Pediatric Annals

Current Therapy of Group A Streptococcal Pharyngitis

Adnan S Dajani, MD

Abstract

The primary objective of treating acute group A streptococcal (GABHS) pharyngitis is the prevention of rheumatic fever.1 Appropriate antimicrobial therapy can also shorten the clinical course, reduce the risk of transmission of the organism, and decrease the likelihood of suppurative complications. In selecting a regimen for the treatment of GABHS pharyngitis, physicians should consider various factors, including bacteriologie and clinical efficacy, ease of adherence to recommended regimen frequency of daily administration, duration of therapy, paiatability), cost, spectrum of activity of the selected agent, and potential side effects.

Penicillin prevents rheumatic fever even when therapy is started as late as 9 days after the onset of the acute pharyngitis. For patients seen early in their illness, the brief delay for processing of the throat culture before therapy is started should not increase the risk of rheumatic fever. However, prevention of rheumatic fever does require the eradication of GABHS from the pharynx. No single regimen eradicates GABHS from the pharynx in 100% of treated patients.

A number of antimicrobials have been effective in eradicating GABHS from the pharynx and in clinical improvement or cure. These agents include penicillin, penicillin derivatives, cephalosporins, macrolides, and clindamycin.1,2

PENICILLIN AND PENICILLIN DERIVATIVES:

Penicillin remains the antimicrobial agent of choice for the treatment of GABHS (Table 1), except in individuals with history of penicillin allergy. Resistance to penicillin has never been documented. Penicillin has a narrow spectrum of activity and a longstanding proven efficacy and is least expensive. It may be administered intramuscularly or orally depending on the patient's likely adherence to an oral regimen and the risks of rheumatic fever in a particular population.

Table

CEPHALOSPORINS

Oral cephalosporins are effective clinically and microbiologically in the treatment of GABHS pharyngitis.13 These include cephalexin, cefadroxil, cefaclor, cefixime, cefprozil, cefuroxime axetil, loracarbef, and cefpodoxime proxetil.14"16 Narrower spectrum cephalosporins such as cefadroxil or cephalexin are probably preferable to those with a broader spectrum, such as cefaclor, cefuroxime axetil, cefixime, and cefpodoxime proxetil. A 10-day course of an oral cephalosporin is an acceptable alternative to penicillin, particularly for penicillinallergic individuals. Some penicillin-allergic persons (< 20%) are also allergic to cephalosporins, and these agents should not be used in patients with immediate (anaphy lactic -type) hypersensitivity to penicillin.17

Several clinical trials indicate that a 10-day course of an oral cephalosporin is superior to 10 days of oral penicillin in eradicating GABHS from the pharynx.13'16 Occasionally, higher clinical cure rates have also been reported. Although these observations have been cited as reason to favor cephalosporins in place of penicillin as the treatment of choice, many still prefer penicillin for the reasons mentioned earlier (Table 1). It should be emphasized again that most oral cephalosporins are considerably more expensive than penicillin.

Recent reports suggest that a 5-day course with selected oral cephalosporins is comparable to a 10-day course of oral penicillin in eradicating GABHS from the pharynx.18'20 This will be discussed in more detail later.

CLINDAMYCIN

Although clindamycin is not usually recommended as a first line therapy for GABHS, it is effective and should be considered in some situations. Clindamycin may be used in individuals who are allergic to penicillins as an alternate to erythromycin. Clindamycin is also recommended for symptomatic patients with repeated GABHS culture-positive episodes of pharyngitis, particularly if these episodes fail to respond to a penicillin regimen.2 Clindamycin is recommended at 20 to 30 mg/kg/day in two to four equally divided doses for 10 days.

SHORT COURSE ANTIMICROBIAL THERAPY

As previously mentioned, treatment of GABHS with oral penicillin, penicillin derivatives, erythromycin, and many cephalosporins requires 10 days for complete eradication of the organisms from the pharynx. An effective treatment course of…

The primary objective of treating acute group A streptococcal (GABHS) pharyngitis is the prevention of rheumatic fever.1 Appropriate antimicrobial therapy can also shorten the clinical course, reduce the risk of transmission of the organism, and decrease the likelihood of suppurative complications. In selecting a regimen for the treatment of GABHS pharyngitis, physicians should consider various factors, including bacteriologie and clinical efficacy, ease of adherence to recommended regimen frequency of daily administration, duration of therapy, paiatability), cost, spectrum of activity of the selected agent, and potential side effects.

Penicillin prevents rheumatic fever even when therapy is started as late as 9 days after the onset of the acute pharyngitis. For patients seen early in their illness, the brief delay for processing of the throat culture before therapy is started should not increase the risk of rheumatic fever. However, prevention of rheumatic fever does require the eradication of GABHS from the pharynx. No single regimen eradicates GABHS from the pharynx in 100% of treated patients.

A number of antimicrobials have been effective in eradicating GABHS from the pharynx and in clinical improvement or cure. These agents include penicillin, penicillin derivatives, cephalosporins, macrolides, and clindamycin.1,2

PENICILLIN AND PENICILLIN DERIVATIVES:

Penicillin remains the antimicrobial agent of choice for the treatment of GABHS (Table 1), except in individuals with history of penicillin allergy. Resistance to penicillin has never been documented. Penicillin has a narrow spectrum of activity and a longstanding proven efficacy and is least expensive. It may be administered intramuscularly or orally depending on the patient's likely adherence to an oral regimen and the risks of rheumatic fever in a particular population.

Table

TABLE 1Advantages of Penicillin Therapy for GABHS Pharyngitis

TABLE 1

Advantages of Penicillin Therapy for GABHS Pharyngitis

Table

TABLE 2Disadvantages of Penicillin Therapy for GABHS Pharyngitis

TABLE 2

Disadvantages of Penicillin Therapy for GABHS Pharyngitis

The oral antibiotic of choice is penicillin V (phenoxymethyl penicillin). In many recent comparative clinical trials, dosages of 40 mg/kg/24 hours given three times daily not to exceed 750 mg were utilized. Generally, 250 mg two or three times daily is recommended for most children.3·"1 Little information is available about comparable doses in adults; therefore, a dose of 500 mg three times daily is recommended for adolescents and adults.1 Au patients should continue to take peniciliin regularly far an entire 10-day period, even though they will likely be asymptomatic after the first few days. Penicillin V is preferred to penicillin G because it is more resistant to gastric acid. Although the broader spectrum penicillin, amoxicillin, is often used for treatment of GABHS pharyngitis,5 it offers no microbiologie advantage over penicillin and is not recommended.

Benzathine penicillin G is particularly preferred for patients who are unlikely to complete a 10-day course of oral therapy. It is also useful for patients with a personal or family history of rheumatic fever or rheumatic heart disease or those who have other environmental factors, such as crowded living conditions or low socioeconomic status, that place them at substantial risk for rheumatic fever. Benzathine penicillin should be given as a single injection in a large muscle mass. This formulation is painful; injections that contain procaine penicillin in addition to benzathine penicillin G are less painful. Less discomfort is also achieved if intramuscular benzathine penicillin G is wanned to room temperature before administration.

The recommended dose is 600,000 units intramuscularly for patients weighing 27 kg (60 Ib) or less, and 1,200,000 units for patients weighing more than 27 kg. The combination of 900,000 units of benzathine penicillin G and 300,000 units of procaine penicillin G is satisfactory for most children.6 The efficacy of this combination for heavier patients such as teenagers or adults requires further study.

In recent years, the utility of penicillin in the treatment of GABHS has been questioned and challenged (Table 2). Failure to eradicate GABHS from the pharynx occurs in approximately 15% of patients treated with oral penicillin,7 and higher rates have been reported. Again, penicillin must be administered two or three times daily and given for 10 days. Allergic reactions are more common in adults than children. These occur in only a small percentage of patients, are more frequent after injection, and often induce urticatia and angioneurotic edema. A serum sicknesS'like reaction, characterized by fever and joint pain, may be mistaken for acute rheumatic fever. Anaphylaxis is rare but serious. A careful history for allergic reactions to penicillin should be obtained.

Why penicillin therapy fails to eradicate GABHS from about 15% of treated individuals is not known but several theories have been proposed (Table 3). Although some presume failure rates have increased over the years, careful review of older and more recent reports suggest that failure rates have remained about the same.

MACROLIDES

Oral erythromycin is an acceptable alternative for patients allergic to penicillin.8 Treatment should also be prescribed for 10 days. Erythromycin estolate (20 to 40 mg/kg/day in two to four divided doses), or erythromycin ethyl succhiate (40 mg/kg/day in two to four divided doses) is effective in treating streptococcal pharyngitis. However, the efficacy of a twicedaily regimen for adults requires further study. The maximum dose of erythromycin is 1 g/day. Although strains of GABHS resistant to erythromycin are prevalent in some areas of the world and these strains have resulted in treatment failures,9 they are uncommon in most parts of the United States.35

The newer macrolides, clarithromycin and azithromycin, have similar susceptibility patterns to that of erythromycin but cause less frequent gastrointestinal side effects. Clarithromycin is well absorbed orally, independent of food ingestion and is given at 15 mg/kg/day twice daily for 10 days.10 Azithromycin should be administered at least I hour before or 2 hours after a meal. It can be administered once daily, and produces high tonsillar tissue concentrations.11·12 A 5-day course of azithromycin is approved by the Food and Drug Administration for the treatment of GABHS pharyngitis. The recommended dosage is 12 mg/kg once a day for 5 days (maximum 500 mg per day).

Table

TABLE 3Possible Reasons for Failure of Penicillin to Eradicate GABHS from the Pharynx

TABLE 3

Possible Reasons for Failure of Penicillin to Eradicate GABHS from the Pharynx

Table

TABLE 4Short Course Therapy for GABHS Pharyngitis

TABLE 4

Short Course Therapy for GABHS Pharyngitis

CEPHALOSPORINS

Oral cephalosporins are effective clinically and microbiologically in the treatment of GABHS pharyngitis.13 These include cephalexin, cefadroxil, cefaclor, cefixime, cefprozil, cefuroxime axetil, loracarbef, and cefpodoxime proxetil.14"16 Narrower spectrum cephalosporins such as cefadroxil or cephalexin are probably preferable to those with a broader spectrum, such as cefaclor, cefuroxime axetil, cefixime, and cefpodoxime proxetil. A 10-day course of an oral cephalosporin is an acceptable alternative to penicillin, particularly for penicillinallergic individuals. Some penicillin-allergic persons (< 20%) are also allergic to cephalosporins, and these agents should not be used in patients with immediate (anaphy lactic -type) hypersensitivity to penicillin.17

Several clinical trials indicate that a 10-day course of an oral cephalosporin is superior to 10 days of oral penicillin in eradicating GABHS from the pharynx.13'16 Occasionally, higher clinical cure rates have also been reported. Although these observations have been cited as reason to favor cephalosporins in place of penicillin as the treatment of choice, many still prefer penicillin for the reasons mentioned earlier (Table 1). It should be emphasized again that most oral cephalosporins are considerably more expensive than penicillin.

Recent reports suggest that a 5-day course with selected oral cephalosporins is comparable to a 10-day course of oral penicillin in eradicating GABHS from the pharynx.18'20 This will be discussed in more detail later.

CLINDAMYCIN

Although clindamycin is not usually recommended as a first line therapy for GABHS, it is effective and should be considered in some situations. Clindamycin may be used in individuals who are allergic to penicillins as an alternate to erythromycin. Clindamycin is also recommended for symptomatic patients with repeated GABHS culture-positive episodes of pharyngitis, particularly if these episodes fail to respond to a penicillin regimen.2 Clindamycin is recommended at 20 to 30 mg/kg/day in two to four equally divided doses for 10 days.

SHORT COURSE ANTIMICROBIAL THERAPY

As previously mentioned, treatment of GABHS with oral penicillin, penicillin derivatives, erythromycin, and many cephalosporins requires 10 days for complete eradication of the organisms from the pharynx. An effective treatment course of less than 10 days offers several obvious advantages. Table 4 lists currently available and variably acceptable therapeutic courses for less than 10 days. The shortest therapeutic course remains a single injection of benzathine penicillin. Although the other regimens offer the advantage of a shorter therapeutic course, this should be balanced against the higher cost of these medications and the fact that they are broader spectrum agents. At this stage, not all of these regimens are approved by the Food and Drug Administration for short -course therapy (Table 4).

AGENTS NOT RECOMMENDED

Certain antimicrobials are not recommended for treatment of streptococcal upper respiratory tract infections.1 Tetracyclines should not be used because of the high prevalence of resistant strains. Sulfonamides and trimethoprim-sulfamethoxazole will not eradicate GABHS in patients with pharyngitis and should not be used to treat active infections. In addition, studies have proved that treatment of acute streptococcal pharyngitis with sulfadiazine does not prevent rheumatic fever.21 Chloramphenicol is not recommended because of unpredictable efficacy and potential serious irreversible marrow suppression.

CONCLUSION

In selecting a regimen to treat GABHS pharyngitis, physicians should consider various factors, including bactériologie and clinical efficacy, ease of adherence to the regimen (frequency of daily administration, duration of therapy, palatability), cost, spectrum of activity of the selected agent, and potential side effects. Most authorities continue to recommend penicillin as the treatment of choice. However, many newer agents are now available, approved, and variably recommended as short course (4 to 5 days) therapy for GABHS pharyngitis. The ultimate choice should be an individualized decision made by the physician and the patient (or parent).

REFERENCES

1. Dajani A. Taubert K, Fernen P, el al. Treatment of streptococcal pharyngitis and prevention of rheumatic fever a statement for health professionals. Pediatrics. 1995;96:758-764.

2. Bisno AL, Geiber MA. Gwaltny JM, et al. Diagnosis and management of group A streptococcal pharyngitis: a practice guideline. 1997;25:574-583.

3. Gerber MA, Spadaccini LJ, Wright LL, et al. Twice-daily penicillin in the treatment of streptococcal pharyngitis. AmJ Dis datateti. 1985;139:1145-1148.

4. Bass JW. Antibiotic management of group A streptococcal pharyngotonsillitis. Pediair Infect Dis J. 1991;10:S43-S49.

5. Hofer C, Bintis HJ, Tanz RR. Strategies for managing group A streptococcal pharyngitis. A survey of board-certified pediatricians. Arcfi Peditur AdoJesc Med. 1997;151:824-829.

6. Bass JW, Crast FW, Knowles CR, Onufer CN. Streptococcal pharyngitis in children. A comparison of four treatment schedules with intramuscular penicillin G beruathine. JAMA. I976;235:1112-11I6.

7. Maikowitz M, Gerber MA, Kaplan EL. Treatment of streptococcal phaiyngotunsillitis: reports of penicillin s demise are premature. ) Pedían. 1993; 1 23:679-685.

8. Derrick CW, Dillon HC. Erythromycin therapy for streptococcal pharyngitis. AmJ Dis Child. 1976;130:175-178.

9. Seppala H, Nissinen A, Jarvinen H, et a!. Resistance to erythromycin in group A streptococci. New Engl. J Mid. 1992;326:292-297.

10. Schrock CG. Clarithromycin vs. penicillin in the treatment of streptococcal pharyngitis. J Fam Pract. 1992;35:6Z2-626.

11. Hooton TM. A comparison of azithromycin and penicillin V for the treatment of stteptococcal pharyngitis. AmJ Mai. 1991;91:23S-30S.

12. Still JG. Management of pediatrie patients with group A beta-hemolytic Streptococcus pharyngitis: treatment options. Pediorr Jn/écl Da }. I995;14;S57-S61.

13. Pichichero ME, Margolis PA. A comparison of cephalosporins and penicillin in the treatment of group A streptococcal pharyngitis: a meta-analysis supporting the concept of microbial copathogenicity. Pediatr Infect Dis J. 1991;10:275-281.

14. Block SL, Hedtick JA. Tyler RD. Comparative study of the effectiveness of cefixime and penicillin V for che treatment of stteptococcal pharyngitis in children and adolescents. Pediatr Infect Dis J. 1992;11:919-925.

15. Gooch WM. McLinn SE, Aronovitz GH, et al. Efficacy of cefuroxime axeril suspension compared with that of penicillin V suspension in childten with group A streptococcal pharyngitis. Antimicrob Agents Chemother. 1993;37:159-163.

16. Dajani AS, Kessler SL, Mendelson R, et al. Cefpodoxime proxetil vs penicillin V in pediatrie streptococcal pharyngitis/tonsillitis. Pedían Infect Dis J. 1993;12:275-279.

17. Petz LD. Immunologie cross-reactivity between penicillins and cephalospotins: a review. J Infect Dis. 1978;137(suppl):S74-S79

18. Dajani AS. Pharyngitis/tonsillitis: European and United States experience with cefpodoxime proxetil. Pediatr Infect Dis J. 1995;14:S7-11.

19. Pichichero ME, Gooch WM, Rodríguez W, et al. Effective short-course treatment of acute group A beta-hemolytic streptococcal tonsillopharyngitis. Ten days of penicillin V vs 5 days or 10 days of cefpodoxime therapy in children. Arch Pediatr Adolesc Med. 1994; 148: 1053-1060.

20. Aujard Y, Boucot I, Brahimi N, et al. Comparative efficacy and safety of four-day cefuroxime axetil and ten-day penicillin treatment of gtoup A beta-hemolytic streptococcai pharyngitis m children. Patiatr Infect Dis J. 1995;14:295-300.

21. Catanzaro FJ, Rammelkamp CH, Chamovitz R. Prevention of rheumatic fever by treatment of streptococca! infections. N Engl J Med. 1958:259:51-57.

TABLE 1

Advantages of Penicillin Therapy for GABHS Pharyngitis

TABLE 2

Disadvantages of Penicillin Therapy for GABHS Pharyngitis

TABLE 3

Possible Reasons for Failure of Penicillin to Eradicate GABHS from the Pharynx

TABLE 4

Short Course Therapy for GABHS Pharyngitis

10.3928/0090-4481-19980501-06

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