Simplified Dosing of Gentamicin for Treatment of Sepsis in Bangladeshi Neonates

Extended-interval dosing of gentamicin has several advantages over conventional multiple-daily dosing for the treatment of sepsis. The study was conducted to evaluate the pharmacokinetics of gentamicin for the treatment of neonatal sepsis in predetermined doses at 24- or 48-hour intervals, according to weight category, and to develop a simplified protocol for use in peripheral healthcare settings in developing countries. This prospective observational study was conducted among 59 neonates admitted to the Special Care Nursery at Dhaka Shishu Hospital, Bangladesh, with suspected sepsis and treated with antibiotics, including gentamicin. Intravenous dosing of gentamicin according to weight category was: 10 mg every 48 hours if the infant weighed <2,000 g (n=23), 10 mg every 24 hours if the infant weighed 2,000–2,249 g (n=12), or 13.5 mg every 24 hours if the infant weighed 2,500–3,000 g (n=24). Peak and trough concentrations of gentamicin and the presence of signs of nephrotoxicity and ototoxicity were determined. The mean±standard deviation peak concentration of gentamicin was 12.3±3.7 µg/mL in infants weighing <2,000 g, 9.6±3.1 µg/mL in infants 2,000–2,249 g, and 10.0±3.4 µg/mL in infants 2,500–3,000 g. Initial peak concentration of gentamicin was >12 µg/mL in 28.8% and initial trough concentration was >2 µg/mL in 6.8% of the subjects. No signs of nephrotoxicity or ototoxicity were detected. Favourable pharmacokinetic parameters found with the simplified dosing regimen suggest that it is safe for the treatment of neonatal sepsis

A Population-based Study of Hospital Admission Incidence Rate and Bacterial Aetiology of Acute Lower Respiratory Infections in Children Aged Less Than Five Years in Bangladesh

The research was carried out to study the rate of population-based hospital admissions due to acute lower respiratory infections (ALRIs) and bacterial aetiology of ALRIs in children aged less than five years in Bangladesh. A cohort of children aged less than five years in a rural surveillance population in Matlab, Bangladesh, was studied for two years. Cases were children admitted to the Matlab Hospital of ICDDR,B with a diagnosis of severe ALRIs. Bacterial aetiology was determined by blood culture. Antimicrobial resistance patterns of Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae (Spn) isolates were determined using the disc-diffusion method. In total, 18,983 children aged less than five years contributed to 24,902 child-years of observation (CYO). The incidence of ALRI-related hospital admissions was 50.2 per 1,000 CYO. The incidences of ALRI were 67% higher in males than in females and were higher in children aged less than two years than in older children. About 34% of the cases received antibiotics prior to hospitalization. Of 840 blood samples cultured, 39.4% grew a bacterial isolate; 11.3% were potential respiratory pathogens, and the rest were considered contaminants. The predominant isolates were Staphylococcus aureus (4.5%). Hib (0.4%) and Spn (0.8%) were rarely isolated; however, resistance of both these pathogens to trimethoprim-sulphamethoxazole was common. The rate of ALRI-related hospitalizations was high. The high rate of contamination, coupled with high background antibiotic use, might have contributed to an underestimation of the burden of Hib and Spn. Future studies should use more sensitive methods and more systematically look for resistance patterns of other pathogens in addition to Hib and Spn

Simplified Dosing of Gentamicin for Treatment of Sepsis in Bangladeshi Neonates

Extended-interval dosing of gentamicin has several advantages over conventional multiple-daily dosing for the treatment of sepsis. The study was conducted to evaluate the pharmacokinetics of gentamicin for the treatment of neonatal sepsis in predetermined doses at 24- or 48-hour intervals, according to weight category, and to develop a simplified protocol for use in peripheral healthcare settings in developing countries. This prospective observational study was conducted among 59 neonates admitted to the Special Care Nursery at Dhaka Shishu Hospital, Bangladesh, with suspected sepsis and treated with antibiotics, including gentamicin. Intravenous dosing of gentamicin according to weight category was: 10 mg every 48 hours if the infant weighed &lt;2,000 g (n=23), 10 mg every 24 hours if the infant weighed 2,000-2,249 g (n=12), or 13.5 mg every 24 hours if the infant weighed 2,500-3,000 g (n=24). Peak and trough concentrations of gentamicin and the presence of signs of nephrotoxicity and ototoxicity were determined. The mean\ub1standard deviation peak concentration of gentamicin was 12.3\ub13.7 \u3bcg/mL in infants weighing &lt;2,000 g, 9.6\ub13.1 \u3bcg/mL in infants 2,000-2,249 g, and 10.0\ub13.4 \u3bcg/mL in infants 2,500-3,000 g. Initial peak concentration of gentamicin was &gt;12 \u3bcg/mL in 28.8% and initial trough concentration was &gt;2 \u3bcg/mL in 6.8% of the subjects. No signs of nephrotoxicity or ototoxicity were detected. Favourable pharmacokinetic parameters found with the simplified dosing regimen suggest that it is safe for the treatment of neonatal sepsis

A Population-based Study of Hospital Admission Incidence Rate and Bacterial Aetiology of Acute Lower Respiratory Infections in Children Aged Less Than Five Years in Bangladesh

The research was carried out to study the rate of population-based hospital admissions due to acute lower respiratory infections (ALRIs) and bacterial aetiology of ALRIs in children aged less than five years in Bangladesh. A cohort of children aged less than five years in a rural surveillance population in Matlab, Bangladesh, was studied for two years. Cases were children admitted to the Matlab Hospital of ICDDR,B with a diagnosis of severe ALRIs. Bacterial aetiology was determined by blood culture. Antimicrobial resistance patterns of Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae (Spn) isolates were determined using the disc-diffusion method. In total, 18,983 children aged less than five years contributed to 24,902 child-years of observation (CYO). The incidence of ALRI-related hospital admissions was 50.2 per 1,000 CYO. The incidences of ALRI were 67% higher in males than in females and were higher in children aged less than two years than in older children. About 34% of the cases received antibiotics prior to hospitalization. Of 840 blood samples cultured, 39.4% grew a bacterial isolate; 11.3% were potential respiratory pathogens, and the rest were considered contami\uadnants. The predominant isolates were Staphylococcus aureus (4.5%). Hib (0.4%) and Spn (0.8%) were rarely isolated; however, resistance of both these pathogens to trimethoprim-sulphamethoxazole was common. The rate of ALRI-related hospitalizations was high. The high rate of contamination, coupled with high background antibiotic use, might have contributed to an underestimation of the burden of Hib and Spn. Future studies should use more sensitive methods and more systematically look for resistance patterns of other pathogens in addition to Hib and Spn

Pneumococcal Conjugate Vaccine impact assessment in Bangladesh [version 1; referees: 1 approved, 2 approved with reservations]

The study examines the impact of the introduction of 10-valent Pneumococcal Conjugate Vaccine (PCV10) into Bangladesh’s national vaccine program. PCV10 is administered to children under 1 year-old; the scheduled ages of administration are at 6, 10, and 18 weeks. The study is conducted in ~770,000 population containing ~90,000 <5 children in Sylhet, Bangladesh and has five objectives: 1) To collect data on community-based pre-PCV incidence rates of invasive pneumococcal diseases (IPD) in 0-59 month-old children in Sylhet, Bangladesh; 2) To evaluate the effectiveness of PCV10 introduction on Vaccine Type (VT) IPD in 3-59 month-old children using an incident case-control study design. Secondary aims include measuring the effects of PCV10 introduction on all IPD in 3-59 month-old children using case-control study design, and quantifying the emergence of Non Vaccine Type IPD; 3) To evaluate the effectiveness of PCV10 introduction on chest radiograph-confirmed pneumonia in children 3-35 months old using incident case-control study design. We will estimate the incidence trend of clinical and radiologically-confirmed pneumonia in 3-35 month-old children in the study area before and after introduction of PCV10; 4) To determine the feasibility and utility of lung ultrasound for the diagnosis of pediatric pneumonia in a large sample of children in a resource-limited setting. We will also evaluate the effectiveness of PCV10 introduction on ultrasound-confirmed pneumonia in 3-35 month-old children using an incident case-control design and to examine the incidence trend of ultrasound-confirmed pneumonia in 3-35 month-old children in the study area before and after PCV10 introduction; and 5) To determine the direct and indirect effects of vaccination status on nasopharyngeal colonization on VT pneumococci among children with pneumonia.  This paper presents the methodology. The study will allow us to conduct a comprehensive and robust assessment of the impact of national introduction of PCV10 on pneumococcal disease in Bangladesh

Multiomics Characterization of Preterm Birth in Low- and Middle-Income Countries.

Importance: Worldwide, preterm birth (PTB) is the single largest cause of deaths in the perinatal and neonatal period and is associated with increased morbidity in young children. The cause of PTB is multifactorial, and the development of generalizable biological models may enable early detection and guide therapeutic studies. Objective: To investigate the ability of transcriptomics and proteomics profiling of plasma and metabolomics analysis of urine to identify early biological measurements associated with PTB. Design, Setting, and Participants: This diagnostic/prognostic study analyzed plasma and urine samples collected from May 2014 to June 2017 from pregnant women in 5 biorepository cohorts in low- and middle-income countries (LMICs; ie, Matlab, Bangladesh; Lusaka, Zambia; Sylhet, Bangladesh; Karachi, Pakistan; and Pemba, Tanzania). These cohorts were established to study maternal and fetal outcomes and were supported by the Alliance for Maternal and Newborn Health Improvement and the Global Alliance to Prevent Prematurity and Stillbirth biorepositories. Data were analyzed from December 2018 to July 2019. Exposures: Blood and urine specimens that were collected early during pregnancy (median sampling time of 13.6 weeks of gestation, according to ultrasonography) were processed, stored, and shipped to the laboratories under uniform protocols. Plasma samples were assayed for targeted measurement of proteins and untargeted cell-free ribonucleic acid profiling; urine samples were assayed for metabolites. Main Outcomes and Measures: The PTB phenotype was defined as the delivery of a live infant before completing 37 weeks of gestation. Results: Of the 81 pregnant women included in this study, 39 had PTBs (48.1%) and 42 had term pregnancies (51.9%) (mean [SD] age of 24.8 [5.3] years). Univariate analysis demonstrated functional biological differences across the 5 cohorts. A cohort-adjusted machine learning algorithm was applied to each biological data set, and then a higher-level machine learning modeling combined the results into a final integrative model. The integrated model was more accurate, with an area under the receiver operating characteristic curve (AUROC) of 0.83 (95% CI, 0.72-0.91) compared with the models derived for each independent biological modality (transcriptomics AUROC, 0.73 [95% CI, 0.61-0.83]; metabolomics AUROC, 0.59 [95% CI, 0.47-0.72]; and proteomics AUROC, 0.75 [95% CI, 0.64-0.85]). Primary features associated with PTB included an inflammatory module as well as a metabolomic module measured in urine associated with the glutamine and glutamate metabolism and valine, leucine, and isoleucine biosynthesis pathways. Conclusions and Relevance: This study found that, in LMICs and high PTB settings, major biological adaptations during term pregnancy follow a generalizable model and the predictive accuracy for PTB was augmented by combining various omics data sets, suggesting that PTB is a condition that manifests within multiple biological systems. These data sets, with machine learning partnerships, may be a key step in developing valuable predictive tests and intervention candidates for preventing PTB

Short Communications

The petroleum ether, chloroform and methanol crude extracts of the two different plant parts (leaves and bark) of Mirabilis jalapa (Nyctaginaceae) were screened for cytotoxicity by brine shrimp lethality bioassay and the crude methanol extract of the bark was screened for antioxidant activity using the 1, 1-diphenyl-2picrylhydrazyl-hydrate (DPPH) free radical scavenging assay. The petroleum ether extract of the bark showed significant cytotoxic activity with the LC50 value 8.12 g/ml compared to vincristine sulphate (LC50 0.33 g/ml). On the other hand, the methanol crude extract of the bark showed mild antioxidant activity with the IC50 value 598.02 µg/ml compared to ascorbic acid(IC50 70.985 g/ml). Above results suggest moderate cytotoxic and antioxidant activity of the extract