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Objectives: To determine the ciprofloxacin population pharmacokinetics in paediatric patients and the impact of underlying disease and evaluate the appropriateness of current dosage regimens.Patients and methods: Plasma concentrations of ciprofloxacin from children treated with ciprofloxacin were measured by HPLC. The pharmacokinetic population analysis was performed using NONMEM v7.2 (Icon Development Solutions, USA).Results: Two datasets were combined and 128 plasma concentrations in 60 patients aged 5.6 years (range 0.3-18.9), treated with a median daily dose of 30.0 mg/kg (range 6.5-52.0) presenting with sickle cell disease (SCD; n = 20, 33%), haemopathy (n = 15, 25%), cystic fibrosis (CF; n = 3, 5%) and other diseases (n  =  22, 37%) were analysed. Data were best described by a two-compartment model with first-order elimination. Ciprofloxacin clearance (mean ±  SD) was 0.81 ± 0.30 L/h/kg, increased allometrically with weight, decreased with increasing creatinine concentration, was 89% higher in SCD compared with non-SCD patients and increased by 0.95 L/h/kg per year of age. The volume of distribution was 6.9 L/kg and depended only on the weight. Monte Carlo simulations were performed separately in SCD and non-SCD patients to target an AUC/MIC ratio >125 at steady-state, required for antibacterial efficacy, and recommendations of dosing regimens were proposed.Conclusions: In addition to known covariates, ciprofloxacin clearance is greater in SCD children compared with non-SCD patients. The dosing of this agent needs to be adapted to this subgroup of patients. [ABSTRACT FROM AUTHOR]

Summary: Persistent and dysregulated inflammation, combined with an exaggerated host response is a major contributor to CF lung disease. As lung disease progresses, neutrophil accumulation in the airways ensues. Modulation of CF airway inflammation may result in either beneficial or deleterious side effects, resulting in more harm than good. Antibiotics, in particular, macrolides which act as a long-term anti-inflammatory agent with an excellent safety profile, and dornase alpha, are very interesting agents; steroids are not indicated in CF except in very special situations, and other promising agents such as leukotriene modifiers, high-dose N-acetylcysteine, anti-elastase and anti-cytokines require further research. Research should focus on early treatment, before lung damage has occurred [Copyright &y& Elsevier]

Abstract: Background: We aimed to evaluate the use of central catheters introduced by a peripheral vein (PICC) in children with CF. Methods: A descriptive study in patients in whom a PICC (Beckton Dickinson) was inserted. Results: 24 children aged (median (range) 10.2 years (0.3–17.3) undergoing 44 procedures were included. PICC was successfully inserted in 93.2% (41/44) of cases. Total procedure duration was (median (range)) 32.5 (10–105) minutes. The operators encountered few difficulties, median (range) 2 (1–10) (1 (absence) to 10 (maximal)); median (range) 1 (1 to 5) attempt per child). No major side effects or infections were observed. PICC obstruction in 5 (12%) cases was successfully unblocked in 4 cases (urokinase). The catheter was functional throughout the antibiotic course in 40/41 cases. A final Doppler scan (30 cases) showed total permeability of the central veins in all cases. Satisfaction index of the operators and the patients were high: median (range) 9.5 (1–10) and 8.0 (6–10) (scale: 1 (worse) to 10 (best)), respectively. Conclusion: PICCs are simple to use, and may be safely inserted in the ward. Such catheters are well tolerated, may increase the well-being of children with CF and prove an effective means by which to deliver IV therapy in this population. [Copyright &y& Elsevier]

Objectives In the ALPINE study ( ClinicalTrials.gov NCT01375049), AZLI treatment for 28 days in children with CF age 3 months to <18 yrs with new onset PA infection resulted in culture-negativity in 89% of patients (pts) at end of treatment and in 75% of pts at 28 days post-treatment. Post-hoc analyses were performed to determine possible factors associated with failure to eradicate or regrowth of PA post-treatment. Methods Children age 3 mos to <18 yrs with CF and new onset PA infection (first lifetime PA -positive culture [throat swab, sputum, BAL] or PA -positive after ≥2-yr history of PA -negative cultures) were treated with AZLI 75 mg 3x/day for 28 days via PARI Investigational eFlow® Nebulizer. Evaluable pts received a full 28 day AZLI course and no additional anti- PA antibiotics. Baseline (BL) factors were compared for pts with post-treatment cultures PA -positive vs. those who were PA -negative. Results 99 treated pts had culture data available at 28d post-treatment: PA was present in 23; absent in 76. No differences were seen in age, CF genotype, history of prior PA infection, FEV1 % predicted, PA antibody status, or presence of co-infecting pathogens at BL in PA present vs. absent groups. 22/23 pts who failed eradication were >90% treatment compliant. MIC50&90 were unchanged in PA strains isolated post-treatment vs. BL (4, 8 mg/mL respectively). Conclusion No BL factors examined predicted PA culture positivity after a 28-day course of AZLI. Inhaled antibiotic treatment is warranted for all pts with new onset PA infection. Further studies are needed to determine optimal treatment strategies for initial eradication failures. Supported by Gilead Sciences. [ABSTRACT FROM AUTHOR]