Acute Sore Throat

NICE 69: National Institute for Health and Clinical Excellence. Prescribing of antibiotics for self-limiting respiratory tract infections in adults and children in primary care. 2008. (Clinical guideline 69) RATIONALE: Acute Sore Throat: NICE 69 includes 3 trials that use a delayed-antibiotic strategy for treating Acute Sore Throat. Two USA studies used a 2-day delayed antibiotic and the UK primary care study used a 3-day-delayed antibiotic.

Spinks A, Glasziou PP, Del Mar C. Antibiotics for sore throat. Cochrane Database of systematic reviews 2006, Issue 4. Art. No CD000023.DOI:10.1002/14651858.CD000023.pub3. (Review content up to date 24 November 2008). RATIONALE: This meta-analysis includes 27 RCTs and 2,835 cases of sore throat. Without antibiotics 40% of sore throats resolve in 3 days and 90% in 7 days. Antibiotics do confer a marginal benefit: To resolve one sore throat at 3 days the NNT is 6 and at 7 days the NNT is 21. However, absolute benefits are modest, especially as the Number Needed to Harm for antibiotic use in respiratory infections is about 15.

Centor RM, Whitherspoon JM, Dalton HP, Brody CE, Link K. The diagnosis of strep throat in adults in the emergency room. Med Decision Making 1981;1:239-46. RATIONALE: Centor Criteria: History of fever; absence of cough; tender anterior cervical lymphadenopathy and tonsillar exudates. A low Centor score (0-2) has a high negative predictive value (80%) and indicates low chance of Group A Beta Haemolytic Streptococci (GABHS). A Centor score of 3-or-4 suggests the chance of GABHS is 40%. If a patient is unwell with a Centor score of 3-or-4 then the chance of developing Quinsy is 1:60.

Peterson 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;335:982-4. RATIONALE: This UK retrospective cohort study looked at the extent to which antibiotics prevent serious suppurative complications of self-limiting upper respiratory tract infections. To prevent an episode of Quinsy the NNT of acute sore throat with antibiotics is >4000. This supports the recommendation that in the UK antibiotics should not be used to prevent suppurative complications of acute sore throat. Most patients with Quinsy develop the condition rapidly and don‟t present first with an acute sore throat.

Kagan, B. Ampicillin Rash. Western Journal of Medicine 1977;126(4):333-335 RATIONALE: Amoxicillin should be avoided in the treatment of acute sore throat due to the high risk of developing a rash, when the Epstein Barr virus is present. Although this is now quite an old study and EBV infection may now not be as common in acute sore throat.

Lan AJ, Colford JM, Colford JMJ. The impact of dosing frequency on the efficacy of 10 day penicillin or amoxicillin therapy for streptococcal tonsillopharyngitis: A meta-analysis. Pediatr 2000;105(2):E19. RATIONALE: This meta analysis provides the evidence that BD dosing with phenoxymethylpenicillin is as effective as QDS in treating GABHS.

Expert opinion is that phenoxymethylpenicillin should be dosed QDS for severe infections in order to optimise the therapeutic drug concentrations.

Schwartz RH, Wientzen RL Jr, Predreira F, Feroli EJ, Mella GW, Guandolo VL. Penicillin V for group A streptococcal pharyngotonsillitis. A randomized trial of seven vs ten days’ therapy. JAMA 1981 Oct 16;246(16):1790-5 RATIONALE: form. This RCT demonstrates that a 10 day course of oral phenoxymethylpenicillin is better than 7 days for resolution of symptoms and eradication of GABHS. In total, 210 middle-class paediatric patients (children aged 1-18 years) with positive group A streptococcal sore throat were admitted to the study. Of the remaining 191 patients available for analysis, 96 were randomly assigned to seven days of penicillin therapy and 95 to ten days of treatment with excelled compliance. Symptomatic recurrence was higher with 7 days treatment (23%) than 10 days (12%).

Altamimi S, Khali A, Khalaiwa KA, Milner R, Pusic MV, Al Othman MA. Short versus standard duration antibiotic therapy for acute streptococcal pharyngitis in children. Cochrane Database of systematic reviews 2009, Issue 1. Art No.: CD004872. DOI: 10/1002/14651858.CD004872.pub2. RATIONALE: This recent meta-analysis shows short-course (including 5 days Clarithromycin) broad-spectrum antibiotics are as efficacious as 10-day-penicillin for sore throat symptom treatment and GABHS eradication. 10-day-phenoxymethylpenicillin remains the treatment of choice. Evidence suggests the use of broader spectrum antibiotics will drive the emergence of bacterial resistance; increase the risk of developing Clostridium difficile Associated Disease; and are associated with more adverse drug reactions. 5 days-clarithromycin should be reserved for those with true penicillin allergy.

Lasseter GM, McNulty CAM, Hobbs FDR, Mant D, Little P on behalf of the PRISM investigators. In vitro analysis of five rapid antigen detection tests for group A beta-haemolytic streptococcal sore throat infections. Family Practice 2009 Dec 26(6): 437-44. RATIONALE: A comparative study of 5 rapid antigen detection kits for group A Streps concluded that the IMI test pack Plus Strep A (Inverness Medical, Bedford, UK) was easy to use with clear kit instructions and a high sensitivity (95% at group A streptococcal concentrations of 10 x 106 CFU/mL) and specificity (100%), thus offering best value for money (although is not the cheapest). The authors note that the quality of any throat swab taken will affect the performance of the test so swabbing technique is as important as the choice of test.

Additional references:

Howie JGR, Foggo BA. Antibiotics, sore throats and rheumatic fever. BJGP 1985;35:223-224. RATIONALE: This Scottish retrospective study confirms the low incidence of Rheumatic Fever in the UK, (0.6 per 100,000 children per year). It would take 12 working GP life times to see one case of Rheumatic Fever. The risk of developing Rheumatic Fever was not reduced in this study by treating sore throats with antibiotics. This supports the recommendation that in the UK antibiotics should not be used to prevent non-suppurative complications of acute sore throat.

Taylor JL, Howie JGR. Antibiotics, sore throat and acute nephritis. BJGP 1983;33:783-86. RATIONALE: This study shows that Glomerulonephritis is a rare condition, (2.1 per 100,000 children per year) and that treating acute sore throat with antibiotics doesn't prevent it occurring.

Maholtra-Kumar S, Lammens C, Coenen S, Van Herck K, Goossens H. Effect of azithromycin and clarithromycin therapy on pharyngeal carriage of macrolide-resistant streptococci in healthy volunteers: a randomised, double-blind, placebo controlled study. Lancet 2007;369:482-490. RATIONALE: This randomised, double blind, placebo controlled study showed both azithromycin and clarithromycin significantly increased the proportion of macrolide-resistant streprococci compared with the placebo at all points studied. Peaking at day 8 in the clarithromycin group (mean increase 50·0%, 95% CI 41·7–58·2; p<0·0001) and at day 4 in the azithromycin group (53·4%, 43·4–63·5; p<0·0001). The proportion of macrolide-resistant streptococci was higher after azithromycin treatment than after clarithromycin use, with the largest diff erence between the two groups at day 28 (17·4% diff erence, 9·2–25·6; p<0·0001). Use of clarithromycin, but not of azithromycin, selected for the erm (B) gene, which confers high-level macrolide resistance.

Shulman TS, Bisno AL, Clegg HW, Gerber MA, Kaplan EL, Lee G, et al. Clinical Practice Guidelines for the Diagnosis and Management of Group A Streptococcal Pharyngitis: 2012 Update by the Infectious Diseases Society of America. CID 2012; 55: e86.

The POCAST project is funded by the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Healthcare Associated Infections and Antimicrobial Resistance at Imperial College London and by the Imperial College Healthcare Charity (Grant Ref No:7006/P36U).