Third-generation fluoroquinolones may not pose the same risk to tendon health as previous-generation agents, as the findings of a new study suggest.
If confirmed, this will be good news for patients allergic to beta-lactam antibiotics and others in whom fluoroquinolones are the antibiotics of choice for their favorable pharmacokinetic properties and broad-spectrum activity, according to Takashi Chinen of the Jichi Medical University of Tochigi. , Japan, principal investigator of the new to study, published in Annals of Family Medicine.
“This is especially notable for patients who are at higher risk for tendon disorders, such as athletes,” Chinen said in an interview.
To investigate the association between third-generation fluoroquinolones and tendinopathy, Chinen and colleagues conducted a self-controlled analysis of case series using administrative claims data for a single prefecture in Japan, focusing specifically on the risk of Rupture of the Achilles tendon.
From a database of 780,000 Kumamoto prefecture residents enrolled in the country’s national health insurance and health insurance, from April 2012 to March 2017, researchers identified 504 patients who they experienced Achilles tendon rupture during the five-year period and were prescribed an antibiotic for some time during that period. They divided the observation period into antibiotic exposure (30 days after prescription) and non-exposure periods based on previous research linking this window of fluoroquinolone exposure to a high risk of tendon injury. They classified antibiotics into fluoroquinolones and non-fluoroquinolones and classified fluoroquinolones for first, second, and third generation, including the following agents:
First generation: Norfloxacin, nalidixic acid, pipemidic acid
Second generation: Levofloxacin, tosufloxacin, ciprofloxacin, ofloxacin, lomefloxacin
Third generation: Garenoxacin, sitafloxacin, prulifloxacin, moxifloxacin, pazufloxacin.
Risk of tendon rupture varied according to the class of fluoroquinolone
When comparing the incidence of Achilles tendon rupture in the exposure period in relation to the non-exposure period, the risk of rupture was not high during exposure to third-generation fluoroquinolones (incidence ratio , 1.05; 95% confidence interval, 0.33-3.37) and non-fluoroquinolones (IRR, 1.08; 95% CI, 0.80-1.47). In contrast to these findings, the researchers found that the risk of tendon rupture was significantly high during exposure to first- and second-generation fluoroquinolones (IRR, 2.94; 95% CI, 1.90-4, 54). The authors noted similar findings in subgroup analyzes by gender and recent corticosteroid use.
The authors noted that the increased risk associated with exposure to first- and second-generation fluoroquinolones is consistent with the high risk observed in previous studies, most of which focused on first- and second-generation agents.
“Our study is the first to investigate the risk of Achilles tendon rupture associated with third-generation fluoroquinolones through self-controlled case series analysis and through a large database of administrative claims,” they said.
Because the study is based on administrative claims data, it does not support conclusions about differential risks.
“Some preclinical studies suggest that there are structural differences [in the drugs] It can affect risks, “Chinen said. In particular, a preclinical study linked the methylpiperazinyl substituent to an increased risk of tendon injury, and this substituent is more common in first- and second-generation fluoroquinolones.
External experts were unable to draw conclusions
The accuracy of the current study is “extremely limited” by its design, according to Karsten Knobloch, a sports medicine doctor in private practice in Hannover, Germany, who has reported the risk of drug-induced tendon disorders.
“This is just a series of cases, which is a very strict limitation; therefore, the ability to generalize the data is also very limited,” he said in an interview. “In my opinion, the study does not add substantial data to support this third generation [fluoroquinolones] they are safer than the previous ones “.
Thomas Lodise, a pharmacist with a doctorate at Albany College of Pharmacy and Health Sciences in New York, pointed to another barrier to determining the value of new research.
“Without knowing how many moxifloxacin and patient descriptors they initially received for each drug, it is difficult to draw any definitive results from the paper,” Lodise noted.
The design and execution of the study had limitations
The authors acknowledged the limitations in the design and execution of the study. In particular, reliance on a database of administrative claims means that the accuracy of diagnoses cannot be validated. In addition, the sample size of the study may not have been sufficient to estimate the risk of rupture of individual fluoroquinolones, they wrote.
Despite these additional limitations, the findings have merit, according to the authors, who noted that the information may be useful for customizing antibiotic therapy for individual patients.
“Fluoroquinolone-induced tendon injury is a rare occurrence and the management of the risk of even rare adverse effects depends on each case,” Chinen explained. The findings of this study along with previous studies indicate that third-generation fluoroquinolones may be a safer option in terms of the risk of Achilles tendon rupture in some patients who cannot be prescribed beta antibiotics. -lactamic and in some conditions, such as Legionella pneumophila, He said.
To increase the internal and external validity of the results, more research is needed, including prospective cohort studies in larger populations, Chinen stressed.
The authors, Lodise and Knobloch, owner of SportPraxis in Hannover, Germany, did not report any conflict.
This story originally appeared on MDedge.com, which is part of the Medscape professional network.