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Discontinuing penicillin prophylaxis in children with sickle cell anemia. Prophylactic Penicillin Study II
J M Falletta1, G M Woods, J I Verter
1Division of Pediatric Hematology-Oncology, Duke Comprehensive Sickle Cell Center, Duke University Medical Center, Durham, North Carolina 27710, USA.
Insights
Discontinuing penicillin prophylaxis at age 5 in children with sickle cell anemia is safe for those without prior severe pneumococcal infections or splenectomy. Parents should seek immediate medical care for any fever in these children.
Area of Science:
- Pediatric Hematology
- Infectious Diseases
- Clinical Trials
Background:
- Sickle cell anemia (SCA) increases susceptibility to severe infections, particularly from Streptococcus pneumoniae.
- Penicillin prophylaxis is standard for young children with SCA to prevent invasive pneumococcal disease.
- The optimal duration of penicillin prophylaxis in SCA is not well-defined, with many children reaching age 5.
Purpose of the Study:
- To evaluate the safety and efficacy of discontinuing penicillin prophylaxis at age 5 in children with SCA.
- To compare the incidence of invasive pneumococcal infections in children with SCA who continue penicillin versus those who stop prophylaxis.
Main Methods:
- Randomized, double-blind, placebo-controlled trial involving 400 children with SCA across 18 US hospitals.
- Children received either penicillin V potassium or placebo twice daily after age 5.
- Follow-up averaged 3.2 years, with regular clinical assessments and history collection.
Main Results:
- Six children experienced invasive Streptococcus pneumoniae infections: 4 in the placebo group and 2 in the penicillin group (relative risk 0.5).
- Infections were caused by specific serotypes, with some isolates showing antibiotic resistance.
- Adverse effects were minimal and similar between groups.
Conclusions:
- Discontinuing penicillin prophylaxis at age 5 appears safe for children with SCA who have received comprehensive care and lack prior severe pneumococcal infections or splenectomy.
- Close medical monitoring and prompt evaluation of febrile episodes are crucial for children with SCA after stopping prophylaxis.
Objective:
To evaluate the consequences of discontinuing penicillin prophylaxis at 5 years of age in children with sickle cell anemia who had received prophylactic penicillin for much of their lives.
Design:
Randomized, double-blind, placebo-controlled trial.
Setting:
Eighteen teaching hospitals throughout the United States.
Patients:
Children with sickle cell anemia (hemoglobin SS or hemoglobin S beta 0-thalassemia) who had received prophylactic penicillin therapy for at least 2 years immediately before their fifth birthday and had received the 23-valent pneumococcal vaccine between 2 and 3 years of age and again at the time of randomization. Of 599 potential candidates, 400 were randomly selected and followed for an average of 3.2 years.
Interventions:
After randomization, patients received the study medication twice daily--either penicillin V potassium, 250 mg, or an identical placebo tablet. Patients were either seen in the clinic or contacted every 3 months thereafter for an interval history and dispensing of the study drug. A physical examination was scheduled every 6 months.
Main Outcome Measures:
The primary end point was a comparison of the incidence of bacteremia or meningitis caused by Streptococcus pneumoniae in children continuing penicillin prophylaxis versus those receiving the placebo.
Results:
Six children had a systemic infection caused by S. pneumoniae, four in the placebo group (2.0%; 95% confidence interval 0.5%, 5.0%) and two in the continued penicillin prophylaxis group (1.0%; 95% confidence interval 0.1%, 3.6%) with a relative risk of 0.5 (95% confidence interval 0.1, 2.7). All invasive isolates were either serotype 6(A or B) or serotype 23F. Four of the isolates were penicillin susceptible, and two (one from each treatment group) were penicillin and multiply antibiotic resistant. Adverse effects of the study drug were reported for three patients (nausea, vomiting, or both), one of whom was in the placebo group.
Conclusion:
Children with sickle cell anemia who have not had a prior severe pneumococcal infection or a splenectomy and are receiving comprehensive care may safely stop prophylactic penicillin therapy at 5 years of age. Parents must be aggressively counseled to seek medical attention for all febrile events in children with sickle cell anemia.