Treatment of GAS pharyngitis and prevention of Rheumatic Fever

1. Treatment of GAS pharyngitis and prevention of Rheumatic Fever D. C. Hilmers MLK Lecture March 23, 2009

2. Objectives • To learn latest AHA guidelines for evaluation of pharyngitis • To review the treatment options for GAS pharyngitis • To discuss the prevention of recurrent rheumatic fever

3. Case 1 • An 8 year old boy comes in with acute sore throat to MLK clinic. • What signs and symptoms make you suspicious for strep pharyngitis? • If you decide not to treat and he has GAS pharyngitis, what is the likelihood that it will progress to rheumatic fever?

4. Low prob of RF in child <3 yo

5. Probability of RF from untreated GAS pharyngitis • Studies from 1961 showed as high as 3% RF rate in areas of epidemics in children • Some feel that there is a shift towards non-RF producing GAS and now risk is probably less than 3 in 1000 of untreated GAS pharyngitis cases • Rate very much lower in adults than in children • One third of cases of RF come from non-apparent infections

6. Case 1 (Cont.) • The child is febrile to 102.3, he has exudates, cervical lymphadenopathy, body aches, and no signs of URI. • What is your next step?

7. Evaluation recommendations • There exist several algorithms for treating GAS (Centor and modified Centor) • However, new guidelines stress importance of rapid testing before treatment to avoid overuse of antibiotics • “Low a priori risk of GAS”, not defined • Do not treat • Suspicion of GAS • Get rapid strep test and/or culture • Treat according to results

8. Centor scoring • Developed as a method to quickly diagnose the presence of Group A streptococcal infection in "adult patients who presented to an urban emergency room complaining of a sore throat.“ The patients are judged on four criteria: • History of fever • Tonsillar exudates • Tender cervical lymphadenopathy • Absence of cough • The presence of all four variables indicates a 40 - 60% positive predictive value for a culture of the throat to test positive for GAS. The absence of all four variables indicates a negative predictive value of greater than 80%. • The high negative predictive value suggests that the Centor Criteria can be more effectively used for ruling out strep throat than for diagnosing strep throat.

9. Evaluation recs (2) • However, testing not helpful in differentiating between viral pharyngitis with GAS colonization and true GAS pharyngitis • Household contacts who have sxs should be tested and treated • Adults have much lower risk of RF from GAS • Some authors recommend Rx based on sxs only • AHA guidelines do not recommend this because of risk of overtreatment • However, rapid antigen testing alone is thought to be sufficient without use of a backup culture

10. Etiology of pharyngitis • Most commonly from a virus or irritation from a URI • HIV • Bacteria • Group A beta hemolytic streptococci • Groups C and G streptococci • Neisseria gonorrhoeae • Mycoplasma pneumoniae • Chlamydia pneumoniae • Arcanobacterium hemolyticum

11. GAS testing • Rapid antigen testing • Sensitivity has improved but older tests only have sensitivities of 70-80% • Highly specific (if positive, they have GAS) • Culture remains gold standard but takes several days • Streptococcal antibody testing • Anti-streptolysin O (ASO), first choice • Antideoxyribonuclease B (anti-DNAase B) • Useful in suspected RF but not useful in decision making of treatment of acute GAS pharyngitis

12. Case 2 • A 6 yo comes to clinic with a sore throat suggestive of GAS pharyngitis. The rapid strep test comes back positive. He has no known drug allergies. What are the recommended treatment options?

13. Only trials which showed that penicillin actually prevents RF were done with a type of penicillin that is no longer used. Therefore, ratings are IB (not based on multiple randomized trials. Bicillin L-A injection is more painful than Bicillin C-R which contains procaine penicillin Less painful if warmed to room temperature first

14. Once daily amoxicillin • Study in NZ compared treatment failures for GABHS pharyngitis • Amoxicillin 1.5 gms once daily (750 mg if <30 kg) x 10 days • Penicillin VK 500 mg bid (250 mg if <20 kg) x 10 days • Similar eradication rates (by culture) during weeks 1, 2, and 4 after starting Rx • Once daily amoxicillin now FDA approved for GAS pharyngitis with long-acting amoxicillin • Only in those >12 yo • 50 mg/kg up to maximum of 1 gm per day • Suspension is much better tasting than penicillin VK suspension

15. Case 2 (cont.) • His symptoms began 5 days ago. Is it safe to wait for the results of throat cultures to return before treating?

16. Treatment delays • Treatment is effective in preventing RF up to 9 days after sxs begin • However, morbidity is lessened by treating earlier • Lowers chance of infecting others if treated earlier • Considered non-contagious 24 hours after treatment begins

17. Case 2 (cont.) • You are about to give the child an injection of bicillin when the mother remembers that he had a bad reaction to amoxicillin the last time he took it. What are your treatment options?

18. The following are not considered acceptable: Tetracyclines (high resistance rates and not for use under 8 yo) Sulfa drugs (do not eradicate GAS) Cipro and older quinolones (high failure rate) Levaquin and newer quinolones (spectrum is too broad) While there is no reported resistance of GAS to beta lactams, there is about a 1% resistance to clindamycin in the US No agent eradicates carrier state 100% of the time, but cephalosporins may be more effective than penicillin Macrolide resistance in the US has been reported to be 5-8%

19. Case 2 (cont.) • Four weeks later the child comes back with a sore throat. This time he has rhinorrhea and cough. You suspect a viral infection but at mother’s insistence you obtain another rapid strep test. The result is positive. What do you do?

20. Colonization with GAS • Single repeat treatment recommended in this case • Usually only need repeat cultures if still symptomatic after several days of Rx or if history of RF • Failure to eradicate the carrier state is more common with oral than IM penicillin • Repeated treatment not recommended if asx and colonization unless history of RF • No consensus among experts about repeated symptomatic infections but reasonable to use: • IM penicillin (especially if compliance an issue) • Cephalosporin (narrow spectrum) • Augmentin • Pen VK with rifampin • Cultures may isolate group C or group G strep • No evidence that they cause RF • No evidence that treating will mitigate the symptoms

21. Case 3 • A mother brings her 21 yo son to MLK clinic. He has a history of rheumatic fever but now has no symptoms. She said that he was on penicillin VK until he stopped seeing the cardiologists at TCH. She wants to know if he should continue to take therapy. What do you tell her?

22. Pts with RF require prophylaxis because even asx infections can cause further damage. If patients have severe valvular disease, prophylaxis should be for life. If RF without carditis, treatment can be until child reaches 21 or 5 years have elapsed since last attack of RF, whichever is longer

23. Case 3 (cont.) • What are options for prophylaxis?

24. If in high risk areas, benzathine penicillin injections should be every 3 weeks (levels drop off after 3 weeks) Risks for recurrence are higher with oral agents. Consider for use in compliant patients and in those who are at lower risk for complications. Sulfa drugs do not eradicate GAS but will prevent infection.

25. References • Rowley, Stanford T. Shulman and Kathryn A. Taubert, Michael A. Gerber, Robert S. Baltimore, Charles B. Eaton, Michael Gewitz, Anne H. “Prevention of Rheumatic Fever and Diagnosis and Treatment of Acute Streptococcal Pharyngitis,” Circulation published online Feb 26, 2009 • Laura Barclay, “Once-Daily Oral Amoxicillin Effective for Streptococcus Pharyngitis in Children,” Medscape.