Pharmacokinetics of ciprofloxacin and fluocinolone acetonide otic solution in pediatric patients.

PURPOSE: To describe the pharmacokinetics (PK) of ciprofloxacin 0.3 % and fluocinolone acetonide 0.025 % otic solution (CIPRO+FLUO), ciprofloxacin 0.3 % otic solution alone (CIPRO), and fluocinolone acetonide 0.025 % otic solution alone (FLUO) administered into the middle ears of pediatric patients with Acute Otitis Media with Tympanostomy Tubes (AOMT). MATERIALS AND METHODS: We performed a PK analysis of patients who participated in two multicenter, randomized, double-blind AOMT clinical trials (SALVAT studies CIFLOTIII/10IA02 and CIFLOTIII/10IA04). Each patient received 0.25 mL of CIPRO+FLUO, CIPRO, or FLUO twice a day instilled into the ear canal(s) for 7 days to treat AOMT. Blood samples of patients with unilateral AOMT were collected before the administration of the first dose of study medication at Visit 1 (day 1) and within 1-2 h after the last dose on day 7. Blood samples were analyzed to detect ciprofloxacin and fluocinolone acetonide concentrations using two validated liquid chromatography-tandem mass spectrometry (LC-MS-MS) methods, with the lower limit of quantification for ciprofloxacin and fluocinolone acetonide in plasma samples being 1 ng/mL. Thirty randomly selected patients between 10 months and 10 years of age (mean age, 4.4 years) were included in the study. Although all available samples were analyzed, only PK data of the 22 patients with both samples and unilateral disease were considered for study purposes. RESULTS: No detectable concentrations of ciprofloxacin or fluocinolone acetonide in plasma were observed (<1 ng/mL). CONCLUSIONS: These results demonstrated negligible systemic exposure to ciprofloxacin and fluocinolone acetonide following topical otic administration in pediatric patients with AOMT.

Rate and risk factors for post-adenotonsillectomy complications in children under 24 months and 24 to 36 months old.

PURPOSE: The primary purpose of this study was to assess the overall rate of postoperative complications after adenotonsillectomy in children under 24 months old relative to children 24-36 months old. Our secondary goal focused on quantifying specific preoperative risk factors that predispose children to postoperative complications. METHODS: We retrospectively reviewed 248 patients who underwent adenotonsillectomy at our ENT office from 2006 to 2011. We stratified these patients into two groups: under 2 years old; and 2-3 years old. We identified 42 preoperative risk factors and 22 postoperative complications for each age group and conducted tests of statistical significance. RESULTS: We found that children under 24 months old had a statistically significant higher postoperative complication rate of 38% compared to 22.3% in children 2-3 years old (p = 0.0320, chi-squared test). For specific complications, younger children had a higher rate of respiratory distress within 24 h (p = 0.0355), endotracheal re-intubation (p = 0.0281), and retractions (p = 0.0281). The only identified risk factors aside from age demonstrating statistical significance were nasal steroid sprays used preoperatively in children under 24 months (p = 0.005) and concurrent tympanostomy tube placement in children 24-36 months (p = 0.026). CONCLUSION: Our data demonstrates that children under 2 years of age have an overall increased rate of postoperative complications after adenotonsillectomy when compared to children between 2 and 3 years old, with a significantly higher rates of early respiratory distress, endotracheal re-intubation, and retractions. This study is one of the largest that compares postoperative complication rates and risk factors after adenotonsillectomy in this age group.

Efficacy and Safety of Ciprofloxacin Plus Fluocinolone in Otitis Media With Tympanostomy Tubes in Pediatric Patients: A Randomized Clinical Trial.

Importance: Acute otitis media with tympanostomy tubes (AOMT) in children commonly presents with otorrhea and negatively affects their daily activities. Objective: To evaluate the efficacy and safety of topical ciprofloxacin, 0.3%, plus fluocinolone acetonide, 0.025%, otic solution relative to ciprofloxacin, 0.3%, otic solution alone and fluocinolone acetonide, 0.025%, otic solution alone in the treatment of AOMT in children. Design, Setting, and Participants: Two twin multicenter, randomized, double-blind clinical trials with identical designs were conducted from June 24, 2011, through June 23, 2014, at ear, nose, and throat pediatric practices, general practices, hospitals, and clinical research centers. The study population comprised 662 children (331 in each trial) with AOMT in at least 1 ear who presented with moderate or severe purulent otorrhea for 3 weeks or less. Data analyses were performed on an intention-to-treat basis. Interventions: Patients were randomly assigned to receive ciprofloxacin plus fluocinolone, ciprofloxacin alone, or fluocinolone alone twice daily for 7 days and were evaluated on days 1 (baseline), 3 to 5 (undergoing therapy), 8 to 10 (end of therapy), and 18 to 22 (test of cure). Main Outcomes and Measures: The primary efficacy measure was time to cessation of otorrhea. The principal secondary end point was sustained microbiological cure, defined as eradication or presumed eradication at end-of-therapy and test-of-cure visits. Results: A total of 662 children participating in the 2 studies were randomized to receive ciprofloxacin plus fluocinolone (n = 223), ciprofloxacin alone (n = 221), or fluocinolone alone (n = 218). The median age was 2.5 years (range, 0.6-12.7 years). The median time to cessation of otorrhea was 4.23 days (95% CI, 3.65-4.95 days) in patients receiving ciprofloxacin plus fluocinolone compared with 6.95 days (95% CI, 5.66-8.20 days) in those receiving ciprofloxacin and not estimable findings in those receiving fluocinolone alone (P < .001). The clinical cure rate at the test-of-cure visit was 80.6% in the ciprofloxacin plus fluocinolone group, 67.4% in the ciprofloxacin group (difference, 13.2%; 95% CI, 5.0%-21.4%; P = .002), and 47.6% in the fluocinolone group (difference, 33.0%; 95% CI, 24.0%-42.0%; P < .001). The sustained microbiological cure rate was 79.7% in the ciprofloxacin plus fluocinolone group vs 67.7% in the ciprofloxacin group (difference, 12.0%; 95% CI, 0.8%-23.0%; P = .04) and 37.6% in the fluocinolone group (difference, 42.1%; 95% CI, 29.3%-54.8%; P < .001). Only 7 (3.1%) of the patients receiving ciprofloxacin plus fluocinolone, 8 (3.6%) of the patients receiving ciprofloxacin, and 10 (4.7%) of the patients receiving fluocinolone presented with adverse events related to study medication. Conclusions and Relevance: The combination of ciprofloxacin plus fluocinolone is more effective than treatment with ciprofloxacin or fluocinolone alone for AOMT, and it is safe and well tolerated in children. Trial Registration: clinicaltrials.gov Identifiers: NCT01395966 and NCT01404611.

Prospective comparative study of pulsed-electron avalanche knife (PEAK) and bipolar radiofrequency ablation (coblation) pediatric tonsillectomy and adenoidectomy.

PURPOSE: To compare post-operative pain severity, analgesic intake, and complications in children undergoing tonsillectomy and adenoidectomy with bipolar radiofrequency ablation (Coblation) vs. pulsed-electron avalanche knife (PEAK) technology. MATERIALS AND METHODS: This was a prospective, non-randomized, non-blinded comparative cohort study in a private practice setting with three fellowship-trained pediatric otolaryngologists. Patients aged 3 to 12years undergoing tonsillectomy and adenoidectomy were assigned to surgery with either bipolar radiofrequency ablation or pulsed electron avalanche knife instrumentation. Daily telephone contact for the first 14 post-operative days obtained the following data: validated proxy pain scale scores, number of post-operative analgesic medication doses consumed, and occurrence and severity of post-operative hemorrhage. RESULTS: One-hundred adenotonsillectomy subjects were enrolled (50 bipolar radiofrequency ablation, 50 pulsed-electron avalanche knife). There were no clinically relevant differences in post-operative pain scores between the two surgical groups on all post-operative days. Total doses of non-narcotic and narcotic analgesics were similar between the groups, with the exception of less acetaminophen doses being consumed in pulsed-electron avalanche knife patients on post-operative days 9, 10, and 12. Post-operative hemorrhage episodes resulting in re-operation and/or hospitalization were equivalent between the two groups. However, bipolar radiofrequency ablation patients were 2.33 times more likely to experience minor bleeding events at home (that did not require medical intervention). CONCLUSION: Pulsed-electron avalanche knife surgery was found to be an adequate technique for pediatric adenotonsillectomy, with similar amounts of post-operative pain and clinically relevant hemorrhage when compared to bipolar radiofrequency ablation.

Risk factors for pediatric post-tonsillectomy hemorrhage.

OBJECTIVES: To determine pre-operative risk factors for post-tonsillectomy secondary hemorrhage in children, and quantify the magnitude of their risk. MATERIALS AND METHODS: Retrospective case-control study of all pediatric tonsillectomy patients experiencing post-operative bleeding from 2005 to 2010 in a community practice consisting of three fellowship-trained pediatric otolaryngologists were identified. The 91 cases were matched with 151 controls that underwent tonsillectomy by the same surgeon on the same day as each identified case. All charts were reviewed, and 41 pre-operative variables were extracted and statistically analyzed with contingency and regression analysis to calculate significance and odds ratios. RESULTS: Three significant predictors of post-operative bleeding were identified. Performing a tonsillectomy on a child with recurrent tonsillitis (vs. other indications) increased the risk of post-operative hemorrhage by 4.5 times (p<0.0001, 95% confidence intervals 2.41-8.38). Performing a tonsillectomy on a child with attention deficit hyperactivity disorder (ADHD) increased the risk by 8.7 times (p=0.029, 95%CI 1.4-53.6). Older children were more predisposed to post-operative bleeding. For every increase in age by one year, the hemorrhage risk increased by 1.1 times (p=0.0025, 95%CI 1.032-1.162). Children 11 years of age and older had double the risk of bleeding compared to younger children (odds ratio 1.98, p=0.0381, 95%CI 1.04-3.79). None of the remaining 38 variables showed significant differences between cases and controls. CONCLUSIONS: The risk of post-tonsillectomy hemorrhage is significantly increased in older children and those with recurrent tonsillitis and ADHD.

Pediatric sialendoscopy: initial experience in a pediatric otolaryngology group practice.

OBJECTIVES/HYPOTHESIS: To describe the initial results of sialendoscopy as a diagnostic and therapeutic tool in pediatric inflammatory salivary gland disease. STUDY DESIGN: Retrospective review of patient medical records from a private practice consisting of three fellowship-trained pediatric otolaryngologists. METHODS: Consecutive pediatric patients with either recurrent or chronic sialadenitis underwent diagnostic and therapeutic sialendoscopy as an alternative to continued antibiotic therapy or surgical gland excision. Data collected included age, gender, indications for surgery, intraoperative findings, complications, recurrences, follow-up intervals, and need for additional procedures. RESULTS: Twelve pediatric patients underwent sialendsocopy (9 cases of juvenile recurrent parotitis, 3 cases of chronic submandibular sialadenitis. Intraoperative findings included ductal stricture (n = 8), thick intraductal mucus (n = 6), and ductal calculus (n = 1). The only postoperative complication was one case of a submandibular gland, which remained enlarged for 1 month postoperatively before resolving. Average follow-up was 16.5 months (range: 1-49 months), during which time two patients had recurrence (17%). One patient had repeated recurrences that only resolved after salvage parotidectomy. Another patient had one isolated recurrence that resolved with antibiotics. To date, 92% of patients have not required any further surgical intervention after a sialendoscopy procedure. CONCLUSIONS: Sialendoscopy was successfully implemented as a safe and effective technique for management of recurrent and chronic parotid and submandibular sialadenitis in a pediatric otolaryngology practice. LEVEL OF EVIDENCE: 4.

Pharmacokinetics of CIPRODEX otic in pediatric and adolescent patients.

OBJECTIVE: Describe the pharmacokinetics of ciprofloxacin and dexamethasone after administration of CIPRODEX Otic Suspension (CIP/DEX) into the middle ears of children. DESIGN: Open-label, single-dose, pharmacokinetic studies, administering four drops of CIP/DEX instilled into each middle ear through the tympanostomy tubes immediately following tube placement. Blood was collected for 6h and analyzed for ciprofloxacin and dexamethasone concentrations using a validated liquid chromatography and tandem mass spectrometry (LC/MS/MS) method. SETTING: The study was conducted through a referral pediatric otolaryngology practice with actual surgical procedures performed in an ambulatory care center. PATIENTS: Twenty-five randomly selected patients, 1-14 years of age (mean age, 5 years), receiving tympanostomy tubes. RESULTS: Peak ciprofloxacin plasma levels were observed at about 1h, with a mean C(max) of 1.33+/-0.96 ng/mL (range <0.5-3.45 ng/mL) and an estimated half-life of 3.0+/-1.2h. Peak dexamethasone plasma levels were observed within 2h with a mean C(max) of 0.90+/-1.04 ng/mL (range <0.05-5.10 ng/mL) and an estimated half-life of 3.9+/-2.9h. CONCLUSION: These results demonstrated low systemic exposure of ciprofloxacin and dexamethasone following topical otic administration in pediatric patients.