Population pharmacokinetics of prophylactic cefoxitin in elective bariatric surgery patients: a prospective monocentric study.

BACKGROUND: This study describes the population pharmacokinetics of cefoxitin in obese patients undergoing elective bariatric surgery and evaluates different dosing regimens for achievement of pre-defined target exposures. METHODS: Serial blood samples were collected during surgery with relevant clinical data. Total serum cefoxitin concentrations were measured by chromatographic assay and analysed using a population PK approach with Pmetrics®. The cefoxitin unbound fraction (fu) was estimated. Dosing simulations were performed to ascertain the probability of target attainment (PTA) to achieve cefoxitin fu above minimum inhibitory concentrations (MIC) from surgical incision to wound closure. Fractional target attainment (FTA) was calculated against MIC distributions of common pathogens. RESULTS: A total of 123 obese patients (median BMI 44.3 kg/m2) were included with 381 cefoxitin concentration values. Cefoxitin was best described by a one-compartment model, with a mean clearance and volume of distribution of 10.9 ± 6.1 L/h and 23.4 ± 10.5 L, respectively. In surgery <2 h, a 2 and a 4 g doses were sufficient for an MIC up to 4 and 8 mg/L (fu 50%), respectively. In prolonged surgery (2-4 h), only continuous infusion enabled optimal PTA for an MIC up to 16 mg/L. Optimal FTAs were obtained against Staphylococcus aureus and Escherichia Coli only when simulating with 50% cefoxitin protein binding (intermittent regimen) and regardless of the protein binding for the continuous infusion. CONCLUSION: Intermittent dosing regimens resulted in optimal FTAs against susceptible MIC distributions of S. aureus and E. coli when simulating with 50% cefoxitin protein binding. Continuous infusion of cefoxitin may improve FTA regardless of protein binding. STUDY REGISTRATION: Registration on ClinicalTrials.gov, NCT03306290.

Comparison of SARS-CoV-2 Variants of Concern Alpha (B.1.1.7) vs. Beta (B.1.351) in Critically Ill Patients: A Multicenter Cohort Study.

Objectives: The clinical outcomes of the Beta (B.1.351) variant of concern (VOC) of the SARS-CoV-2 virus remain poorly understood. In early 2021, northeastern France experienced an outbreak of Beta that was not observed elsewhere. This outbreak slightly preceded and then overlapped with a second outbreak of the better understood VOC Alpha (B.1.1.7) in the region. This situation allowed us to contemporaneously compare Alpha and Beta in terms of the characteristics, management, and outcomes of critically ill patients. Methods: A multicenter prospective cohort study was conducted on all consecutive adult patients who had laboratory confirmed SARS CoV-2 infection, underwent variant screening, and were admitted to one of four intensive care units (ICU) for acute respiratory failure between January 9th and May 15th, 2021. Primary outcome was 60-day mortality. Differences between Alpha and Beta in terms of other outcomes, patient variables, management, and vaccination characteristics were also explored by univariate analysis. The factors that associated with 60-day death in Alpha- and Beta-infected patients were examined with logistic regression analysis. Results: In total, 333 patients (median age, 63 years; 68% male) were enrolled. Of these, 174 and 159 had Alpha and Beta, respectively. The two groups did not differ significantly in terms of 60-day mortality (19 vs. 23%), 28-day mortality (17 vs. 20%), need for mechanical ventilation (60 vs. 61%), mechanical ventilation duration (14 vs. 15 days), other management variables, patient demographic variables, comorbidities, or clinical variables on ICU admission. The vast majority of patients were unvaccinated (94%). The remaining 18 patients had received a partial vaccine course and 2 were fully vaccinated. The vaccinated patients were equally likely to have Alpha and Beta. Conclusions: Beta did not differ from Alpha in terms of patient characteristics, management, or outcomes in critically ill patients. Trial Registration: ClinicalTrials.gov, identifier: NCT04906850.

Infection related catheter complications in patients undergoing prone positioning for acute respiratory distress syndrome: an exposed/unexposed study.

BACKGROUND: Prone positioning (PP) is a standard of care for patients with moderate-severe acute respiratory distress syndrome (ARDS). While adverse events associated with PP are well-documented in the literature, research examining the effect of PP on the risk of infectious complications of intravascular catheters is lacking. METHOD: All consecutive ARDS patients treated with PP were recruited retrospectively over a two-year period and formed the exposed group. Intensive care unit (ICU) patients during the same period without ARDS for whom PP was not conducted but who had an equivalent disease severity were matched 1:1 to the exposed group based on age, sex, centre, length of ICU stay and SAPS II (unexposed group). Infection-related catheter complications were defined by a composite criterion, including catheter tip colonization or intravascular catheter-related infection. RESULTS: A total of 101 exposed patients were included in the study. Most had direct ARDS (pneumonia). The median [Q1-Q3] PP session number was 2 [1-4]. These patients were matched with 101 unexposed patients. The mortality rates of the exposed and unexposed groups were 31 and 30%, respectively. The incidence of the composite criterion was 14.2/1000 in the exposed group compared with 8.2/1000 days in the control group (p = 0.09). Multivariate analysis identified PP as a factor related to catheter colonization or infection (p = 0.04). CONCLUSION: Our data suggest that PP is associated with a higher risk of CVC infectious complications.

Influence of the Obesity Phenotype on the Adequacy of Antibiotic Prophylaxis with Cefoxitin for Obese Patients Undergoing Bariatric Surgery: Lessons Learnt and Future Considerations.

BACKGROUND AND OBJECTIVES: A high inter-individual variability in pharmacokinetic parameters in obese patients is observed. The objective of this study was to evaluate the effect of obesity parameters on the pharmacokinetics of cefoxitin administered for antibiotic prophylaxis during bariatric surgery. METHODS: This a secondary analysis of a pharmacokinetic study involving 174 obese patients scheduled for bariatric surgery and receiving a 4-g dose of cefoxitin. Blood samples were collected at incision and wound closure. The total plasma concentrations were assessed utilising a validated high-performance liquid chromatography-tandem mass spectrometry method. The pharmacokinetic and pharmacodynamic target was defined as an estimated free concentration of cefoxitin at the time of wound closure >8 mg/L. Specific evaluated obesity parameters were fat body mass, fat body mass/height2, lean body mass, lean body mass/height2, visceral adipose tissue and presence of a metabolic syndrome. RESULTS: A total of 174 patients (median age 47 years) with a majority of women (75.3%) and a median BMI of 44 kg/m2 were analysed. The percentage of patients who met the pharmacokinetic and pharmacodynamic target was 85.1%. In the whole population, a tendency to fail to reach the target was observed with a higher lean mass over height2 [OR = 0.79; 95% CI (0.62-1.01); P = 0.060]. In the female subgroup, higher lean mass over height2 [OR = 0.63; 95% CI (0.41-0.97); P = 0.037] and the presence of a metabolic syndrome [OR = 0.17; 95% CI (0.03-0.83); P = 0.030] were associated with failure to reach the pharmacokinetic and pharmacodynamic target. CONCLUSION: Obese patients with a higher lean mass and a metabolic syndrome could constitute a subgroup at risk for cefoxitin under-dosage.

Serratus Plane Block Is Effective for Pain Control in Patients With Blunt Chest Trauma: A Case Series.

BACKGROUND: Rib fractures occur frequently following blunt chest trauma and induce morbidity and mortality. Analgesia is a cornerstone for their management, and regional analgesia is one of the tools available to reach this objective. Epidural and paravertebral blocks are the classical techniques used, but the serratus plane block (SPB) has recently been described as an effective technique for thoracic analgesia. METHODS: This case series reported and analyzed 10 consecutive cases of SPB for blunt chest trauma analgesia in a level 1 trauma center from May to October 2018. SPB was performed with either a single shot of local anesthetic or a catheter infusion. RESULTS: Ten patients were treated with 3 single shots and 7 catheter infusions (median length 3 days [interquartile range (IQR) 2.5 to 3.5]). The Median Injury Severity Score was 16 (IQR 16 to 23), and the number of broken ribs ranged from 3 to 22. Daily equivalent oral morphine consumption was significantly decreased after SPB from 108 mg (IQR 67 to 120) to 19 mg (IQR 0 to 58) (P = 0.015). The Numeric Pain Rating Scale (NPRS) score during cough was significantly decreased from 7.3 (IQR 5.3 to 8.8) to 4 (IQR 3.6 to 4.6) (P = 0.03). The NPRS score at rest remained unchanged. One complication occurred, due to a catheter section. CONCLUSIONS: The SPB technique (with or without catheter insertion) in 10 patients who had blunt chest trauma with rib fractures is effective for cough pain control, with a significant decrease in morphine consumption.

Antibiotic prophylaxis with high-dose cefoxitin in bariatric surgery: an observational prospective single center study.

BACKGROUND: The optimal dose of cefoxitin for antibiotic prophylaxis in obese patients remains uncertain. We evaluated the adequacy of a 4-gram dosing regimen of cefoxitin against the most frequent pathogens that infect patients undergoing bariatric surgery. METHODS: This observational prospective study included obese patients who required bariatric surgery and a 4-gram dose of cefoxitin as an antibiotic prophylaxis. Serum concentrations were measured during surgery (incision, wound closure and in case of reinjection). The pharmacokinetic/pharmacodynamic (PK/PD) target was to obtain free cefoxitin concentrations above 4× MIC, from incision to wound closure (100% ƒT>4xMIC). The targeted MIC was based on the worst-case scenario (the highest ECOFF value of Staphylococcus aureus, Enterobacteriaceae and anaerobic bacteria). The secondary outcomes were the factors related to underdosage. RESULTS: Two hundred patients were included. The mean age of the patients was 46 (±12) years-old, and the mean BMI was 45.8 (±6.9) kg/m2 Bypass surgery was the preferred technique (84%). The percentages of patients who met the PK/PD target (100% fT>4xMIC) of cefoxitin were 37.3%, 1.1% and 0% for S. aureus, Enterobacteriaceae and anaerobic bacteria, respectively. BMIs below 50 kg/m2 (OR 0.29, 95% CI [0.11-0.75], P = 0.0107) and a shorter duration of surgery (OR 0.97, 95% CI [0.95-0.99], P = 0.004) were associated with reaching the target concentrations. CONCLUSIONS: In obese patients undergoing bariatric surgery, a regimen of 4 grams of cefoxitin led to an inadequate coverage for most common pathogens. A longer surgery duration and BMI over 50 kg/m2 increase the risk of underdosage.

Spontaneous breathing during extracorporeal membrane oxygenation treatment of sickle cell disease acute chest syndrome.

Sickle cell disease (SCD) is a hereditary hemoglobinopathy resulting in sickling hemoglobin. Acute chest syndrome (ACS) is a serious complication of SCD and an important cause of morbidity and mortality. Management of ACS is complex and may necessitate mechanical ventilation and veno-venous extracorporeal membrane oxygenation (VV-ECMO) therapy in the more severe cases. We present herein the case of a young female adult (19 y.o.) with SCD who developed severe respiratory failure due to ACS occurring twice within 15 months and treated by VV-ECMO. We describe the management of ACS with VV-ECMO using two different approaches, namely with and without mechanical ventilation.