12 research outputs found
Effects of antibiotic resistance, drug target attainment, bacterial pathogenicity and virulence, and antibiotic access and affordability on outcomes in neonatal sepsis: an international microbiology and drug evaluation prospective substudy (BARNARDS)
Background
Sepsis is a major contributor to neonatal mortality, particularly in low-income and middle-income countries (LMICs). WHO advocates ampicillin–gentamicin as first-line therapy for the management of neonatal sepsis. In the BARNARDS observational cohort study of neonatal sepsis and antimicrobial resistance in LMICs, common sepsis pathogens were characterised via whole genome sequencing (WGS) and antimicrobial resistance profiles. In this substudy of BARNARDS, we aimed to assess the use and efficacy of empirical antibiotic therapies commonly used in LMICs for neonatal sepsis.
Methods
In BARNARDS, consenting mother–neonates aged 0–60 days dyads were enrolled on delivery or neonatal presentation with suspected sepsis at 12 BARNARDS clinical sites in Bangladesh, Ethiopia, India, Pakistan, Nigeria, Rwanda, and South Africa. Stillborn babies were excluded from the study. Blood samples were collected from neonates presenting with clinical signs of sepsis, and WGS and minimum inhibitory concentrations for antibiotic treatment were determined for bacterial isolates from culture-confirmed sepsis. Neonatal outcome data were collected following enrolment until 60 days of life. Antibiotic usage and neonatal outcome data were assessed. Survival analyses were adjusted to take into account potential clinical confounding variables related to the birth and pathogen. Additionally, resistance profiles, pharmacokinetic–pharmacodynamic probability of target attainment, and frequency of resistance (ie, resistance defined by in-vitro growth of isolates when challenged by antibiotics) were assessed. Questionnaires on health structures and antibiotic costs evaluated accessibility and affordability.
Findings
Between Nov 12, 2015, and Feb 1, 2018, 36 285 neonates were enrolled into the main BARNARDS study, of whom 9874 had clinically diagnosed sepsis and 5749 had available antibiotic data. The four most commonly prescribed antibiotic combinations given to 4451 neonates (77·42%) of 5749 were ampicillin–gentamicin, ceftazidime–amikacin, piperacillin–tazobactam–amikacin, and amoxicillin clavulanate–amikacin. This dataset assessed 476 prescriptions for 442 neonates treated with one of these antibiotic combinations with WGS data (all BARNARDS countries were represented in this subset except India). Multiple pathogens were isolated, totalling 457 isolates. Reported mortality was lower for neonates treated with ceftazidime–amikacin than for neonates treated with ampicillin–gentamicin (hazard ratio [adjusted for clinical variables considered potential confounders to outcomes] 0·32, 95% CI 0·14–0·72; p=0·0060). Of 390 Gram-negative isolates, 379 (97·2%) were resistant to ampicillin and 274 (70·3%) were resistant to gentamicin. Susceptibility of Gram-negative isolates to at least one antibiotic in a treatment combination was noted in 111 (28·5%) to ampicillin–gentamicin; 286 (73·3%) to amoxicillin clavulanate–amikacin; 301 (77·2%) to ceftazidime–amikacin; and 312 (80·0%) to piperacillin–tazobactam–amikacin. A probability of target attainment of 80% or more was noted in 26 neonates (33·7% [SD 0·59]) of 78 with ampicillin–gentamicin; 15 (68·0% [3·84]) of 27 with amoxicillin clavulanate–amikacin; 93 (92·7% [0·24]) of 109 with ceftazidime–amikacin; and 70 (85·3% [0·47]) of 76 with piperacillin–tazobactam–amikacin. However, antibiotic and country effects could not be distinguished. Frequency of resistance was recorded most frequently with fosfomycin (in 78 isolates [68·4%] of 114), followed by colistin (55 isolates [57·3%] of 96), and gentamicin (62 isolates [53·0%] of 117). Sites in six of the seven countries (excluding South Africa) stated that the cost of antibiotics would influence treatment of neonatal sepsis
Not Available
Not AvailableNet profit from raw jute (jute and mesta together are called raw jute) cultivation is very poor owing to its
high cost involvement (35-40% of the total cost of cultivation) in conventional manual weeding process.
So far only post-emergence grass weed killing herbicides have been found to be successful in jute. After
controlling grassy weeds, Cyperus rotundus and other broad-leaved weeds have become menace to these
fibre crops which were effectively controlled adopting stale seedbed technique (herbicides applied on
established weeds 10 days ahead of sowing jute and mesta) in Bararckpore, West Bengal. In stale seedbed
method in jute,(cv ‘JRO-524’), glyphosate 2.46 kg SL/ha and 2,4-D 2 kg/ha in combination, and glyphosate
2.46 kg SL/ha and pyrazosulfuron-ethyl 60g/ha in combination followed by one hand weeding were found
promising to control mixed weed flora in jute field. After two years’ cycle, these herbicide combinations
reduced the Cyperus rotundus population by more than 80% over control and produced a mean of fibre
yield of 28 to 3.04 t/ha and a maximum of 4.3 t jute fibre/ha in 2006-08. In mesta (cv. ‘HC-583’), in stale
seedbed method, butacholor 0.75 kg/ha and 2, 4-D 2 kg/ha in combination followed by 2-HW produced a
mean fibre yield of 2.65 t/ha with a maximum 3.2 t mesta fibre/ha in 2007-08 and kept the mesta field free
from weed for a couple of weeks. Pretilachlor (0.5 kg/ha) and paraquat (0.48 kg SL/ha) in combination,
when applied 10 days ahead of mesta sowing on established weeds, it controlled mixed weed flora and
produced a mean mesta fibre yield of 2.68 t/ha. Quizalofop-ethyl 5% EC 60 g/ha and Dhanuvit 0.5 to 0.6
l/ha at 21 DAE and one hand weeding produced a mean mesta fibre yield of 2.76 t/ha with a maximum of
3.45 t fibre/ha in 2007-08. Except chlorimuron-ethyl, other herbicides did not affect the soil microbial
flora in post harvest jute soil. All these methods produced mean fibre yields at par with two manual
weedings.Not Availabl
Validation of a Short Questionnaire in English and French for Use in Patients with Persistent Upper Gastrointestinal Symptoms Despite Proton Pump Inhibitor Therapy: The Pass (Proton Pump Inhibitor Acid Suppression Symptom) Test
BACKGROUND: The management of persistent symptoms during acid suppression therapy in patients with gastroesophageal reflux disease or dyspepsia might be improved if patient-physician communication regarding the presence and character of these persistent symptoms were facilitated