Safety and efficacy of alternative antibiotic regimens compared with 7 day injectable procaine benzylpenicillin and gentamicin for outpatient treatment of neonates and young infants with clinical signs of severe infection when referral is not possible: a randomised, open-label, equivalence trial

Baqui, Abdullah H; Saha, Samir K.; Ahmed, A.S.M. Nawshad Uddin; Shahidullah, Mohammad; Quasem, Iftekhar; Roth, Daniel; Samsuzzaman, A K M; Ahmed, Wazir; Tabib, Seyed Masoud; Mitra, Dipak Kumar; Begum, Nazma; Islam, Maksuda; Mahmud, Arif; Rahman, Mohammad Hefzur; Moin, Mamun Ibne; Mullany, Luke C.; Cousens, Simon; Arifeen, Shams El; Wall, Stephen; Brandes, Neal; Santosham, Mathuram; Black, Robert E.

doi:10.1016/s2214-109x(14)70347-x

Cited by 86 publications

(117 citation statements)

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“…This finding is consistent with those of two similar trials from Africa, 9 and Bangladesh 10 . Results from these trials have contributed to development of new WHO guidelines for management of young infants with possible serious bacterial infection where referral is not feasible 21 …”

Section: Discussionsupporting

confidence: 88%

“…A strength of our Pakistan study is that we included a much higher representation of infants aged 0–6 days with clinical severe infection (44% of all enrolled children) compared with the other randomised equivalence trials of the simplified antibiotic regimens from Bangladesh 10 and Africa (Kenya, Nigeria, and Democratic Republic of Congo) 9 . Additional strengths of our study are the availability of bacterial aetiological data and antimicrobial susceptibility data.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, randomised controlled trials assessing simplified antibiotic regimens—ie, fewer injections, addition of high-dose oral amoxicillin in lieu of penicillin—for outpatient management of young infants with clinical severe infection were undertaken in several countries (Democratic Republic of Congo, Bangladesh, Kenya, Nigeria, and Pakistan) to ensure wide generalisability 7, 8, 9, 10. These trials were not designed to show that the simpler regimens were better than the standard regimen but rather that they had similar efficacy to the reference regimen—namely, an equivalence or non-inferiority design 11 .…”

Section: Introductionmentioning

confidence: 99%

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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

Mir

Nisar

Tikmani

et al. 2017

The Lancet Global Health

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SummaryBackgroundParenteral antibiotic therapy for young infants (aged 0–59 days) with suspected sepsis is sometimes not available or feasible in countries with high neonatal mortality. Outpatient treatment could save lives in such settings. We aimed to assess the equivalence of two simplified antibiotic regimens, comprising fewer injections and oral rather than parenteral administration, compared with a reference treatment for young infants with clinical severe infection.MethodsWe undertook the Simplified Antibiotic Therapy Trial (SATT), a three-arm, randomised, open-label, equivalence trial in five communities in Karachi, Pakistan. We enrolled young infants (aged 0–59 days) who either presented at a primary health-care clinic or were identified by a community health worker with signs of clinical severe infection. We included infants who were not critically ill and whose family refused admission. We randomly assigned infants to either intramuscular procaine benzylpenicillin and gentamicin once a day for 7 days (reference); oral amoxicillin twice daily and intramuscular gentamicin once a day for 7 days; or intramuscular procaine benzylpenicillin and gentamicin once a day for 2 days followed by oral amoxicillin twice daily for 5 days. The primary outcome was treatment failure within 7 days of enrolment and the primary analysis was per protocol. We judged experimental treatments as efficacious as the reference if the upper bound of the 95% CI for the difference in treatment failure was less than 5·0. This trial is registered at ClinicalTrials.gov, number NCT01027429.FindingsBetween Jan 1, 2010, and Dec 26, 2013, 2780 infants were deemed eligible for the trial, of whom 2453 (88%) were enrolled. Because of inadequate clinical follow-up or treatment adherence, 2251 infants were included in the per-protocol analysis. 820 infants (747 per protocol) were assigned the reference treatment of procaine benzylpenicillin and gentamicin, 816 (751 per protocol) were allocated amoxicillin and gentamicin, and 817 (753 per protocol) were assigned procaine benzylpenicillin, gentamicin, and amoxicillin. Treatment failure within 7 days of enrolment was reported in 90 (12%) infants who received procaine benzylpenicillin and gentamicin (reference), 76 (10%) of those given amoxicillin and gentamicin (risk difference with reference −1·9, 95% CI −5·1 to 1·3), and 99 (13%) of those treated with procaine benzylpenicillin, gentamicin, and amoxicillin (risk difference with reference 1·1, −2·3 to 4·5).InterpretationTwo simplified antibiotic regimens requiring fewer injections are equivalent to a reference treatment for young infants with signs of clinical severe infection but without signs of critical illness. The use of these simplified regimens has the potential to increase access to treatment for sick young infants who cannot be referred to hospital.FundingThe Saving Newborn Lives initiative of Save the Children, through support from the Bill & Melinda Gates, and by WHO and USAID.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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

Mir

Nisar

Tikmani

et al. 2017

The Lancet Global Health

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“…A similar study was performed by Baqui et al 18 in Bangladesh. Infants aged 0 to 59 days were again visited by community health workers and those who had clinical signs of severe infection, but whose families refused hospital referral, were enrolled.…”

Section: Discussionsupporting

confidence: 68%

Global Emergency Medicine: A Review of the Literature From 2015

Becker

Hansoti

Bartels

et al. 2016

Academic Emergency Medicine

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Objectives: The Global Emergency Medicine Literature Review (GEMLR) conducts an annual search of peer-reviewed and gray literature relevant to global emergency medicine (EM) to identify, review, and disseminate the most important new research in this field to a global audience of academics and clinical practitioners.Methods: This year 12,435 articles written in six languages were identified by our search. These articles were distributed among 20 reviewers for initial screening based on their relevance to the field of global EM. An additional two reviewers searched the gray literature. A total of 723 articles were deemed appropriate by at least one reviewer and approved by their editor for formal scoring of overall quality and importance. Two independent reviewers scored all articles.Results: A total of 723 articles met our predetermined inclusion criteria and underwent full review. Sixty percent were categorized as emergency care in resource-limited settings (ECRLS), 17% as EM development (EMD), and 23% as disaster and humanitarian response (DHR). Twenty-four articles received scores of 18.5 or higher out of a maximum score 20 and were selected for formal summary and critique. Inter-rater reliability between reviewers gave an intraclass correlation coefficient of 0.71 (95% confidence interval = 0.66 to 0.75). Studies and reviews with a focus on infectious diseases, trauma, and the diagnosis and treatment of diseases common in resource-limited settings represented the majority of articles selected for final review.

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“…New WHO guidelines on antibiotic management of neonatal infections have been released based on the results of the Simplified Antibiotic Therapy Trial 33, 34, 35, 36. These guidelines could further encourage community treatment and reduce mortality from neonatal infections.…”

Section: Discussionmentioning

confidence: 99%

Global, regional, and national causes of under-5 mortality in 2000–15: an updated systematic analysis with implications for the Sustainable Development Goals

et al. 2016

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SummaryBackgroundDespite remarkable progress in the improvement of child survival between 1990 and 2015, the Millennium Development Goal (MDG) 4 target of a two-thirds reduction of under-5 mortality rate (U5MR) was not achieved globally. In this paper, we updated our annual estimates of child mortality by cause to 2000–15 to reflect on progress toward the MDG 4 and consider implications for the Sustainable Development Goals (SDG) target for child survival.MethodsWe increased the estimation input data for causes of deaths by 43% among neonates and 23% among 1–59-month-olds, respectively. We used adequate vital registration (VR) data where available, and modelled cause-specific mortality fractions applying multinomial logistic regressions using adequate VR for low U5MR countries and verbal autopsy data for high U5MR countries. We updated the estimation to use Plasmodium falciparum parasite rate in place of malaria index in the modelling of malaria deaths; to use adjusted empirical estimates instead of modelled estimates for China; and to consider the effects of pneumococcal conjugate vaccine and rotavirus vaccine in the estimation.FindingsIn 2015, among the 5·9 million under-5 deaths, 2·7 million occurred in the neonatal period. The leading under-5 causes were preterm birth complications (1·055 million [95% uncertainty range (UR) 0·935–1·179]), pneumonia (0·921 million [0·812 −1·117]), and intrapartum-related events (0·691 million [0·598 −0·778]). In the two MDG regions with the most under-5 deaths, the leading cause was pneumonia in sub-Saharan Africa and preterm birth complications in southern Asia. Reductions in mortality rates for pneumonia, diarrhoea, neonatal intrapartum-related events, malaria, and measles were responsible for 61% of the total reduction of 35 per 1000 livebirths in U5MR in 2000–15. Stratified by U5MR, pneumonia was the leading cause in countries with very high U5MR. Preterm birth complications and pneumonia were both important in high, medium high, and medium child mortality countries; whereas congenital abnormalities was the most important cause in countries with low and very low U5MR.InterpretationIn the SDG era, countries are advised to prioritise child survival policy and programmes based on their child cause-of-death composition. Continued and enhanced efforts to scale up proven life-saving interventions are needed to achieve the SDG child survival target.FundingBill & Melinda Gates Foundation, WHO.

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Safety and efficacy of alternative antibiotic regimens compared with 7 day injectable procaine benzylpenicillin and gentamicin for outpatient treatment of neonates and young infants with clinical signs of severe infection when referral is not possible: a randomised, open-label, equivalence trial

Cited by 86 publications

References 29 publications

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

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

Global Emergency Medicine: A Review of the Literature From 2015

Global, regional, and national causes of under-5 mortality in 2000–15: an updated systematic analysis with implications for the Sustainable Development Goals

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