Group A Streptococcal Tonsillopharyngitis: Cost-Effective Diagnosis and Treatment,☆☆,

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Abstract

See related editorial, "Acute Pharyngitis: The Case for Empiric Antimicrobial Therapy"

Most patients who seek medical attention for sore throat are concerned about streptococcal tonsillopharyngitis, but fewer than 10% of adults and 30% of children actually have a streptococcal infection. Group A β-hemolytic streptococci (GAS) are most often responsible for bacterial tonsillopharyngitis, although Neisseria gonorrhea, Arcanobacterium haemolyticum (formerly Corynebacterium haemolyticum), Chlamydia pneumoniae (TWAR agent), and Mycoplasma pneumoniae have also been suggested as possible, infrequent, sporadic pathogens. Viruses or idiopathic causes account for the remainder of sore throat complaints. Reliance on clinical impression to diagnose GAS tonsillopharyngitis is problematic; an overestimation of 80% to 95% by experienced clinicians typically occurs for adult patients. Overtreatment promotes bacterial resistance, disturbs natural microbial ecology, and may produce unnecessary side effects. Existing data suggest that rapid GAS antigen testing as an aid to clinical diagnosis can be very useful. When used appropriately, it is sensitive (79% to 88%) in detecting GAS-infected patients and is specific (90% to 96%) and cost-effective. Penicillin has been the treatment of choice for GAS tonsillopharyngitis since the 1950s; 10 days of treatment are necessary for bacterial eradication. A single IM injection of benzathine penicillin is effective and obviates compliance issues. Until the early 1970s, the bacteriologic failure rate for the treatment of GAS tonsillopharyngitis ranged from 2% to 10% and was attributed to chronic GAS carriers. Since the late 1970s, the penicillin failure rate has frequently exceeded 20% in published reports. Explanations for recurrent GAS tonsillopharyngitis include poor patient compliance; reacquisition from a family member or peer, copathogenic colonization by Staphylococcus aureus, Haemophilus influenzae, Moraxella catarrhalis, anaerobes that inactivate penicillin with β-lactamase, or all these organisms; suppression of natural immune response by too-early administration of antibiotics; GAS tolerance to penicillin; antibiotic eradication of normal pharyngeal flora that normally act as natural host defenses; and establishment of a true carrier state. When therapy fails, milder symptoms may occur during the relapse. Several antimicrobials have demonstrated superior efficacy compared with penicillin in eradicating GAS and are administered less frequently to enhance patient compliance. In previously untreated GAS throat infections, cephalosporins produce a 5% to 22% higher bacteriologic cure rate; after a penicillin treatment failure, these differences are greater. Amoxicillin/clavulanate and the extended-spectrum macrolides clarithromycin and azithromycin may also produce enhanced bacteriologic eradication in comparison to penicillin. Future research is needed in the development of more sensitive rapid-detection assays for GAS and other possible pathogens in tonsillopharyngitis and of shorter-course regimens of therapy and in determining the necessity and benefit of treatment of non-GAS tonsillopharyngeal isolates.

[Pichichero ME: Group A streptococcal tonsillopharyngitis: Cost-effective diagnosis and treatment. Ann Emerg Med March 1995;25:390-403.]

Section snippets

INTRODUCTION

A chief complaint of sore throat is frequently encountered by emergency physicians. It is the third most commonly seen infectious disease (preceded by viral upper respiratory infections and otitis media) and therefore the second most common reason (following otitis media) for which an antibiotic might be appropriately prescribed. The controversial issues in tonsillopharyngitis diagnosis and management are the focus of this review. Controversies to be addressed include (1) the relative

CAUSES OF TONSILLOPHARYNGITIS

The various causes of tonsillopharyngitis have epidemiologic differences in their clinical presentation. GAS tonsillopharyngitis tends to occur in temperate climates during the late fall through early spring. During that time of year, approximately 30% of children and 10% of adults presenting with sore throat will have GAS as the cause (Table 1).11, 12, 16, 19, 20, 21, 22, 23 Thus, strictly on a percentage basis, physicians who elect to treat all patients with sore throat as if they had GAS

CLINICAL DIAGNOSIS

GAS tonsillopharyngitis cannot be diagnosed solely on clinical grounds with accuracy in most patients.31, 32, 41, 42, 43, 44, 45, 46, 47 Even in the patient with fever, tonsillopharyngeal erythema and exudate, swollen and tender anterior cervical adenopathy, and an elevated WBC count, during midwinter to early spring and without rhinorrhea and cough (the classic clinical symptom constellation for GAS tonsillopharyngitis), the clinical likelihood that GAS is present does not exceed 70% in

THROAT CULTURE, RAPID DIAGNOSTIC TEST, OR EMPIRIC THERAPY?

GAS antigen detection tests can be performed quickly at a cost that is comparable to a 10-day supply of even the least expensive antimicrobial.10, 46, 47, 48, 49 To be most effectively used, the test should be performed in immediate proximity to where patients are seen. Such availability allows the integration of rapid GAS antigen detection testing into clinical decision making despite the busy flow of patients in emergency department or urgent care settings.50, 51, 52, 53, 54, 55 Performance

COST-EFFECTIVENESS ANALYSIS

Are throat cultures and rapid antigen detection tests for GAS cost-effective? This question is frequently asked and has been addressed in several separate studies.62, 63, 64, 65 From these reports, it appears that throat culture or rapid GAS antigen detection testing is cost-effective, particularly for selected clinical situations, when properly used. In 1977, Tompkins et al62 performed a cost-effectiveness analysis of tonsillopharyngitis management for the primary prevention of acute rheumatic

PENICILLIN TREATMENT

In 1951, Denny et al66 and Wannamaker et al67 published their studies on the efficacy of injectable penicillin therapy for the primary prevention of acute rheumatic fever. These studies were conducted at the Warren Air Force Base, a military setting where recruits living in close-quartered barracks volunteered to receive injections of penicillin G suspended in either sesame oil or peanut oil. These preparations were shown to maintain adequate therapeutic serum concentrations of penicillin for

ERYTHROMYCIN TREATMENT

An analysis of the bacterial pathogens putatively involved in tonsillopharyngitis might lead one to consider use of erythromycin or one of its derivatives for empiric treatment of sore throat. Rapid GAS antigen detection testing and throat cultures are targeted for identification or isolation of GAS exclusively. However, in some patients, group C, G, and F streptococci, A hemolyticum, M pneumoniae, and Chlamydia pneumoniae produce symptomatic tonsillopharyngitis. Erythromycin has a low serious

CEPHALOSPORIN TREATMENT

In 1986, Stillerman78 brought forward the suggestion that cephalosporins might outperform penicillin in the treatment of GAS tonsillopharyngitis. In 1991, a metaanalysis of trials in which cephalosporins were compared with penicillin for the treatment of acute GAS tonsillopharyngitis corroborated Stillerman's hypothesis.13 In this analysis of 19 studies covering the 20-year time span of 1970 to 1990, the overall bacteriologic failure rate for 1,169 penicillin-treated patients was 16% compared

OTHER ALTERNATIVE TREATMENTS

Amoxicillin/clavulanate has been evaluated for the treatment of GAS tonsillopharyngitis; it has been shown to be as efficacious85 or more efficacious86, 87 than penicillin V. Kaplan and Johnson86 evaluated amoxicillin/clavulanate for its potential role in treatment of penicillin failures. One hundred thirty-one patients were treated with oral penicillin V, and 50 failed therapy (38%). These 50 patients were asked to continue, and 45 agreed to do so. Twenty-four received a second course of oral

SHORTENED-COURSE ANTIMICROBIAL THERAPY

Although it has been amply shown that approximately 10-day therapy with oral penicillin V is necessary for optimal bacteriologic eradication of GAS70, 71, 72, new studies suggest that a shortened course of therapy with cephalosporins may be efficacious. Investigations from the United Kingdom92, France93, 94, Germany95, and the United States96 have compared 4 to 7 days of a cephalosporin with 10 days of penicillin for the treatment of GAS tonsillopharyngitis. The European investigations showed

EXPLANATIONS FOR ANTIMICROBIAL TREATMENT FAILURE

Lack of Compliance Patient compliance diminishes with more frequent dosing requirements per day.96, 97, 98 Thus, administration of an antimicrobial once or twice a day is preferred to three or four times a day. Twice-daily dosing with penicillin is adequate for GAS bacteriologic eradication99, 100; however, if patients fail to take one of their two doses of penicillin, this will be inadequate therapy.99, 101 Twice-daily administration of erythromycin for treatment of GAS tonsillopharyngitis is

ANTIBIOTIC SUPPRESSION OF IMMUNITY

With the advent of rapid GAS antigen detection testing and several convincing studies of more rapid clinical improvement of GAS tonsillopharyngitis from prompt antimicrobial treatment110, 111, 112, 113, many physicians prescribe antibiotics at the initial patient contact visit rather than waiting for throat culture confirmation of their clinical suspicion. Studies from decades ago had shown that prompt antimicrobial treatment of GAS tonsillopharyngitis suppresses the immune response to the

PENICILLIN TOLERANCE

All GAS remain exquisitely sensitive to penicillin in vitro; however, some strains have developed evidence of resistance to the bactericidal effects of this antimicrobial.124 Several clinical studies have associated penicillin tolerance with penicillin failure in the treatment of GAS tonsillopharyngitis.125, 126 This is probably a rare occurrence and may be related to uncommon clinical strains, but the possibility that such a phenomenon may occur within a given patient population must be kept

DISTURBANCE OF MICROBIAL ECOLOGY

α-Hemolytic streptococci (eg, Streptococcus sanguis and Streptococcus mitis) normally inhabit the tonsillopharynx, where they are not pathogenic. The presence of these microbes may represent an important element in host defense in preventing the establishment of GAS colonization and infection.127, 128, 129, 130, 131, 132, 133, 134 α-Hemolytic streptococci are believed to exert their protective effect against GAS infection through microbial interference, ie, through the elaboration of

GAS-CARRIER STATE

It has been well established that GAS can be carried as a nonpathogenic microbe for weeks to months in selected patients. The carrier condition predominates in the pediatric age group, in whom acute GAS tonsillopharyngitis is common (ie, 4- to 12-year-olds). Thus, in this patient population, the physician is continuously confronted with the possibility that a patient with acute sore throat may have a viral etiology while concomitantly carrying nonpathogenic GAS. It is easier to recognize the

CONCLUSION

Although the most common concern in the minds of patients and physicians regards the presence of GAS as a cause of tonsillopharyngitis, this microbe occurs in fewer than 10% of adult cases and fewer than 30% of pediatric cases. Other bacteria that cause pharyngitis do so infrequently, and are usually associated with other symptoms not typical for GAS infection, and symptomatic improvement with antimicrobial therapy for tonsillopharyngitis caused by these other organisms has not been proven. GAS

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    From the Departments of Pediatrics and Medicine, University of Rochester Medical Center, New York.

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