Background Antimicrobial resistance (AMR) poses a major threat to human health around the world. Previous publications have estimated the effect of AMR on incidence, deaths, hospital length of stay, and health-care costs for specific pathogen-drug combinations in select locations. To our knowledge, this study presents the most comprehensive estimates of AMR burden to date. MethodsWe estimated deaths and disability-adjusted life-years (DALYs) attributable to and associated with bacterial AMR for 23 pathogens and 88 pathogen-drug combinations in 204 countries and territories in 2019. We obtained data from systematic literature reviews, hospital systems, surveillance systems, and other sources, covering 471 million individual records or isolates and 7585 study-location-years. We used predictive statistical modelling to produce estimates of AMR burden for all locations, including for locations with no data. Our approach can be divided into five broad components: number of deaths where infection played a role, proportion of infectious deaths attributable to a given infectious syndrome, proportion of infectious syndrome deaths attributable to a given pathogen, the percentage of a given pathogen resistant to an antibiotic of interest, and the excess risk of death or duration of an infection associated with this resistance. Using these components, we estimated disease burden based on two counterfactuals: deaths attributable to AMR (based on an alternative scenario in which all drugresistant infections were replaced by drug-susceptible infections), and deaths associated with AMR (based on an alternative scenario in which all drug-resistant infections were replaced by no infection). We generated 95% uncertainty intervals (UIs) for final estimates as the 25th and 975th ordered values across 1000 posterior draws, and models were cross-validated for out-of-sample predictive validity. We present final estimates aggregated to the global and regional level. FindingsOn the basis of our predictive statistical models, there were an estimated 4•95 million (3•62-6•57) deaths associated with bacterial AMR in 2019, including 1•27 million (95% UI 0•911-1•71) deaths attributable to bacterial AMR. At the regional level, we estimated the all-age death rate attributable to resistance to be highest in western sub-Saharan Africa, at 27•3 deaths per 100 000 (20•9-35•3), and lowest in Australasia, at 6•5 deaths (4•3-9•4) per 100 000. Lower respiratory infections accounted for more than 1•5 million deaths associated with resistance in 2019, making it the most burdensome infectious syndrome. The six leading pathogens for deaths associated with resistance (Escherichia coli, followed by Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa) were responsible for 929 000 (660 000-1 270 000) deaths attributable to AMR and 3•57 million (2•62-4•78) deaths associated with AMR in 2019. One pathogen-drug combination, meticillinresistant S aureus, caused more than 100 000 deaths attributa...

The aim of the study was to determine whether neonates resuscitated with room air compared with 100 per cent oxygen in the delivery room were less likely to have hypoxic ischemic encephalopathy and/or death before discharge. A controlled clinical trial was carried out at a tertiary care institute. All newborns weighing 1000 g or more with apnea or gasping respiration and/or heart rate less than 100 beats/min requiring positive pressure ventilation after initial steps of resuscitation were included. All eligible neonates were randomized to receive room air or 100 per cent oxygen for the first 90 s after birth if they required positive pressure ventilation. The composite primary outcome variable was hypoxic ischemic encephalopathy (HIE) and/or death before discharge. A total of 204 neonates fulfilling the inclusion criteria were enrolled. Of these, 107 neonates received room air and 97 neonates received 100 per cent oxygen for resuscitation. The composite primary outcome occurred in 41.1 per cent of the neonates assigned to receive room air and 43.3 per cent of those in the 100 per cent oxygen group (odds ratio in the group assigned to room air, 0.92; 95 per cent confidence interval, 0.52-1.60). Resuscitation of a newborn baby with room air instead of the current practice of 100 per cent oxygen does not confer a benefit in terms of reduced HIE and/or mortality. Significantly, there is no increase in adverse outcome with the use of room air, which can be recommended for resuscitation if oxygen is not available.

High RDW is associated with neonatal sepsis and is an independent outcome predictor for mortality associated with neonatal sepsis.

Aim:This study aimed to compare Neonatal Pain, Agitation, and Sedation Scale (N-PASS) with Premature Infant Pain Profile (PIPP) for the assessment of acute prolonged pain in ventilated neonates.Methods:This study was conducted in two phases. In phase 1 of the study, we assessed whether neonates on assisted ventilation experienced acute prolonged pain. In phase 2, the aim was to compare N-PASS with PIPP for the assessment of acute prolonged pain in neonates on assisted ventilation..Design:This is a prospective observational study.Study Setting and Duration:This study was conducted at a tertiary care neonatal intensive care unit for 6 months.Inclusion Criteria:Neonates on assisted ventilation for >48 h were selected for this study.Exclusion Criteria:Neonates with lethal congenital anomalies and severe encephalopathy were excluded from the study. N-PASS and PIPP tools were used to assess acute prolonged pain in ventilated neonates. Taking PIPP as gold standard and N-PASS as a new test, the correlation coefficient was calculated. The sensitivity, specificity, positive predictive value, and negative predictive value were also computed. The time taken to administer the tools was also computed.Results:The average PIPP score for ventilated neonates was 8.33. The correlation coefficient of N-PASS when compared to PIPP was 0.62. The average time taken to apply the N-PASS scale was 4.42 min as compared to 8.20 min for PIPP scale. In term neonates, the sensitivity, specificity, positive predictive value, and negative predictive value of N-PASS were 75%, 100%, 100%, and 60%, respectively. The corresponding values in preterm neonates were lesser.Conclusions:The study proves that neonates on assisted ventilation experience acute prolonged pain. N-PASS is clinically reliable and valid to assess acute prolonged pain in ventilated term neonates. The N-PASS is quicker than PIPP in assessing acute prolonged pain in ventilated neonates.Future Directions:The modified N-PASS tool (including the gestational age) should be developed.

Background Neonatal sepsis is a leading cause of child mortality, and increasing antimicrobial resistance threatens progress towards the Sustainable Development Goals. Evidence to guide antibiotic treatment for sepsis in neonates and young infants from randomized controlled trials or observational studies in low- and middle-income countries (LMICs) is scarce. We aimed to describe patterns of antibiotic use, pathogens and outcomes in LMIC hospital settings globally to inform future clinical trials on the management of neonatal sepsis. Methods & Findings Hospitalised infants aged <60 days with clinical sepsis were enrolled during 2018-2020 by 19 sites in 11 countries (mainly Asia and Africa). Prospective daily data was collected on clinical signs, supportive care, antibiotic treatment, microbiology and clinical outcome at 28 days. The study was observational, with no changes to routine clinical practice. 3204 infants were enrolled, with median birth weight 2500g (IQR 1400-3000) and postnatal age 5 days (IQR 2-15). Of 309 enrolled aged 28-60 days, 58.6% (n=181) were ex-preterm and/or a neonate at admission. 2215 (69%) infants had been in hospital since birth. 206 different empiric antibiotic combinations were used, which were structured into 5 groups that were developed from the World Health Organisation (WHO) AWaRe classification. 25.9% (n=814) of infants started a WHO first line regimen (Group 1 Access, penicillin-based regimen) and 13.8% (n=432) started WHO second-line cephalosporins (cefotaxime/ceftriaxone) (Group 2 Low Watch). The largest group (34.0%, n=1068) started a regimen providing partial extended-spectrum beta-lactamase (ESBL)/pseudomonal coverage (piperacillin-tazobactam, ceftazidime, or fluoroquinolone-based) (Group 3 Medium Watch), 18.0% (n=566) started a carbapenem (Group 4 High Watch), and 1.8% (n=57) started a Reserve antibiotic (Group 5, largely colistin-based). Predictors of starting non-WHO recommended regimens included lower birth weight, longer in-hospital stay, central vascular catheter use, previous culture positive sepsis or antibiotic exposure, previous surgery and greater sepsis severity. 728/2880 (25.3%) of initial regimens in Group 1-4 were escalated, mainly to carbapenems, and usually for clinical indications (n=480; 65.9%). 564 infants (17.6%) isolated a pathogen from their baseline blood culture, of which 62.9% (n=355) had a Gram-negative organism, predominantly Klebsiella pneumoniae (n=132) and Acinetobacter spp. (n=72). These leading Gram-negatives were both mostly resistant to WHO-recommended regimens, and also resistant to carbapenems in 32.6% and 71.4% of cases respectively. MRSA accounted for 61.1% of Staphylococcus aureus (n=54) isolates. Overall, 350/3204 infants died (11.3%; 95%CI 10.2-12.5%), with 17.7% case fatality rate among infants with a pathogen in baseline culture (95%CI 14.7-20.1%, n=99/564). Gram-negative infections accounted for 75/99 (75.8%) of pathogen-positive deaths, especially Klebsiella pneumoniae (n=28; 28.3%), and Acinetobacter spp. (n=24; 24.2%). Conclusion A very wide range of antibiotic regimens are now used to treat neonatal sepsis globally. There is common use of higher-level Watch antibiotics, frequent early switching and very infrequent de-escalation of therapy. Future hospital based neonatal sepsis trials will ideally need to account for the multiple regimens used as standard of care globally and include both empiric first line regimens and subsequent switching in the trial design.