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Table 1 Independent predictors of oral antibiotic failure in fast breathing WHO non-severe childhood pneumoniaa

From: Predictors of treatment failure for non-severe childhood pneumonia in developing countries – systematic literature review and expert survey – the first step towards a community focused mHealth risk-assessment tool?

Study overview Awasthi S et al. CATCH UP MASCOT Agarwal G et al. Noorani QA et al. Hazir T et al.
Region (country) Asia (India) Asia (Pakistan) Asia (Pakistan) Asia (India) Asia (Pakistan) Asia (Pakistan)
Data collection dates 2004–2006 1998–1999 1999–2001 2000–2002 2000–2001 2005–2008
Enrollment criteria 2–59 months old 2–59 months old 2–59 months of age 2–59 months of age 2–59 months of age 2–59 months of age
Study design Cluster randomized study Randomized multicenter equivalency study Randomized multicenter equivalency study Randomized multicenter equivalency study Multicenter observational study Randomized multicenter equivalency study
  Intervention arm Oral amoxicillin 31–51 mg/kg/day for 3 days Oral amoxicillin 50 mg/kg/day for 5 days Oral amoxicillin 45 mg/kg/day for 3 days Oral amoxicillin 31–54 mg/kg/day for 3 days - Placebo for 3 days
  Control arm (or standard of care) Oral trimethoprim (7–11 mg/kg/day)-sulfamethoxazole for 5 days Oral trimethoprim (8 mg/kg/day)-sulfamethoxazole for 5 days Oral amoxicillin 45 mg/kg/day for 5 days Oral amoxicillin 31–54 mg/kg/day for 5 days Oral trimethoprim (8 mg/kg/day)-sulfamethoxazole for 5 days Oral amoxicillin 45 mg/kg/day for 3 days
  Blinding No Yes Yes Yes - Yes
  Study site types Health centers Tertiary care and secondary-level hospitals, and health center Tertiary care and secondary-level hospitals Tertiary care hospitals Health centers Tertiary care hospitals
  Number of sites 14 8 7 7 14 4
  Primary outcome Treatment failure Equivalency Equivalency Equivalency Treatment failure Equivalency
Treatment failure definition
  Day of assignment Day 3 (intervention); Day 5 (control) Days 3 to 5 Day 5 Days 3 to 5 Day 5 Day 3
  Respiratory ratea Yes, elevated for age (days 3–5) Yes, +/−5 breaths/min or higher versus enrollment (days 3–5) Yes, elevated for age (days 3–5) Yes, elevated for age (days 3–5) Yes, +/−5 breaths/min or higher versus enrollment (days 3–5) No
  Fever >38 °C and LCI No No No No No No
  Fever >38 °C Yes (days 3–5) No No No No No
  LCI Yes (days 1–5) Yes (days 3–5) Yes (days 1–5) Yes (days 1–5) Yes (days 1–5) Yes (days 1–3)
  Convulsions Yes (days 1–5) Yes (days 3–5) Not specified Yes (days 1–5) Not specified Yes (days 1–3)
  Abnormally sleepy Yes (days 1–5) Yes (days 3–5) Not specified Yes (days 1–5) Not specified Yes (days 1–3)
  Inability to drink Yes (days 1–5) Yes (days 3–5) Not specified Yes (days 1–5) Not specified Yes (days 1–3)
  Stridor in calm child Yes (days 1–5) Yes (days 3–5) No No No Yes (days 1–3)
  Malnutrition No Yes (days 3–5) No No No Yes (days 1–3)
  Cyanosis Yes (days 1–5) No Yes No Yes No
  SpO2 No No No Yes, <90 % (on day 3 only) No No
  Antibiotic change No Yes (days 3–5) Yes (days 1–5) No Yes (days 1–5) No
  Hospitalization No Yes (days 1–5) No No No No
  Lost to follow-up Yes (days 3–5) Yes (days 3–5) No Yes (days 1–5) Yes (days 5–11) No
  Study withdrawal Yes (days 1–5) No No Yes (days 1–5) No No
  Death Yes (days 1–14) Yes (days 1–5) Yes (days 1–5) Yes (days 1–5) Yes (days 1–5) Yes (days 1–5)
Study participants and description
Sample sizeb 2009 1459 1953 2188 944 873
Age 2–11 months 594/2009 (29.6 %) 732/1459 (50.2 %) 1051/1953 (53.8 %) 954/2188 (43.6 %) 334/944 (35.4 %) 573/873 (65.6 %)
Age 12–59 months 1415/2009 (70.4 %) 727/1459 (49.8 %) 902/1953 (46.2 %) 1234/2188 (56.4 %) 610/944 (64.6 %) 300/873 (34.4 %)
Treatment failure rateb 234/2009 (11.6 %) 256/1459 (17.5 %) 364/1953 (22.9 %) 225/2188 (10.3 %) 110/944 (11.6 %) 68/873 (7.8 %)
Independent predictors of treatment failure OR (95 % CI)c,d Diarrhea, 1.65 (1.24–2.19) History of difficulty breathing, 1.61 (1.13–2.15) Excess respiratory rate >10 breaths/min for agea, 1.4 (1.1–1.9) Excess respiratory rate >10 breaths/min for agea, 2.89 (1.83–4.55) Excess respiratory rate ≥15 breaths/min for agea, 2.0 (1.2–3.4) History of difficulty breathing, 2.86 (1.29–7.23)
  Age 12–59 months, 1.5 (1.12–1.91) Antibiotic non-adherence, 4.5 (95 % CI 2.9–7.0) Antibiotic non-adherence, 11.57 (7.4–18.0 Wheeze on examination, 1.7 (1.1–2.6) Temperature >37.5 °C at enrollment, 1.99 (1.37–2.90)
  Illness >3 days, 1.4 (1.03–1.8) Illness ≥3 days, 1.7 (1.3–2.1) RSV, 1.95 (1.0–3.8)   
   Age 2–11 months, 1.7 (1.1–2.1)    
   Persistent vomiting, 1.4 (1.0–2.0)    
  1. Serious adverse event or drug reaction, and new comorbid condition were not considered in the treatment failure definitions for any of the studies. WHO: World Health Organization; LCI: lower chest wall indrawing; SpO2: peripheral oxygen saturation; OR: odds ratio; CI: confidence interval; RSV: human respiratory syncytial virus
  2. aRespiratory rate norms: <50 breaths/min for ages 2–11 months; <40 breaths/min for ages 12–59 months
  3. bIf primary outcome of trial was equivalency or no difference was found then intervention and control arm data was combined
  4. cMultivariate logistic regression modeling was performed to determine independent predictors of treatment failure in all included studies. CATCHUP trial modeled age, history of difficulty breathing, duration of illness, and respiratory rate. The models were not reported for the MASCOT trial, Agarwal G et al., Noorani QA et al., Awasthi S et al., and Hazir T et al
  5. dFor Hazir T et al. multivariate logistic regression modeling was performed on cumulative treatment failure data from day 5 although primary outcome data was analyzed from day 3 treatment failure data