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