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

Quality of hospital care for sick newborns and severely malnourished children in Kenya: A two-year descriptive study in 8 hospitals

BACKGROUND: Given the high mortality associated with neonatal illnesses and severe malnutrition and the development of packages of interventions that provide similar challenges for service delivery mechanisms we set out to explore how well such services are provided in Kenya. METHODS: As a sub-component of a larger study we evaluated care during surveys conducted in 8 rural district hospitals using convenience samples of case records. After baseline hospitals received either a full multifaceted intervention (intervention hospitals) or a partial intervention (control hospitals) aimed largely at improving inpatient paediatric care for malaria, pneumonia and diarrhea/dehydration. Additional data were collected to: i) examine the availability of routine information at baseline and their value for morbidity, mortality and quality of care reporting, and ii) compare the care received against national guidelines disseminated to all hospitals. RESULTS: Clinical documentation for neonatal and malnutrition admissions was often very poor at baseline with case records often entirely missing. Introducing a standard newborn admission record (NAR) form was associated with an increase in median assessment (IQR) score to 25/28 (22-27) from 2/28 (1-4) at baseline. Inadequate and incorrect prescribing of penicillin and gentamicin were common at baseline. For newborns considerable improvements in prescribing in the post baseline period were seen for penicillin but potentially serious errors persisted when prescribing gentamicin, particularly to low-birth weight newborns in the first week of life. Prescribing essential feeds appeared almost universally inadequate at baseline and showed limited improvement after guideline dissemination. CONCLUSION: Routine records are inadequate to assess newborn care and thus for monitoring newborn survival interventions. Quality of documented inpatient care for neonates and severely malnourished children is poor with limited improvement after the dissemination of clinical practice guidelines. Further research evaluating approaches to improving care for these vulnerable groups is urgently needed. We also suggest pre-service training curricula should be better aligned to help improve newborn survival particularly

Bacterial meningitis in Malawian infants:etiology and susceptibility to world health organization first-line antibiotics

Background: Neonatal meningitis is an important cause of morbidity in sub-Saharan Africa and requires urgent empiric treatment with parenteral administered antibiotics. Here we describe the etiology, antimicrobial susceptibility and suitability of the World Health Organization first-line recommended antibiotics (penicillin and gentamicin) for bacterial meningitis in young infants in Malawi. Methods: We reviewed all cerebrospinal fluid samples received from infants <=2 months of age with clinically suspected meningitis between January 1, 2002, and December 31, 2008, at the Queen Elizabeth Central Hospital in Blantyre, Malawi. Results: We identified 259 culture-positive isolates from 259 infants 7 days and <=2 months of age. In this group, the most common isolates were S. pneumoniae (80/191; 41.9%), Group B Streptococcus (38/191; 19.9%) and nontyphoidal Salmonella enterica (34/191; 17.8%). More isolates were susceptible to ceftriaxone than to the combination of penicillin and gentamicin (218/220; 99.1% vs. 202/220; 91.8%, Fisher’s exact test P = 0.006). In particular, Gram-negative isolates were significantly more susceptible to ceftriaxone than to gentamicin (72/74; 97.3% vs. 63/74; 85.1%, Fisher’s exact test P = 0.020). Penicillin and gentamicin provided less coverage for Gram-negative than Gram-positive isolates (74/86; 86.0% vs. 155/163; 95.1%, [chi]2 = 6.24, P = 0.012). Conclusions: In view of these results, the World Health Organization recommendations for empiric penicillin and gentamicin for suspected neonatal meningitis should be reevaluated

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

Treatment of Childhood Pneumonia in Developing Countries

Non

Randomised controlled trial of fosfomycin in neonatal sepsis: pharmacokinetics and safety in relation to sodium overload.

OBJECTIVE: To assess pharmacokinetics and changes to sodium levels in addition to adverse events (AEs) associated with fosfomycin among neonates with clinical sepsis. DESIGN: A single-centre open-label randomised controlled trial. SETTING: Kilifi County Hospital, Kenya. PATIENTS: 120 neonates aged ≤28 days admitted being treated with standard-of-care (SOC) antibiotics for sepsis: ampicillin and gentamicin between March 2018 and February 2019. INTERVENTION: We randomly assigned half the participants to receive additional intravenous then oral fosfomycin at 100 mg/kg two times per day for up to 7 days (SOC-F) and followed up for 28 days. MAIN OUTCOMES AND MEASURES: Serum sodium, AEs and fosfomycin pharmacokinetics. RESULTS: 61 and 59 infants aged 0-23 days were assigned to SOC-F and SOC, respectively. There was no evidence of impact of fosfomycin on serum sodium or gastrointestinal side effects. We observed 35 AEs among 25 SOC-F participants and 50 AEs among 34 SOC participants during 1560 and 1565 infant-days observation, respectively (2.2 vs 3.2 events/100 infant-days; incidence rate difference -0.95 events/100 infant-days (95% CI -2.1 to 0.20)). Four SOC-F and 3 SOC participants died. From 238 pharmacokinetic samples, modelling suggests an intravenous dose of 150 mg/kg two times per day is required for pharmacodynamic target attainment in most children, reduced to 100 mg/kg two times per day in neonates aged <7 days or weighing <1500 g. CONCLUSION AND RELEVANCE: Fosfomycin offers potential as an affordable regimen with a simple dosing schedule for neonatal sepsis. Further research on its safety is needed in larger cohorts of hospitalised neonates, including very preterm neonates or those critically ill. Resistance suppression would only be achieved for the most sensitive of organisms so fosfomycin is recommended to be used in combination with another antimicrobial. TRIAL REGISTRATION NUMBER: NCT03453177

Extended-interval Dosing of Gentamicin for Treatment of Neonatal Sepsis in Developed and Developing Countries

Serious bacterial infections are the single most important cause of neonatal mortality in developing countries. Case-fatality rates for neonatal sepsis in developing countries are high, partly because of inadequate administration of necessary antibiotics. For the treatment of neonatal sepsis in resource-poor, high-mortality settings in developing countries where most neonatal deaths occur, simplified treatment regimens are needed. Recommended therapy for neonatal sepsis includes gentamicin, a parenteral aminoglycoside antibiotic, which has excellent activity against gram-negative bacteria, in combination with an antimicrobial with potent gram-positive activity. Traditionally, gentamicin has been administered 2–3 times daily. However, recent evidence suggests that extended-interval (i.e. ≥24 hours) dosing may be applicable to neonates. This review examines the available data from randomized and non-randomized studies of extended-interval dosing of gentamicin in neonates from both developed and developing countries. Available data on the use of gentamicin among neonates suggest that extended dosing intervals and higher doses (>4 mg/kg) confer a favourable pharmacokinetic profile, the potential for enhanced clinical efficacy and decreased toxicity at reduced cost. In conclusion, the following simplified weight-based dosing regimen for the treatment of serious neonatal infections in developing countries is recommended: 13.5 mg (absolute dose) every 24 hours for neonates of ≥2,500 g, 10 mg every 24 hours for neonates of 2,000–2,499 g, and 10 mg every 48 hours for neonates of <2,000 g

Extended-interval Dosing of Gentamicin for Treatment of Neonatal Sepsis in Developed and Developing Countries

Serious bacterial infections are the single most important cause of neonatal mortality in developing countries. Case-fatality rates for neonatal sepsis in developing countries are high, partly because of inadequate administration of necessary antibiotics. For the treatment of neonatal sepsis in resource-poor, high-mortality settings in developing countries where most neonatal deaths occur, simplified treatment regimens are needed. Recommended therapy for neonatal sepsis includes gentamicin, a parenteral aminoglycoside antibiotic, which has excellent activity against gram-negative bacteria, in combination with an antimicrobial with potent gram-positive activity. Traditionally, gentamicin has been administered 2-3 times daily. However, recent evidence suggests that extended-interval (i.e. 65 24 hours) dosing may be applicable to neonates. This review examines the available data from randomized and non-randomized studies of extended-interval dosing of gentamicin in neonates from both developed and developing countries. Available data on the use of gentamicin among neonates suggest that extended dosing intervals and higher doses (&gt;4 mg/kg) confer a favourable pharmacokinetic profile, the potential for enhanced clinical efficacy and decreased toxicity at reduced cost. In conclusion, the following simplified weight-based dosing regimen for the treatment of serious neonatal infections in developing countries is recommended: 13.5 mg (absolute dose) every 24 hours for neonates of 65 2,500 g, 10 mg every 24 hours for neonates of 2,000-2,499 g, and 10 mg every 48 hours for neonates of &lt;2,000 g