Fluoroquinolone-induced ligament and tendon injuries

Ross Hauser, MD

Fluoroquinolones, antibiotics prescribed for acute bacterial infections have been associated with  potentially permanent side effects involving damage to tendons, muscles, ligaments and nerves.

There are many different causes or tendinopathy or tendon injury or ligamentosis or ligament injury. One of the causes that isn’t as well known as other causes is antibiotic use. There is a a class of antibiotics called fluoroquinolones. Amazingly, we see people who had no joint pain. They get the flu or some other type of bacterial infection and their doctors prescribed antibiotics. After the antibiotic use, these people start having a lot of tendon and joint pain. In people we see and as noted in the literature below fluoroquinolones antibiotic use can cause this type of pain very quickly.

What we see in our office is tendinopathy or degenerated tendon which we document by ultrasound. Certain antibiotics and medications hamper the configuration of collagen or produce inferior collagen. Type 1 collagen gives tendons and ligaments their strength.

In the video below Dr. Hauser discusses cases of ligament and tendon damage after fluoroquinolone antibiotic use.

As we will see in the research below: Tendon rupture or drug-induced tendinopathy should be strongly considered in those who have a tendon injury and have recently taken these drugs. Let’s point out that these side-effects do not occur in all people, it is considered somewhat rare, but a sudden tendon rupture should be explored for all contributing factors.

As noted in a 2007 paper (1) : “Tendinitis and tendon ruptures induced by fluoroquinolones, while uncommon, have been documented in the literature since 1983.” Therefore this is a decades old problem.

A November 2022 paper in the Journal of the American Academy of Physician Assistants (2) describes the problems of  Fluoroquinolones this way: “Fluoroquinolones, such as ciprofloxacin and levofloxacin, are broad-spectrum antibacterial agents that have historically been widely used for urinary tract infections, pneumonia, and intra-abdominal infections but are associated with several serious adverse reactions, including tendinopathy and tendon rupture, peripheral neuropathy, and aortic aneurysm. These drugs should not be used for uncomplicated infections unless no other antimicrobial treatment is feasible.” This article presented a case history of a patient who experienced life-altering disability from a fluoroquinolone.

Most of the medical literature surrounding research on fluoroquinolones-induced tendinopathy are case histories. Here doctors describe challenging and unique cases. As this is considered a somewhat rare event, when a patient presents a case, often the doctor will report the case to a medical journal.

What type of Fluoroquinolones history does it take to create tendinopathy?

At our center we have had people discuss “Fluoroquinolone toxicity,” and Fluoroquinolone-Associated Disability. Their stories follow a common theme and have been edited for clarity.

I was diagnosed with Posterior tibial tendonitis caused by Fluoroquinolone toxicity. I also have Tarsal tunnel syndrome, heel and calf pain, Walking and balance issues. I had a recent normal MRI and my doctors are not helping me. I think I need surgery but they don’t. Pain is debilitating. Swelling along the side of the tendon, x-ray showed fallen arches.

I have a painful and stiff neck. The pain is close to the base of the skull. I also have vertigo that comes and goes. All symptoms started at the same time when I took Fluoroquinolone Ciprofloaxin for an eye infection. I also have headaches twice or three times a month, hard to concentrate, and sometimes confusion when I wake up.

 I developed  Fluoroquinolone-Associated Disability. In particular, my knees are so painful that I am limited in walking and stair-climbing. My Achilles have issues, too. I have completed physical therapy in a therapeutic pool, which has helped my overall energy level, but anything I do that involves my knees hurts.

The caption of this image reads: Achilles tendon pathology from fluoroquinolone antibiotic use. Ultrasound revealed that the patient’s Achilles pathology and pain was from degenerative tendinopathy and tendon tears.

Achilles tendon pathology from fluoroquinolone antibiotic use

In March 2019, doctors writing in the journal Clinical medicine insights. Arthritis and musculoskeletal disorders (3) suggested: “These adverse effects (Fluoroquinolone-induced damage) can occur within hours after initial treatment to up to 6 months after withdrawal.” In this paper the doctors reported on their case of a diagnosis of a bilateral rupture of Achilles tendon in an older patient.

A December 2019 paper from Poland’s National Institute of Geriatrics, Rheumatology and Rehabilitation (4) reported a case of a 67-year-old woman with giant cell arteritis (inflammation of the arteries) with acute Achilles tendon rupture, which occurred after 3 days of levofloxacin therapy introduced because of newly diagnosed erosive gastritis associated with Helicobacter pylori infection. The Achilles tendon rupture was surgically treated and the patient made a complete recovery. In view of the widespread use of levofloxacin in practice, this case report raises important clinical implications. Tendinopathies are a known complication, quite rare in the healthy population, but the risk of rupture significantly increases in the population of patients over 60 years of age . . . ”

In both these case histories, older patients are presented.

A September 2022 study in the Frontiers in pharmacology (5) “scientifically and systematically” explored the association between fluoroquinolones (ciprofloxacin, levofloxacin, and moxifloxacin) and tendonitis and tendon rupture through the Food and Drug Administration Adverse Event Reporting System (FAERS) database.” These are case reported between  January 2016 to March 2021.

Here are some of the learning points of this study:

  • Results: Out of 35,667 fluoroquinolone-associated adverse events recorded during the study period 1,771 tendonitis and 1,018 tendon ruptures induced by fluoroquinolones as the suspected drug were analyzed. The average age of these patients was about 50 to about 64 years old.
    • Ciprofloxacin had the strongest statistical association with tendonitis.
    • Levofloxacin showed the strongest statistical association with tendon rupture.
    • Compared with ciprofloxacin and levofloxacin, moxifloxacin was relatively weakly associated with tendonitis and tendon rupture.
  • The majority of fluroquinolone-related suspected tendonitis and tendon rupture tended to occur within a few days or one month.

Fluoroquinolones and ligament damage

A September 2020 paper in the Journal of biological regulators & homeostatic agents (6) examined the toxic effects of fluoroquinolones and steroid on ligaments. To do this they took cells from people’s anterior cruciate ligament and put them is a laboratory dish. There, the cells were exposed to ciprofloxacin, which showed a significant decrease in cell viability and collagen type I building and an increase of apoptotic cells (cells that are waiting to be killed off). “(fluoroquinolones) seem to induce cell apoptosis (death).”

In May 2018, doctors at the University of Miami presented two case histories in the American journal of physical medicine & rehabilitation (7) of Ciprofloxacin-associated injuries. The doctors noted that much of the focus on medicine is on the possible damage ciprofloxacin can cause, especially on the Achilles tendon. However, “patients on fluoroquinolones with non-Achilles tendinopathy symptoms at risk of misdiagnosis.” The reason is that “There have not been any documented instances of ligament damage with ciprofloxacin administration in the literature, although ligament and tendon compositions are similar and should have similar susceptibility.” In their paper the doctors reported on two cases.

Case 1: The patient had right lateral thumb pain and a medical history of gastroenteritis treated with ciprofloxacin. Physical examination showed swelling of the right metacarpophalangeal joint and ultrasound confirmed disruption of the radial collateral ligament at insertion on first metacarpal.

Case 2: The patient had right hip pain. She had chronic recurrent diverticulitis treated with ciprofloxacin. She received work-up for lumbar disc disease and spondylosis. After standard therapy with pharmacotherapy and physical therapy for (lumbar) radiculopathy failed, magnetic resonance imaging was performed showing near complete avulsion of the right hamstring tendons from the ischial tuberosity.

A Note on Functional Gastrointestinal Disorders

A December 2021 study (10) from Bucknell University and the University of South Carolina discussed gastrointestinal disorder as a result of fluoroquinolones impact on the vagus nerve. The vagus nerve is of keen interest to our treatments. We extensively cover the topic of vagus nerve and the digestive tract in our articles: Cervical spine instability and digestive disorders: Indigestion and irritable bowel syndrome caused by cervical spondylosis and How neck pain and cervical spine instability cause nausea, gastroparesis and other digestive problems.

This study suggests fluoroquinolones could potentially affect functionality of the vagus nerve at the forefront of gastrointestinal (GI) tract function. The authors write: “Alterations in neural control of digestion have been shown to be linked to Functional Gastrointestinal Disorders, which are usually diagnosed based on self-reported symptoms. The results of this study suggested that “six different fluoroquinolones are associated with a wide range of GI symptoms not currently reported in the drugs’ labels. The responses from the survey suggested that more than 70% of fluoroquinolones users scored positive for Functional Gastrointestinal Disorders. . . This study showed that GI disorders other than nausea, vomiting and diarrhea are more common than currently reported on the drug labels, and that Functional Gastrointestinal Disorders are possibly a common consequence of fluoroquinolones use even after single use.”

We see many patients who have joint pain and are on medications for chronic or acute infection, and, they have sudden joint pain. If you have questions about Statin-induced tendon injuries, you can get help and information from our Caring Medical Staff.

1 Medrano San Ildefonso M, JA ML. Fluoroquinolone-induced tendon diseases. InAnales de medicina interna (Madrid, Spain: 1984) 2007 May 1 (Vol. 24, No. 5, pp. 227-230). [Google Scholar]
2 Wildermuth A, Holmes M. A preventable, life-altering case of fluoroquinolone-associated tendonitis. JAAPA. 2022 Nov 1;35(11):33-6. [Google Scholar]
3 Fernández-Cuadros ME, Casique-Bocanegra LO, Albaladejo-Florín MJ, Gómez-Dueñas S, Ramos-Gonzalez C, Pérez-Moro OS. Bilateral levofloxacin-induced Achilles tendon rupture: an uncommon case report and review of the literature. Clinical Medicine Insights: Arthritis and Musculoskeletal Disorders. 2019 Mar;12:1179544119835222. [Google Scholar]
4 Stasiek M, Głuszko P. Acute Achilles tendon rupture after levofloxacin in a patient with giant cell arteritis. Reumatologia/Rheumatology. 2019 Dec 31;57(6):343-6. [Google Scholar]
5 Shu Y, Zhang Q, He X, Liu Y, Wu P, Chen L. Fluoroquinolone-associated suspected tendonitis and tendon rupture: A pharmacovigilance analysis from 2016 to 2021 based on the FAERS database. Frontiers in Pharmacology. 2022;13. [Google Scholar]
6 Luciani P, Bottegoni C, Manzotti S, Solfanelli G, Farinelli L, Gigante A. The metabolic effects of quinolones and steroids on human ligament cells: an in vitro study. Journal of Biological Regulators and Homeostatic Agents. 2020 Sep 1;34(5 Suppl. 1):93-9. [Google Scholar]
7 Smith JD, Irwin RW, Wolff ET. Two Unique Cases of Ciprofloxacin-Associated Avulsion of Ligament and Tendon. American journal of physical medicine & rehabilitation. 2018 May 1;97(5):e33-6. [Google Scholar]

 

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