Experience developing national evidence-based clinical guidelines for childhood pneumonia in a low-income setting - making the GRADE?

Table 6 GRADE evidence profile 3: Benzyl penicillin plus gentamicin versus ceftriaxone for very severe pneumonia^†

Quality assessment					Summary of findings
					Number of patients		Effect	Quality of evidence
No of studies/Design	Limitations	Inconsistency	Indirectness	Imprecision	ceftriaxone	benzyl penicillin and gentamicin	(P value)
Outcome 1: Time to resolution of signs and symptoms of pneumonia Importance: Critical
1 RCT [32]	serious¹	no serious inconsistency	very serious²	serious³	51	46	(P > 0.05)	Very low
Outcome 2: Treatment failure/time to resolution of clinical signs of pneumonia Importance: Critical
1 RCT [33]	no serious limitations	no serious inconsistency	very serious⁴	Serious⁵	33	38	(P > 0.1)	Very low
Outcome 3: Mortality Importance: Critical
No studies	-	-	-	-	-	-	-	-
Outcome 4: Cost Importance: Important
No studies	-	-	-	-	-	-	-	-
Overall quality of evidence: Very low quality evidence suggests no advantage of ceftriaxone over benzyl penicillin/ampicillin and gentamicin
Benefits or desired effects	Lower risks, less discomfort associated with single injection
Risks or undesired effects	Potential emergence of extended spectrum beta-lactamase (ESBL)-producing organisms; concern of 'overuse' of important second line drug and what next if it doesn't work?
Values and preferences	Favourable once-daily dosing schedule
Costs	Ceftriaxone more costly than penicillin/gentamicin. However availability of cheap generic preparations and additional costs (consumables and human resource) associated with multiple injections may outweigh apparent cost disadvantage of ceftriaxone.
Feasibility	Ceftriaxone already widely available and in use

^† Clinical question: For HIV-unexposed Kenyan children aged 2 - 59 months without clinical signs of severe malnutrition who meet WHO criteria for very severe pneumonia, should benzyl penicillin/ampicillin plus gentamicin be replaced by ceftriaxone?
¹ Limitation due to failure to lack of description of randomisation/allocation concealment
² Indirectness of comparison (compared penicillin chloramphenicol versus ceftriaxone) and population (Conducted in Turkey),
³ Imprecision due to small sample size
⁴ Indirectness of: 1) comparison (compared benzyl penicillin gentamicin versus amoxicillin/clavulanate), 2) population (India),
⁵ Imprecision due to small sample size

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