Simplified antibiotic regimens for treatment of clinical severe infection in the outpatient setting when referral is not possible for young infants in Pakistan (Simplified Antibiotic Therapy Trial [SATT]): a randomised, open-label, equivalence trial (original) (raw)
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The Pediatric Infectious Disease Journal, 2013
Background: Infection in young infants is a major cause of morbidity and mortality in low-middle income countries, with high neonatal mortality rates. timely case management is lifesaving, but the current standard of hospitalization for parenteral antibiotic therapy is not always feasible. Alternative, simpler antibiotic regimens that could be used in outpatient settings have the potential to save thousands of lives. Methods: this trial aims to determine whether 2 simplified antibiotic regimens are equivalent to the reference therapy with 7 days of oncedaily (OD) intramuscular (Im) procaine penicillin and gentamicin for outpatient management of young infants with clinically presumed systemic bacterial infection treated in primary health-care clinics in 5 communities in Karachi, pakistan. the reference regimen is close to the current recommendation of the hospital-based intravenous ampicillin and gentamicin therapy for neonatal sepsis. the 2 comparison arms are (1) Im gentamicin OD and oral amoxicillin twice daily for 7 days; and (2) Im penicillin and gentamicin OD for 2 days, followed by oral amoxicillin twice daily for 5 days; 2250 "evaluable" infants will be enrolled. the primary outcome of this trial is treatment failure (death, deterioration or lack of improvement) within 7 days of enrollment. Results are expected by early 2014. Discussion: this trial will determine whether simplified antibiotic regimens with fewer injections in combination with high-dose amoxicillin are equivalent to 7 days of Im procaine penicillin and gentamicin in young infants with clinical severe infection. Results will have program and policy implications in countries with limited access to hospital care and high burden of neonatal deaths.
The Pediatric infectious disease journal, 2012
Sepsis in the neonatal period is a major cause of child mortality in low-income countries. Hospitalization and parenteral penicillin/ampicillin and gentamicin therapy are recommended for management. Many families, however, are unable to access hospital care, and most home-delivered newborns who develop sepsis die without receiving antibiotic therapy. Appropriate community-based therapy in such situations is undefined. We compared failure rates of 3 clinic-based antibiotic regimens in 0- to 59-day-old infants with possible serious bacterial infection whose families refused hospitalization in Karachi communities with high neonatal mortality rates>45/1000 live births. Eligible infants were randomly assigned to 7 days of: (1) procaine penicillin [50,000 units/kg once daily (OD) by intramuscular injection (IM)] and gentamicin (5 mg/kg OD IM) reference arm, (2) ceftriaxone (50 mg/kg OD IM), or (3) oral trimethoprim-sulfamethoxazole (TMP-SMX) at 10 mg/kg/day divided twice daily and gent...
and efficacy of simplified antibiotic regimens for outpatient treatment of serious infection in neonates and young infants 0-59 days of age in Bangladesh: design of a randomized controlled trial. The Pediatric infectious disease journal, 32 Suppl 1. Supplement Background: Because access to care is limited in settings with high mortality , exclusive reliance on the current recommendation of 7–10 days of par-enteral antibiotic treatment is a barrier to provision of adequate treatment of newborn infections. Methods: We are conducting a trial to determine if simplified antibiotic regimens with fewer injections are as efficacious as the standard course of parenteral antibiotics for empiric treatment of young infants with clinical signs suggestive of severe infection in 4 urban hospitals and in a rural surveillance site in Bangladesh. the reference regimen of intramuscular pro-caine-benzyl penicillin and gentamicin given once daily for 7 days is being compared with (1) intramuscular genta...
The Pediatric Infectious Disease Journal, 2013
Background: Because access to care is limited in settings with high mortality, exclusive reliance on the current recommendation of 7-10 days of parenteral antibiotic treatment is a barrier to provision of adequate treatment of newborn infections. Methods: We are conducting a trial to determine if simplified antibiotic regimens with fewer injections are as efficacious as the standard course of parenteral antibiotics for empiric treatment of young infants with clinical signs suggestive of severe infection in 4 urban hospitals and in a rural surveillance site in Bangladesh. the reference regimen of intramuscular procaine-benzyl penicillin and gentamicin given once daily for 7 days is being compared with (1) intramuscular gentamicin once daily and oral amoxicillin twice daily for 7 days and (2) intramuscular penicillin and gentamicin once daily for 2 days followed by oral amoxicillin twice daily for additional 5 days. All regimens are provided in the infant's home. the primary outcome is treatment failure (death or lack of clinical improvement) within 7 days of enrolment. the sample size is 750 evaluable infants enrolled per treatment group, and results will be reported at the end of 2013. Discussion: the trial builds upon previous studies of community case management of clinical severe infections in young infants conducted by our research team in Bangladesh. the approach although effective was not widely accepted in part because of feasibility concerns about the large number of injections. the proposed research that includes fewer doses of parenteral antibiotics if shown efficacious will address this concern.
Background: Because access to care is limited in settings with high mortality, exclusive reliance on the current recommendation of 7-10 days of parenteral antibiotic treatment is a barrier to provision of adequate treatment of newborn infections. Methods: We are conducting a trial to determine if simplified antibiotic regimens with fewer injections are as efficacious as the standard course of parenteral antibiotics for empiric treatment of young infants with clinical signs suggestive of severe infection in 4 urban hospitals and in a rural surveillance site in Bangladesh. the reference regimen of intramuscular procaine-benzyl penicillin and gentamicin given once daily for 7 days is being compared with (1) intramuscular gentamicin once daily and oral amoxicillin twice daily for 7 days and (2) intramuscular penicillin and gentamicin once daily for 2 days followed by oral amoxicillin twice daily for additional 5 days. All regimens are provided in the infant's home. the primary outcome is treatment failure (death or lack of clinical improvement) within 7 days of enrolment. the sample size is 750 evaluable infants enrolled per treatment group, and results will be reported at the end of 2013. Discussion: the trial builds upon previous studies of community case management of clinical severe infections in young infants conducted by our research team in Bangladesh. the approach although effective was not widely accepted in part because of feasibility concerns about the large number of injections. the proposed research that includes fewer doses of parenteral antibiotics if shown efficacious will address this concern.
o find out commonly used antibiotic combinations in the management of neonatal sepsis, prevalence of early onset sepsis (EOS) and late onset sepsis (LOS) in a public sector tertiary care hospital of Lahore. Neonatal sepsis is a clinical syndrome of bacteremia with systemic signs and symptoms of infection in the first 4 weeks of life. Neonatal sepsis is an important and common cause of morbidity and mortality in full term as well as preterm neonates. A retrospective observational study was conducted at the Neonatal Intensive Care Unit of a tertiary care hospital of Lahore from September 2013 to November 2013. 50 cases of neonatal sepsis suspected on clinical grounds were included in this study. LOS was more prevalent (60%) as compared to EOS (40%). Three combinations of antibiotics were frequently being used. Combination of Amikacin, Ampicillin & Ceftazidime was the most frequently used (48%) followed by combination of Amikacin, Ampicillin and Cefotaxime (30%), and combination of Van...
Community-based Treatment of Serious Bacterial Infections in Newborns and Young Infants
Background: Sepsis in the neonatal period is a major cause of child mortality in low-income countries. Hospitalization and parenteral penicillin/ampicillin and gentamicin therapy are recommended for management. Many families, however, are unable to access hospital care, and most home-delivered newborns who develop sepsis die without receiving antibiotic therapy. Appropriate community-based therapy in such situations is undefined. We compared failure rates of 3 clinic-based antibiotic regimens in 0-to 59-dayold infants with possible serious bacterial infection whose families refused hospitalization in Karachi communities with high neonatal mortality rates >45/1000 live births. Methods: Eligible infants were randomly assigned to 7 days of: (1) procaine penicillin [50,000 units/kg once daily (OD) by intramuscular injection (IM)] and gentamicin (5 mg/kg OD IM) reference arm, (2) ceftriaxone (50 mg/kg OD IM), or (3) oral trimethoprim-sulfamethoxazole (TMP-SMX) at 10 mg/kg/day divided twice daily and gentamicin IM OD. Primary outcome was treatment failure, defined as death, deterioration in clinical condition during therapy or no improvement after 2 days. Results: Possible serious bacterial infection was diagnosed in 704 infants, among 5766 screened. Among 434 (61.6%) randomized to clinic-based therapy, there were 13 of 145 failures with penicillin-gentamicin, 22 of 145 with ceftriaxone and 26 of 143 with TMP-SMX-gentamicin. Treatment failure was significantly higher with TMP-SMX-gentamicin compared with penicillingentamicin [relative risk 2.03, 95% confidence interval: 1.09 -3.79] by intention-to-treat analysis. Differences were not significant in the ceftriaxone versus penicillin-gentamicin comparison [relative risk 1.69, 95% confidence interval 0.89-3.23). By 14 days, there were 2 deaths in the penicillin-gentamicin group, 3 in the ceftriaxone group and 11 in the TMP-SMX-gentamicin group [relative risk 5.58, 95% confidence interval: 1.26-24.72 (group 3 versus 1)]. Conclusion: When hospitalization of sick infants is unfeasible, outpatient therapy with injectable antibiotics is an effective option. Procaine penicillin-gentamicin was superior to TMP-SMX-gentamicin. Ceftriaxone is a more expensive option, and may be less effective, although this requires further research.
The Pediatric infectious disease journal, 2013
In resource-limited settings, most young infants with signs of severe infection do not receive the recommended inpatient treatment with intravenous broad spectrum antibiotics for 10 days or more because such treatment is not accessible, acceptable or affordable to families. This trial was initiated in the Democratic Republic of Congo, Kenya and Nigeria to assess the safety and efficacy of simplified treatment regimens for the young infants with signs of severe infection who cannot receive hospital care. This is a randomized, open-label equivalence trial in which 3600 young infants with signs of clinical severe infection will be enrolled. The primary outcome is treatment failure in 7 days after enrollment, which includes death or worsening of the clinical condition on any day, or no improvement in the clinical condition by day 4 of treatment. Secondary outcomes include compliance with study therapy, adverse effects due to the study drugs and relapse or death during the week after com...