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Update Treatment and Prophylaxis of Pertussis with Macrolide Antibiotics

Update Treatment and Prophylaxis of Pertussis with Macrolide Antibiotics. Tejpratap Tiwari, M. D., Bacterial Vaccine Preventable Diseases Branch Epidemiology and Surveillance Division National Immunization Program Centers for Disease Control and Prevention.

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Update Treatment and Prophylaxis of Pertussis with Macrolide Antibiotics

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  1. Update Treatment and Prophylaxis of Pertussis with Macrolide Antibiotics Tejpratap Tiwari, M. D., Bacterial Vaccine Preventable Diseases Branch Epidemiology and Surveillance Division National Immunization Program Centers for Disease Control and Prevention National Immunization Conference March 22, 2005

  2. Background: Erythromycin • Accepted antibiotic of choice for pertussis treatment, prophylaxis • Usually recommended as 14-day course to prevent bacteriologic relapse • Inexpensive

  3. Erythromycin Compliance and Safety • Compliance: ~20% patients discontinue • Gastrointestinal side effects (~30%) • Demanding regimen (3- 4 daily doses, 14 days) • Safety • Increased risk infantile hypertrophic pyloric stenosis (IHPS), infants <2 weeks old* • Drug-interactions, cytochrome P450 *Mahon et al. J Pediatr 2001;139:380 –4

  4. Azithromycin and Clarithromycin vs Erythromycin • Good in vitro activity against Bordetella pertussis • More resistant to acid pH, better absorbed • Greater tissue concentrations, longer plasma half-life • Fewer (1 or 2) daily doses, shorter course (5 days or 7 days)

  5. Azithromycin (A) and Clarithromycin (C) Clinical Studies *Abstract

  6. Treatment for Pertussis by Age-group

  7. Summary • Macrolides, preferred antimicrobial agents • Erythromycin, clarithromycin, or azithromycin are appropriate first-line agents for persons age >1 month • Azithromycin, preferred choice for infants <1 month of age • Use TMX-SMZ as alternate agent • Consider safety, evaluate concurrent medications for potential interactions, adherence to the prescribed regimen, and cost

  8. Acknowledgements • CDC/NIP • Colleagues at Bacterial VPD Branch, Epidemiology and Surveillance Division • AAP/COID • AAFP • HICPAC

  9. Thank You

  10. RED BOOK 2003: Pertussis Treatment • “The drug of choice is erythromycin estolate (40 –50 mg per day, orally in 4 divided doses; maximum 2 g/day. The recommended duration of therapy to prevent relapse is 14 days. Studies have documented that the newer macrolides, azithromycin dihydrate (10–12 mg kg per day, orally, in 1 dose for 5 days; maximum 600 mg day) or clarithromycin (15–20 mg/kg per day, orally, in 2 divided doses; maximum 1 g/day for 7 days), may be as effective as erythromycin and have fewer adverse effects and better compliance.”

  11. EXTRA SLIDES

  12. HICPAC Guidelines, 2004Pertussis Treatment and Prophylaxis • Adults • Erythromycin estolate, 500 mg, 4 times/day • Erythromycin delayed-release tablet, 333 mg, 3 times daily, • Children age >2 weeks, • Erythromycin 40–50 mg/kg day for 14 days • Infants aged <2 weeks, or adults intolerant to EE • Azithromycin 10–12 mg/kg/day x 5–7 days • Azithromycin 10mg/kg on Day 1 then 5 mg/kg/day x 4 days (single dose) • Clarithromycin for 10–14 days 15–20 mg/kg/day in two divided doses

  13. Control of Communicable Diseases, 2004 Pertussis Treatment and Prophylaxis • Treatment • Minimum 7-day course of macrolide antibiotics • Chemoprophylaxis (selective) • A 7-day course of erythromycin, clarithromycin or azithromycin

  14. Langley et al., 2004 *Azithromycin vs Erythromycin • Multi-center, randomized, equivalence trial • Suspect pertussis cases (n=477), aged 6 months –16 years • Azithromycin (n=238) • 10 mg/kg single dose day 1; then 5mg/kg/day single daily dose days 2–5 • Erythromycin estolate (n=239) • 40 mg/kg/day, 3 doses/day x 10 days *Langley et al. Pediatrics 2004;114:96 –101

  15. Langley et al., 2004* Safety Cohort (N=477) • Rate of gastrointestinal adverse events • Azithromycin group (n=238): 18% • Erythromycin group (n=239): 40% • Compliance with 100% doses • Azithromycin, 90% • Erythromycin, 55% *Langley et al. Pediatrics 2004;114:96 –101

  16. Efficacy Cohort*Culture-confirmed pertussis (N=114) • Bacterial eradication at end of treatment • Azithromycin (days 5 –7) • (n=53), 100% (95% CI:93–100) • Erythromycin (days 10 –12) • (n=53), 100% (95% CI: 93 –100) • Recurrence, 1 week post-treatment • Azithromycin (n=51), 0% (95% CI: 0–7) • Erythromycin (n=53), 0% (95% CI: 0–6.7) *Langley et al. Pediatrics 2004;114:96 –101

  17. Lebel et al., 2001*Clarithromycin vs Erythromycin • Randomized, prospective, single-blind • Compared safety, efficacy • Suspect pertussis (n=153) • Ages 1 month –16 years • Erythromycin estolate, 40 mg/kg/day (max 1 gm daily), 3 doses/day X 14 days (n=77) • Clarithromycin, 15 mg/kg/day (max 1 gm daily), 2 doses/day X 7 days (n=76) *Lebel et al. PIDJ 2001;20:1149 –54.

  18. Lebel et al., 2001*Safety Cohort (N=153) • Rates of gastrointestinal adverse events • Clarithromycin (n=76): 32% • Erythromycin (n=77): 44% • Compliance (mean % of drug taken) • Clarithromycin, 98.5% • Erythromycin, 88.6% *Lebel et al. PIDJ 2001;20:1149 –54.

  19. Efficacy Cohort Culture-confirmed pertussis (N=62) • Post-treatment bacterial eradication similar • Clarithromycin (days 8–10 ), (31/31) • Erythromycin (days 15–18), (22/23) • Study limitation • Sample size insufficient to demonstrate equivalence Lebel et al. PIDJ, 2001;20:1149 –54.

  20. Azithromycin, Clarithromycin Safety in Infants Age <6 months • Not labeled for use in infants <6 months age* • No published report IHPS or severe adverse events in neonates *http://pdrel.thomsonhc.com/

  21. Macrolides Safety: FDA Pregnancy Label • Erythromycin, azithromycin (Category B) • Animal studies, no adverse effect on fetus • No clinical trials in pregnant women • Clarithromycin (Category C) • Animal studies, adverse effects on fetus • No clinical trials in pregnancy http://pdrel.thomsonhc.com/

  22. HIPAC GuidelinesHypersensitivity to Macrolides • Adults: • Trimethoprim (TMP) –sulfamethoxazole (SXT) 1 double-strength tablet, twice daily X 14 days • Children: • 8 mg/kg/day TMP, 40 mg/kg/day SXT, 2 divided doses • Exception: • Pregnant woman at term • Nursing mother • Infant aged <2 months)

  23. Differences in Microbiologic Eradication Rates, 95% CI

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