Safety and Efficacy of Gatifloxacin Therapy for Children with Recurrent Acute Otitis Media (AOM) and/or AOM Treatment Failure

Pichichero, Michael E.; Arguedas, Adriano; Dagan, Ron; Sher, Larry; Sáez-Llorens, Xavier; Hamed, Kamal; Echols, Roger

doi:10.1086/431584

Cited by 55 publications

(29 citation statements)

References 24 publications

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“…Rare but well-documented cases of joint damage in children treated with quinolones have been reported. The few pediatric trials for which data are available included too few patients to identify rare adverse effects on joints or to show a causal relationship between treatment and joint damage (2,13,14). The chondrotoxic potentials of different quinolones obviously differ, probably due to differences in pharmacokinetic behaviors as well as different affinities for magnesium (9).…”

Section: Discussionmentioning

confidence: 99%

“…The vast majority of these patients were treated with ciprofloxacin, and the authors of a previous report discussed the possibility that pefloxacin may be an exception to these findings (1). Recent experience with gatifloxacin administered to children with acute severe otitis media showed that this quinolone seems to be safe for children (13). On the other hand, some clinical case reports describe severe arthropathy in humans also and an extensive number of publications indicate that tendon disorders as a result of the toxic quinolone effects on connective tissue structures can be induced by quinolones under therapeutic conditions (12,22).…”

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confidence: 99%

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Diminished Ciprofloxacin-Induced Chondrotoxicity by Supplementation with Magnesium and Vitamin E in Immature Rats

Pfister

Mazur

Vormann³

et al. 2007

Antimicrob Agents Chemother

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Quinolone-induced chondrotoxicity in juvenile rats and multiple other species has been demonstrated previously. Identical damages can be induced in immature rats by feeding them a magnesium-deficient diet. The objective of the present study was to investigate whether, in reverse, oral supplementation with magnesium, vitamin E, or both can diminish the typical quinolone-induced arthropathy in juvenile Wistar rats. Four groups of 12 (6 male, 6 female) 24-day-old Wistar rats were each fed either normal feed (group A), a vitamin E-enriched diet (group B), a magnesium-enriched diet (group C), or a diet enriched with both vitamin E and magnesium (group D) for 10 days. All rats received two subcutaneous ciprofloxacin doses of 600 mg/kg of body weight on postnatal day 32. Two days later, the rats were sacrificed and cartilage samples from knee joints were examined under a light microscope for the presence of typical quinolone-induced joint cartilage lesions. In addition, magnesium, calcium, and vitamin E concentrations in cartilage and plasma were determined. In the samples from rats fed a normal diet (group A), 17 quinolone-induced joint cartilage lesions were observed. In groups fed an enriched diet, the incidence of specific lesions (n) was significantly lower: group B, n ‫؍‬ 10 (41% reduction compared to the incidence for group A; P < 0.05); group C, n ‫؍‬ 6 (65% reduction; P < 0.01); and group D, n ‫؍‬ 3 (82% reduction; P < 0.01). In comparison to the standard diet, diets with magnesium and vitamin E supplementation resulted in significantly higher magnesium and vitamin E concentrations in plasma and articular cartilage. Supplementation with magnesium and vitamin E alone or in combination may relevantly diminish joint cartilage lesions induced by quinolones in immature rats, with an additive effect of combined supplementation. The data further support the proposed pathomechanism of quinolone-induced arthropathy and the crucial role of magnesium in immature joint cartilage.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Diminished Ciprofloxacin-Induced Chondrotoxicity by Supplementation with Magnesium and Vitamin E in Immature Rats

Pfister

Mazur

Vormann³

et al. 2007

Antimicrob Agents Chemother

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“…19 However, no musculoskeletal safety issues were raised in the investigator-blinded, published pediatric studies of gatifloxacin, with similar rates of reported and observed musculoskeletal events occurring in gatifloxacin and amoxicillin-clavulanate over 1 year of follow-up. [4][5][6][7] Of 108 children treated with trovafloxacin and 95 treated with ceftriaxone for acute bacterial meningitis, only 1 child in the trovafloxacin-treated arm and 3 in the ceftriaxone arm demonstrated any joint abnormalities during the 6 to 12 months after therapy. No long-term bone or joint sequelae were noted during the followup period in either arm.…”

Section: Figurementioning

confidence: 99%

Assessment of Musculoskeletal Toxicity 5 Years After Therapy With Levofloxacin

et al. 2014

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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.

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“…Finally, pharmaceutical manufacturers initiated clinical trial programs with quinolones that have antibacterial activity against drug-resistant pathogens. One of these manufacturers, Bristol-Meyers Squibb, sponsored trials of gatifloxacin for AOM, and this experience is described by Pichichero et al [3] in this issue of Clinical Infectious Diseases. Gatifloxacin eliminates middle-ear pathogens at rates comparable or superior to those achieved by other antibacterial agents, and as a result, high clinical response rates are achieved [3,4].…”

mentioning

confidence: 99%

“…One of these manufacturers, Bristol-Meyers Squibb, sponsored trials of gatifloxacin for AOM, and this experience is described by Pichichero et al [3] in this issue of Clinical Infectious Diseases. Gatifloxacin eliminates middle-ear pathogens at rates comparable or superior to those achieved by other antibacterial agents, and as a result, high clinical response rates are achieved [3,4]. Clinical trials comparing gatifloxacin with the comparator amoxicillin-clavulanate also uncovered no clinically important adverse events [3].…”

mentioning

confidence: 99%

Gatifloxacin Therapy for Children: An Antibiotic Still in the "Back Room"

Marchant

2005

Clinical Infectious Diseases

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Safety and Efficacy of Gatifloxacin Therapy for Children with Recurrent Acute Otitis Media (AOM) and/or AOM Treatment Failure

Abstract: Gatifloxacin appears to be safe for children, with no evidence of producing arthrotoxicity in 867 children exposed to the antibiotic when used as treatment for ROM and AOMTF.

Cited by 55 publications

References 24 publications

Diminished Ciprofloxacin-Induced Chondrotoxicity by Supplementation with Magnesium and Vitamin E in Immature Rats

Diminished Ciprofloxacin-Induced Chondrotoxicity by Supplementation with Magnesium and Vitamin E in Immature Rats

Assessment of Musculoskeletal Toxicity 5 Years After Therapy With Levofloxacin

Gatifloxacin Therapy for Children: An Antibiotic Still in the "Back Room"

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