Medscape: 

Beth Skwarecki

June 02, 2014

 

Levofloxacin, a fluoroquinolone antibiotic, was not linked to joint cartilage injuries in a nonblinded study that followed-up children for 5 years after they took the drug. As the first long-term follow-up (LTFU) study on levofloxacin's effects on the joints of growing children, one expert says the study provides reassurance for pediatricians who use the drug, especially with regard to multidrug-resistant infections for which there are few treatment options.

 

Joint injuries resulting from fluoroquinolone use have been observed in animal studies, leading to caution about using these drugs in children.

 

"If long-term injury occurs with levofloxacin, the rate of these events is low," John S. Bradley, MD, from the University of California, San Diego, School of Medicine, and colleagues write in an article published online June 2 in Pediatrics.

 

The study included 124 children who had taken levofloxacin and 83 children who had taken a nonfluoroquinolone drug, all of whom had been identified during a 12-month surveillance phase follow-up study as having more than 1 of the following: growth impairment or possible growth impairment 12 months posttreatment, abnormal bone or joint symptoms during the 12 months after treatment, musculoskeletal adverse events that persisted at the end of the 12-month study, or concerns about joint toxicity. Participants were not randomized at the time of entry into the LTFU study, and parents were not blinded.

 

The researchers asked patients to return for annual examinations, during which they gave them a questionnaire about musculoskeletal injuries and measured their height to assess growth. However, many children did not return for all of the follow-up visits or visited outside the requested window for each visit.

 

The investigators considered a wide range of musculoskeletal injuries, including arthritis, arthralgia, gait abnormality, tendinopathy, and growth impairment caused by damage to an epiphyseal plate.

 

At the beginning of the LTFU study, 1 year after taking the drug, 29 children in the levofloxacin group (2% of those exposed) and 10 children in the comparator group (1%) were judged to have a "possible" drug-related injury. After 5 years, 1 child in each group had ongoing concerns about possible joint toxicity, although the Data Safety and Monitoring Committee did not consider these "likely" to be drug-related.

 

In total, 30% of the levofloxacin group and 35% of the comparator group were lost to follow-up, and only 49% of patients completed the study.

 

This is "one of the biggest limitations" of the study, Jennifer L. Goldman, MD, a pediatric infectious disease physician at Children's Mercy Hospital in Kansas City, Missouri, told Medscape Medical News. Dr. Goldman, who was not involved in the current study, also noted that the investigators excluded children who did not develop injuries in the first year after taking the drug.

 

Still, the study provides additional reassurance, she said, to pediatricians who must weigh the benefits and risks of the drug on a case-by-case basis, consistent with American Academy of Pediatrics' guidelines on fluoroquinolones, which recommend the drugs when there is no safe and effective alternative; for example, in the case of multidrug-resistant infections.

 

This study was funded by Janssen Research and Development (JRD). Dr. Bradley reports work as an unpaid scientific advisor to JRD, and consulting services were contracted by the Regents of the University of California to JRD, for which Dr. Bradley’s department received funding to support research and other university activities. Three coauthors are currently employees of Johnson & Johnson/JRD. The other authors and Dr. Goldman have disclosed no relevant financial relationships.

 

Pediatrics. Published online June 2, 2014.