2013; 6(4):321–325.
4. Lee C, Duffy C, Gerbino PJ, et al. Tendon or joint disorders in children after treatment with fluoroquinolones or azithromycin. Infect Dis Clin Pract. 2002;11(3):164–165.
5. Kim GK. The risk of fluoroquinolone-induced tendinopathy and tendon rupture. J Clin Aesth Dermatol. 2010; 3(4):49–54.
6. Melhus A, Apelqvist J, Larsson J, Eneroth M. Levofloxacin-associated Achilles tendon rupture and tendinopathy. Scand J Infect Dis. 2003; 35(10):768–770.
7. Van der Linden PD, Sturkenboom MD, Herings RM, et al. Increased risk of Achilles tendon rupture with quinolone antibacterial use, especially in elderly patients taking oral corticosteroids. Arch Intern Med. 2003; 163(15):1801.
8. Sode J, Obel N, Hallas J, Lassen A. Use of fluoroquinolone and risk of Achilles tendon rupture: A population-based cohort study. Eur J Clin Pharmacol. 2007;63(5):499-503.
9. FDA Reports. Azithromycin and tendonitis. Available at https://www.ehealthme.com/ds/azithromycin/tendonitis/ .
10. Bailey RR, Kirk JA, Peddie BA. Norfloxacin-induced rheumatic disease [letter]. N Z Med J. 1983; 96(736):590.
11. FDA Reports. Tetracycline hydrochloride and tendonitis. Available at https://www.ehealthme.com .
12. Pasternak B, Fellenius M, Aspenberg P. Doxcycline impairs tendon repair in rats. Acta Orthopaedica Belgica. 2006; 72:756-760.
13. Wilton LV, Pearce GL, Mann RD, et al. A comparison of ciprofloxacin, norfloxacin, ofloxacin, azithromycin and cefixime examined by observational cohort studies. Br J Clin Pharmacol. 2003; 41(4):277–284.
14. Young JS, Kumta SM, Maffulli N. Achilles tendon rupture and tendinopathy: management of complications. Foot Ankle Clin. 2005; 10(2):371–382.
15. Study of possible correlation between tendon injury and doxycycline. Available at http://factmed.com/study-DOXYCYCLINE-causing-TENDON%20INJURY.php .
16. Bedi A, Fox AJ, Kovacevic D, et al. Doxycycline-mediated inhibition of matrix metalloproteinases improves healing after rotator cuff repair. Am J Sports Med. 2010;38(2):308–17.