Oxidative transformation of levofloxacin by δ-MnO2: products, pathways and toxicity assessment.

The characteristics of the oxidative transformation of the antibiotic levofloxacin (abbreviated as LEV) by manganese oxide were investigated. Up to 91% of LEV were removed with an equivalent of 200 units (abbreviated as equiv) of manganese oxide within a 35-day treatment period. A total of ten transformation products were identified, and five of them were newly reported. A tentative transformation pathway of LEV in the manganese oxide system involving oxidation and dealkylation was proposed. In addition, the variation in the genotoxicity and antibacterial activity along with the treatment by manganese oxide were traced using a SOS/umu assay and Escherichia coli growth inhibition assay, respectively. The results indicated that the genotoxicity significantly decreased in response to treatment with manganese oxide, while the antibacterial activity was not markedly affected until 160-equiv of δ-MnO2 were added. This study suggests that the oxidative degradation of LEV by manganese oxide can play an important role in the natural attenuation of LEV in sediment or soil matrices. The transformation reaction may be further optimized for removing quinolone antibiotics from wastewater or other environmental matrices to reduce the potential risk.

Assessment of musculoskeletal toxicity 5 years after therapy with levofloxacin.

BACKGROUND: Safety concerns for fluoroquinolones exist from animal studies demonstrating cartilage injury in weight-bearing joints, dependent on dose and duration of therapy. For children treated with levofloxacin or comparator in randomized, prospective, comparative studies for acute otitis media and community-acquired pneumonia, this 5-year follow-up safety study was designed to assess the presence/absence of cartilage injury. METHODS: Children enrolled in treatment studies were also enrolled in a 1-year follow-up safety study, which; focused on musculoskeletal adverse events (MSAE). Those with persisting MSAEs, protocol-defined musculoskeletal disorders, or of concern to the Data Safety and Monitoring Committee were requested to enroll in four additional years of follow-up, the subject of this report. RESULTS: Of the 2233 subjects participating in the 12-month follow-up study, 124 of 1340 (9%) of the levofloxacin subjects, and 83 of 893 (9%) of the comparator subjects were continued for 5-year posttreatment assessment. From children identified with an MSAE during years 2 through 5 posttreatment, the number that were "possibly related" to drug therapy was equal for both arms: 1 of 1340 for levofloxacin and 1 of 893 for comparator. Of all cases of MSAE assessed by the Data Safety and Monitoring Committee at 5 years' posttreatment, no case was assessed as "likely related" to study drug. CONCLUSIONS: With no clinically detectable difference between levofloxacin- and comparator-treated children in MSAEs presenting between 1 and 5 years in these safety studies, risks of cartilage injury with levofloxacin appear to be uncommon, are clinically undetectable during 5 years, or are reversible.