Population pharmacokinetics of intravenous and oral ciprofloxacin in children to optimize dosing regimens.

PURPOSE: This study aimed to characterize pharmacokinetics of intravenous and oral ciprofloxacin in children to optimize dosing scheme. METHODS: Children treated with ciprofloxacin were included. Pharmacokinetics were described using non-linear mixed-effect modelling and validated with an external dataset. Monte Carlo simulations investigated dosing regimens to achieve a target AUC0-24 h/MIC ratio ≥ 125. RESULTS: A total of 189 children (492 concentrations) were included. A two-compartment model with first-order absorption and elimination best described the data. An allometric model was used to describe bodyweight (BW) influence, and effects of estimated glomerular filtration rate (eGFR) and age were significant on ciprofloxacin clearance. CONCLUSION: The recommended IV dose of 10 mg/kg q8h, not exceeding 400 mg q8h, would achieve AUC0-24 h to successfully treat bacteria with MICs ≤ 0.25 (e.g. Salmonella, Escherichia coli, Proteus, Haemophilus, Enterobacter, and Klebsiella). A dose increase to 600 mg q8h in children > 40 kg and to 15 mg/kg q8h (max 400 mg q8h, max 600 mg q8h if augmented renal clearance, i.e., eGFR > 200 mL/min/1.73 m2) in children < 40 kg would be needed for the strains with highest MIC (16% of Pseudomonas aeruginosa and 47% of Staphylococcus aureus). The oral recommended dose of 20 mg/kg q12h (not exceeding 750 mg) would cover bacteria with MICs ≤ 0.125 but may be insufficient for bacteria with higher MIC and a dose increase according bodyweight and eGFR would be needed. These doses should be prospectively confirmed, and a therapeutic drug monitoring could be used to refine them individually.

Combined robotic approach and enhanced recovery after surgery pathway for optimization of costs in patients undergoing proctectomy.

BACKGROUND: Enhanced recovery after surgery (ERAS) pathways are beneficial in proctocolectomy, but their impact on robotic low rectal proctectomy is not fully investigated. This study assessed the impact of an ERAS pathway on the outcomes and cost of robotic (RTME) versus laparoscopic (LTME) total mesorectal excision. METHODS: A retrospective review was performed of patients with rectal cancer in a single French tertiary centre for three yearly periods: 2011, LTME; 2015, RTME; and 2018, RTME with ERAS. Patient characteristics, operative and postoperative data, and costs were compared among the groups. RESULTS: A total of 220 consecutive proctectomies were analysed (71 LTME, 58 RTME and 91 RTME with ERAS). A prevalence of lower and locally advanced tumours was observed with RTME. The median duration of surgery increased with the introduction of RTME, but became shorter than that for LTME with greater robotic experience (226, 233 and 180 min for 2011, 2015 and 2018 respectively; P < 0·001). The median duration of hospital stay decreased significantly for RTME with ERAS (11, 10 and 8 days respectively; P = 0·011), as did the overall morbidity rate (39, 38 and 16 per cent; P = 0·002). Pathology results, conversion and defunctioning stoma rates remained stable. RTME alone increased the total cost by €2348 compared with LTME. The introduction of ERAS and improved robotic experience decreased costs by €1960, compared with RTME performed in 2015 without ERAS implementation. In patients with no co-morbidity, costs decreased by €596 for RTME with ERAS versus LTME alone. CONCLUSION: ERAS is associated with cost reductions in patients undergoing robotic proctectomy.

ANTECEDENTES: Las vías clínicas ERAS son beneficiosas en la proctocolectomía, pero su impacto en la proctectomía rectal baja robótica no se ha investigado exhaustivamente. El objetivo de este estudio fue evaluar el impacto de la vía clínica ERAS sobre los resultados y el coste de la proctectomía robótica (resección total del mesorrecto robótica, robotic total mesorectal excision, RTME) versus procedimientos laparoscópicos de resección total del mesorrecto (laparoscopic total mesorectal excision, LTME). MÉTODOS: Revisión retrospectiva de pacientes con cáncer de recto tratados en un único centro terciario francés durante un periodo de tres años: 1) 2011: resección total del mesorrecto laparoscópica (LTME); 2) 2015: TME robótica y 3) 2018: TME robótica plus ERAS. Se compararon las características de los pacientes, los datos operatorios y postoperatorios, y los costes entre subgrupos utilizando análisis estadísticos. RESULTADOS: Se analizaron 220 proctectomías consecutivas que incluían 71 LTME, 58 RTME y 91 RTME plus ERAS. Se observó un predominio de tumores inferiores y localmente avanzados en la RTME. La mediana del tiempo operatorio aumentó con la introducción de RTME, pero llegó a ser inferior que en la LTME con una mayor experiencia robótica (226, 233 y 180 minutos para los periodos 1, 2 y 3, respectivamente; P = 0,0001). La mediana de la estancia hospitalaria disminuyó significativamente con la RTME plus ERAS (11, 10 y 8 días; P = 0,01), así como la morbilidad global (40%, 38% y 16%; P = 0,002). Los resultados de la anatomía patológica, las tasas de conversión y de estomas de protección permanecieron estables. La RTME sola aumentó el coste total en €2.348 comparado con la LTME. La introducción de ERAS y una mejora en la experiencia robótica disminuyeron los costes en €1.960 versus RTME realizada en 2015 sin la implementación de ERAS. En pacientes sin comorbilidades, los costes disminuyeron en €1.196 con RTME plus ERAS versus LTME sola. CONCLUSIÓN: ERAS se asocia con reducciones de coste en la proctectomía robótica.