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

Comparative Assessment of Serum Homocysteine and High Sensitivity C-reactive Protein in type 2 Diabetic and non Diabetic Patients with ACS

Background: Increased level of serum homocysteine (Hcy) and high sensitivity C-reactive protein (hs-CRP) have a proven implication with epithelial injury leading to coronary artery disease ((CAD). These are strongly associated with different metabolic syndrome variables, although different studies have shown both positive and negative responses when correlated with type 2 diabetes malitus (T2DM). In this study we explored the role of these markers of CAD in type II diabetic and non diabetic patients with newly diagnosed acute coronary syndrome (ACS) at a tertiary care hospital among Bangladeshi population.&#x0D; Methods: We wanted to identify whether Hcy and hs- CRP link positively or negatively with type 2 diabetes in this cross sectional observentional study. A total of 260 patients with new onset ACS were included in the study, out of which 72 patients with T2DM and 188 patients without diabetes were considered as group I and group II respectively. Clinical and biochemical data were compared in between the groups.&#x0D; Results: The mean age of the study population was 50.33±15.50 years and 45.86±18.76 years in group I and II respectivly. Male female ratio was 4:1 among the whole study subjects. There was significantly higher level of serum homocysteine in group II than group I 18.41±15.49 μmol/L vs. 14.11±6.48 μmol/L respectively (p &lt;0.05). Similarly hs-CRP in group I was 26.84±30.30 mg/L and in group II 37.48±37.99mg/L, higher in group II (p&lt;0.05). Both Hcy and hs-CRP were higher in male and female patients in group II. Dyslipidaemia was significant risk factor in group I and smoking in group II (p&lt;0.05).&#x0D; Conclusion: In patients with ACS serum Hcy and hs-CRP were significantly higher in non-daibetic patients then in patients with type 2 diabetes. This association may be population or ethenicity specific which provide further scope for future elaborate studies.&#x0D; Bangladesh Heart Journal 2020; 35(2) : 114-120</jats:p