Ceftaroline and Avibactam Removal by Continuous Renal Replacement Therapies: An in vitro Study.

INTRODUCTION: Continuous renal replacement therapies (CRRTs) are frequently used in critically ill patients; however, there are scarce in vitro and in vivo studies showing the extracorporeal elimination of ceftaroline and avibactam. The aim of this study was to assess, through an in vitro model, the extracorporeal elimination of ceftaroline and avibactam by continuous veno-venous hemofiltration (CVVH), continuous veno-venous hemodiafiltration (CVVHDF), and continuous veno-venous hemodialysis (CVVHD), using a polysulfone hemofilter. METHODS: Simulated in vitro experiments were performed using a multiFiltrate machine with a 1.4 m2 Ultraflux® AV600S polysulfone hemofilter. Isofundin® without or with bovine serum albumin was circulated as vehicle for ceftaroline or avibactam. Pre-filter, post-filter, and effluent samples were taken over a period of 60 min, and they were immediately stored at 4°C until processed in the same day. The quantification of ceftaroline and avibactam in the samples was performed by high-performance liquid chromatography with ultraviolet detection. Protein binding, extraction coefficient (EC), and extracorporeal clearance (CLCRRT) were calculated. RESULTS: The elimination of both ceftaroline and avibactam during the three extracorporeal modalities followed first-order pharmacokinetics. Regardless of the CRRT technique, EC values for both molecules were around 1, similar to the unbound fraction of avibactam (0.96) and higher than the unbound fraction of ceftaroline (0.79). CLCRRT of ceftaroline ranged from 15.63 to 17.66 mL/min when CVVH and CVVHD were used with a flow rate of 1,000 mL/h, and from 29.25 to 32.95 mL/min for the CVVHDF modality with a flow rate of 2,000 mL/h. For avibactam, CLCRRT ranged from 15.07 to 18.82 mL/min for CVVH and CVVHD, and from 33.74 to 34.13 mL/min for CVVHDF. DISCUSSION: Avibactam and ceftaroline are extensively removed through the polysulfone membrane, and a dose adjustment may be recommended for patients under CRRT to ensure pharmacodynamic target achievement.

Influence of photoperiod and protocol length on metabolic rate traits in ballan wrasse Labrus bergylta.

In this study, ballan wrasse Labrus bergylta were subjected to either a conventional 1-day or an extended 5-day respirometry protocol. Additionally, in the 5-day protocol the fish were subjected to a 12 h light-dark cycle to assess the effects of photoperiods on metabolic rates (MO2 ). Diurnal patterns in routine and resting MO2 were not observed, suggesting that circadian rhythms in metabolism largely are driven by activity patterns rather than being of endogenous origin. Moreover, lack of a detectable circadian MO2 may be an adaptation to lower costs of living in ballan wrasse. Protocol length influenced standard metabolic rates (SMR) where estimates decreased by 13% and 17% when using 48 h and 5 days, respectively, compared to 24 h. The maximum metabolic rate (MMR) and the derived absolute aerobic scope (MMR-SMR) were unaffected by protocol length. However, factorial scopes (MMR/SMR) were reduced from 8.5 to 6.4 in the 5-day protocol, showing that factorial scopes are more sensitive to how SMR are obtained. The critical oxygen tension (Pcrit ) was reduced from 15% PO2 in the 1-day group to 11% PO2 in the 5-day group. However, MO2 in response to decreasing PO2 was similar, which together with a similar oxygen extraction coefficient, α (MO2 /PO2 ), suggested that the higher Pcrit in the 1-day group was an artefact of overestimating SMR. Finally, α was 12% lower at MMR compared to at Pcrit , which either means that MMR was underestimated in proportion to this difference or that α is not constant in the entire PO2 range. In summary, this study found that a conventional 1-day respirometry protocol may overestimate SMR and thereby alter the derived Pcrit and aerobic scope, while α is unaffected by protocol length. Moreover, alternating light conditions in the absence of other stressors did not influence MO2 in ballan wrasse.

Kinetics studies on effects of extraction techniques on bioactive compounds from Vernonia cinerea leaf.

Recently, unconventional methods especially microwave-assisted hydrodistillation extraction (MAHE) is being used as an alternative technique for extracting bioactive compounds from plant materials due to its advantages over conventional methods such as Soxhlet extraction (SE). In this study, bioactive compounds were extracted from Vernonia cinerea leaf using both MAHE and SE methods. In addition, the kinetic study of MAHE and SE methods were carried out using first- and second-order kinetic models. The results obtained showed that MAHE can extract higher yield of bioactive compounds from V. cinerea leaf in a shorter time and reduced used of extracting solvent compared with SE method. Based on the results obtained, second-order kinetic models can actually describe the extraction of bioactive compounds from V. cinerea leaf through MAHE with extraction rate coefficient of 0.1172 L/gmin and extraction capacity of 1.0547 L/g as compared to SE with 0.0157 L/gmin and 1.1626 L/g of extraction rate coefficient and extraction capacity, respectively. The gas chromatography-mass spectrometry analysis of the oil showed the presence of numerous heavy fractions in the oil obtained through MAHE as compared with the SE method. Moreover, the electric consumption and environmental impacts analysis of the oil suggested that MAHE can be a suitable green technique for extracting bioactive compounds from V. cinerea leaf.

Comparison of four near-infrared spectroscopy devices shows that they are only suitable for monitoring cerebral oxygenation trends in preterm infants.

AIM: Measuring cerebral oxygenation using near-infrared spectroscopy (NIRS) has taken on an increasingly important role in the field of neonatology. Several companies have already developed commercial devices, and more publications are reporting absolute boundary values or percentiles for neonates. We compared four commercially used devices to discover whether they provided consistent results in the same patients. METHODS: We recruited nine preterm infants and tested them for 2 h, using sensors from two different devices. The measurements were carried out six times on each child, so that all four devices were compared with each other. A total of 54 measurements were conducted. The following devices were compared: the NIRO 200 (Hamamatsu Photonics K.K), the INVOS 5100c (Somanetics), the Fore-Sight (CAS Med.) and the SenSmart X-100 (NONIN). RESULTS: The cerebral tissue oxygenation data yielded by the individual devices differed significantly from each other, ranging from a minimum difference of 2.93% to a maximum difference of 12.66%. CONCLUSION: The commercially available NIRS devices showed highly significant differences in local cerebral tissue oxygenation levels, to the extent that the industry cannot agree on uniform and reproducible standards. Therefore, NIRS should only be used for trend measurements in preterm infants.