1109. Pharmacokinetics and Exposure of Cefepime in Critically Ill Patients Receiving Extracorporeal Membrane Oxygenation (ECMO)

Background ECMO is a life-saving tool utilized in critically ill patients that require respiratory and/or cardiac support. ECMO may also affect the pharmacokinetics (PK) of certain medications, including some antibiotics. Cefepime is a widely used antibiotic in this population due to its broad spectrum activity but limited data are available to guide dosing in patients requiring ECMO. Methods This was a prospective, single-center study of 6 critically ill adult patients requiring ECMO and receiving cefepime 2g q8h as a 3h infusion. After obtaining informed consent, 4-6 blood samples within the dosing interval were collected to determine cefepime concentrations. Population PK was conducted in Pmetrics using R. Final MAP Bayesian parameter estimates were used to simulate free time above MIC (%ƒT >MIC) for various cefepime dosing regimens. The target pharmacodynamic exposure was 70% fT >MIC. Results Patients were between 31-62 years old; 4/6 (66.7%) were on veno-venous (VV) ECMO and 2 veno-arterial (VA) ECMO. Two patients required continuous venovenous hemodiafiltration (CVVHDF) while the other 4 had a CrCL between 92-199 ml/min. A two compartment model fitted the data better than a one compartment model. Median (range) final population PK parameters were: clearance (CL), 9.8 L/h (7.6-33.1); volume of central compartment (VC ), 6.9 L (4.7-49.8); and intercompartment transfer constants (k12), 2.04 h-1 (1.48-2.29); and k21, 1.49 h-1 (0.75-1.71). The 2g q8h (3h infusion) regimen resulted in target exposure in all patients up to an MIC of 8 mg/L (the susceptibility breakpoint for Pseudomonas), with 5/6 patients achieving this at 16 mg/L. A standard 2g q12h (0.5h infusion) regimen would have resulted in 5/6 patients achieving 70% ƒT >MIC at 8 mg/L and 1/6 at 16 mg/L. Conclusion These are the first data describing cefepime PK and exposure attainment in critically ill patients receiving ECMO. Cefepime 2g q8h (3h infusion) achieved target pharmacodynamic exposure up to the susceptibility breakpoint of 8 mg/L in all 6 patients, including 2 with concomitant CVVHDF. Additional studies are warranted to define cefepime PK in patients on ECMO across a robust range of CrCL to guide dosing. Disclosures David P. Nicolau, PharmD, Abbvie, Cepheid, Merck, Paratek, Pfizer, Wockhardt, Shionogi, Tetraphase (Other Financial or Material Support, I have been a consultant, speakers bureau member, or have received research funding from the above listed companies.) Joseph L. Kuti, PharmD, Allergan (Speaker’s Bureau)BioMérieux (Consultant, Research Grant or Support, Speaker’s Bureau)Contrafect (Scientific Research Study Investigator)GSK (Consultant)Merck (Research Grant or Support)Paratek (Speaker’s Bureau)Roche Diagnostics (Research Grant or Support)Shionogi (Research Grant or Support)Summit (Scientific Research Study Investigator)

Antibacterial therapy of endometritis after cesarian section: optimizing the dosing regime

Purpose. To study the pharmacokinetics of -lactam antibiotics in the development of endometritis after cesarean section to select the optimal dosage regimen. Methods. A prospective, randomized, single-center study included 52 women in puerperas with endometritis after a caesarean section, divided into four groups. The patients of the first group (n = 17) received a course of ceftriaxone bolus in a single dose of 2.0 g (n = 10) and in the mode of prolonged perioperative infusion (n = 7). The patients of the second group (n = 10) received cefepim bolus at a dose of 2.0 g 2 times a day (n = 5) and in the extended infusion mode (n = 5). The patients of the third group (n = 14) received amoxicillin / clavulanic acid (Amoxiclav 1000 mg + 200 mg) bolus at a dose of 1.0 g 3 times a day (n = 7) and in the extended infusion regimen (n = 7). The patients of the fourth group (n = 11) received ampicillin / sulbactam (Ampisid 1000 mg + 500 mg) bolus at a dose of 1.0 g 4 times a day (n = 6) and in the extended infusion regimen (n = 5). We have compared the concentration of the studied antibiotics in the uterine cavity in the four groups using high performance liquid chromatography. Results. The effective bactericidal concentration (C 4MIC) was not maintained throughout the entire dose interval in any of the treatment groups. The clinical efficacy and safety of the studied antibiotic regimens were similar. However, prolonged infusion of cefepime and aminopenicillins provided significantly higher concentrations in lochia. Conclusion. Prolonged intravenous infusion of cefepime, ceftriaxone, amoxicillin / clavulanic acid and ampicillin / sulbactam in the treatment of endometritis after a caesarean section improves the pharmacokinetic / pharmacodynamic characteristics of these -lactams in the uterine cavity, compared with the traditional bolus administration.

Comparison of Patient-Controlled Epidural Analgesia (PCEA) with Basal Infusion and Programmed Intermittent Epidural Bolus (PIEB) with PCEA in Labour Analgesia – A One-Year Retrospective Study

Introduction: For the past thirty years, patient-controlled epidural analgesia (PCEA) with basal infusion regimen has successfully improved the variable intensity of labour pain due to its advantage in allowing self-titration by the parturient. However, a recent review on programmed intermittent epidural bolus (PIEB) with PCEA regimen proved to be superior compared to PCEA with basal infusion, in terms of higher maternal satisfaction with longer duration of analgesia and lower local anaesthetic consumption. Following the introduction of PIEB at our institution, we did a study to compare maternal satisfaction, mode of delivery and neonatal outcome between these two methods of epidural labour analgesia. Methodology: We conducted a one-year retrospective analysis of data from obstetric analgesia service (OAS) record sheet and hospital information system evaluating outcomes after labour analgesia delivered by PCEA with basal infusion regimen (PCEA + basal infusion) and PIEB with PCEA regimen (PIEB+PCEA). The primary outcome was maternal satisfaction towards their labour analgesia. Other outcome parameters were the mode of delivery and neonatal Apgar scores. Outcomes were compared using independent t-test and Chi-square test. Result: There was no significant difference in maternal satisfaction between the two groups (P=0.398). However, a higher percentage of excellent satisfaction was found in the PIEB + PCEA group compared to that in the PCEA + basal infusion group (PIEB+PCEA 146/172 (84.9%) vs PCEA + basal infusion 138/171 (80.7%) respectively). There was no significant difference in the mode of delivery (P=0.296). However, PIEB+PCEA group had a higher percentage of spontaneous vaginal deliveries (PIEB+PCEA 87/172 (50.6%) vs PCEA + basal infusion 70/171 (40.9%) respectively) and a lower percentage of Caesarean deliveries (PIEB + PCEA 71/172 (41.3%) vs PCEA + basal infusion 87/171 (50.9%) respectively). Despite statistically significant differences found in Apgar scores in 1 minute (P=0.036), there was no significant difference in the scores at 5 minutes (P=0.107). Apgar scores and mean (SD) at 1 minute and 5 minutes for PIEB + PCEA were 7.77(0.85) and 8.91(0.55) respectively, and for PCEA + basal infusion the scores at 1 minute and 5 minutes were 7.92(0.39) and 8.98(0.19) respectively. Conclusion: PIEB with PCEA regimen is a newer epidural delivery technique for labour analgesia in our centre, which produced a comparable outcome to PCEA with basal infusion regimen.

Effect of Cisplatin Arterial Infusion (CAI) on Primary Nonmetastatic Pelvic Osteosarcoma: A Preliminary Study

Background: The critical role of arterial infusion chemotherapy in the multimodal treatment of extremity bone cancer has been investigated extensively, but few studies have focused on pelvic osteosarcoma. Therefore, we attempted to evaluate the clinical significance of arterial infusion chemotherapy in the treatment of pelvic osteosarcoma.Methods: We combined a cisplatin arterial infusion regimen with multidrug systematic chemotherapy as a neoadjuvant protocol for the treatment of pelvic osteosarcoma. The course number and dosage of cisplatin arterial infusion were adjusted to achieve a maximal tumor response evaluated by contrast-enhanced MRI per RECIST 1.1. Good responders received the same systematic combination for postoperative chemotherapy, and poor responders received second-line therapy. Twelve patients with nonmetastatic high-grade pelvic osteosarcoma were included. Survival, chemotherapy response and adverse events data were analyzed. Results: The mean follow-up period was 56.1 months. Four patients died of refractory tumor progression, and 1 patient with local recurrence had no evidence of disease for 27 months after receiving secondary amputation and resection. Kaplan-Meier survival analysis demonstrated a 57.8% overall survival and 52.5% event-free survival rate at 5 years. Eight of 12 patients had a >90% tumor necrosis rate according to histopathologic examinations. The rates of local adverse events were lower than those reported for extremity osteosarcoma. Conclusions: Our study initially indicated that the cisplatin arterial infusion regimen was a potential therapy with good tolerance in the treatment of pelvic osteosarcoma.

Qualitative factors shaping MS patients’ experiences of infusible disease-modifying drugs: a critical incident technique analysis

ObjectiveTo explore factors shaping the experiences of patients with relapsing-remitting multiple sclerosis with infusible disease-modifying drugs in a hospital setting.Design and settingsThe critical incident technique served as a framework for collecting and analysing patients’ qualitative account practices involving infusible disease-modifying drugs. Data were collected through semistructured interviews and one single-case study. Participants were recruited from all five regions in Denmark. Inductive thematic analysis was used to identify and interpret factors shaping patients’ infusion journey over time.ParticipantsTwenty-two patients with relapsing-remitting multiple sclerosis receiving infusion with disease-modifying drugs (natalizumab, alemtuzumab and ocrelizumab).ResultsFour time scenarios—preinfusion, day of infusion, long-term infusion and switch of infusion—associated with the infusion of disease-modifying drugs were analysed to reveal how different factors could both positively and negatively affect patient experience. Time taken to make the treatment decision was affected by participants’ subjective perceptions of their disease activity; this may have set off a treatment dilemma in the event of a pressing need for treatment. Planning and routine made infusion practices manageable, but external and internal surroundings, including infusion room ambience and the quality of relationships with healthcare professionals and fellow patients, affected patients’ cognitive state and well-being irrespective of the infusion regimen. Switching the infusion regimen can reactivate worries akin to the preinfusion scenario.ConclusionThis study provides novel insight into the positive and negative factors that shape patients’ experience of infusion care practices. From a patient’s perspective, an infusion practice is not a solitary event in time but includes planning and routine which become an integral part of their multiple sclerosis management. The quality of space and the ambience of the infusion room, combined with the relationship with healthcare professionals and fellow patients, can be a significant source of knowledge and support people with relapsing-remitting multiple sclerosis in their experience of agency in life.

Variable versus fixed-rate infusion of phenylephrine during cesarean delivery: a randomized controlled trial

Background Phenylephrine is the most commonly used vasopressor for prophylaxis against maternal hypotension during cesarean delivery; however, the best regimen for its administration is not well established. Although variable infusion protocols had been suggested for phenylephrine infusion, evidence-based evaluation of variable infusion regimens are lacking. The aim of this work is to compare variable infusion, fixed on-and-off infusion, and intermittent boluses of phenylephrine for prophylaxis against maternal hypotension during cesarean delivery. Methods A randomized controlled study was conducted, including full-term pregnant women scheduled for elective cesarean delivery. Participants were divided into three groups which received phenylephrine by either intermittent boluses (1.5 mcg/Kg phenylephrine), fixed on-and-off infusion (with a dose of 0.75 mcg/Kg/min), or variable infusion (with a starting dose of 0.75 mcg/Kg/min). The three groups were compared with regard to frequency of: maternal hypotension (primary outcome), second episode hypotension, reactive hypertension, and bradycardia. Other outcomes included heart rate, systolic blood pressure, physician interventions, and neonatal outcomes. Results Two-hundred and seventeen mothers were available for final analysis. The 2 infusion groups showed less incidence of maternal hypotension {26/70 (37%), 22/71 (31%), and (51/76 (67%)} and higher incidence of reactive hypertension compared to the intermittent boluses group without significant differences between the two former groups. The number of physician interventions was highest in the variable infusion group compared to the other two groups. The intermittent boluses group showed lower systolic blood pressure and higher heart rate compared to the two infusion groups; whilst the two later groups were comparable. Conclusion Both phenylephrine infusion regimens equally prevented maternal hypotension during cesarean delivery compared to intermittent boluses regimen. Due to higher number of physician interventions in the variable infusion regimen, the current recommendations which favor this regimen over fixed infusion regimen might need re-evaluation.