Practice Recommendation for the Management of Acute Pharyngitis
Acute pharyngitis is commonly seen in children, and the majority of cases are caused by viral infection. Group A streptococcus (GAS) is the only common bacterial cause for which antibiotic therapy is definitely indicated. With the weak differentiating power of clinical features between GAS and non-streptococcal causes, clinicians are encouraged to perform either throat culture or rapid antigen detection test for GAS confirmation before initiating antibiotic therapy if doubt exists. Based on latest literature and approved by The Working Group on The Development of Clinical Practice Guidelines of the Hong Kong College of Paediatricians, this practice recommendation is intended for use by paediatricians and primary care physicians for their evidence-based management of acute pharyngitis in children.
Keyword : Children; Management; Pharyngitis
Acute pharyngitis is one of the most frequent illnesses for which paediatricians and primary care physicians are consulted. Being the most common bacterial cause of acute pharyngitis, group A streptococcus (GAS) is responsible for a relatively small percentage (20-30%) of sore throat visits in children aged 5 to 15 years.1 A local study at an accident and emergency department in Hong Kong showed a 38.6% detection rate of GAS pharyngitis in children presented with sorethroat.2 Accurate diagnosis of GAS pharyngitis followed by appropriate antibiotic therapy is important for the prevention of non-suppurative complications (e.g. acute rheumatic fever) and suppurative complications (e.g. peritonsillar abscess, and mastoiditis); the improvement of clinical symptoms; and the reduction in transmission of GAS to household members, classmates, and other close contacts of the patient.3 Except very rare infections by certain organisms such as Neisseria gonorrhoeae and Corynebacterium diphtheria, antibiotic therapy is of no proven benefit as treatment for acute pharyngitis caused by other bacterial pathogens other than GAS. Moreover, the clinical features of GAS pharyngitis and non-streptococcal pharyngitis overlap so broadly that diagnosis based solely on clinical grounds is often inaccurate.4,5 As a result, inappropriate administration of antibiotics to large numbers of patients with non-streptococcal pharyngitis are not uncommonly seen.6-8 In addition to unnecessary exposure of patients to the adverse effects and costs of antibiotics, inappropriate prescription of antibiotics has been an important attributing factor to the emergence of antimicrobial resistance among common bacterial pathogens.8,9
A panel of 6 multidisciplinary experts in the management of streptococcal pharyngitis in children was convened in 2010. The panel consisted of paediatric infectious disease specialist, paediatric respirology specialist, and general paediatricians in both public hospitals and private sector. The group convened face-to-face meetings in which an outline of the guideline and the process of development of the guideline were discussed. This was followed by a series of telecommunications in which a list of clinical questions to be addressed in the guideline was generated, discussed, and prioritised. We identified up-to-date valid systematic reviews from the MEDLINE database, PubMed, and the Cochrane Library. Unless specified otherwise, the search period was 1980-2014 and was restricted to the English-language literature. Articles were also retrieved by searches for clinical diagnosis, laboratory diagnosis, symptoms and signs, and microbiology. The panel members contributed reference lists in these areas. Primary key search terms included as follows pharyngitis, streptococcus, throat culture, rapid streptococcal tests, and pharyngeal carriers. All members of the Panel participated in the preparation and review of the draft guideline. Feedback was obtained from external peer reviews. The guideline was reviewed and approved by the Paediatric Practice Guidelines Committee of the Hong Kong College of Paediatricians prior to dissemination.
I. Diagnosis of Group A Streptococcal Pharyngitis
Indications for GAS Testing
Acute pharyngitis is most commonly caused by viruses (Table 1).1 Among all other bacterial pathogens causing acute pharyngitis, GAS is the only common bacterial cause for which antibiotic therapy is definitely indicated. In order to appropriately prescribe antibiotic therapy, it is important for clinicians to rule out the possibility of GAS pharyngitis. Although acute GAS pharyngitis has certain characteristic clinical and epidemiological features (Table 2), there is often broad overlap between the symptoms and signs of GAS and non-streptococcal pharyngitis.1,4 Various scoring systems, such as the modified Centor or McIsaac scores, have been used to predict the probability of GAS pharyngitis based on clinical features.10-13 However, these scoring systems generally have a relatively lower positive predictive values, with only about 35-50% confirmed GAS pharyngitis even in patients with all typical clinical features in a particular scoring system.11,14 The use of clinical signs and symptoms is not for diagnosis, but to select those necessary for GAS laboratory testing. On the other hand, studies have shown that the prevalence of GAS pharyngitis is significantly lower for children under 3 years of age (10-14%), compared to school-age children (37%).15,16 A local study at an accident and emergency department in Hong Kong reported that none of the children aged <3 years had GAS pharyngitis in their study cohort.2 Furthermore, studies have reported only a very rare occurrence of acute rheumatic fever complicating acute pharyngitis in children aged below 3 years.17-23
An additional consideration for GAS testing would lie on history of household contacts. A high rate of secondary streptococcal infections as high as 25% from symptomatic index case among household contacts has been reported in previous studies.3,24 During an outbreak, up to one-third of persons in a semi-closed community could become infected and develop symptomatic pharyngitis.25-27 Therefore, it is recommend for symptomatic children in day care or institution setting to have GAS testing. However, routine testing or treatment of asymptomatic household contacts of patients with GAS pharyngitis is not generally indicated.
In summary, acute onset of sore throat in children with signs and symptoms suggestive of bacterial cause (Table 2), age greater than 3 years or with known GAS contact is recommended to have GAS laboratory testing, such as throat culture or rapid antigen detection test (RADT) (Figure 1).1,23 Otherwise, no further investigation or treatment is indicated.
a) Throat Culture
b) Rapid Antigen Detection Tests
A major disadvantage of throat cultures is the long turnaround time (around 2-3 days for positive growth). Rapid antigen detection tests (RADTs) directly from throat swabs have been developed with a shorter turnaround time.30,34,35 With a specificity of around 95%, one can be reasonably certain about the diagnosis of GAS with a positive RADT result, and subsequent antibiotic therapy can be commenced without a follow-up throat culture.34-36 The sensitivity of RADTs is 70%-90%. Hence, a negative RADT warrants a follow-up throat culture before GAS can be confidently excluded.34,35 However, RADT is not routinely available in Hospital Authority hospitals.
c) Anti-streptococcal Antibody Titers
Measurement of anti-streptococcal antibody titers, such as antistreptolysin O (ASO) and anti-DNase B, can help the diagnosis of the nonsuppurative sequelae of GAS pharyngitis, such as acute rheumatic fever and acute glomerulonephritis.37 However, antibody titers may not reach maximum levels until 3-8 weeks after acute GAS infection and may remain elevated for months even without active GAS infection.14,38 Therefore, such testing is not recommended in the diagnosis of acute GAS pharyngitis.
II. Treatment for GAS Pharyngitis
While early antibiotic therapy hastens clinical recovery and decreases spread of GAS to other children, the predominant rationale for antibiotic treatment of this self-limited illness is to prevent both non-suppurative complications (e.g. acute rheumatic fever), and suppurative complications (e.g. peritonsillar abscess, acute otitis media, and acute sinusitis).39-42 Table 3 shows the list of recommended antibiotics effective in treating GAS pharyngitis. Penicillin remains the treatment of choice because of its proven efficacy and safety, its narrow spectrum and its low cost.43-46 Penicillin-resistant GAS has never been documented. Alternative oral therapy with amoxicillin is often used in place of penicillin V for young children with a similar efficacy. Studies have demonstrated that once-daily amoxicillin (50 mg/kg, to a maximum of 1000 mg) for 10 days is effective for GAS pharyngitis.47-51 Amoxicillin has the advantage of once-daily dosing, which may enhance adherence, and is relatively inexpensive and palatable. In order to achieve maximal rates of pharyngeal eradication of GAS, most oral antibiotics are recommended for a conventional 10-day course. For most penicillin-allergic individuals (after allergic history being ascertained), an oral narrow-spectrum cephalosporin, such as cephalexin, is recommended. For those who are also allergic to cephalosporins (up to 10%), or immediate anaphylactic-type hypersensitivity to penicillin, cephalosporins should be avoided.52 Azithromycin for 5 days can be a reasonable alternative.53 A follow-up appointment can be arranged to watch out for any treatment failure.
Multiple studies support the benefits of acetaminophen or NSAIDs such as ibuprofen in reducing fever and pain relative to placebo among children with non-GAS pharyngitis.54-57 Due to the risk of Reye syndrome, aspirin for pain relief is not recommended.
III. Chronic Pharyngeal Carrier of GAS
Chronic pharyngeal carriers have GAS present in the pharynx for ≥6 months but there is absence of active immunologic response to the organism.38,58 As many as 20% of asymptomatic schoolchildren may be GAS carriers during winter and spring. Chronic pharyngeal GAS carriers may experience episodes of intercurrent viral pharyngitis.59,60 Repeated positive GAS testing results of such patients often cannot be distinguished from those with recurrent GAS infections. It appears that carriers are unlikely to spread the organism to their close contacts. They are also at very low risk, if any, for developing complications such as acute rheumatic fever.38,58,61 Chronic pharyngeal GAS carriers are therefore not recommended for further antibiotic therapy. One may consider antibiotic therapy in GAS carriers under special situations, including community outbreak of acute rheumatic fever or post-streptococcal glomerulonephritis, GAS pharyngitis outbreak in a closed or partially closed community, or family/personal history of acute rheumatic fever. To eliminate chronic GAS carriage, several antibiotic schedules are recommended which are more effective than penicillin or amoxicillin (Table 4).
In conclusion, acute pharyngitis is commonly seen in children, and is most commonly caused by viral infection. Among all other bacterial cause of acute pharyngitis, GAS is the only common bacterial cause for which antibiotic therapy is definitely indicated. With the weak differentiating power of clinical features between GAS and non-streptococcal cause, clinicians are encouraged to perform either throat culture or RADT for GAS confirmation before initiating appropriate antibiotic therapy if doubt exists (Table 5).
Declaration of Interest
1. Bisno AL. Acute pharyngitis: etiology and diagnosis. Pediatrics 1996;97:949-54.
2. Wong MC, Chung CH. Group A streptococcal infection in patients presenting with a sore throat at an accident and emergency department: prospective observational study. Hong Kong Med J 2002;8:92-8.
3. Lindbaek M, Francis N, Cannings-John R, Butler CC, Hjortdahl P. Clinical course of suspected viral sore throat in young adults: cohort study. Scand J Prim Health Care 2006;24:93-7.
4. Wannamaker LW. Perplexity and precision in the diagnosis of streptococcal pharyngitis. Am J Dis Child 1972;124:352-8.
5. Shulman ST, Bisno AL, Clegg HW, et al. Clinical Practice Guideline for the Diagnosis and Management of Group A Streptococcal Pharyngitis: 2012 Update by the Infectious Diseases Society of America. Clin Infect Dis 2012;55:1279-82.
6. Linder JA, Bates DW, Lee GM, Finkelstein JA. Antibiotic treatment of children with sore throat. JAMA 2005;294:2315-22.
7. Linder JA, Chan JC, Bates DW. Evaluation and treatment of pharyngitis in primary care practice: the difference between guidelines is largely academic. Arch Intern Med 2006;166:1374-9.
8. McCaig LF, Besser RE, Hughes JM. Trends in antimicrobial prescribing rates for children and adolescents. JAMA 2002;287:3096-102.
9. Hersh AL, Jackson MA, Hicks LA; American Academy of Pediatrics Committee on Infectious Diseases. Principles of judicious antibiotic prescribing for upper respiratory tract infections in pediatrics. Pediatrics 2013;132:1146-54.
10. Breese BB. A simple scorecard for the tentative diagnosis of streptococcal pharyngitis. Am J Dis Child 1977;131:514-7.
11. McIsaac WJ, Kellner JD, Aufricht P, Vanjaka A, Low DE. Empirical validation of guidelines for the management of pharyngitis in children and adults. JAMA 2004;291:1587-95.
12. Centor RM, Witherspoon JM, Dalton HP, Brody CE, Link K. The diagnosis of strep throat in adults in the emergency room. Med Decis Making 1981;1:239-46.
13. Fine AM, Nizet V, Mandl KD. Large-scale validation of the Centor and McIsaac scores to predict group A streptococcal pharyngitis. Arch Intern Med 2012;172:847-52.
14. Kaplan EL, Top FH Jr, Dudding BA, Wannamaker LW. Diagnosis of streptococcal pharyngitis: differentiation of active infection from the carrier state in the symptomatic child. J Infect Dis 1971;123:490-501.
15. Nussinovitch M, Finkelstein Y, Amir J, Varsano I. Group A beta-hemolytic streptococcal pharyngitis in preschool children aged 3 months to 5 years. Clin Pediatr (Phila) 1999;38:357-60.
16. Amir J, Shechter Y, Eilam N, Varsano I. Group A beta-hemolytic streptococcal pharyngitis in children younger than 5 years. Isr J Med Sci 1994;30:619-22.
17. Carapetis JR, Steer AC, Mulholland EK, Weber M. The global burden of group a streptococcal diseases. Lancet Infect Dis 2005;5:685-94.
18. Tani LY, Veasy LG, Minich LL, Shaddy RE. Rheumatic fever in children younger than 5 years: is the presentation different? Pediatrics 2003;112:1065-8.
19. Gordis L. The virtual disappearance of rheumatic fever in the United States: lessons in the rise and fall of disease. T. Duckett Jones Memorial Lecture. Circulation 1985;72:1155-62.
20. Ramanan PV, Premkumar S, Ramnath B. Youngest patient with Sydenham's chorea: a case report. J Indian Med Assoc 2009;107:246-53.
21. Vinker S, Zohar E, Hoffman R, Elhayany A. Incidence and clinical manifestations of rheumatic fever: a 6 year community-based survey. Isr Med Assoc J 2010;12:78-81.
22. Paulo LT, Terreri MT, Barbosa CM, Len CA, Hilario MO. [Is rheumatic fever a more severe disease in pre-school children?]. Acta Reumatol Port 2009;34:66-70.
23. Poses RM, Cebul RD, Collins M, Fager SS. The accuracy of experienced physicians' probability estimates for patients with sore throats. implications for decision making. JAMA 1985;254:925-9.
24. James WE, Badger GF, Dingle JH. A study of illness in a group of Cleveland families. XIX. The epidemiology of the acquisition of group A streptococci and of associated illnesses. N Engl J Med 1960;262:687-94.
25. Gastanaduy AS, Kaplan EL, Huwe BB, McKay C, Wannamaker LW. Failure of penicillin to eradicate group A streptococci during an outbreak of pharyngitis. Lancet 1980;2:498-502.
26. Dingle JH, Badger G, Jordan WS Jr. Illness in the home. Cleveland: Case Western Reserve University Press, 1964:97-119.
27. Musher DM. How contagious are common respiratory tract infections? N Engl J Med 2003;348:1256-66.
28. Snow V, Mottur-Pilson C, Cooper RJ, Hoffman JR. Principles of appropriate antibiotic use for acute pharyngitis in adults. Ann Intern Med 2001;134:506-8.
29. Gerber MA. Diagnosis of pharyngitis: methodology of throat cultures. In: Shulman ST, ed. Pharyngitis: management in an era of declining rheumatic fever. New York: Praeger, 1984:61-72.
30. Gerber MA. Comparison of throat cultures and rapid strep tests for diagnosis of streptococcal pharyngitis. Pediatr Infect Dis J 1989;8:820-4.
31. Schwartz RH, Gerber MA, McCoy P. Effect of atmosphere of incubation on the isolation of group A streptococci from throat cultures. J Lab Clin Med 1985;106:88-92.
32. Brien JH, Bass JW. Streptococcal pharyngitis: optimal site for throat culture. J Pediatr 1985;106:781-3.
33. Kellogg JA. Suitability of throat culture procedures for detection of group A streptococci and as reference standards for evaluation of streptococcal antigen detection kits. J Clin Microbiol 1990;28:165-9.
34. Gerber MA, Shulman ST. Rapid diagnosis of pharyngitis caused by group A streptococci. Clin Microbiol Rev 2004;17:571-80.
35. Tanz RR, Gerber MA, Kabat W, Rippe J, Seshadri R, Shulman ST. Performance of a rapid antigen-detection test and throat culture in community pediatric offices: implications for management of pharyngitis. Pediatrics 2009;123:437-44.
36. Johnson DR, Kaplan EL. False-positive rapid antigen detection test results: reduced specificity in the absence of group A streptococci in the upper respiratory tract. J Infect Dis 2001;183:1135-7.
37. Shet A, Kaplan EL. Clinical use and interpretation of group a streptococcal antibody tests: a practical approach for the pediatrician or primary care physician. Pediatr Infect Dis J 2002;21:420-6.
38. Johnson DR, Kurlan R, Leckman J, Kaplan EL. The human immune response to streptococcal extracellular antigens: clinical, diagnostic, and potential pathogenetic implications. Clin Infect Dis 2010;50:481-90.
39. Wannamaker LW, Rammelkamp CH Jr, Denny FW, et al. Prophylaxis of acute rheumatic fever by treatment of the preceding streptococcal infection with various amounts of depot penicillin. Am J Med 1951;10:673-95.
40. Del Mar CB, Glasziou PP, Spinks AB. Anti- biotics for sore throat. Cochrane Database Syst Rev 2004;(2):CD000023.
41. Robertson KA, Volmink JA, Mayosi BM. Antibiotics for the primary prevention of acute rheumatic fever: a meta-analysis. BMC Cardiovasc Disord 2005;5:11.
42. Petersen I, Johnson AM, Islam A, Duckworth G, Livermore DM, Hayward AC. Protective effect of antibiotics against serious complications of common respiratory tract infections: retrospective cohort study with the UK General Practice Research Database. BMJ 2007;335:982.
43. Report of the Committee on Infectious Disease. Pickering LK, editor. 29th Edition, Group A Streptococcal Infections. Elk Grove Village, IL: American Academy of Pediatrics, 2012:668-80.
44. Dajani A, Taubert K, Ferrieri P, Peter G, Shulman S. Treatment of acute streptococcal pharyngitis and prevention of rheumatic fever: a statement for health professionals. Committee on Rheumatic Fever,Endocarditis, and Kawasaki Disease of the Council on Cardiovascular Disease in the Young, the American Heart Association. Pediatrics 1995;96:758-64.
45. No authors listed. Rheumatic fever and rheumatic heart disease. Report of a WHO Study Group. World Health Organ Tech Rep Ser 1988;764:1-58.
46. Shulman ST, Gerber MA, Tanz RR, Markowitz M. Streptococcal pharyngitis: the case for penicillin therapy. Pediatr Infect Dis J 1994;13:1-7.
47. Feder HM Jr, Gerber MA, Randolph MF, Stelmach PS, Kaplan EL. Once-daily therapy for streptococcal pharyngitis with amoxicillin. Pediatrics 1999;103:47-51.
48. Gerber MA, Tanz RR. New approaches to the treatment of group A streptococcal pharyngitis. Curr Opin Pediatr 2001;13:51-5.
49. Clegg HW, Ryan AG, Dallas SD, et al. Treatment of streptococcal pharyngitis with once-daily compared with twice-daily amoxicillin: a noninferiority trial. Pediatr Infect Dis J 2006;25:761-7.
50. Lennon DR, Farrell E, Martin DR, Stewart JM. Once-daily amoxicillin versus twice-daily penicillin V in group A beta-haemolytic streptococcal pharyngitis. Arch Dis Child 2008;93:474-8.
51. Shvartzman P, Tabenkin H, Rosentzwaig A, Dolginov F. Treatment of streptococcal pharyngitis with amoxycillin once a day. BMJ 1993;306:1170-2.
52. Pichichero ME. A review of evidence supporting the American Academy of Pediatrics recommendation for prescribing cephalosporin antibiotics for penicillin-allergic patients. Pediatrics 2005;115:1048-57.
53. Tanz RR, Shulman ST, Shortridge VD, et al. Community-based surveillance in the united states of macrolide-resistant pediatric pharyngeal group A streptococci during 3 respiratory disease seasons. Clin Infect Dis 2004;39:1794-801.
54. Schachtel BP, Thoden WR. A placebo-controlled model for assaying systemic analgesics in children. Clin Pharmacol Ther 1993;53:593-601.
55. Gehanno P, Dreiser RL, Ionescu E, Gold M, Liu JM. Lowest effective single dose of diclofenac for antipyretic and analgesic effects in acute febrile sore throat. Clin Drug Investig 2003;23:263-71.
56. Bertin L, Pons G, d'Athis P, et al. Randomized, double-blind, multicenter, controlled trial of ibuprofen versus acetaminophen (paracetamol) and placebo for treatment of symptoms of tonsillitis and pharyngitis in children. J Pediatr 1991;119:811-4.
57. McNally D, Simpson M, Morris C, Shephard A, Goulder M. Rapid relief of acute sore throat with AMC/DCBA throat lozenges: randomized controlled trial. Int J Clin Pract 2010;64:194-207.
58. Kaplan EL, Gastanaduy AS, Huwe BB. The role of the carrier in treatment failures after antibiotic for group A streptococci in the upper respiratory tract. J Lab Clin Med 1981;98:326-35.
59. Martin JM, Green M, Barbadora KA, Wald ER. Group A streptococci among school-aged children: clinical characteristics and the carrier state. Pediatrics 2004;114:1212-9.
60. Shulman ST. Streptococcal pharyngitis: diagnostic considerations. Pediatr Infect Dis J 1994;13:567-71.
61. Gerber MA, Tanz RR, Kabat W, et al. Potential mechanisms for failure to eradicate group A streptococci from the pharynx. Pediatrics 1999;104:911-7.
This web site is sponsored by Johnson & Johnson (HK) Ltd.