ICIUM Conference, Thailand Shamim Qazi Department of Child and Adolescent Health Development

1. Health System Implications of Short Course Antibiotic Treatment Case study: pneumonia therapy in children ICIUM Conference, Thailand Shamim Qazi Department of Child and Adolescent Health Development World Health Organization, Geneva

2. Outline of presentation • Current recommendations for pneumonia therapy in children • Efficacy of various therapeutic regimens for pneumonia therapy in children • Benefits of short course antibiotic therapy • Implications for health system

3. Current recommendations for pneumonia therapy in children • β-lactum / macrolides for community acquired pneumonia • Duration of therapy: • Most European and North American: for 7-10 days • Canadian experts recommended 7-14 days therapy • AAP refrain from recommending any specific duration of therapy • BTS recommended 7-10 days of therapy • WHO ARI case management guidelines: • Non severe pneumonia 5 days • Severe/very severe pneumonia 7-10 days • Sources: McIntosh K, 2002; Ruuskanen O, 1999; AAP Red Book 2000; McCracken GH, 2000; BTL. Thorax 2002;WHO 1990 WHO/ARI/90.5, Qazi et al 1996

4. Different antibiotics Different antibiotics OR same antibiotic different dose Same antibiotic for Different duration Same duration Different duration Review of literature Definition: short course therapy < 5 days therapy

5. Azithromycin vs. amox/clav & erythromycin (2 studies) Azithromycin vs. erythromycin Azithromycin vs. amoxicillin & erythromycin Different antibiotics - switch therapy Methods & Results Duration 3 - 14 days Follow-up 2-5 weeks 1 study used switch therapy Clinical efficacy 83 - 100% Treatment difference - none Limitations: - different antibiotics & duration - small sample sizes - variable pneumonia definitions Different antibiotics for different duration Source: Roord JJ et al 1996, Harris JA et al 1998, Wubbel L et al 1999, Al-Eiden FA et al 1999 & Kogan R et al 2003

6. Cotrimoxazole vs. procaine penicillin Cotrimoxazole vs. ampicillin Cotrimoxazole vs. amoxicillin (2 studies) Cotrimoxazole standard dose vs. double dose Methods & Results Used WHO ARI guidelines Duration 5 days Follow-up up to 2 weeks Clinical efficacy 79 - 92% Treatment difference - none Limitations: - small sample size for 3 studies Different antibiotics OR same antibiotic same duration Source: Campbell H et al 1988, Keeley DJ et al 1990, Straus WL et al 1998, CATCHUP 2002, WHO/FCH/CAH/04.2

7. Azythromycin Procaine penicillin and cefuroxime Cotrimoxazole Amoxicillin (2 studies) Methods & Results 3 studies used WHO ARI guidelines 4 studies compared 3 vs 5 days Follow-up 2-3 weeks Clinical efficacy 80 - 97% Treatment difference - none Less AMR with 3 days therapy Limitations: - small sample size for 2 studies Same antibiotic for different duration Source: Ficnar B et al 1997, Vouri-Holopainen E et al 2000, Peltola H et al 2001, MASCOT 2002, ISCAP 2004 (in press), WHO/FCH/CAH/04.02

8. Conclusions of the review • Most episodes of pneumonia can be treated for a shorter duration • Hospitalized severe pneumonia can be treated with switch therapy • Ambulatory non-severe pneumonia can be treated with 3 days of oral antibiotics • Shorter course results in less prevalence of resistant organisms

9. Benefits of short course antibiotic therapy

10. Lower costs: Hospitalized patients • United Kingdom: patients cost estimates: • excess cost of 7-day vs. 5-day therapy £1.9 to £7.2 million (Harris CM, BMJ 1994) • Ireland: estimated saving of £ 58,000 for 45 hospitalised patients (Al-Eidan et al JAC 1999)

11. Oral cotrimoxazole 0.081 $/ (400 mg SMZ, 80 mg TMP tab) 6-9 kg requires 1 tab/day 3-day course: 3 tab 18.2 m tab costing 0.15 m $ 5-day course: 5 tab 30.4 m tab costing 0.25 m $ Oral amoxicillin 0.0177 $/ (250 mg tab) 6-9 kg requires 1.5 tab/day 3-day course: 4.5 tab 27.3 m tab costing 4.8 m $ 5-day course: 7.5 tab 45.5 m tab costing 8.1 m $ Theoretical example: Cost and logistics of non-severe pneumonia therapy in children Pakistan Pakistan < 5 year old population: 22.5 million Episodes of pneumonia: 6.75 million (0.3/child/year) Ambulatory pneumonia: 90% - 6.075 million episodes Source: MSH, Campbell et al Bull WHO 2004, in press, UNICEF

12. 5 vs 10 days(Schrag et al JAMA 2001) 3 vs 5 days(MASCOT Lancet 2002) 3 vs 5 days(ISCAP BMJ 2004) 82% vs 74% 98.2% vs 94.9% 94.2% vs 85.8% Improved adherence: amoxicillin Short course preferred by patients and caretakers (Pechere JC 2001 & Branthwaite A 1996)

13. 5 vs 10 days cefuroxime(Gooch et al PIDJ 1996) 5 vs 10 days co-amoxiclav(Hoberman PIDJ) 3 day azithromycin vs 10 days co-amoxiclav(Schaad U JAC 1993) 5 days azithromycin vs 10 days co-amoxiclav(Khurana CM PIDJ 1996) 12% vs 17% 8.7% vs 9.6% 2.6% vs 16.9% 7.2% vs 17.2% Less adverse events

14. 5 vs 10 days(Schrag et al JAMA 2001) 3 vs 5 days(ISCAP BMJ 2004) 3 vs 5 days(SCC WHO report 2003) S. pneumoniae 34% vs 44% H. influenzae 57% vs 61% S. pneumoniae 67% vs 78% H. influenzae 54% vs 62% S. pneumoniae 62% vs 64% Reduced antimicrobial resistance Carriage of cotrimoxazole non-susceptible organisms 2-4 weeks after antibiotic therapy

15. Traditional Health System Framework: service provision functions per level of care Individual Local community First level health facility District health department and hospital Regional hospital Ministries Adapted from Amonoo-Lartson District Health Care, 1984

16. Family and individual benefits • Improved adherence • Less antibiotic related adverse events • Lower costs • Direct and indirect • Less antimicrobial resistance

17. Public health benefits • Lower costs • Less health service utilisation • Improved logistics • Less antimicrobial resistance

18. Summary and recommendation • Lower costs • Less health service utilisation • Improved logistics • Less antimicrobial resistance • Improved adherence • Less antibiotic related adverse events Need for research to determine appropriate duration of antibiotic therapy for other infections