Ciprofloxacin Decreases Collagen in Mouse Tympanic Membrane Fibroblasts

Self Cite

Objective Considering emerging safety concerns involving otic quinolones, we assessed the extent of otic quinolone use for questionable indications. Study Design Descriptive cross-sectional study of a national sample of privately insured patients. Setting Outpatient encounters in the United States. Subjects and Methods Children and adults with outpatient pharmacy-dispensing claims for new prescriptions of otic or ophthalmic quinolones in 2017 were identified within the IBM MarketScan Commercial Claims & Encounters and the Medicare Supplemental Database. Each dispensing ≥30 days apart constituted a unique episode. Only claims with supporting ear-related diagnoses on outpatient encounters ±3 days of dispensing were considered. Ophthalmic drops were excluded if eye-related diagnoses were found ±30 days. Prescribing was classified as appropriate, questionable, or undetermined. Results We found 214,897 episodes in 200,270 patients. Adults were twice as likely as children to have otic treatment with questionable indications (6.2% vs 3.0%). Sensitivity analyses with broader time windows to ascertain diagnoses showed similar proportions of questionable use. Otalgia and cerumen impaction constituted 90% of questionable indications. Family physicians (6.8%) and internists (8.0%) had higher percentages of questionable use than other specialties. Conclusion Based on the demonstrated risks of quinolone ear drops, opportunities exist to decrease otic quinolone use, especially in adults.

mentioning

confidence: 99%

Appropriateness of Otic Quinolone Use among Privately Insured US Patients

Tran

Winterstein

et al. 2019

Self Cite

“…The cytotoxicity of these “excipients” may have contributed to the toxicity that has previously been attributed to quinolones and steroids in commercial ear drops. 1-6…”

Section: Discussionmentioning

confidence: 99%

Cytotoxicity of Ear Drop Excipients in Human and Mouse Tympanic Membrane Fibroblasts

Dirain

Karnani

Antonelli

2019

Self Cite

Objective Commercial ear drops contain ingredients reported to be inactive. We sought to evaluate such excipients for possible cytotoxicity on human and mouse tympanic membrane (TM) fibroblasts. Study Design Prospective, in vitro. Setting Tertiary academic center. Subjects and Methods Mouse and human TM fibroblasts were treated with 1:10 dilutions of benzalkonium chloride (BKC) 0.0025%, 0.006%, or 0.01%; benzyl alcohol 0.9%; polysorbate 80 (PSB) 2.5%; glycerin 2.4%; povidone 0.2%; or water (control), twice within 24 hours or 4 times within 48 hours, for 2 hours each time. Cells were placed back in growth media after the treatments. Cells were observed with phase-contrast microscopy until the cytotoxicity assay was performed. Results Mouse fibroblasts had lower survival in only the PSB-treated cells compared to the control ( P < .0001) after 24 hours. After 48 hours, PSB killed nearly all mouse fibroblasts ( P < .0001). BKC decreased fibroblast survival in a dose-dependent manner ( P < .001). In human TM fibroblasts, all excipients except povidone and benzyl alcohol after 24 hours and povidone after 48 hours reduced cell survival compared to control ( P = .012 to P < .0001). The cytotoxicity of BKC in human TM fibroblasts was also dose dependent (<.0001). PSB was less cytotoxic to human fibroblasts. Phase-contrast images mirrored the cytotoxicity findings. Conclusion Polysorbate 80 and benzalkonium chloride, at concentrations found in commercial ear drops, may be cytotoxic to human and mouse TM fibroblasts. “Inactive” ingredients may need to be considered when evaluating clinical outcomes with commercial ear drops.

“…Cells were grown in tissue culture plates at 37°C with 5% CO 2 until they reached approximately 75% confluence, at which point experimentation was performed, as previously described. 15,16…”

Section: Methodsmentioning

confidence: 99%

“…Cells added with PBS without antibiotic treatment (negative control) were not different with HCl-treated fibroblasts. 15,16 The pH of the culture media after addition of the treatment solutions was checked, and all were within the neutral pH, around 7.2. Cells were exposed to the treatment solutions twice a day (once in the morning and once in the afternoon) for 2 hours each time and were placed back in growth media after the solution treatments.…”

Section: Cell Culture and Treatmentmentioning

confidence: 99%

“…Last year, an FDA review committee advised that the benefits of quinolones in certain instances might not outweigh the serious side effects associated with quinolones and that their use should be reserved for those who do not have alternative treatment options. 14 In the past few years, we have been studying the impact of ototopical quinolones and steroids on TM fibroblast survival and protein production in cell culture, 15,16 as well as TM wound healing in vivo in animal models. 17 The in vitro studies demonstrated that cipro, at levels found in eardrops, is cytotoxic to mouse TM fibroblasts and reduces TM collagen and tubulin protein levels.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Cytotoxicity of Ciprofloxacin and Steroids in Mouse Tympanic Membrane Fibroblasts

Redula

Antonelli

Dirain

2018

Self Cite

Objective Ciprofloxacin, commonly given as eardrops, has been shown to adversely affect tympanic membrane fibroblasts. Dexamethasone potentiates this effect. A newly available eardrop contains ciprofloxacin and fluocinolone, a more potent steroid. We evaluated the cytotoxic effects of this preparation on mouse tympanic membrane fibroblasts. Study Design Prospective, in vitro. Setting Academic laboratory. Subjects and Methods In experiment 1, fibroblasts were exposed to 1:10 dilutions of commercially available 0.3% ofloxacin, 0.3% ciprofloxacin, 0.3% ciprofloxacin + 0.1% dexamethasone, 0.3% ciprofloxacin + 0.025% fluocinolone, or dilute hydrochloric acid (control), twice within 24 hours. In experiment 2, cells were also treated with the dilutions of the pure form of dexamethasone 0.1% or fluocinolone 0.025%, alone and in combination with ofloxacin or ciprofloxacin. Cells were exposed to the solutions for 2 hours each time and were placed back in growth media after the treatments. Cells were observed with phase-contrast microscope until the cytotoxicity assay was performed. Results Survival of fibroblasts treated with ofloxacin was not different from the control. Fibroblasts treated with ciprofloxacin, ciprofloxacin + dexamethasone, or ciprofloxacin + fluocinolone had much lower survival (all P < .0001). Cells treated with ciprofloxacin + fluocinolone had lower survival than ciprofloxacin ( P < .0001) and ciprofloxacin + dexamethasone ( P = .0001). Steroids alone also decreased fibroblast survival compared to control ( P < .0001). The combination of dexamethasone or fluocinolone with ciprofloxacin, but not ofloxacin, further decreased fibroblast survival ( P < .0001). Phase-contrast images mirrored the cytotoxicity findings. Conclusion Tympanic membrane fibroblast cytotoxicity of ciprofloxacin is potentiated by corticosteroids. This effect may be deleterious when treating a healing perforation but beneficial when treating granulation tissue on the tympanic membrane.