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

Depression in pregnancy and the postpartum period: balancing adverse effects of untreated illness with treatment risks

The author reviews the risks and benefits of untreated maternal depression during pregnancy and the postnatal period and its effects on the well-being of the mother and infant. She then discusses the significant role psychiatrists can play in detecting and managing maternal depression as a primary measure for preventing future child psychopathology. A literature search was conducted on PubMed to identify both preclinical and clinical studies concerning deleterious effects of maternal depression on offspring. Additional searches focused on available safety data concerning the use of antidepressants during pregnancy and lactation. Key search items included depression during pregnancy, postpartum depression, lactation, and antidepressants. Burgeoning evidence was found concerning the adverse effects of maternal depression on the developing fetus and infant in the perinatal period. No controlled studies on the safety of antidepressant use in pregnancy and lactation were found; therefore, case reports, and some retrospective and prospective case series, must serve as guidelines for the treating clinician. Each case of maternal depression needs to be evaluated on an individual basis and decisions about treatment interventions should involve both the patient and family. Maternal depression during pregnancy and the postnatal period is associated with a significant disease burden in that it affects not only the mother but may also have both short- and long-term effects on offspring. Therefore, early detection and management of maternal depression, of which perinatal screening of mothers is an important component, are warranted

Terrorism in Pakistan and its impact on children\u27s mental health

At the end of the session, participants will be able to do the following: 1) discuss the context of the school killings in the Army Public School (APS) in Peshawar, Pakistan; 2) appreciate the psychological impact of school killings on children and the community at large; and 3) differentiate interventions designed for violence-based disasters versus natural ones

The one truly serious philosophical problem: ethical aspects of suicide

Suicide is a major global public health problem with an estimated one million deaths every year. It is one of the most personal yet one of the most complex acts anyone can perform, as it goes to the very core of the concept of human existence and the meaning of life. The philosophical debate on suicide has spanned centuries with no clear answers. Juxtaposed within the various perspectives that suicide can be studied from is the ethical perspective that brings into sharp focus the conflict between personal autonomy and societal responsibility towards suicidal individuals. Mental health professionals find themselves in the midst of this conflict as they are assumed to have the responsibility to prevent suicide in their Patients, while Patients\u27 responsibility towards themselves is frequently overlooked. Mental health professionals need to be aware of the ethical concerns that arise in the care of suicidal Patients