Simplified Antibiotic Regimens

Community Management of
Possible Serious Newborn
Infections: Simplified
Antibiotic Regimens
Bina Valsangkar, MD, MPH
Saving Newborn Lives/Save the Children
LAC Neonatal Alliance Annual Meeting
September 23, 2014
Background and rationale for simplified regimens
Relevant pathogens
Study design and methodology
Preliminary results
Programmatic implications
Background and Rationale
• Infection is a major contributor to neonatal
mortality in developing countries
• Clinically-diagnosed sepsis rate is as high
as 170/1000 in rural India (Bang, et. al.)
• Most deaths from neonatal sepsis occur at
home, never coming to medical attention
• Current WHO recommendation for treating
serious bacterial infection in infants <2
months: hospital admission and 10 days
parenteral antibiotics
Background and Rationale
• Is there a safe way to provide neonatal sepsis
management closer to home?
• Good evidence for community-based
management of pneumonia already exists (Bang,
• Evidence for neonatal sepsis management, as part
of greater home-based packages also exists
• SEARCH trial (India): 62% reduction in mortality w/
7 days gent + cotrimoxazole
• Projahnmo trial (Bangladesh): 34% reduction in
mortality w/ 7 days gent + procaine penicillin
Background and Rationale
• Global Consultation in 2007, convened by WHO,
• Conclusions:
• Reasonable evidence of feasibility and impact of
community-based sepsis management
• But, insufficient evidence of antibiotic regimens that
would be feasible for weak health systems, acceptable
to families, and effective in treating infections
• Recommendation: conduct robust research to
evaluate simplified antibiotic regimens
Relevant Pathogens
• In Asia:
• Klebsiella (predominate)
• E. Coli
• Staph Aureus
• In Africa:
• Klebsiella
• E.Coli
• Staph Aureus
• Strep pneumo
• Strep pyogenes
Study Design and Methodology
• Objective: To evaluate simpler antibiotic
regimens for equivalence compared to the
standard course of parenteral antibiotics for the
empiric treatment of clinical severe infections
in young infants whose families do not accept
Study Design and Methodology
• SATT= Simplified Antibiotic Therapy Trial
• AFRINEST= African Neonatal Sepsis Trial
• SATT – Bangladesh
• SATT – Pakistan
• Kenya
• Nigeria
• Common study protocol
Study Design and Methodology
Control arm (reference treatment)
– A : IM Gent and Procaine Pen once daily for 7 days
14 injections
Experimental arms
– B: IM Gentamicin once daily and Oral Amoxicillin twice daily
for 7 days
7 injections
– C: IM Gentamicin and Procaine Penicillin once daily for 2 days,
thereafter oral Amoxicillin twice daily for 5 days 4 injections
– D: IM Gentamicin once daily and Oral Amoxicillin twice daily
for 2 days, thereafter oral Amoxicillin twice daily for 5 days
2 injections
Study Design and Methodology
WHO IMNCI Case definition
SATT/AFRINEST inclusion criteria
History of convulsions
Respiratory rate > 60/min
Severe chest indrawing
Severe chest indrawing
Axillary temp >37.5
Axillary temp > 38
Axillary temp <35.5
Axillary temp <35.5
Movement only when stimulated, or
none at all
Movement only with stimulation
Not feeding well
Feeding difficulty, confirmed by
observation or poor suck
Study Design and Methodology
• Randomization
• Infants were randomized to one of the
antibiotic regimens using site and agespecific (<7 days or 7-59 days) computergenerated randomization sequences
Study Design and Methodology
Treatment and Follow-up
• Study physicians provided injections at home
• Families were instructed to give evening doses of amox
• Enrolled infants visited for 7 days by study physician,
assess for treatment failure
• Families brought infant to outpatient clinic for 7 days for
treatment by study nurse
• Families gave evening dose of amox at home
• Outcome assessment by independent study nurse for
“treatment failure” on days 4, 8, 11, and 15
Main Findings
• SATT-Bangladesh, SATT-Pakistan and AFRINEST
• Arms B (7 injections) and Arm C (4 injections) were
equivalent to the reference regimen in each of the 3
• Pooled analysis of all 3 studies found each of these
simplified regimens to be equivalent to reference
Arm D (2 injections) was equivalent to the reference
Programmatic Implications
• Awaiting peer-reviewed publication and subsequent
WHO guideline
• Some countries are proceeding with scale-up of
community-based sepsis management prior to
official guidance from WHO
• Ethiopia implementing Arm B
• Health extension workers to deliver treatment in
the health post
• Families, with support from Health
Development Army, self-refers for care

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