Achilles tendon rupture and its association with fluoroquinolone antibiotics and other potential risk factors in a managed care population

Seeger, John D.; West, William; Fife, Daniel; Noel, Gary J.; Johnson, Lois B.; Walker, Alexander M.

doi:10.1002/pds.1214

Cited by 96 publications

(72 citation statements)

References 30 publications

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“…A putative side effect of fluoroquinolones is chondrotenotoxicity (29) that can lead to arthropathies (93) and ruptured tendons (82). These particular side effects are mostly observed in juvenile patients (49) in whom tendons and joints are rapidly proliferating.…”

Section: Fluoroquinolones and Chondrotoxicitymentioning

confidence: 99%

Adverse Effects of Antimicrobials via Predictable or Idiosyncratic Inhibition of Host Mitochondrial Components

Barnhill

Brewer

Carlson

2012

Antimicrob Agents Chemother

108

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This minireview explores mitochondria as a site for antibiotic-host interactions that lead to pathophysiologic responses manifested as nonantibacterial side effects. Mitochondrion-based side effects are possibly related to the notion that these organelles are archaic bacterial ancestors or commandeered remnants that have co-evolved in eukaryotic cells; thus, this minireview focuses on mitochondrial damage that may be analogous to the antibacterial effects of the drugs. Special attention is devoted to aminoglycosides, chloramphenicol, and fluoroquinolones and their respective single side effects related to mitochondrial disturbances. Linezolid/oxazolidinone multisystemic toxicity is also discussed. Aminoglycosides and oxazolidinones are inhibitors of bacterial ribosomes, and some of their side effects appear to be based on direct inhibition of mitochondrial ribosomes. Chloramphenicol and fluoroquinolones target bacterial ribosomes and gyrases/topoisomerases, respectively, both of which are present in mitochondria. However, the side effects of chloramphenicol and the fluoroquinolones appear to be based on idiosyncratic damage to host mitochondria. Nonetheless, it appears that mitochondrion-associated side effects are a potential aspect of antibiotics whose targets are shared by prokaryotes and mitochondria-an important consideration for future drug design. SIDE EFFECTS OF ANTIBACTERIAL DRUGST he desired activity of an antibiotic is to kill or prevent the growth of offending pathogenic bacteria, and yet these drugs may impact the host in an injurious manner. Generalized adverse events are common to most antibiotics (e.g., gastrointestinal distress with any oral antibacterial drug), but certain antibiotics are associated with specific effects (Table 1). Some adverse events are mild, e.g., yellowing of the teeth for tetracyclines (77, 79), increased intestinal peristalsis related to erythromycin therapy (7, 67), and reversible orange discoloration of skin and body fluids as observed with rifampin treatment (23, 31). Altered drug metabolism (106) is a common side effect that, in the absence of co-drug therapy, could also be considered mild. More serious side effects include photosensitivity (44) and anaphylactoid reactions (34) observed with many agents, ototoxicity (27, 83) following aminoglycoside therapy, chondrotoxicity (85, 88) and retinopathy (95) with fluoroquinolones, neuropathies associated with metronidazole (30, 107) and linezolid (15), and lactic acidosis and serotonin syndrome attributed to linezolid (21, 61). Other consequences can be severe or even devastating such as: the dermonecrolytic Stevens-Johnson syndrome associated with sulfonamide antimicrobial agents (74, 81); nephrotoxicity related to aminoglycosides (63, 73); aplastic anemia due to chloramphenicol (9, 91); hepatitis caused by many drugs, including isoniazid (72, 89); neuromuscular blockade related to aminoglycoside (64, 65) or lincosamide (4, 70) therapy; myopathies due to ionophores (5, 28, 75); and neoplasia related to metronidazole (19)....

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Section: Fluoroquinolones and Chondrotoxicitymentioning

confidence: 99%

Adverse Effects of Antimicrobials via Predictable or Idiosyncratic Inhibition of Host Mitochondrial Components

Barnhill

Brewer

Carlson

2012

Antimicrob Agents Chemother

108

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“…There is limited evidence that oral corticosteroids and local steroid injections are risk factors for Achilles tendon ruptures [ 23 , 24 ]. The use of fl uoroquinolones is also associated with Achilles tendinopathy and tendon ruptures [ 25 ], and the administration of fl uoroquinolones should be carefully considered, especially in patients undergoing corticosteroid treatment [ 26 ]. Achilles tendon rupture can also be associated with systemic diseases such as gout, lupus erythematosus, and rheumatoid arthritis.…”

Section: Etiologymentioning

confidence: 99%

Achilles Tendon Lesions in Soccer Players

Karlsson

Olsson

Helander

2015

Football Traumatology

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The Achilles tendon is the thickest and strongest tendon in the human body and needs to resist forces of up to 9 kN (approximately 12 times the weight of the body) during running [ 1 ]. For optimal function, the tendon must be capable of resisting high tensile forces with limited elongation and at the same time storing elastic energy when activated. Despite its strength, it is susceptible to both overuse injury and acute injury, such as a complete rupture.Functional defi cits are commonly described after an Achilles tendon rupture [ 2 -5 ], and several studies have shown that only approximately 50 % of the patients return to previous activity level and sports [ 2 , 6 , 7 ]. Accordingly, an Achilles tendon rupture might be career-ending for the professional athlete [ 8 ].A large number of medical reports have been published in the fi eld of Achilles tendon rupture, but there is still a lack of consensus in terms of the best treatment. EpidemiologyThe annual incidence of Achilles tendon ruptures in the population is increasing with a peak incidence of 37 per 100,000 persons [ 9 -11 ]. A bimodal age distribution has been reported with the highest incidence in the 30-39-year age group [ 9 , 12 ]. A study by Houshian et al. [ 9 ] showed that 73 % of the injuries were sports-related and the peak of sports-related injuries occurred in the 30-49-year age group. There is a second nonsports-related peak in incidence occurring at a mean age of 53 years [ 10 ]. Epidemiological studies generally show much a higher incidence of Achilles tendon ruptures in men, and the ratio between men and women is between 3:1 and 18:1, in general approximately 10:1 [ 9 , 13 ].A recently published study of the UEFA Champions League injury showed that Achilles tendon disorders (tendinopathies and ruptures) accounted for 2.5 % of all injuries and 3.8 % of layoff times in male professional football players [ 14 ]. In this cohort of 203 football players, only 4 % were classifi ed as partial or total ruptures. EtiologyThe etiology of Achilles tendon ruptures is regarded as multifactorial, and many factors have been proposed, but the pathology still remains unclear.

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“…Arthropathy and tendon disorders have been reported in patients being treated with, or following treatment with, fluoroquinolones; 65,[116][117][118][119][120] estimates of the prevalence of these events vary. In a case-control study, the event rate of Achilles tendonitis and rupture associated with fl uoroquinolones was 3.2/1000 patient treatment-years.…”

Section: Tendonopathymentioning

confidence: 99%

“…117 Patients older than 60 years and persons taking corticosteroids may be at increased risk of tendonopathy, 117,118 Sporadic case reports also suggest that transplant patients may also be at higher risk. A case-controlled study aimed at identifying factors associated with Achilles tendon rupture with fl uroquinolones 119 reported an odds ratio (adjusted for age, gender, obesity, skin and soft tissue infection, oral steroid use, injected steroid use, other non-fl uoroquinolone antibiotic, arthritis, diabetes, and trauma) associated with rupture for fl uoroquinolone use in the preceding 90 days to be 1.2 (95% CI 0.8-1.8). This did not appear to differ substantially from the odds ratio observed for treatment with azithromycin (1.2; 95% CI 0.9-1.6) but appeared to be considerably lower than the odds ratio observed for patients given two or more corticosteroid injections (2.4; 95% CI 1.4-4.1).…”

Section: Tendonopathymentioning

confidence: 99%

A Review of Levofloxacin for the Treatment of Bacterial Infections

Noel

2009

Clinical Medicine. Therapeutics

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Abstract:Completing its initial phases of drug development in the mid 1990s as the one of the fi rst fl uoroquinolones that could be used with confi dence to treat respiratory tract infections, levofl oxacin went on to become one of the most widely prescribed antibiotics in the world. Available in both oral (po) and intravenous (IV) formulations and with characteristics of over 90% bioavailability, distribution into both extracellular and intracellular pulmonary compartments, highly predictable pharmacokinetics with over 90% of the drug being excreted unchanged in urine, and reliable activity against a broad spectrum of clinically important pathogens, levofl oxacin has been used successfully to treat patients with a variety of serious infectious diseases as well as common infections most often treated outside of the hospital setting. Results of clinical trials involving patients with respiratory tract, urinary tract, and skin infections have consistently shown rates of clinical success and bacteriological eradication that were comparable to other widely used broad-spectrum agents. Regimens of levofl oxacin, initially involving total daily doses of 250 mg to 500 mg, but more recently regimens involving 750 mg doses, have been shown to be safe and effective. Nearly a decade and a half of clinical experience has defi ned a safety and tolerability profi le that permits data-driven assessment of the risks and benefi ts of using levofl oxacin. As resistance to currently available fl uoroquinolones has emerged, the clinical value of levofl oxacin deserves continued evaluation. However, consistently high rates of susceptibility of clinically important bacteria, especially among those bacteria that commonly cause respiratory tract infections, such as Streptococcus pneumoniae and Haemophilus infl uenzae, suggest that this agent will continue to be a widely used well past the 20-year anniversary of its introduction into the antibacterial armamentarium.

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Achilles tendon rupture and its association with fluoroquinolone antibiotics and other potential risk factors in a managed care population

Abstract: The elevation in ATR risk associated with fluoroquinolones was similar in magnitude to that associated with oral corticosteroids or non-fluoroquinolone antibiotics. Trauma and male sex were more strongly associated with ATR, as were obesity and injected corticosteroids.

Cited by 96 publications

References 30 publications

Adverse Effects of Antimicrobials via Predictable or Idiosyncratic Inhibition of Host Mitochondrial Components

Adverse Effects of Antimicrobials via Predictable or Idiosyncratic Inhibition of Host Mitochondrial Components

Achilles Tendon Lesions in Soccer Players

A Review of Levofloxacin for the Treatment of Bacterial Infections

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