In vitro assessment of potential endocrine disrupting activities of chlorinated paraffins of various chain lengths.

The production of chlorinated paraffins (CPs) has risen in the past two decades due to their versatile industrial applications. Consequently, CPs are now widely detected in human food sources, the environment, and in human matrices such as serum, the placenta and breast milk. This raises concern about prenatal and postnatal exposure. While some studies suggest that certain short-chained CPs (SCCPs) may have endocrine disrupting properties, knowledge about potential endocrine disrupting potential of medium- (MCCP) and long-chained CPs (LCCPs) remains relativity sparse. Here, we used a panel of in vitro assays to investigate seven pure CPs and two technical mixtures of CPs. These varied in chain length and, chlorination degree. The in vitro panel covered androgen, estrogen, and retinoic acid receptor activities, transthyretin displacement, and steroidogenesis. One of the SCCPs inhibited androgen receptor (AR) activity. All SCCPs induced estrogen receptor (ER) activity. Some SCCPs and MCCPs increased 17ß-estradiol levels in the steroidogenesis assay, though not consistently across all substances in these groups. SCCPs exhibited the most pronounced effects in multiple in vitro assays, while the tested LCCPs showed no effects. Based on our results, some CPs can have endocrine disrupting potential in vitro. These findings warrant further examinations to ensure that CPs do not cause issues in intact organisms, including humans.

Balancing growth amidst salt stress - lifestyle perspectives from the extremophyte model Schrenkiella parvula.

Schrenkiella parvula, a leading extremophyte model in Brassicaceae, can grow and complete its lifecycle under multiple environmental stresses, including high salinity. Yet, the key physiological and structural traits underlying its stress-adapted lifestyle are unknown along with trade-offs when surviving salt stress at the expense of growth and reproduction. We aimed to identify the influential adaptive trait responses that lead to stress-resilient and uncompromised growth across developmental stages when treated with salt at levels known to inhibit growth in Arabidopsis and most crops. Its resilient growth was promoted by traits that synergistically allowed primary root growth in seedlings, the expansion of xylem vessels across the root-shoot continuum, and a high capacity to maintain tissue water levels by developing thicker succulent leaves while enabling photosynthesis during salt stress. A successful transition from vegetative to reproductive phase was initiated by salt-induced early flowering, resulting in viable seeds. Self-fertilization in salt-induced early flowering was dependent upon filament elongation in flowers otherwise aborted in the absence of salt during comparable plant ages. The maintenance of leaf water status promoting growth, and early flowering to ensure reproductive success in a changing environment, were among the most influential traits that contributed to the extremophytic lifestyle of S. parvula.

Feasibility, acceptability, and bacterial recovery for community-based sample collection to estimate antibiotic resistance in commensal gut and upper respiratory tract bacteria.

Vietnam has high rates of antibiotic use and resistance. Measuring resistance in commensal bacteria could provide an objective indicator for evaluating the impact of interventions to reduce antibiotic use and resistance. This study aimed to evaluate the feasibility, acceptability, and bacterial recovery for different sampling strategies. We conducted a cross-sectional mixed methods study in a rural community in Ha Nam Province, northern Vietnam, and collected structured interviews, samples, and in-depth interviews from households. Out of 389 households invited, 324 participated (83%), representing 1502 individuals. Samples were collected from these individuals (1498 stool, 1002 self-administered nasal swabs, and 496 HW-administered nasopharyngeal swabs). Pneumococci were recovered from 11.1% (128/1149) of the total population and 26.2% (48/183) of those under 5-years. Recovery was higher for health-worker (HW)-administered swabs (13.7%, 48/350) than self-administered swabs (10.0%, 80/799) (OR 2.06, 95% CI 1.07-3.96). Cost per swab was cheaper for self-administered ($7.26) than HW-administered ($8.63) swabs, but the overall cost for 100 positive samples was higher ($7260 and $6300 respectively). Qualitative interviews revealed that HW-administered nasopharyngeal swabs took longer to collect, caused more discomfort, and were more difficult to take from children. Factors affecting participation included sense of contribution, perceived trade-offs between benefits and effort, and peer influence. Reluctance was related to stool sampling and negative perceptions of research. This study provides important evidence for planning community-based carriage studies, including cost, logistics, and acceptability. Self-administered swabs had lower recovery, and though cheaper and quicker, this would translate to higher costs for large population-based studies. Recovery might be improved by swab-type, transport medium, and better cold-chain to lab.

Precision medicine in pediatric temporal epilepsy surgery: optimization of outcomes through functional MRI memory tasks and tailored surgeries.

OBJECTIVE: The goal of epilepsy surgery is both seizure cessation and maximal preservation of function. In temporal lobe (TL) cases, the lack of functional MRI (fMRI) tasks that effectively activate mesial temporal structures hampers preoperative memory risk assessment, especially in children. This study evaluated pediatric TL surgery outcome optimization associated with tailored resection informed by an fMRI memory task. METHODS: The authors identified focal onset TL epilepsy patients with 1) TL resections; 2) viable fMRI memory scans; and 3) pre- and postoperative neuropsychological (NP) evaluations. They retrospectively evaluated preoperative fMRI memory scans, available Wada tests, pre- and postoperative NP scores, postoperative MRI scans, and postoperative Engel class outcomes. To assess fMRI memory task outcome prediction, the authors 1) overlaid preoperative fMRI activation onto postoperative structural images; 2) classified patients as having "overlap" or "no overlap" of activation and resection cavities; and 3) compared these findings with memory improvement, stability, or decline, based on Reliable Change Index calculations. RESULTS: Twenty patients met the inclusion criteria. At a median of 2.1 postoperative years, 16 patients had Engel class IA outcomes and 1 each had Engel class IB, ID, IIA, and IID outcomes. Functional MRI activation was linked to NP memory outcome in 19 of 20 cases (95%). Otherwise, heterogeneity characterized the cohort. CONCLUSIONS: Functional MRI memory task activation effectively predicted individual NP outcomes in the context of tailored TL resections. Patients had excellent seizure and overall good NP outcomes. This small study adds to extant literature indicating that pediatric TL epilepsy does not represent a single clinical syndrome. Findings support individualized surgical intervention using fMRI memory activation to help guide this precision medicine approach.

Divergence in the ABA gene regulatory network underlies differential growth control.

The phytohormone abscisic acid (ABA) is a central regulator of acclimation to environmental stress; however, its contribution to differences in stress tolerance between species is unclear. To establish a comparative framework for understanding how stress hormone signalling pathways diverge across species, we studied the growth response of four Brassicaceae species to ABA treatment and generated transcriptomic and DNA affinity purification and sequencing datasets to construct a cross-species gene regulatory network (GRN) for ABA. Comparison of genes bound directly by ABA-responsive element binding factors suggests that cis-factors are most important for determining the target loci represented in the ABA GRN of a particular species. Using this GRN, we reveal how rewiring of growth hormone subnetworks contributes to stark differences in the response to ABA in the extremophyte Schrenkiella parvula. Our study provides a model for understanding how divergence in gene regulation can lead to species-specific physiological outcomes in response to hormonal cues.

Application of Responsive Neurostimulation as both a Diagnostic Tool for Seizure Localization and a Supplementary Tool for Surgical Management in Patients with Multiple Epileptogenic Foci: A Case Series.

AIM: To present a series of medically refractory focal epilepsy patients with multiple or eloquent epileptogenic zones (EZs) in whom a responsive neurostimulation (RNS) system was used as a complementary modality to surgical resection. RNS was also used as a diagnostic tool to monitor long-term epileptogenic activity for enhanced localization, especially in patients with bilateral temporal seizures. MATERIAL AND METHODS: Ten consecutive patients who underwent RNS system placement and surgical resection at a single institution were assessed. RESULTS: The RNS system, with its capacity for chronic ambulatory electrocorticography (ECoG), provided important diagnostic information that helped to modify the plan of surgical resection in one patient with bitemporal epilepsy in order to improve seizure outcomes. In addition, the RNS facilitated the surgical management of patients with multiple or eloquent EZs. CONCLUSION: The authors report a population of 10 patients in which the RNS system was used as a diagnostic tool for improved localization of EZs over a long interval or as a complementary therapeutic tool in patients with multiple or eloquent EZs.

Probiotic potential of lactic acid bacteria isolated from Vietnamese sour-fermented fish product

Aims@#To isolate and characterize the lactic acid bacteria (LAB) strains from the “mam chua ca ro” (sour fermented fish) in the South of Vietnam and investigate their potential anti-bacterial properties.@*Methodology and results@#Four LAB strains (MCR1, MCR2, MCR3 and MCR4) were isolated from the "mam chua ca ro" product and their anti-bacterial activity was determined using the spot assay and the paper disc diffusion method. The isolated LABs can inhibit Escherichia coli ATCC 25922, Staphyloccocus aureus ATCC 25923 and Vibrio parahaemolyticus BV016 and produce bacteriocin to control the growth of E. coli ATCC 25922 and S. aureus ATCC 25923, except V. parahaemolyticus. MCR2 was chosen to sequence 16S rRNA of Pediococcus acidilactic.@*Conclusion, significance and impact of study@#On the basis of their prominent anti-pathogenic bacteria activity, LAB strains isolated from Vietnamese sour-fermented fish products were verified as prospective probiotics.

Deep Eutectic Solvent Based on Lithium Bis[(trifluoromethyl)sulfonyl] Imide (LiTFSI) and 2,2,2-Trifluoroacetamide (TFA) as a Promising Electrolyte for a High Voltage Lithium-Ion Battery with a LiMn2O4 Cathode.

To design safe and electrochemically stable electrolytes for lithium-ion batteries, this study describes the synthesis and the utilization of new deep eutectic solvents (DESs) based on the mixture of 2,2,2-trifluoroacetamide (TFA) with a lithium salt (LiTFSI, lithium bis[(trifluoromethane)sulfonyl]imide). These prepared DESs were characterized in terms of thermal properties, ionic conductivity, viscosity, and electrochemical properties. Based on the appearance of the product and DSC measurements, it appears that this system is liquid at room temperature for LiTFSI mole fraction ranging from 0.25 to 0.5. At χLiTFSI = 0.25, DESs exhibited favorable electrolyte properties, such as thermal stability (up to 148 °C), relatively low viscosity (42.2 mPa.s at 30 °C), high ionic conductivity (1.5 mS.cm-1 at 30 °C), and quite large electrochemical stability window up to 4.9-5.3 V. With these interesting properties, selected DES was diluted with slight amount of ethylene carbonate (EC). Different amounts of EC (x = 0-30 %wt) were used to form hybrid electrolytes for battery testing with high voltage LiMn2O4 cathode and Li anode. The addition of the EC solvent into DES expectedly aims at enhancing the battery cycling performance at room temperature due to reducing the viscosity. Preliminary results tests clearly show that LiTFSI-based DES can be successfully introduced as an electrolyte in the lithium-ion batteries cell with a LiMn2O4 cathode material. Among all of the studied electrolytes, DES (LiTFSI: TFA = 4:1 + 10 %wt EC) is the most promising. The EC-based system exhibited a good specific capacity of 102 mAh.g-1 at C/10 with the theoretical capacity of 148 mAh.g-1 and a good cycling behavior maintaining at 84% after 50 cycles.

Concordance of Vancomycin Population-Predicted Pharmacokinetics with Patient-Specific Pharmacokinetics in Adult Hospitalized Patients: A Case Series.

BACKGROUND: Vancomycin empiric therapy is commonly dosed using clinical algorithms adapted from population-predicted pharmacokinetic parameters. However, precise dosing of vancomycin can be designed using patient-specific pharmacokinetic calculations. OBJECTIVE: The objective of this study is to assess the correlational fit between vancomycin population-predicted and patient-specific pharmacokinetic parameters [elimination rate constant (Ke) and half-life (t1/2)] in a case series of adult hospitalized patients. METHODS: This is a single-center case series of hospitalized adult patients who received vancomycin, had creatinine clearance calculation for derivation of population-predicted pharmacokinetic parameters, and had two vancomycin concentrations for calculation of patient-specific pharmacokinetic parameters. The primary objective of this case series is to evaluate the correlation between population-predicted and patient-specific pharmacokinetic parameters. The secondary objectives of this study are to evaluate the mean bias and precision between the population-predicted and patient-specific pharmacokinetic parameters and to assess the correlation between population-predicted and patient-specific pharmacokinetic parameters in special population subgroups (obese patients with body mass index ≥ 30 kg/m2 and patients with renal dysfunction). All correlation analyses were performed on the population-predicted pharmacokinetics using diverse methods of estimating renal function (Salazar-Corcoran and Cockcroft-Gault methods using either ideal, actual, or adjusted body weights). All significance testing was set at an α of < 0.05. IBM SPSS Statistics version 25 and SAS version 9.4 were used to conduct all statistical analyses. RESULTS: A total of 30 patients were included in the study; 33.3% (10/30) of the patients were obese and 56.7% (17/30) had renal dysfunction. In all patients in the study, the calculated population-predicted Ke and t1/2 using all four creatinine clearance estimation methods were each significantly correlated with patient-specific Ke and t1/2 (all Pearson correlation coefficients [r]: > + 0.7, p < 0.001). The population-predicted Ke and t1/2 calculated using Cockcroft-Gault creatinine clearance using adjusted body weight showed the strongest association with patient-specific Ke and t1/2. In the subgroup analyses, all the population-predicted Ke and t1/2 using four creatinine clearance estimation methods were each significantly correlated with patient-specific Ke and t1/2. The exception was the population-predicted t1/2 derived from Cockcroft-Gault creatinine clearance using actual body weight that did not show a significant correlation with patient-specific t1/2 in obese patients. CONCLUSIONS: In this case series, population-predicted pharmacokinetic parameters were strongly correlated with patient-specific pharmacokinetic parameters. The vancomycin population-predicted pharmacokinetic formula can be used safely to predict a patient's vancomycin pharmacokinetic disposition and can be maintained as an empiric dosing strategy in various hospitalized adult patients.

Is supported self-management for depression effective for adults in community-based settings in Vietnam?: a modified stepped-wedge cluster randomized controlled trial.

BACKGROUND: This study tested the effectiveness of a supported self-management (SSM) intervention to reduce symptoms of depression among adults compared with enhanced treatment as usual in community-based and primary care settings in Vietnam. METHODS: The cluster randomized trial included 376 adults in 32 communes in eight provinces. Eligible participants scored > 7 on the SRQ-20 depression scale. Patients with severe symptoms were excluded and referred to tertiary care. Randomization took place at the commune level. The immediate intervention group included 16 communes with 190 participants and the delayed group included 16 communes with 186 participants. Participants in communes randomized to the immediate intervention group received a two-month course of SSM, consisting of a workbook and supportive coaching. Those in communes randomized to the delayed group received enhanced treatment as usual and, for ethical purposes, received the SSM intervention after 4 months. The primary outcome is the effect of SSM on reduction in depression scores as indicated by a reduced proportion of participants with SRQ-20 scores > 7 at 2 months after commencement of SSM intervention. Blinding was not possible during intervention delivery but outcome assessors were blinded. Analysis was intention-to-treat. RESULTS: At 2 months, 26.4% of the intervention group and 42.3% of the delayed group had SRQ-20 scores > 7. The adjusted odds ratio of having depression between the intervention and control was 0.42 (p < 0.0001), 95% CI (0.28, 0.63). Receiving the intervention thus reduces the odds of having depression by 58%, compared with receiving the control after 2 months of treatment. No adverse events were reported. CONCLUSIONS: Results suggest that SSM is effective for decreasing depression symptoms among adults in community-based settings in Vietnam.Trial Registration This trial is registered at ClinicalTrials.gov, number NCT03001063.

Establishment and Benefits of a Normal Pressure Hydrocephalus Support Group on Patient Education and Experience.

INTRODUCTION: Normal pressure hydrocephalus (NPH) is a debilitating, neurological condition that can lead to mental deterioration. With the diagnosis and treatment of NPH constantly evolving and its symptoms worsening with age, education for patients and their families is crucial. In this study, we aim to explore the potential educational benefits of a physician-led NPH support group. METHODS: Between December 2015 and November 2018, six semiannual NPH support group meetings were held for patients and their families. Attendees, ages 20-90, completed a Likert scale-based survey designed to assess the support group's educational benefits using the following primary outcome variables: (1) subjective knowledge, (2) perceived utility/efficacy, and (3) patient satisfaction. RESULTS: Our survey data suggests that patients and their family members agree on the efficacy of the support group in learning about NPH. They felt that the support group served its purpose and improved their comfort/knowledge regarding NPH. There was consensus about sustaining and maintaining the support group for the future. Of 65 survey responses, the composite average score of questions pertaining to subjective knowledge, perceived utility/efficacy, and patient satisfaction was 4.5 out of 5.0. CONCLUSION: We demonstrated that support groups are effective in educating the adult NPH population and their family/friends about NPH onset and treatment. Enhanced educational awareness for patients and families can help patients cope with their neurological condition and improve patient adherence to follow-up and physician recommendations.

Effect of the Optimize Heart Failure Care Program on clinical and patient outcomes - The pilot implementation in Vietnam.

BACKGROUND: The Ho-Chi-Minh-city Heart Institute in Vietnam took part in the Optimize Heart Failure (OHF) Care Program, designed to improve outcomes following heart failure (HF) hospitalization by increasing patient awareness and optimizing HF treatment. METHODS: HF patients hospitalized with left ventricular ejection-fraction (LVEF) <50% were included. Patients received guideline-recommended HF treatment and education. Clinical signs, treatments and outcomes were assessed at admission, discharge, 2 and 6 months (M2, M6). Patients' knowledge and practice were assessed at M6 by telephone survey. RESULTS: 257 patients were included. Between admission and M2 and M6, heart rate decreased significantly, and clinical symptoms improved significantly. LVEF increased significantly from admission to M6. 85% to 99% of patients received education. At M6, 45% to 78% of patients acquired knowledge and adhered to practice regarding diet, exercise, weight control, and detection of worsening symptoms. High use of renin-angiotensin-aldosterone-system inhibitors (91%), mineralocorticoid-receptor-antagonists (77%) and diuretics (85%) was noted at discharge. Beta-blocker and ivabradine use was less frequent at discharge but increased significantly at M6 (from 33% to 51% and from 9% to 20%, respectively, p < 0.001). There were no in-hospital deaths. Readmission rates at 30 and 60 days after discharge were 8.3% and 12.5%, respectively. Mortality rates at 30 days, 60 days and 6 months were 1.2%, 2.5% and 6.4%, respectively. CONCLUSIONS: The OHF Care Program could be implemented in Vietnam without difficulty and was associated with high usage of guideline-recommended drug therapy. Although education was delivered, patient knowledge and practice could be further improved at M6 after discharge.

Plant Growth and Agrobacterium-mediated Floral-dip Transformation of the Extremophyte Schrenkiella parvula.

Schrenkiella parvula is an extremophyte adapted to various abiotic stresses, including multiple ion toxicity stresses. Despite high-quality genomic resources available to study how plants adapt to environmental stresses, its value as a functional genomics model and tool has been limited by the lack of a feasible transformation system. In this protocol, we report how to generate stable transgenic S. parvula lines using an Agrobacterium-mediated floral-dip method. We modified the transformation protocol used for A. thaliana to account for unique traits of S. parvula, such as an indeterminate flowering habit and a high epicuticular wax content on leaves. Briefly, S. parvula seeds were stratified at 4 °C for five days before planting. Plants were grown at a photoperiod of a 14 h light and 10 h dark and a 130 µmol m-2s-1 light intensity, at 22 °C to 24 °C. Eight to nine week-old plants with multiple inflorescences were selected for transformation. These inflorescences were dipped in an infiltration solution of Agrobacterium tumefaciens GV3101 carrying the pMP90RK plasmid. We performed two rounds of flower dipping with an interval of three to four weeks to increase the transformation efficiency. The T1 seeds were collected and dried for four weeks in a container with desiccants before germination to screen for candidate transformed lines. Resistance to BASTA was used to screen T1 plants. We sprayed the BASTA solution three times with an interval of three days starting at two week-old plants to reduce false positives. A BASTA drop test was performed on surviving individual plants to identify true positive transformants. The transformation efficiency was 0.033%, yielding 3-4 transgenic plants per 10,000 T1 seeds propagated.

Transcriptomic view of survival during early seedling growth of the extremophyte Haloxylon ammodendron.

Seedling establishment in an extreme environment requires an integrated genomic and physiological response to survive multiple abiotic stresses. The extremophyte, Haloxylon ammodendron is a pioneer species capable of colonizing temperate desert sand dunes. We investigated the induced and basal transcriptomes in H. ammodendron under water-deficit stress during early seedling establishment. We find that not only drought-responsive genes, but multiple genes in pathways associated with salt, osmotic, cold, UV, and high-light stresses were induced, suggesting an altered regulatory stress response system. Additionally, H. ammodendron exhibited enhanced biotic stress tolerance by down-regulation of genes that were generally up-regulated during pathogen entry in susceptible plants. By comparing the H. ammodendron basal transcriptome to six closely related transcriptomes in Amaranthaceae, we detected enriched basal level transcripts in H. ammodendron that shows preadaptation to abiotic stress and pathogens. We found transcripts that were generally maintained at low levels and some induced only under abiotic stress in the stress-sensitive model, Arabidopsis thaliana to be highly expressed under basal conditions in the Amaranthaceae transcriptomes including H. ammodendron. H. ammodendron shows coordinated expression of genes that regulate stress tolerance and seedling development resource allocation to support survival against multiple stresses in a sand dune dominated temperate desert environment.

Making Epidermal Bladder Cells Bigger: Developmental- and Salinity-Induced Endopolyploidy in a Model Halophyte.

Endopolyploidy occurs when DNA replication takes place without subsequent mitotic nuclear division, resulting in cell-specific ploidy levels within tissues. In plants, endopolyploidy plays an important role in sustaining growth and development, but only a few studies have demonstrated a role in abiotic stress response. In this study, we investigated the function of ploidy level and nuclear and cell size in leaf expansion throughout development and tracked cell type-specific ploidy in the halophyte Mesembryanthemum crystallinum In addition to developmental endopolyploidy, we examined the effects of salinity stress on ploidy level. We focused specifically on epidermal bladder cells (EBC), which are modified balloon-like trichomes, due to their large size and role in salt accumulation. Our results demonstrate that ploidy increases as the leaves expand in a similar manner for each leaf type, and ploidy levels up to 512C were recorded for nuclei in EBC of leaves of adult plants. Salt treatment led to a significant increase in ploidy levels in the EBC, and these cells showed spatially related differences in their ploidy and nuclear and cell size depending on the positions on the leaf and stem surface. Transcriptome analysis highlighted salinity-induced changes in genes involved in DNA replication, cell cycle, endoreduplication, and trichome development in EBC. The increase in cell size and ploidy observed in M. crystallinum under salinity stress may contribute to salt tolerance by increasing the storage capacity for sodium sequestration brought about by higher metabolic activity driving rapid cell enlargement in the leaf tissue and EBC.

Antimicrobial susceptibility and clarithromycin resistance patterns of Helicobacter pylori clinical isolates in Vietnam.

Helicobacter pylori is a gastric pathogen that causes several gastroduodenal disorders such as peptic ulcer disease and gastric cancer.  Eradication efforts of H. pylori are often hampered by antimicrobial resistance in many countries, including Vietnam.  Here, the study aimed to investigate the occurrence of antimicrobial resistance among H. pylori clinical isolates across 13 hospitals in Vietnam.  The study further evaluated the clarithromycin resistance patterns of H. pylori strains.  In order to address the study interests, antimicrobial susceptibility testing, epsilometer test and PCR-based sequencing were performed on a total of 193 strains isolated from patients, including 136 children (3-15 years of age) and 57 adults (19-69 years of age).  Antimicrobial susceptibility testing showed that the overall resistance to amoxicillin, clarithromycin, levofloxacin, metronidazole, and tetracycline was 10.4%, 85.5%, 24.4%, 37.8%, and 23.8% respectively.  The distribution of minimum inhibitory concentrations (MICs) of clarithromycin-resistant strains was 85.5% with MIC >0.5 µg/mL.  The majority of the clarithromycin resistant isolates (135 of 165 subjects) have MICs ranging from 2 µg/mL to 16 µg/mL.  Furthermore, sequencing detection of mutations in 23S rRNA gene revealed that strains resistant and susceptible to clarithromycin contained both A2143G and T2182C mutations.  Of all isolates, eight clarithromycin-resistant isolates (MIC >0.5 µg/mL) had no mutations in the 23S rRNA gene.  Collectively, these results demonstrated that a proportion of clarithromycin-resistant H. pylori strains, which are not related to the 23S rRNA gene mutations, could be potentially related to other mechanisms such as the presence of an efflux pump or polymorphisms in the CYP2C19 gene.  Therefore, the present study suggests that providing susceptibility testing prior to treatment or alternative screening strategies for antimicrobial resistance is important for future clinical practice.  Further studies on clinical guidelines and treatment efficacy are pivotal for successful eradication of H. pylori infection.

Ceftobiprole and ampicillin increase daptomycin susceptibility of daptomycin-susceptible and -resistant VRE.

OBJECTIVES: The synergistic combination of daptomycin plus ampicillin has proven to be effective against VRE including daptomycin-non-susceptible strains. Ceftobiprole is a cephalosporin with broad binding affinity for enterococcal PBP subtypes including PBP5. Given the synergy between ß-lactams and daptomycin against VRE, it was of interest to determine whether ceftobiprole offered any synergistic advantage with daptomycin compared with ampicillin. METHODS: MICs were determined by broth microdilution in the presence and absence of ampicillin or ceftobiprole for 20 ampicillin-resistant VRE. Six strains, including two isogenic pairs of vancomycin-resistant Enterococcus faecium and two vancomycin-resistant Enterococcus faecalis, were evaluated for synergy using time-kill methods. Synergy was defined as a ≥2 log10 cfu/mL reduction of the combination over the most active single agent. Binding of daptomycin-bodipy in the presence and absence of ceftobiprole was quantified. RESULTS: Daptomycin MICs ranged from 2 to 256 mg/L. The addition of ceftobiprole and ampicillin reduced daptomycin MICs by a median of 3 and 4 log2 dilutions, respectively. In time-kill studies, daptomycin plus either ceftobiprole or ampicillin was synergistic against four of six strains, but not the same strains. Both combinations were synergistic against the vancomycin-resistant E. faecalis strains. Ceftobiprole exposure increased daptomycin-bodipy binding by 2.8 times (P<0.0001). CONCLUSIONS: Ceftobiprole appears to offer a similar degree of synergistic activity to ampicillin when combined with daptomycin against VRE. Further research should explore the genetic and phenotypic qualities of strains that respond preferentially to ceftobiprole as opposed to ampicillin.