The Novel ß-Lactam Enhancer Zidebactam Augments the In Vivo Pharmacodynamic Activity of Cefepime in a Neutropenic Mouse Lung Acinetobacter baumannii Infection Model.

WCK 5222 is a combination of cefepime and the high-affinity PBP2-binding ß-lactam enhancer zidebactam. The cefepime-zidebactam combination is active against multidrug-resistant Gram-negative bacteria, including carbapenemase-expressing Acinetobacter baumannii The mechanism of action of the combination involves concurrent multiple penicillin binding protein inhibition, leading to the enhanced bactericidal action of cefepime. The aim of the present study was to assess the impact of the zidebactam-mediated enhanced in vitro bactericidal action in modulating the percentage of the time that the free drug concentration remains above the MIC (percent fT>MIC) for cefepime required for the in vivo killing of A. baumannii Cefepime and cefepime-zidebactam MICs were comparable and ranged from 2 to 16 mg/liter for the A. baumannii strains (n = 5) employed in the study. Time-kill studies revealed the improved killing of these strains by the cefepime-zidebactam combination compared to that by the constituents alone. Employing a neutropenic mouse lung infection model, exposure-response analyses for all the A. baumannii strains showed that the cefepime fT>MIC required for 1-log10 kill was 38.9%. In the presence of a noneffective dose of zidebactam, the cefepime fT>MIC requirement dropped significantly to 15.5%, but it still rendered a 1-log10 kill effect. Thus, zidebactam mediated the improvement in cefepime's bactericidal effect observed in time-kill studies, manifested in vivo through the lowering of cefepime's pharmacodynamic requirement. This is a first-ever study demonstrating a ß-lactam enhancer role of zidebactam that helps augment the in vivo activity of cefepime by reducing the magnitude of its pharmacodynamically relevant exposures against A. baumannii.

Use of Genomic Estimated Breeding Values Results in Rapid Genetic Gains for Drought Tolerance in Maize.

More than 80% of the 19 million ha of maize ( L.) in tropical Asia is rainfed and prone to drought. The breeding methods for improving drought tolerance (DT), including genomic selection (GS), are geared to increase the frequency of favorable alleles. Two biparental populations (CIMMYT-Asia Population 1 [CAP1] and CAP2) were generated by crossing elite Asian-adapted yellow inbreds (CML470 and VL1012767) with an African white drought-tolerant line, CML444. Marker effects of polymorphic single-nucleotide polymorphisms (SNPs) were determined from testcross (TC) performance of F families under drought and optimal conditions. Cycle 1 (C1) was formed by recombining the top 10% of the F families based on TC data. Subsequently, (i) C2[PerSe_PS] was derived by recombining those C1 plants that exhibited superior per se phenotypes (phenotype-only selection), and (ii) C2[TC-GS] was derived by recombining a second set of C1 plants with high genomic estimated breeding values (GEBVs) derived from TC phenotypes of F families (marker-only selection). All the generations and their top crosses to testers were evaluated under drought and optimal conditions. Per se grain yields (GYs) of C2[PerSe_PS] and that of C2[TC-GS] were 23 to 39 and 31 to 53% better, respectively, than that of the corresponding F population. The C2[TC-GS] populations showed superiority of 10 to 20% over C2[PerSe-PS] of respective populations. Top crosses of C2[TC-GS] showed 4 to 43% superiority of GY over that of C2[PerSe_PS] of respective populations. Thus, GEBV-enabled selection of superior phenotypes (without the target stress) resulted in rapid genetic gains for DT.

Design of Upelow Anaerobic Sludge Blanket reactor for treatment of organic wastewaters.

The Upflow Anaerobic Sludge Blanket (UASB) Reactor is widely applied anaerobic wastewater treatment method all over the world. Uniform distribution of wastewater at reactor bottom is necessary to establish proper contact between sludge and wastewater. In addition, proper functioning of Gas-Liquid-Solid (GLS) separator is crucial to ensure maximum sludge retention in the reactor and to achieve maximum COD removal rate in the reactor. Hence, proper design of reactor is necessary for appropriate functioning of various components for a given wastewater flow rate and COD concentration. The design procedure for UASB reactor taking due consideration to the GLS design and design of inlet arrangement is discussed in this paper for various wastewater strength and flow rates. A software is developed to make economical design of UASB reactor for different type of wastewater by adopting maximum loading conditions, based on literature recommendations, and at the same time to satisfy all design recommendation, as far as possible.