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There is limited data on antibiotic treatment in hospitalized neonates in low- and middle-income countries (LMICs). We aimed to describe patterns of antibiotic use, pathogens, and clinical outcomes, and to develop a severity score predicting mortality in neonatal sepsis to inform future clinical trial design. Hospitalized infants <60 days with clinical sepsis were enrolled during 2018 to 2020 by 19 sites in 11 countries (mainly Asia and Africa). Prospective daily observational data was collected on clinical signs, supportive care, antibiotic treatment, microbiology, and 28-day mortality. Two prediction models were developed for (1) 28-day mortality from baseline variables (baseline NeoSep Severity Score); and (2) daily risk of death on IV antibiotics from daily updated assessments (NeoSep Recovery Score). Multivariable Cox regression models included a randomly selected 85% of infants, with 15% for validation. A total of 3,204 infants were enrolled, with median birth weight of 2,500 g (IQR 1,400 to 3,000) and postnatal age of 5 days (IQR 1 to 15). 206 different empiric antibiotic combinations were started in 3,141 infants, which were structured into 5 groups based on the World Health Organization (WHO) AWaRe classification. Approximately 25.9% (n = 814) of infants started WHO first line regimens (Group 1-Access) and 13.8% (n = 432) started WHO second-line cephalosporins (cefotaxime/ceftriaxone) (Group 2-\"Low\" Watch). The largest group (34.0%, n = 1,068) 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) a Reserve antibiotic (Group 5, largely colistin-based), and 728/2,880 (25.3%) of initial regimens in Groups 1 to 4 were escalated, mainly to carbapenems, usually for clinical deterioration (n = 480; 65.9%). A total of 564/3,195 infants (17.7%) were blood culture pathogen positive, of whom 62.9% (n = 355) had a gram-negative organism, predominantly Klebsiella pneumoniae (n = 132) or Acinetobacter spp. (n = 72). Both were commonly resistant to WHO-recommended regimens and to carbapenems in 43 (32.6%) and 50 (71.4%) of cases, respectively. MRSA accounted for 33 (61.1%) of 54 Staphylococcus aureus isolates. Overall, 350/3,204 infants died (11.3%; 95% CI 10.2% to 12.5%), 17.7% if blood cultures were positive for pathogens (95% CI 14.7% to 21.1%, n = 99/564). A baseline NeoSep Severity Score had a C-index of 0.76 (0.69 to 0.82) in the validation sample, with mortality of 1.6% (3/189; 95% CI: 0.5% to 4.6%), 11.0% (27/245; 7.7% to 15.6%), and 27.3% (12/44; 16.3% to 41.8%) in low (score 0 to 4), medium (5 to 8), and high (9 to 16) risk groups, respectively, with similar performance across subgroups. A related NeoSep Recovery Score had an area under the receiver operating curve for predicting death the next day between 0.8 and 0.9 over the first week. There was significant variation in outcomes between sites and external validation would strengthen score applicability. Antibiotic regimens used in neonatal sepsis commonly diverge from WHO guidelines, and trials of novel empiric regimens are urgently needed in the context of increasing antimicrobial resistance (AMR). The baseline NeoSep Severity Score identifies high mortality risk criteria for trial entry, while the NeoSep Recovery Score can help guide decisions on regimen change. NeoOBS data informed the NeoSep1 antibiotic trial (ISRCTN48721236), which aims to identify novel first- and second-line empiric antibiotic regimens for neonatal sepsis. ClinicalTrials.gov, (NCT03721302).

The use of azithromycin reduces maternal infection in women during unplanned cesarean delivery, but its effect on those with planned vaginal delivery is unknown. Data are needed on whether an intrapartum oral dose of azithromycin would reduce maternal and offspring sepsis or death. In this multicountry, placebo-controlled, randomized trial, we assigned women who were in labor at 28 weeks' gestation or more and who were planning a vaginal delivery to receive a single 2-g oral dose of azithromycin or placebo. The two primary outcomes were a composite of maternal sepsis or death and a composite of stillbirth or neonatal death or sepsis. During an interim analysis, the data and safety monitoring committee recommended stopping the trial for maternal benefit. A total of 29,278 women underwent randomization. The incidence of maternal sepsis or death was lower in the azithromycin group than in the placebo group (1.6% vs. 2.4%), with a relative risk of 0.67 (95% confidence interval [CI], 0.56 to 0.79; P<0.001), but the incidence of stillbirth or neonatal death or sepsis was similar (10.5% vs. 10.3%), with a relative risk of 1.02 (95% CI, 0.95 to 1.09; P = 0.56). The difference in the maternal primary outcome appeared to be driven mainly by the incidence of sepsis (1.5% in the azithromycin group and 2.3% in the placebo group), with a relative risk of 0.65 (95% CI, 0.55 to 0.77); the incidence of death from any cause was 0.1% in the two groups (relative risk, 1.23; 95% CI, 0.51 to 2.97). Neonatal sepsis occurred in 9.8% and 9.6% of the infants, respectively (relative risk, 1.03; 95% CI, 0.96 to 1.10). The incidence of stillbirth was 0.4% in the two groups (relative risk, 1.06; 95% CI, 0.74 to 1.53); neonatal death within 4 weeks after birth occurred in 1.5% in both groups (relative risk, 1.03; 95% CI, 0.86 to 1.24). Azithromycin was not associated with a higher incidence in adverse events. Among women planning a vaginal delivery, a single oral dose of azithromycin resulted in a significantly lower risk of maternal sepsis or death than placebo but had little effect on newborn sepsis or death. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; A-PLUS ClinicalTrials.gov number, NCT03871491.).

Background The high rates of culture-positive sepsis, sepsis-related mortality, and multidrug resistance in neonates admitted to special care newborn units in district hospitals (DH) in India necessitate urgent actions to prevent infections in these settings. Immediate kangaroo mother care (iKMC), initiated before stabilization within the first few hours of life, has been shown to reduce neonatal mortality among low birth weight (LBW) neonates admitted to tertiary care hospitals. However, the effect of iKMC on sepsis and sepsis-related mortality, particularly in DH, remains unclear. This study aims to evaluate whether iKMC can lower the incidence of mortality or culture-positive sepsis in LBW neonates admitted to neonatal units in district hospitals. Methods This stepped-wedge cluster randomized trial will be conducted in ten district hospitals in Chhattisgarh, India, over 42 months. All neonates weighing between 1000 and 1799 g at birth and admitted to the participating hospitals, in whom KMC can be initiated within 12 h of life, will be eligible for inclusion. During the pre-intervention period (control), routine KMC will be practiced at the sites as is. Following a baseline period of 6 months, iKMC will be implemented sequentially in ten steps across the ten study sites at intervals of 3 months. The intervention includes initiating continuous skin-to-skin contact with the mother or relatives within 12 h of life, continuing KMC until discharge or weight 2.5 kg, and providing breastfeeding support. The primary outcome is the incidence of all-cause neonatal mortality and/or culture-positive sepsis until 28 days of life. Relative risks with 95% confidence intervals will be reported and analyzed using a generalized linear mixed model. An intention-to-treat analysis will be conducted. Discussion The PRISM (Protective Role of Immediate KMC in neonatal Sepsis and Mortality) trial will sequentially implement iKMC for LBW neonates in ten district hospitals with a relatively high burden of sepsis in India. If proven effective in reducing the risks of sepsis or neonatal mortality, the trial will provide necessary evidence for its safety and efficacy, as well as the impetus for implementing and upscaling the intervention in district hospitals across India and other low- and middle-income countries. Trial registration Clinical Trial Registry of India, CTRI/2024/09/074269. Registered on 24/09/2024, https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=MTE0MzY3&Enc=&userName=immediate%20kangaroo%20mother%20care .

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Sepsis is present in many hospitalizations that culminate in death. The contribution of sepsis to these deaths, and the extent to which they are preventable, is unknown. To estimate the prevalence, underlying causes, and preventability of sepsis-associated mortality in acute care hospitals. Cohort study in which a retrospective medical record review was conducted of 568 randomly selected adults admitted to 6 US academic and community hospitals from January 1, 2014, to December 31, 2015, who died in the hospital or were discharged to hospice and not readmitted. Medical records were reviewed from January 1, 2017, to March 31, 2018. Clinicians reviewed cases for sepsis during hospitalization using Sepsis-3 criteria, hospice-qualifying criteria on admission, immediate and underlying causes of death, and suboptimal sepsis-related care such as inappropriate or delayed antibiotics, inadequate source control, or other medical errors. The preventability of each sepsis-associated death was rated on a 6-point Likert scale. The study cohort included 568 patients (289 [50.9%] men; mean [SD] age, 70.5 [16.1] years) who died in the hospital or were discharged to hospice. Sepsis was present in 300 hospitalizations (52.8%; 95% CI, 48.6%-57.0%) and was the immediate cause of death in 198 cases (34.9%; 95% CI, 30.9%-38.9%). The next most common immediate causes of death were progressive cancer (92 [16.2%]) and heart failure (39 [6.9%]). The most common underlying causes of death in patients with sepsis were solid cancer (63 of 300 [21.0%]), chronic heart disease (46 of 300 [15.3%]), hematologic cancer (31 of 300 [10.3%]), dementia (29 of 300 [9.7%]), and chronic lung disease (27 of 300 [9.0%]). Hospice-qualifying conditions were present on admission in 121 of 300 sepsis-associated deaths (40.3%; 95% CI 34.7%-46.1%), most commonly end-stage cancer. Suboptimal care, most commonly delays in antibiotics, was identified in 68 of 300 sepsis-associated deaths (22.7%). However, only 11 sepsis-associated deaths (3.7%) were judged definitely or moderately likely preventable; another 25 sepsis-associated deaths (8.3%) were considered possibly preventable. In this cohort from 6 US hospitals, sepsis was the most common immediate cause of death. However, most underlying causes of death were related to severe chronic comorbidities and most sepsis-associated deaths were unlikely to be preventable through better hospital-based care. Further innovations in the prevention and care of underlying conditions may be necessary before a major reduction in sepsis-associated deaths can be achieved.

Background: Capnocytophaga canimorsus is a fastidious, zoonotic Gram-negative bacillus that can cause rapidly fatal septicaemia. Delays in microbiological diagnosis due to slow growth are common, reducing survival chances. This case uniquely highlights both an atypical gastrointestinal presentation and the resolution of a diagnostic impasse through extended CO₂ incubation triggered by astute clinical suspicion. Case Presentation: A 57-year-old male, recently tapered off corticosteroids for inflammatory arthritis, presented with diarrhoea, vomiting, and hypotensive collapse. He rapidly developed disseminated intravascular coagulation and multi-organ failure. Empirical piperacillin-tazobactam and gentamicin failed; cultures flagged positive at 72 hours with no initial growth. Only after clinicians alerted the laboratory, extended incubation under CO₂ enabled growth of C. canimorsus by day seven, confirmed via MALDI-TOF. Switching to meropenem led to recovery, although amputations of the necrotic tissues, including both toes and digits from his right hand were necessary due disseminated intravascular coagulation. Conclusion: This case demonstrates that C. canimorsus infection may initially mimic gastroenteritis and progress rapidly to fulminant sepsis. Early clinical suspicion, timely communication with microbiology for adapted incubation protocols, and prompt escalation to effective antimicrobial therapy are critical for survival.

This trial comparing treatment strategies that emphasized the use of vasopressors or intravenous fluids for early treatment of sepsis-induced hypotension showed no difference in 90-day mortality before discharge home.