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Clinical Therapeutics/Volume 33, Number 1, 2011

Analysis of Different Recommendations From International Guidelines for the Management of Acute Pharyngitis in Adults and Children
Elena Chiappini, MD, PhD; Marta Regoli, MD; Francesca Bonsignori, MD; Sara Sollai, MD; Alessandra Parretti, MD; Luisa Galli, MD; and Maurizio de Martino, MD
Department of Sciences for Woman and Childs Health, University of Florence, Florence, Italy
ABSTRACT Background: Streptococcal pharyngitis is a frequently observed condition, but its optimal management continues to be debated. Objective: The goal of this study was to evaluate the available guidelines, developed at the national level, for the management of streptococcal pharyngitis in Western countries, with a focus on their differences. Methods: A literature search was conducted of the Cochrane Library, EMBASE, TRIP, and MEDLINE databases from their inception (1993 for the Cochrane Library, 1980 for EMBASE, 1997 for TRIP, and 1966 for MEDLINE) through April 25, 2010. The following search terms were used: pharyngitis, sore throat, tonsillitis, pharyngotonsillitis, Streptococcus pyogenes, Group A -haemolytic Streptococcus pyogenes, and streptococcal pharyngitis. Searches were limited to type of article or document (practice guideline or guideline) with no language restrictions or language limits. Results: Twelve national guidelines were identied: 6 from European countries (France, United Kingdom, Finland, Holland, Scotland, and Belgium), 5 from the United States, and 1 from Canada. Recommendations differ substantially with regard to the use of a rapid antigen diagnostic test or throat culture and the indications for antibiotic treatment. The North American, Finnish, and French guidelines recommend performing one timely microbiologic investigation in suspected cases, and prescribing antibiotics in conrmed cases to prevent suppurative complications and acute rheumatic fever. According to the remaining European guidelines, however, acute sore throat is considered a benign, self-limiting disease. Microbiologic tests are not routinely recommended by these latter guidelines, and antibiotic treatment is reserved for well-selected cases. The use of the Centor score, for evaluation of the risk of streptococcal infection, is recommended by several guidelines, but subsequent decisions on the basis of the results differ in terms of which subjects should undergo microbiologic investigation. All guidelines agree that narrow-spectrum penicillin is the rst choice of antibiotic for the treatment of streptococcal pharyngitis and that treatment should last for 10 days to eradicate the microorganism. Once-daily amoxicillin was recommended by 2 US guidelines as equally effective. Conclusion: The present review found substantial discrepancies in the recommendations for the management of pharyngitis among national guidelines in Europe and North America. (Clin Ther. 2011;33:48 58) 2011 Key words: adult, children, guidelines, pharyngitis, Streptococcus pyogenes.

INTRODUCTION
Acute pharyngitis is common in adults and children, accounting for 5% of medical visits.1 Most cases are viral, benign, and self-limited. Group A -hemolytic streptococci (GABHS) is the most common bacterial etiology. Among children of all ages who present with sore throat, the prevalence of GABHS has been estimated to be 37% (95% CI, 32 43). Streptococcal pharyngitis occurs at all ages but is most common among school-aged children and adolescents. It is rare in children younger than 3 years. The peak incidence in temperate climates occurs during late autumn, winter, and early spring. The incubation period is 2 to 5 days, and communicability of the infection is highest during the acute phase. Patients are no longer contagious within 24 hours of starting antibiotic treatment.2 Because the signs and symptoms of GABHS pharyngitis
Accepted for publication December 8, 2010. doi:10.1016/j.clinthera.2011.02.001 0149-2918/$ - see front matter 2011 Published by Elsevier HS Journals, Inc.

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E. Chiappini et al. overlap extensively with pharyngitis not caused by GABHS, it is not possible to make a diagnosis based solely on clinical ndings. No single element of the patients history or physical examination reliably conrms or excludes GABHS pharyngitis.3 Sore throat, sudden onset of fever ( 38C), and documented exposure to GABHS within the preceding 2 weeks may suggest streptococcal infection.2 Cervical node adenopathy and pharyngeal or tonsillar inammation or exudates are common signs, whereas palatal petechiae and scarlatiniform rash are highly specic but uncommon.2 Cough, coryza, conjunctivitis, and diarrhea are more common in viral pharyngitis,4 although toddlers (13 years of age) with GABHS pharyngitis initially can have serous rhinitis.2 Suppurative complications include cervical lymphadenitis, peritonsillar abscess, retropharyngeal abscess, otitis media, mastoiditis, and sinusitis occurring in patients in whom the primary illness has gone unnoticed or untreated. Nonsuppurative sequelae are acute rheumatic fever, acute poststreptococcal glomerulonephritis, Sydenham chorea, reactive arthritis, and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections.5 Conrmation of GABHS pharyngitis can be performed using a throat culture or rapid antigen diagnostic test (RADT). Several RADTs are available; most are based on nitrous acid extraction of group A carbohydrate antigen from organisms obtained by throat swab. The specicity of these tests is high (89.7%99%), but the reported sensitivity varies considerably (55%99%) and is lower with older latex agglutination assays compared with more recent enzyme-linked immunosorbent assays, optical immunoassays, and chemiluminescent DNA probes.2,6,7 Several guidelines have been published in North America and Europe. The goal of the present study was to evaluate the available guidelines, which have been developed at the national level, for the management of streptococcal pharyngitis in Western countries, with a focus on their differences. streptococcal pharyngitis. Searches were limited to type of article or document (practice guideline or guideline) with no language restrictions or language limits. Results of these searches were closely evaluated, and articles and documents that were not pertinent or redundant were excluded. This review was focused on guidelines developed at the national level.

RESULTS
Twelve guidelines were identied: 6 from European countries (France, United Kingdom, Finland, Holland, Scotland, and Belgium), 5 from the United States, and 1 from Canada. Table I2,8 18 lists the recommendations and their years of publication.

Comparison of Recommendations
Substantial differences in the recommendations for the management of pharyngitis were found, allowing for 2 groups of guidelines: the rst one comprised North American,2,8 12 French,13 and Finnish14 guidelines, the second UK,15 Scottish,16 Dutch,17 and Belgian18 guidelines. According to the rst group, the microbiologic conrmation of GABHS pharyngitis is fundamental to its treatment and the prevention of suppurative complications and acute rheumatic fever. The second group considers acute sore throat, and even streptococcal infection, as a benign, self-limiting disease, given the low incidence of suppurative complications and rheumatic disease; their focus is on the judicious use of antibiotics. According to these guidelines, microbiologic tests should not be routinely executed because antibiotics have only a limited effect on shortening the clinical evolution, and do not substantially affect the incidence of suppurative complications and rheumatic fever in developed countries. Antimicrobial treatment should therefore be reserved for well-selected cases.

Differences Regarding Diagnosis MATERIALS AND METHODS


A literature search was conducted of the Cochrane Library, EMBASE, TRIP, and MEDLINE databases from their inception (1993 for the Cochrane Library, 1980 for EMBASE, 1997 for TRIP, and 1966 for MEDLINE) through April 25, 2010. The following search terms were used: pharyngitis, sore throat, tonsillitis, pharyngotonsillitis, Streptococcus pyogenes, Group A -haemolytic Streptococcus pyogenes, and All of the guidelines are in agreement that blood tests (antistreptolysin O, C-reactive protein, and leukocyte count) are not recommended for the diagnosis of GABHS pharyngitis. Major differences concern the use of microbiologic investigations (throat culture or RADT). For those guidelines that do not recommend performing microbiologic investigations, their no-testing rationale is based on the fact that the major issuethe

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Table I. National guidelines considered in the present analysis, their year of publication, and corresponding reference. Country United States Guideline American Academy of Pediatrics American College of Physicians-American Society of Internal Medicine American Heart Association Infectious Diseases Society of America Institute for Clinical System Improvement Canadian Medical Association Agence Franaise de Scurit Sanitaire des Produits de Sant Finnish Medical Association National Institute for Health and Clinical Excellence Scottish Intercollegiate Guidelines Network Dutch College of General Practitioners Scientic Society of Flemish General Practitioners Year 2009 2001 2009 2002 2005 2003 2005 2007 2008 1999 2008 1999 Reference 2 11 8 9 10 12 13 14 15 16 17 18

Canada France Finland United Kingdom Scotland Holland Belgium

prevention of rheumatic fever has been demonstrated exclusively in studies from the 1950s and the 1960s.15 In addition, the incidence of rhematic fever is low in developed countries, and the costs and adverse effects of antibiotics given to many to prevent rare complications in a few is not a cost-effective practice. For those guidelines that do recommend microbiologic investigations, their rationale relies on the fact that the goal principally is to prevent rheumatic fever, which, even if rare, may be a severe disease. Thus, accurate recognition and prompt antibiotic treatment of streptococcal pharyngitis are recommended by guideline authors.8 Table II and Table III2,8 18 display the differences among the guideline recommendations for the diagnosis and treatment of GABHS pharyngitis. According to the UK guidelines,15 diagnosis should rely on evaluation of clinical signs and symptoms by calculating the Centor score19 (Table IV). The Centor score, which is calculated based on the patients age, uses 4 signs and symptoms to estimate the probability of acute streptococcal pharyngitis in adults and children.20 Similarly, the Scottish guidelines state that neither throat swab nor RADT should be conducted routinely.16 Conversely, according to the US8 11 and French13 guidelines, microbiologic conrmation is required for the diagnosis of GABHS pharyngitis, and RADT or throat culture should be routinely performed in suspected cases. Among the US guidelines, the American College of PhysiciansAmerican Society of Inter-

nal Medicine (ACP-ASIM)11 recommends the use of the Centor score to identify patients for whom RADT is indicated. However, the algorithms differ slightly. ACP-ASIM recommends microbiologic conrmation only if the Centor score is 2 to 3. In adults with a Centor score of 4, the diagnosis of GABHS pharyngitis should be made clinically; microbiologic conrmation is not required, and treatment should be initiated promptly. However, it has been argued that this latter approach would result in overtreatment, as only 50% of patients with a Centor score of 4 actually experience streptococcal pharyngitis.19 Because highly sensitive RADT assays are now available, some US guidelines9,11 do not recommend that a negative result be conrmed by throat culture in adults. However, this approach is recommended in children.2,9,11 Thus, in children a culture should be taken in the presence of a negative RADT.21 This strategy for children is recommended by all the US guidelines, as well as the French (if the child is aged 5 years) and the Finnish (if the child is aged 3 years) guidelines.2,8 11,13,14 The recent American Heart Association (AHA) guidelines differ in the fact that, in the presence of a negative RADT, they recommend performing a throat culture both in adults and in children.8 The French guidelines recommend performing RADT, but a throat culture is not considered a routine procedure.13 They reserve diagnostic conrmation of a negative RADT by throat culture for selected cases with risk factors for acute rheumatic

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E. Chiappini et al.

Table II. Comparison of the different guideline recommendations for the diagnosis of group A -hemolytic streptococci pharyngitis. Guideline United States AAP2 AHA8 IDSA9 ICSI10 ACP-ASIM11 Canada12 France13 Finland14 United Kingdom15 Scotland16 Holland17 Belgium18 History Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Clinical Examination Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Centor Score No No No No Yes Yes No No Yes Yes No No Rapid Antigen Diagnostic Test Yes Yes Yes Yes Yes No Yes Yes No No No No Culture Yes Yes Yes Yes Yes Yes No Yes No No No No

AAP American Academy of Pediatrics; AHA American Heart Association; IDSA Infectious Diseases Society of America; ICSI Institute for Clinical System Improvement; ACP-ASIM American College of Physicians-American Society of Internal Medicine.

fever (ie, personal history of acute rheumatic fever, epidemics of rheumatogenic strains, overcrowded living conditions). The American Academy of Pediatrics (AAP) guidelines2 recommend laboratory conrmation of GABHS infection, at the pediatricians discretion. Factors to be considered in the decision to obtain throat swab specimens are: age 3 years, presence of clinical signs and symptoms suggestive of GABHS infection, seasonality, and family and community epidemiology, including contacts with GABHS infection or presence in the family of a person with a history of acute rheumatic fever or with poststreptococcal glomerulonephritis. Children with signs or symptoms suggesting viral infection (coryza, conjunctivitis, hoarseness, cough, stomatitis, or diarrhea) should not be tested. Posttreatment throat swab cultures are indicated only for patients at high risk for acute rheumatic fever or poststreptococcal glomerulonephritis.

When and Whether to Treat


The UKs National Institute for Health and Clinical Excellence (NICE) guidelines suggest considering antibiotic treatment if the patients Centor score is 3.15

No further investigations are routinely required. An immediate antibiotic prescription and further appropriate investigation and management should be offered if the patient is systemically very unwell or has signs and symptoms suggestive of serious illness or complications (particularly pneumonia, mastoiditis, peritonsillar abscess, peritonsillar cellulitis, or intraorbital and intracranial complications) or is at high risk for serious complications because of preexisting comorbidity (signicant heart, lung, renal, liver, or neuromuscular disease; immunosuppression; or cystic brosis). Young children who were born prematurely should also undergo additional testing. Because current UK general practice does not use throat swabs or RADTs to detect the presence or absence of GABHS, primary care clinicians must rely only on signs and symptoms to decide on treatment.21 The recent AHA guidelines consider that prompt administration of penicillin therapy shortens the clinical course, decreases the incidence of suppurative sequelae and the risk of transmission, and prevents acute rheumatic fever even when given up to 9 days after onset of illness.8 According to the AHA and IDSA guidelines, antibacterial treatment should be per-

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52 Screening Diagnosis Throat Culture if RADT Is Negative When to Treat? Perform RADT only if Centor score is 23 Perform throat culture or RADT in all patients at risk Adults: no Children: yes Adults: no Children: yes Centor score of 4 or RADT or throat culture positive RADT or throat culture positive RADT or throat culture positive RADT or throat culture positive Adults: yes Children: yes Adults: yes8 Children: yes2,8 Not applicable Not applicable Not applicable Centor score 3, presence of other clinical ndings (see text) Throat culture positive Antibiotics should not be used routinely. In severe cases, in which the practitioner is concerned about the clinical condition of the patient, antibiotics should not be withheld Perform throat culture or RADT in all patients at risk Perform throat culture or RADT in all patients at risk Clinical diagnosis if Centor score is 3 Perform throat culture (not RADT) in all patients at risk Throat swabs should not be conducted routinely. They may be used to establish etiology of recurrent severe episodes in adults when considering referral for tonsillectomy

Clinical Therapeutics

Table III. Comparison among different guideline recommendations for the diagnosis and treatment of group A -hemolytic streptococci pharyngitis.

Guideline

ACP-ASIM11

Centor score

IDSA9

ICSI10

AHA,8 AAP2

United Kingdom15

Clinical and epidemiological parameters Clinical and epidemiologic parameters Clinical and epidemiologic parameters Centor score

Canada12

Scotland16

Clinical and epidemiologic parameters The Centor score should be used to assist the decision on whether to prescribe an antibiotic but cannot be relied on for a precise diagnosis

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January 2011 Screening Perform throat culture or RADT in all patients at risk RADT or throat culture positive Diagnosis Throat Culture if RADT Is Negative When to Treat? Perform only RADT in all patients at risk RADT or throat culture positive Throat swabs should not be conducted routinely In adults and children aged 3 years: yes In children aged 3 years streptococcal tonsillitis is so rare that a negative antigen test need not be controlled by culture Adults: no, except in the presence of risk factors for acute rheumatic fever. Children: if aged 5 years Not applicable RADT/throat swabs not recommended Not applicable Prescribing antibiotics is only recommended for patients who have an increased risk of complications Prescribing antibiotics is only recommended for patients who have an increased risk of severe complications E. Chiappini et al.

Table III (continued).

Guideline

Finland14

Clinical and epidemiologic parameters

France13

Clinical and epidemiologic parameters

Holland17

Clinical and epidemiologic parameters

Belgium18

Clinical and epidemiologic parameters

RADT rapid antigen diagnostic test; ACP-ASIM American College of Physicians-American Society of Internal Medicine; IDSA Infectious Diseases Society of America; ICSI Institute for Clinical Symptom Improvement; AHA American Heart Association; AAP American Academy of Pediatrics.

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Clinical Therapeutics Antimicrobial therapy is not indicated for GABHS pharyngeal carriers, with few exceptions (eg, outbreak of acute rheumatic fever or poststreptococcal glomerulonephritis, family history of acute rheumatic fever, multiple episodes of documented symptomatic GABHS pharyngitis occurring within a family despite appropriate therapy).2

Table IV. Modied Centor score used for the diagnosis of group A -hemolytic streptococci pharyngitis.19 Criteria Absence of cough Tonsillar exudates or swelling Swollen and tender anterior cervical nodes Temperature 38C Age, y 314 1544 45 Points 1 1 1 1 1 0 1

Type of Antibiotic Treatment


The literature review found no reports of a GABHS infection resistant to penicillin. Accordingly, all guidelines agree that narrow-spectrum penicillin is the rst choice of antibiotic for the treatment of GABHS pharyngitis. Although penicillin V is the drug of choice, amoxicillin is reported to be equally effective and has high palatability, which makes it a suitable option in children.2,8 Treatment options for patients allergic and nonallergic to penicillin are summarized in Table V. Macrolides are not indicated because of the spread of a high proportion of resistant GABHS isolates in the United States and in European countries.22

formed in all cases conrmed by a laboratory test (culture or RADT).8,9 In contrast, a position paper by the ACP-ASIM states that adult patients with a Centor score of 4 should be treated directly with no microbiologic conrmation; this should be reserved for those with a Centor score of 2 or 3.11

Table V. Therapeutic options for the treatment of group A -hemolytic streptococci pharyngitis as recommended by the American Heart Association8 and the American Academy of Pediatrics2 for adults and children allergic and nonallergic to penicillins. Agent For individuals allergic to penicillin: Narrow-spectrum cephalosporin (cephalexin, cefadroxil) Clindamycin Azithromycin Clarithromycin For individuals nonallergic to penicillin: Penicillin V Dose Mode Duration

Variable

Oral*

10 Days

20 mg/kg/d divided in 3 doses (maximum, 1.8 g/d) 12 mg/kg once daily (maximum, 500 mg) 15 mg/kg/d divided BID (maximum, 250 mg BID)

Oral Oral Oral

10 Days 5 Days 10 Days

Children 27 kg: 400,000 U (250 mg) 2 to 3 times Oral daily; children 27 kg, adolescents, and adults: 800,000 (500 mg) 2 to 3 times daily Amoxicillin 50 mg/kg once daily (maximum 1 g) Oral Benzathine/penicillin G Children 27 kg: 600,000 U (375 mg); children 27 kg, Intramuscular adolescents, and adults: 1,200,000 U (750 mg)

10 Days

10 Days Once

* Patients with immediate or type I hypersensitivity to penicillin should not be treated with a cephalosporin.2

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E. Chiappini et al. Use of once-daily amoxicillin has recently been proposed by the AHA guidelines,8 but it is not universally accepted. The AAP considers this approach an acceptable treatment option if strict adherence to once-daily dosing can be ensured.2 The AHA recommendation relies on the results of 3 randomized controlled trials (RCTs), including 662 children overall with GABHS pharyngitis, randomized to receive amoxicillin once daily versus penicillin V BID or TID, which found the noninferiority of amoxicillin once daily.2325 Only one RCT (including 652 children) compared amoxicillin once daily with amoxicillin BID in the treatment of streptococcal sore throat; there were no signicant differences in outcomes between the study groups, suggesting that once-daily amoxicillin treatment may be a good option that is associated with higher compliance.26 Nevertheless, amoxicillin given once daily is currently not approved by the US Food and Drug Administration or the European Medicines Agency for primary prophylaxis of acute rheumatic fever. Some authors have suggested that cephalosporins may have higher efcacy than penicillin in the treatment of GABHS pharyngitis.27,28 However, it should be noted that no guideline recommends cephalosporins as the rst-choice option for the treatment of GABHS pharyngitis because of their higher costs with respect to penicillin or amoxicillin, and the risk of resistant bacteria dissemination.29 Their use is limited to patients allergic to penicillin for whom they may represent an alternative to macrolides.2,8 17 They also may have a role in the treatment of relapses.30 CI, 0.67 0.94). No signicant difference in early bacteriologic treatment failure (OR 1.08; 95% CI, 0.971.20) or late clinical recurrence (OR 0.95; 95% CI, 0.831.08) was observed. The overall risk of late bacteriologic recurrence was inferior in patients who had received the short therapy (OR 1.31; 95% CI, 1.16 1.48), although no signicant difference was found after excluding studies using low doses of azithromycin (10 mg/kg). The authors of the meta-analysis concluded that a short course (2 6 days) of oral antibiotics has efcacy comparable to the standard 10-day oral penicillin course in patients with acute GABHS pharyngitis. However, these results have been widely criticized.32 At least one eligible large trial33 (579 children; age range, 6 months12 years) was not included. In addition, most included trials had methodologic biases (ie, randomization was not described or inappropriate, only 3 of the 20 included studies were blinded). Finally, the prevention of acute rheumatic fever was not considered as a main outcome in most of the included studies. Only 3 of the 20 studies addressed this issue, globally registering 3 events.32 Conversely, in a 2008 meta-analysis of randomized trials, Falagas et al34 found that short therapy was associated with lower clinical success and bacteriologic eradication rates. Clinical success was inferior in patients who received short-course treatment (5 RCTs, 1217 patients; OR 0.49; 95% CI, 0.25 0.96). In the primary analysis, microbiologic eradication rates of GABHS were inferior for short-versus long-course treatment (8 RCTs, 1607 patients; OR 0.49; 95% CI, 0.32 0.74). This nding was conrmed also considering only trials including penicillin V treatment (3 RCTs, 500 patients; OR 0.36; 95% CI, 0.13 0.99) but was no more evident considering trials limited to cephalosporins (4 RCTs, 1018 patients; OR 0.62; 95% CI, 0.38 1.03). Adverse events did not differ between compared groups.

Duration of Antibiotic Treatment


Another controversial argument in the treatment of pharyngitis is the possibility of shortening the duration of antibiotic therapy to 10 days. To date, all the guidelines agree that the treatment of streptococcal pharyngitis should last for 10 days to eradicate the microorganism.2,8 18 However, since compliance may be poor in children, a shorter therapy (3 6 days) has been proposed.31 A Cochrane review of 20 studies (including 13,102 acute GABHS pharyngitis cases) on this topic was published in 2009. Short antibiotic therapy (3 6 days and considering all type of antibiotics) was compared with the standard 10day treatment. Short therapy was associated with shorter periods of fever and lower risk of early clinical treatment failure (odds ratio [OR] 0.80; 95%

DISCUSSION
In the present review, 12 national guidelines (6 from European countries, 5 from the United States, and 1 from Canada) were analyzed. Recommendations differ substantially with regard to the use of RADT or throat culture and the indications for antibiotic treatment. In general, North American, Finnish, and French guidelines recommend performing one timely microbiologic

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Clinical Therapeutics investigation in suspected cases, and prescribing antibiotics in conrmed cases to prevent suppurative complications and acute rheumatic fever. This approach is supported also by the results of a 2006 Cochrane metaanalysis, which included 27 RCTs and 12,835 study subjects and found that antibiotics reduce acute rheumatic fever by more than two thirds (relative risk [RR] 0.22; 95% CI, 0.022.08). Moreover, antibiotics reduce the incidence of acute otitis media (RR 0.30; 95% CI, 0.15 0.58), acute sinusitis (RR 0.48; 95% CI, 0.08 2.76), and peritonsillar abscess compared with placebo (RR, 0.15; 95% CI, 0.05 0.47), but they shorten the duration of symptoms only by 16 hours overall.35 According to the remaining European guidelines, however, acute sore throat is considered a benign, selflimiting disease. Microbiologic tests are not routinely recommended by these guidelines, and antibiotic treatment is reserved for well-selected cases, considering the low incidence of acute rheumatic fever in developed countries and the need for a judicious use of antibiotics. The use of the Centor score to evaluate the risk of streptococcal infection is recommended by several of the guidelines, but subsequent decisions on the basis of the results are different. Once-daily amoxicillin was recommended by 2 US guidelines. Some literature reports claimed that both the NICE and US recommendations are at risk of being ignored in the clinical practice by physicians and pediatricians. In a retrospective cohort study, Thompson et al36 found that antibiotic prescribing declined by 24% between 1996 and 2000 in the United Kingdom but increased again by 10% during 2003 and 2006 despite the NICE recommendation. This increase was not observed among patients with a diagnosis of pharyngitis but was associated with an increase in nonspecic upper respiratory tract infection diagnoses, suggesting that general practitioners might have avoided using a specic diagnosis where formal guidance suggested antibiotic prescribing was not indicated. In one US study, it was reported that GABHS tests were underused compared with the indications of available guidelines.37 Antibiotics were prescribed to 53% of children with sore throat, in excess of the maximum expected prevalence of GABHS. GABHS testing was not signicantly associated with a lower antibiotic prescribing rate overall (48% tested vs 51% not tested), but testing was associated with a lower antibiotic prescribing rate for children with diagnosis codes for pharyngitis, tonsillitis, and streptococcal sore throat (57% tested vs 73% not tested; P 0.001). A uniform approach to the management of acute GABHS pharyngitis in Western countries would be of help for clinicians who face this issue in everyday practice. In our opinion, prudentially, clinicians and pediatricians could perform at least one microbiologic test (RADT or throat culture) in case of suspected pharyngitis, to make the correct diagnosis. Most RADTs can provide results in a few minutes, and their sensitivity is generally high.2 In children, a negative RADT could be conrmed by a throat culture only if suspicion of GABHS pharyngitis remains high on a clinical and epidemiologic basis. Although penicillin V is the rstchoice drug, amoxicillin is equally effective and demonstrates higher palatability, which makes it a suitable option in children.6 It should be noted that macrolides have no indication in the treatment of GABHS pharyngitis except for those patients with a conrmed allergy to penicillin. However, for this selected group of patients, cephalosporins represent a good option (with the exception of children with type I hypersensitivity reaction to penicillin). The inadequate use of macrolides for treatment of GABHS infection is one of the main causes for the dissemination of resistant strains in Western countries.22 It should also be noted that the treatment should be given for 10 days in every case. Parents of children and adult patients should be alerted that clinical improvement usually occurs within 4 to 5 days, but therapy should be continued until day 10 to eradicate the bacterium.

Limitations
The present review has some limitations. Our search strategy might have missed some guidelines, and our decision to include only national guidelines has excluded those developed at a regional level.

CONCLUSION
The present review found substantial discrepancies in the recommendations for the management of pharyngitis among national guidelines in Europe and North America.

ACKNOWLEDGMENTS
The present research was supported by Tecnimed SRL (Varese, Italy). The authors have indicated that they

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E. Chiappini et al. have no conicts of interest with regard to the content of this article. Drs. Chiappini, Regoli, Bonsignori, and Sollai performed the literature search and data interpretation, and wrote the manuscript. Drs. Galli and de Martino performed the data interpretation and nal revision of the manuscript.
of Physicians-American Society of Internal Medicine; Centers for Disease Control. Principles of appropriate antibiotic use pharyngitis in adults. Ann Intern Med. 2001;134:506 508. British Columbia Ministry of Science. Sore throat-diagnosis and management. http://www.bcguidelines.ca/gpac/ guideline_throat.html. Accessed May 26, 2010. Agence Franaise de Scurit Sanitaire des Produits de Sant. Systemic antibiotic treatment in upper and lower respiratory tract infections: Ofcial French guidelines. Clin Microbiol Infect. 2003;9:11621178. National Guideline Clearing-House. Duodecim: Tonsillitis and pharyngitis in children. http://www.guideline.gov/ content.aspx?id 11049&search nland sore. Accessed October 14, 2010. National Institute for Health and Clinical Excellence (NICE). Respiratory tract infections-antibiotic prescribing. Prescribing of antibiotics for self limiting respiratory tract infections in adults and children in primary care (clinical guideline 69). London, UK: NICE; 2008. http://www. nice.org.uk/nicemedia/pdf/CG69FullGuideline.pdf. Accessed May 26, 2010. Scottish Intercollegiate Guidelines Network. Management of sore throat and indication for tonsillectomy. http:// www.sign.ac.uk/pdf/sign117.pdf. Accessed October 14, 2010. Starreveld JS, Zwart S, Boukes FS, et al. Summary of the practice guideline sore throat (second revision) from the Dutch College of General Practitioners [in Dutch]. Ned Tijdschr Geneeskd. 2008;152:431 435. De Meyere M, Matthys J. Guideline acute sore throat. Huisarts Nu. 1999;28:193201. Centor RM, Allison JJ, Cohen SJ. Pharyngitis management: Dening the controversy. J Gen Intern Med. 2007;22:127 130. McIsaac WJ, Goel V, To T, Low DE. The validity of a sore throat score in family practice. CMAJ. 2000;163:811 815. Dowell SF, Marcy SM, Phillips WR, et al. Principles of judicious use of antimicrobial agents for pediatric upper respiratory tract infections. Pediatrics. 1998;101(Suppl 1): 163165. Myers AL, Jackson MA, Selvarangan R, et al. Genetic commonality of macrolide-resistant group A beta hemolytic streptococcus pharyngeal strains. Ann Clin Microbiol Antimicrob. 2009;8:33. Shvartzman P, Tabenkin H, Rosentzwaig A, Dolginov F. Treatment of streptococcal pharyngitis with amoxycillin once a day. BMJ. 1993;306:1170 1172. Feder HM Jr, Gerber MA, Randolph MF, et al. Once-daily therapy for streptococcal pharyngitis with amoxicillin. Pediatrics. 1999;103:4751. Lennon DR, Farrell E, Martin DR, Stewart JM. Once-daily amoxicillin versus twice-daily penicillin V in group A

12.

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Address correspondence to: Maurizio de Martino, MD, Department of Sciences for Woman and Childs Health, University of Florence, Viale Pieraccini 24, I-50139, Florence, Italy. maurizio.demartino@uni.it

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