NATIONAL PRESCRIBING CENTRE VOLUME 10 Contents: NUMBER 11, 1999 Managing sore throats Managing sore throats Sore throat is a common complaint, which occurs predominantly in children and young adults, and more often in winter than summer. A GP with 2,000 patients can expect to see around 120 cases of acute throat infection every year.1 Throat infections are usually self-limiting and resolve within a week.1 Complications are rare, but can include quinsy and rheumatic fever. This Bulletin discusses the management of sore throats, and the evidence for and against treatment with antibiotics. Causes of sore throats Sore throats may be caused by either bacterial or viral infections; viruses are the predominant cause.2 Group A beta-haemolytic streptococcus (GABHS) is the most common causative bacteria1 and may be isolated in up to 30% of patients.3 It should be borne in mind that an acute sore throat occurring in a young adult may also be caused by infectious mononucleosis. It is not possible to distinguish reliably between bacterial and viral causes of sore throat on clinical grounds. Pain on swallowing is usually a predominant feature, regardless of aetiology. Fever, headache, tonsillar exudate, nausea, vomiting and abdominal pain may also be present. Cough, rhinorrhoea and hoarseness are uncommon with bacterial infection, and may be suggestive of a viral aetiology.2 Acute throat infections occur most commonly in children SUMMARY * Sore throat occurs predominantly in children and young adults, and is a common complaint in the winter months. It is usually self-limiting, and most patients recover within one week. * Most sore throats are viral in origin. The most common bacterial cause is group A beta-haemolytic streptococcus (GABHS). It is not possible to distinguish clinically between viral and bacterial infections. * Throat swabs have been used to try to identify GABHS infection. However, they are not able to distinguish carriage from clinical infection. It takes time for results to be available, which limits their usefulness in general practice. Rapid antigen tests produce results quickly, but are insufficiently sensitive for routine use. * Symptomatic relief of sore throat can be achieved using simple analgesics and antipyretics. Non-medical measures such as increasing fluid intake and gargling with salt water may also be helpful. Antibiotics have a small effect on the duration of symptoms of sore throat. However, no studies have demonstrated any reduction in time to return to school or work. * Sore throat caused by GABHS may rarely lead to complications such as quinsy, nephritis or rheumatic fever. Antibiotics reduce the incidence of complications but, as these events are rare, large numbers of patients need to receive antibiotics in order to prevent one episode of a complication. * High prescribing of antibiotics is associated with the developing problem of antibiotic resistance. Reducing prescribing for minor, self-limiting illnesses such as sore throat may help to contain this problem. The MeReC Bulletin is produced by the NHS for the NHS MeReC Bulletin Volume 10, Number 11, 1999 41 between 5 and 10 years, and in young adults in the 15-25 age group.1 The majority of patients with GABHS do not have the ‘classic’ symptoms; only 15% of cases present with the triad of fever, pharyngeal exudate and anterior cervical adenopathy.4 Even in patients suffering from pharyngeal exudate and fever, GABHS accounts for only a minority of infections.2 Complications The complications of acute sore throat caused by GABHS may be classified as suppurative or non-suppurative. Suppurative complications include sinusitis, otitis media, quinsy and cervical adenitis. Non-suppurative complications include acute nephritis and rheumatic fever. Diagnostic tests Two different types of test have been used to try to identify sore throats of bacterial origin - throat swabs and rapid antigen tests. Each is associated with different advantages and disadvantages. Throat culture results can take 24 to 48 hours to be reported. This limits their usefulness to prescribers, who prefer to decide during the consultation whether or not to prescribe antibiotics. Additionally, there is a high asymptomatic carrier rate of GABHS, of up to 40% of the population.5 Throat cultures cannot distinguish between carriage and infection with GABHS. This means that some patients who are not suffering from a bacterial infection will nevertheless produce a positive throat culture result. Rapid antigen tests use enzyme immunoassay or agglutination to detect the presence of group A streptococcal antigen on a throat swab. These tests produce a result in a few minutes. A study in general practice in the Netherlands assessed the value of a rapid streptococcal antigen detection test, in addition to four clinical features, in patients with sore throat. Throat culture and antibody titres were used as 42 reference tests.6 Clinical features recorded were: fever ≥38.00C, lack of cough, tonsillar exudate and anterior cervical lymphadenopathy. Compared with throat culture, the sensitivity of the rapid test was 65% and specificity 96%. In those patients with three or four clinical features, sensitivity increased to 75%. The authors concluded that the use of a rapid test might have value in general practice, although they felt that tests with a higher sensitivity would be needed (to minimise false negative results) before routine use could be considered.6 Neither throat cultures nor rapid antigen tests seem sufficiently accurate for routine use. Some prescribers may wish to employ them in specific patients, such as those with recurrent infections. However, there is no clinical trial evidence to support such a strategy. Treatment of sore throat The aims of treatment for sore throat are: to relieve symptoms, shorten illness duration, and prevent complications. Symptomatic relief of sore throat may be achieved using simple analgesics such as paracetamol. Adults may wish to take aspirin as an alternative. Non-medical measures, such as increasing fluid intake, or gargling with salt water, may also bring relief. Do antibiotics relieve sore throat symptoms? Evidence for the effects of antibiotics on the symptoms of sore throat comes from a systematic review carried out by the Cochrane collaboration, which analysed the results of 22 trials involving 10,484 cases.7 This review concluded that antibiotic treatment could shorten the duration of symptoms, but only by a mean of about eight hours overall. About 90% of all patients were symptom-free by one week, regardless of therapy. One open study included in this review compared three strategies for managing sore throat.8 These were an immediate ten day prescription for penicillin V or erythromycin, no prescription, or a delayed prescription, to be collected if symptoms were not beginning to settle after three days. All patients were given structured advice, which included recommendations to take analgesics or antipyretics. The three groups did not differ in symptom resolution at three days, or in the median duration of any symptom except fever. The study also recorded the time taken for patients to return to work or school. This did not differ significantly between the groups. In another study involving 371 patients, penicillin V was compared with placebo as initial therapy for pharyngitis. All patients also received education and standard symptomatic therapy.9 While there was a statistically significant increase in the number of patients whose sore throat had improved after 48 hours with penicillin V, there was no difference in fever reduction or in rates of return to school or work. In summary, antibiotic treatment of sore throat may have a small effect on symptom resolution. However, there is no evidence that antibiotic treatment results in an earlier return to school or work, which may be important to many patients. Do antibiotics reduce the complications of sore throat? The Cochrane review estimated that antibiotic treatment of sore throat reduced the incidence of acute otitis media to about one quarter of that in the placebo group, and that of acute sinusitis to about one third of that in the placebo group.7 Data from two studies indicated that the incidence of quinsy was also reduced. However, the relative benefits described do not translate into significant clinical benefits, as the underlying incidence of these complications is very low. The Cochrane review estimated that, in order to prevent one episode of otitis media, about 30 children and 145 adults with a sore throat would have to receive antibiotics.7 MeReC Bulletin Volume 10, Number 11, 1999 One Scottish retrospective study assessed the incidence of rheumatic fever in children as 0.6 per 100,000 per year (or 27 cases per 4.4 million child years).10 This study also found that the risks of developing rheumatic fever after a sore throat were similar regardless of whether or not it had been treated with antibiotics. Another study found that there was no clear evidence that antibiotic treatment of GABHS throat infection prevents acute glomerulonephritis.3 In the Cochrane review, a trend towards protection against acute glomerulonephritis was noted, but the numbers of cases in the studies were too low to be sure of this effect.7 It would seem from this evidence that antibiotic treatment of sore throat does have some small protective effect against both suppurative and non-suppurative complications. However, the absolute incidence of these complications is very low. Therefore, large numbers of patients would need to receive antibiotics in order to prevent one episode of a complication. Do antibiotics reduce the rate of recurrence of sore throat? There is no evidence from clinical trials as to whether antibiotic treatment reduces the rate of recurrence of sore throat. However, there is a theory that the early use of antibiotic treatment might increase recurrence; this is thought to be a result of inhibition of formation of type-specific antibodies to GABHS. Two studies have investigated this theory by comparing recurrence rates in patients given immediate antibiotic therapy and those whose treatment was delayed for 48 hours after presentation.11,12 In the first study, 113 patients were followed up for four months after completion of antibiotic therapy, as well as during any interim episodes of acute pharyngitis. No significant differences were seen between the immediate and delayed treatment groups in the number of patients with positive follow-up throat cultures, recurrences, symptomatic recurrences, or new infections.11 The second study followed up 229 children with culture-positive GABHS infection for four months.12 This study found that both early (within seven weeks) and late (within the same streptococcal season) recurrences were more common in patients who began treatment immediately. These studies provide evidence that delaying antibiotic treatment will not be harmful, and may have some benefits. Choosing an antibiotic In those patients for whom antibiotic therapy is felt to be necessary, the prescriber has to decide which antibiotic to choose. A study of samples of group A streptococcal strains collected over a period of 80 years showed no development of resistance to penicillin.13 Use of ampicillin, amoxicillin and co-amoxiclav should be avoided in patients with a sore throat. This is because of the risk of precipitating a maculopapular rash if the patient is suffering from infectious mononucleosis. Most clinical trials in this area used penicillin V 250mg, three or four times daily, for ten days. A review of studies of shorter courses concluded that five to seven days of penicillin V was less effective than a ten day course at achieving eradication of GABHS from the pharynx.14 However, there is no clear relationship between ‘microbiological’ cure and ‘clinical’ cure, in terms of relief of symptoms. Furthermore, patient compliance might be expected to be better if shorter courses are given. No studies of shorter courses of penicillin V have addressed these issues. Erythromycin is an appropriate choice for penicillin-allergic patients. It may be given twice or four times daily. Again, ten days treatment effectively eradicates GABHS from the pharynx.15 Antibiotic prescribing and bacterial resistance Increasing bacterial resistance to antibiotics is becoming a MeReC Bulletin Volume 10, Number 11, 1999 significant issue, both in primary and secondary care. The Standing Medical Advisory Committee (SMAC) report ‘The path of least resistance’ points out that some 50 million prescriptions for antibiotics are dispensed each year in England alone; 80% of this activity occurs in primary care.16 A twofold variation exists in levels of antibiotic usage between the areas of highest and lowest prescribing, for which there is no apparent explanation. Although antibiotic resistance is a worldwide problem, there is evidence that local antibiotic prescribing practices can affect local resistance patterns. A study in Wales investigated antibiotic prescribing in general practitioners’ surgeries and resistance to antibiotics over the period from March 1996 to April 1998. Rates of prescribing for urinary tract infections and resistance rates in coliform organisms were examined.17 A correlation between the rate of prescribing of an antibiotic and the rate of resistance to that agent was demonstrated. A cross-sectional survey in Iceland also found that carriage of penicillin resistant pneumococci was strongly associated with both individual and communitywide levels of antibiotic use.18 In Finland, the incidence of erythromycin resistance in group A streptococcus reduced by half over three years following a campaign to reduce the use of macrolide antibiotics.19 Disadvantages of antibiotic prescribing Antibiotics are associated with several well documented common side-effects, including diarrhoea and rashes, as well as rare, but potentially life-threatening, anaphylactic reactions. The risk of side-effects should always be considered before prescribing any medication. Prescribing antibiotics can also have other, perhaps unforeseen, consequences. In the open study comparing three approaches to the management of sore throat, patients who received an immediate prescription for antibiotics were more likely to believe that antibiotics 43 were effective in this condition.8 They were also more likely than other patients to intend consulting a GP in future episodes. In a follow-up study, a higher reconsultation rate in those patients who had been given immediate antibiotic treatment was demonstrated.20 Other strategies for managing sore throat expectation of a prescription for antibiotics for coughs, colds and sore throats. They have produced a patient information leaflet titled ‘Antibiotics. Don’t wear me out’, featuring a character called Andy Biotic. This is available on the Department of Health website (www.doh.gov.uk/ antibioticresistance/) or from the Department of Health, PO Box 777, London SE1 6XH. 4 5 6 7 8 9 10 The open study mentioned earlier compared immediate prescription, no treatment, or delayed prescription for managing sore throat, involving a total of 716 patients.8 Very ill patients were excluded from the study. Of the patients offered a delayed prescription, 69% did not use it. The proportion of patients who were better by day three, and the overall duration of illness, did not differ between the groups. Patients’ satisfaction with the consultation, and how their worries were dealt with, also did not differ between groups. Satisfaction was closely associated with illness duration, whereas antibiotic use was not, suggesting that psychological issues are important in the management of sore throat. Information leaflets may be helpful in explaining to patients the reasons for not prescribing antibiotics, and may provide a useful substitute for a prescription in some consultations. The PRODIGY decision-support system includes an information leaflet on sore throat, which can be found on the PRODIGY web site (www.schin.ncl.ac.uk/ prodigy/guidance/browser/pils/ pl154.htm). The Scottish Intercollegiate Guidelines Network have also produced a guideline on the management of sore throat and indications for tonsillectomy, which includes a patient information leaflet on tonsillitis and sore throat. This guideline can also be found on the internet (www.show.scot.nhs.uk/sign/ html/htmtxt34.htm). The Department of Health has produced an advertising campaign aimed at reducing the Conclusions 11 Evidence for the effectiveness of antibiotic therapy in reducing symptoms and preventing complications of sore throat is modest. GPs should therefore aim to avoid prescribing antibiotics for most sore throats. Symptomatic measures may be recommended. Patients should be educated about the very small benefits of antibiotic therapy and its associated side effects. The possibility of a delayed prescription, to be collected if symptoms do not improve in a few days, can also be discussed. The prescriber and patient can then make a joint decision on the course of action. Although this may require extra time initially, it should reap benefits in the long term, by avoiding the increased reconsultation rate associated with prescribing antibiotics. Several information leaflets explaining why antibiotics are unnecessary for simple sore throats are available. Prescribers may find these a useful substitute for a prescription. If antibiotics are considered necessary (for example, in very ill patients or those who have previously suffered a complication), penicillin V remains the agent of choice, as it is both effective and inexpensive. Erythromycin may be useful in those patients allergic to penicillin. References 1 Fry J, Sandler G. Chapter 6, Acute throat infections. In: Common diseases: their nature, presentation and care, 5th ed. Kluwer Academic Publishers, Lancaster 1993: 66-73 2 Dowell SF, Schwartz B, et al. Appropriate use of antibiotics for URIs in children: Part II. Cough, pharyngitis and the common cold. Am Fam Physician 1998; 58: 1335-1345 3 Taylor JL, Howie JG. Antibiotics, sore throats and acute nephritis. J R Coll Gen Pract 1983; 33: 783-786 12 13 14 15 16 17 18 19 20 Kiselica D. Group A beta-hemolytic streptococcal pharyngitis: current clinical concepts. Am Fam Physician 1994; 49: 1147-1154 Del Mar C. Managing sore throat: a literature review. I. Making the diagnosis. Med J Aust 1992; 156: 572-575 Dagnelie CF, Bartelink ML, et al. Towards a better diagnosis of throat infections (with group A β-haemolytic streptococcus) in general practice. Br J Gen Pract 1998; 48: 959-962 Del Mar CB, Glasziou PP. Antibiotics for sore throat (Cochrane review). In: The Cochrane Library Issue 3, 1999. Oxford: Update Software Little P, Williamson I, et al. Open randomised trial of prescribing strategies in managing sore throat. BMJ 1997; 314: 722-727 Middleton DB, D’Amico F, Merenstein JH. Standardized symptomatic treatment versus penicillin as initial therapy for streptococcal pharyngitis. J Pediatr 1988; 113: 1089-1094 Howie JGR, Foggo BA. Antibiotics, sore throats and rheumatic fever. J R Coll Gen Pract 1985: 35: 223-224 Gerber MA, Randolph MF, et al. Lack of impact of early antitbiotic therapy for streptococcal pharyngitis on recurrence rates. J Pediatr 1990; 117: 853-858 El-Daher NT, Hijazi SS, et al. Immediate vs. delayed treatment of group A beta-hemolytic streptococcal pharyngitis with penicillin V. Pediatr Infect Dis J 1991; 10: 126-130 Macris MH, Hartman MD, et al. Studies of the continuing susceptibility of group A streptococcal strains to penicillin during eight decades. Pediatr Infect Dis J 1998; 17: 377-381 Pichichero ME, Cohen R. Shortened course of antibiotic therapy for acute otitis media, sinusitis and tonsillopharyngitis. Pediatr Infect Dis J 1997; 16: 680-695 Ginsburg CM, McCracken GH, et al. Erythromycin therapy for group A streptococcal pharyngitis. Am J Dis Child 1984; 138: 536-539 Standing Medical Advisory Committee Subgroup on Antimicrobial Resistance. The path of least resistance. September 1998 Magee JT, Pritchard EL, et al. Antibiotic prescribing and antibiotic resistance in community practice: retrospective study, 1996-8. BMJ 1999; 319: 1239-1240 Arason VA, Kristinsson KG, et al. Do antimicrobials increase the carriage rate of penicillin resistant pneumococci in children? Cross sectional prevalence study. BMJ 1996; 313: 387-391 Seppala H, Klaukka T, et al. The effect of changes in the consumption of macrolide antibiotics on erythromycin resistance in group A streptococci in Finland. N Engl J Med 1997; 337: 441-446 Little P, Gould C, et al. Reattendance and complications in a randomised trial of prescribing strategies for sore throat: the medicalising effect of prescribing antibiotics. BMJ 1997; 315: 350-352 Corrections Prices of two calcium and vitamin D products were omitted from the cost information in MeReC Bulletin Vol. 10 No. 7. Calcichew D3 Forte costs £69.35 per year, at a dose of two tablets daily. Adcal-D3 costs £54.75 per year, at a dose of one tablet twice daily. The licensed dose of Erymax for the treatment of acne (MeReC Bulletin Vol. 10 No. 8) is different from the BNF recommendations for erythromycin in acne. Erymax is licensed at a dose of 250mg twice daily for the first month, and 250mg daily thereafter. Costs for these doses are £10.82 and £5.41 per month, respectively. Date of preparation: January 2000 The National Prescribing Centre, The Infirmary, 70 Pembroke Place, Liverpool, L69 3GF. Telephone: 0151-794 8146/8140/8143/8145 Fax: 0151-794-8139/44 44 MeReC Bulletin Volume 10, Number 11, 1999
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