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Diagnosis and Treatment
        of Streptococcal Pharyngitis
        BETH	A.	CHOBY,	MD,	University of Tennessee College of Medicine–Chattanooga, Chattanooga, Tennessee

        Common signs and symptoms of streptococcal pharyngitis include sore throat, temperature greater than 100.4°F
        (38°C), tonsillar exudates, and cervical adenopathy. Cough, coryza, and diarrhea are more common with viral phar-
        yngitis. Available diagnostic tests include throat culture and rapid antigen detection testing. Throat culture is consid-
        ered the diagnostic standard, although the sensitivity and specificity of rapid antigen detection testing have improved
        significantly. The modified Centor score can be used to help physicians decide which patients need no testing, throat
        culture/rapid antigen detection testing, or empiric antibiotic therapy. Penicillin (10 days of oral therapy or one injec-
        tion of intramuscular benzathine penicillin) is the treatment of choice because of cost, narrow spectrum of activity,
        and effectiveness. Amoxicillin is equally effective and more palatable. Erythromycin and first-generation cephalospo-
        rins are options in patients with penicillin allergy. Increased group A
        beta-hemolytic streptococcus (GABHS) treatment failure with peni-
        cillin has been reported. Although current guidelines recommend
        first-generation cephalosporins for persons with penicillin allergy,
        some advocate the use of cephalosporins in all nonallergic patients
        because of better GABHS eradication and effectiveness against
        chronic GABHS carriage. Chronic GABHS colonization is common
        despite appropriate use of antibiotic therapy. Chronic carriers are




                                                                                                                                                                     ILLUSTRATION BY MICHAEL KRESS-RUSSICK
        at low risk of transmitting disease or developing invasive GABHS
        infections, and there is generally no need to treat carriers. Whether
        tonsillectomy or adenoidectomy decreases the incidence of GABHS
        pharyngitis is poorly understood. At this time, the benefits are too
        small to outweigh the associated costs and surgical risks. (Am Fam
        Physician. 2009;79(5):383-390. Copyright © 2009 American Acad-
        emy of Family Physicians.)




                                        P
                                        	
           Patient information:                     haryngitis	 is	 diagnosed	 in	 11	 mil-                is	transmitted	via	respiratory	secretions,	and	
        ▲




        A handout on strep throat,                  lion	 patients	 in	 U.S.	 emergency	                   the	incubation	period	is	24	to	72	hours.
        written by the author of
                                                    departments	 and	 ambulatory	 set-
        this article, is available
        at http://www.aafp.                         tings	 annually.1	 Most	 episodes	 are	                Diagnosis of Streptococcal Pharyngitis
        org/afp/20090301/383-s1.         viral.	Group	A	beta-hemolytic	streptococcus	                      CLINICAL DIAGNOSIS
                                         (GABHS),	the	most	common	bacterial	etiol-                         Because	the	signs	and	symptoms	of	GABHS	
                                         ogy,	accounts	for	15	to	30	percent	of	cases	of	                   pharyngitis	 overlap	 extensively	 with	 other	
                                         acute	pharyngitis	in	children	and	5	to	20	per-                    infectious	causes,	making	a	diagnosis	based	
                                         cent	in	adults.2	Among	school-aged	children,	                     solely	 on	 clinical	 findings	 is	 difficult.	 In	
                                         the	 incidences	 of	 acute	 sore	 throat,	 swab-	                 patients	with	acute	febrile	respiratory	illness,	
                                         positive	GABHS,	and	serologically	confirmed	                      physicians	 accurately	 differentiate	 bacterial	
                                         GABHS	 infection	 are	 33,	 13,	 and	 eight	 per	                 from	viral	infections	using	only	the	history	
                                         100	 child-years,	 respectively.3	 Thus,	 about	                  and	 physical	 findings	 about	 one	 half	 of	 the	
                                         one	 in	 four	 children	 with	 acute	 sore	 throat	               time.4	No	single	element	of	the	patient’s	his-
                                         has	 serologically	 confirmed	 GABHS	 phar-                       tory	 or	 physical	 examination	 reliably	 con-
                                         yngitis.	Forty-three	percent	of	families	with	                    firms	or	excludes	GABHS	pharyngitis.5	Sore	
                                         an	index	case	of	GABHS	pharyngitis	have	a	                        throat,	fever	with	sudden	onset	(temperature	
                                         secondary	case.3	Late	winter	and	early	spring	                    greater	than	100.4°	F	[38°	C]),	and	exposure	
                                         are	 peak	 GABHS	 seasons.	 The	 infection	       	               to	 Streptococcus	 within	 the	 preceding	 two	

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Streptococcal Pharyngitis




    SORT: KEY RECOMMENDATIONS FOR PRACTICE

                                                                                                                          Evidence
   Clinical recommendation                                                                                                rating        References

   Use of clinical decision rules for diagnosing GABHS pharyngitis improves quality of care while reducing                A             5-8, 18, 37, 38
    unwarranted treatment and overall cost.
   Penicillin is the treatment of choice for GABHS pharyngitis in persons who are not allergic to penicillin.             A             2, 18-20
   Treatment is not typically indicated in chronic carriers of pharyngeal GABHS.                                          C             39

   GABHS = group A beta-hemolytic streptococcus.
   A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented
   evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to http://www.aafp.org/afpsort.xml.




weeks	suggest	GABHS	infection.	Cervical	node	lymph-                               at	very	low	risk	for	streptococcal	pharyngitis	and	do	not	
adenopathy	 and	 pharyngeal	 or	 tonsillar	 inflammation	                         require	testing	(i.e.,	throat	culture	or	rapid	antigen	detec-
or	 exudates	 are	 common	 signs.	 Palatal	 petechiae	 and	                       tion	testing	[RADT])	or	antibiotic	therapy.	Patients	with	a	
scarlatiniform	rash	are	highly	specific	but	uncommon;	a	                          score	of	2	or	3	should	be	tested	using	RADT	or	throat	cul-
swollen	uvula	is	sometimes	noted.	Cough,	coryza,	con-                             ture;	positive	results	warrant	antibiotic	therapy.	Patients	
junctivitis,	 and	 diarrhea	 are	 more	 common	 with	 viral	                      with	a	score	of	4	or	higher	are	at	high	risk	of	streptococcal	
pharyngitis.	The	diagnostic	accuracy	of	these	signs	and	                          pharyngitis,	and	empiric	treatment	may	be	considered.
symptoms	is	listed	in	Table 1.5
                                                                                  LABORATORY DIAGNOSIS
CLINICAL DECISION RULES                                                           With	correct	sampling	and	plating	techniques,	a	single-
The	original	Centor	score	uses	four	signs	and	symptoms	                           swab	throat	culture	is	90	to	95	percent	sensitive.10	RADT	
to	 estimate	 the	 probability	 of	 acute	 streptococcal	 phar-                   allows	for	earlier	treatment,	symptom	improvement,	and	
yngitis	in	adults	with	a	sore	throat.6	The	score	was	later	                       reduced	 disease	 spread.	 RADT	 specificity	 ranges	 from	
modified	by	adding	age	and	validated	in	600	adults	and	                           90	 to	 99	 percent.	 Sensitivity	 depends	 on	 the	 commer-
children.7,8	 The	 cumulative	 score	 determines	 the	 likeli-                    cial	 RADT	 kit	 used	 and	 was	 approximately	 70	 percent	
hood	of	streptococcal	pharyngitis	and	the	need	for	anti-                          with	older	latex	agglutination	assays.11,12	Newer	enzyme-
biotics	(Figure 19).	Patients	with	a	score	of	zero	or	1	are	                      linked	 immunosorbent	 assays,	 optical	 immunoassays,	


  Table 1. History and Physical Examination Findings Suggesting GABHS Pharyngitis

  Factor                                                Sensitivity (%)      Specificity (%)     Positive likelihood ratio     Negative likelihood ratio

  Absence of cough                                      51 to 79             36 to 68            1.1 to 1.7                    0.53 to 0.89
  Anterior cervical nodes swollen or enlarged           55 to 82             34 to 73            0.47 to 2.9                   0.58 to 0.92
  Headache                                              48                   50 to 80            0.81 to 2.6                   0.55 to 1.1
  Myalgia                                                49                  60                  1.2                           0.84
  Palatine petechiae                                      7                  95                  1.4                           0.98
  Pharyngeal exudates                                    26                  88                  2                             0.85
  Streptococcal exposure in past two weeks               19                  91                  2                             0.9
  Temperature ≥ 100.9° F (38.3° C)                      22 to 58             53 to 92            0.68 to 3.9                   0.54 to 1.3
  Tonsillar exudates                                     36                  85                  2.3                           0.76
  Tonsillar or pharyngeal exudates                       45                  75                  1.8                           0.74

  GABHS = group A beta-hemolytic streptococcus.
  Adapted with permission from Ebell MH, Smith MA, Barry HC, Ives K, Carey M. The rational clinical examination. Does this patient have strep throat?
  JAMA. 2000;284(22):2915.




384  American Family Physician                                     www.aafp.org/afp	                             Volume 79, Number 5         ◆   March 1, 2009
Streptococcal Pharyngitis




                                                                                                recommends	 that	 negative	 RADT	 results	
  Clinical Decision Rule for Management                                                         in	children	be	confirmed	using	throat	cul-
  of Sore Throat                                                                                ture	 unless	 physicians	 can	 guarantee	 that	
                                                                                                RADT	sensitivity	is	similar	to	that	of	throat	
                                 Patient with sore throat
                                 Apply streptococcal score                                      culture	 in	 their	 practice.13	 False-negative	
                                                                                                RADT	 results	 may	 lead	 to	 misdiagnosis	
                                                                                                and	 GABHS	 spread	 and,	 very	 rarely,	 to	
                         Criteria                               Points                          increased	 suppurative	 and	 nonsuppurative	
                         Absence of cough                        1                              complications.	 Other	 studies	 suggest	 that	
                         Swollen and tender anterior             1                              the	sensitivity	of	newer	optical	immunoas-
                         cervical nodes
                                                                                                says	 approaches	 that	 of	 single-plate	 throat	
                         Temperature > 100.4° F (38° C)          1
                                                                                                culture,	obviating	the	need	for	back-up	cul-
                         Tonsillar exudates or swelling          1
                                                                                                ture.14,15	 In	 many	 clinical	 practices,	 confir-
                         Age
                           3 to 14 years                         1
                                                                                                matory	 throat	 culture	 is	 not	 performed	 in	
                           15 to 44 years                        0
                                                                                                children	 at	 low	 risk	 for	 GABHS	 infection.	
                           45 years and older                   –1                              The	precipitous	drop	in	rheumatic	fever	in	
                         Cumulative score:                                                      the	United	States,	significant	costs	of	addi-
                                                                                                tional	testing	and	follow-up,	and	concerns	
                                                                                                about	inappropriate	antibiotic	use	are	valid	
                                                                                                reasons	 why	 back-up	 cultures	 are	 not	 rou-
   Score ≤ 0            Score = 1           Score = 2         Score = 3          Score ≥ 4      tinely	performed.16
                                                                                                   Streptococcal	antibody	titers	are	not	use-
                                                                                                ful	 for	 diagnosing	 streptococcal	 pharyn-
   Risk of              Risk of            Risk of            Risk of            Risk of
   GABHS                GABHS              GABHS              GABHS              GABHS
                                                                                                gitis	 and	 are	 not	 routinely	 recommended.	
   pharyngitis          pharyngitis        pharyngitis        pharyngitis        pharyngitis    They	may	be	indicated	to	confirm	previous	
   1 to 2.5%            5 to 10%           11 to 17%          28 to 35%          51 to 53%      infection	 in	 persons	 with	 suspected	 acute	
                                    Option                                                      poststreptococcal	 glomerulonephritis	 or	
                                                                             Consider empiric   rheumatic	fever.	They	may	also	help	distin-
                                                                             treatment with     guish	 acute	 infection	 from	 chronic	 carrier	
          No further           Perform throat culture or RADT                antibiotics
          testing or                                                                            status,	 although	 they	 are	 not	 routinely	 rec-
          antibiotics                                                                           ommended	for	this	purpose.
          indicated

                            Negative                           Positive
                                                                                                Treatment of GABHS Pharyngitis 
                                                                                                JUSTIFICATION FOR TREATMENT
                                                                                          GABHS	 pharyngitis	 is	 self-limited	 and	
                     No antibiotics indicated           Treat with antibiotics
                                                                                          resolves	 within	 a	 few	 days,	 even	 without	
                                                                                          treatment.17	 Arguments	 for	 antibiotic	 treat-
Figure 1. Modified Centor score and management options using clini- ment	include	acute	symptom	relief,	preven-
cal decision rule. Other factors should be considered (e.g., a score of 1, tion	 of	 suppurative	 and	 nonsuppurative	
but recent family contact with documented streptococcal infection).
                                                                                          complications,	and	reduced	communicabil-
(GABHS = group A beta-hemolytic streptococcus; RADT = rapid anti-
gen detection testing.)                                                                   ity	(Table 2).2,18-21	Antibiotics	shorten	symp-
Adapted with permission from McIsaac WJ, White D, Tannenbaum D, Low DE. A clinical score
                                                                                          tom	duration	by	about	16	hours;	the	number	
to reduce unnecessary antibiotic use in patients with sore throat. CMAJ. 1998;158(1):79.  needed	to	treat	(NNT)	for	symptom	relief	at	
                                                                                          72	hours	is	four	in	those	with	positive	throat	
and	chemiluminescent	DNA	probes	are	90	to	99	percent	 swabs.22	 In	 addition,	 rates	 of	 suppurative	 peritonsillar	
sensitive.11,12	However,	newer	tests	may	be	more	expen- and	 retropharyngeal	 abscesses	 are	 reduced	 (approxi-
sive,	and	not	all	tests	are	waived	by	the	Clinical	Labora- mately	one	in	1,000	cases).23	
tory	Improvement	Act	of	1988.                                                    Antibiotics	also	reduce	the	incidence	of	acute	rheu-
   Whether	negative	RADT	results	in	children	and	ado- matic	fever	(relative	risk	reduction	=	0.28).24	Although	
lescents	 require	 confirmatory	 throat	 culture	 is	 contro- rheumatic	 heart	 disease	 is	 a	 major	 public	 health	
versial.	 The	 American	 Academy	 of	 Pediatrics	 (AAP)	 issue	 in	 low-	 and	 middle-income	 countries	 (annual	                          	

March 1, 2009    ◆   Volume 79, Number 5	                                 www.aafp.org/afp	                      American Family Physician  385
Table 2. Complications of GABHS Pharyngitis 

  Suppurative                         Nonsuppurative
  Bacteremia                          Poststreptococcal
                                        glomerulonephritis
  Cervical lymphadenitis                                              injection	(Bicillin	C-R)	lessens	injection-associated	dis-
  Endocarditis                        Rheumatic fever
                                                                      comfort.	Over	the	past	50	years,	no	increase	in	minimal	
  Mastoiditis                                                         inhibitory	 concentration	 or	 resistance	 to	 GABHS	 has	
  Meningitis                                                          been	documented	for	penicillins	or	cephalosporins.28
  Otitis media                                                           Oral	 amoxicillin	 suspension	 is	 often	 substituted	 for	
  Peritonsillar/retropharyngeal                                       penicillin	 because	 it	 tastes	 better.	 The	 medication	 is	
    abscess
                                                                      also	 available	 as	 chewable	 tablets.	 Five	 of	 eight	 trials	
  Pneumonia
                                                                      (1966	to	2000)	showed	greater	than	85	percent	GABHS	
  GABHS = group A beta-hemolytic streptococcus.                       eradication	 with	 the	 use	 of	 amoxicillin.29	 Ten	 days	 of	
  Information from references 2, and 18 through 21.                   therapy	 is	 standard;	 common	 dosages	 are	 provided	 in	       	
                                                                      Table 3.2,17-20,28-34	Amoxicillin	taken	once	per	day	is	likely	
                                                                      as	effective	as	a	regimen	of	three	times	per	day.	One	ran-
incidence	of	five	per	100,000	persons),	it	has	largely	been	          domized	 controlled	 trial	 (RCT)	 demonstrated	 compa-
controlled	in	industrialized	nations	since	the	1950s.25	It	           rable	 symptom	 relief	 with	 once-daily	 dosing,	 although	
is	estimated	that	3,000	to	4,000	patients	must	be	given	              like	almost	all	studies	of	pharyngitis	treatment,	the	trial	
antibiotics	to	prevent	one	case	of	acute	rheumatic	fever	             was	 not	 powered	 to	 detect	 nonsuppurative	 complica-
in	 developed	 nations.18	 Rates	 of	 acute	 rheumatic	 fever	        tions.30	 A	 recent	 study	 of	 children	 three	 to	 18	 years	 of	
and	 retropharyngeal	 abscess	 have	 not	 increased	 fol-             age	showed	that	once-daily	dosing	of	amoxicillin	was	not	
lowing	 more	 judicious	 antibiotic	 use	 in	 children	 with	         inferior	to	twice-daily	dosing;	both	regimens	had	failure	
respiratory	 infections.26	 Children	 with	 GABHS	 phar-              rates	of	about	20	percent.31	It	should	be	noted	that	once-
yngitis	may	return	to	school	after	24	hours	of	antibiotic	            daily	therapy	is	not	approved	by	the	U.S.	Food	and	Drug	
therapy.27                                                            Administration	(FDA).
   Non–group	A	beta-hemolytic	streptococci	(groups	C	                    Current	 U.S.	 treatment	 guidelines	 recommend	
and	 G)	 also	 can	 cause	 acute	 pharyngitis;	 these	 strains	       erythromycin	for	patients	with	penicillin	allergy.	Gas-
are	usually	treated	with	antibiotics,	although	good	clini-            trointestinal	 side	 effects	 of	 erythromycin	 cause	 many	
cal	trials	are	lacking.	Fusobacterium necrophorum	causes	             physicians	 to	 instead	 prescribe	 the	 FDA-approved	            	
endemic	 acute	 pharyngitis,	 peritonsillar	 abscess,	 and	           second-generation	 macrolides	 azithromycin	 (Zith-
persistent	 sore	 throat.	 Untreated	 Fusobacterium	 infec-           romax)	 and	 clarithromycin	 (Biaxin).	 Azithromycin	
tions	may	lead	to	Lemierre	syndrome,	an	internal	jugular	             reaches	 higher	 concentrations	 in	 pharyngeal	 tissue	
vein	thrombus	caused	by	inflammation.	Complications	                  and	 requires	 only	 five	 days	 of	 treatment.	 Macrolide	
occur	 when	 septic	 plaques	 break	 loose	 and	 embolize.	           resistance	 is	 increasing	 among	 GABHS	 isolates	 in	 the	
Empiric	antibiotic	therapy	may	reduce	the	incidence	of	               United	States,	likely	because	of	azithromycin	overuse.32	
complications.                                                        Reported	 GABHS	 resistance	 in	 certain	 areas	 of	 the	
                                                                      United	States	and	Canada	approaches	8	to	9	percent.33	
ANTIBIOTIC SELECTION                                                  Most	 guidelines	 recommend	 reserving	 erythromycin	
Effectiveness,	spectrum	of	activity,	safety,	dosing	sched-            for	patients	who	are	allergic	to	penicillin.
ule,	 cost,	 and	 compliance	 issues	 all	 require	 consider-            First-generation	 oral	 cephalosporins	 are	 recom-
ation.	 Penicillin,	 penicillin	 congeners	 (ampicillin	 or	          mended	 for	 patients	 with	 penicillin	 allergy	 who	 do	
amoxicillin),	clindamycin	(Cleocin),	and	certain	cepha-               not	 have	 immediate-type	 hypersensitivity	 to	 beta-
losporins	 and	 macrolides	 are	 effective	 against	 GABHS.	          lactam	 antibiotics.	 Bacteriologic	 failure	 rates	 for	         	
Based	on	cost,	narrow	spectrum	of	activity,	safety,	and	              penicillin-treated	 GABHS	 pharyngitis	 increased	 from	
effectiveness,	penicillin	is	recommended	by	the	Ameri-                about	10	percent	in	the	1970s	to	more	than	30	percent	
can	Academy	of	Family	Physicians	(AAFP),18	the	AAP,19	                in	the	past	decade.29	Several	studies	suggest	that	cepha-
the	 American	 Heart	 Association,20	 the	 Infectious	 Dis-           losporins	are	more	effective	against	GABHS	than	peni-
eases	Society	of	America	(IDSA),2	and	the	World	Health	               cillin.	 Higher	 rates	 of	 GABHS	 eradication	 and	 shorter	
Organization	 for	 the	 treatment	 of	 streptococcal	 phar-           courses	of	therapy	that	are	possible	with	cephalosporins	
yngitis.25	 Options	 for	 penicillin	 dosing	 are	 listed	 in	   	    may	be	beneficial.	One	meta-analysis	of	35	trials	com-
Table 3.2,17-20,28-34	When	patients	are	unlikely	to	complete	         paring	various	cephalosporins	against	penicillin	noted	
the	 entire	 course	 of	 antibiotics,	 a	 single	 intramuscu-         significantly	more	bacteriologic	and	clinical	cures	in	the	
lar	 dose	 of	 penicillin	 G	 benzathine	 (Bicillin	 L-A)	 is	 an	    cephalosporin	group	(NNT	=	13).34	However,	the	poor	
option.	 A	 premixed	 penicillin	 G	 benzathine/procaine	             quality	 of	 included	 studies	 limited	 these	 findings,	 and	

386  American Family Physician                               www.aafp.org/afp	                    Volume 79, Number 5   ◆   March 1, 2009
Streptococcal Pharyngitis




  Table 3. Antibiotic Options for GABHS Pharyngitis

                                Class of                Route of                                                                 Duration
  Drug                          antimicrobial           administration     Dosage                                                of therapy    Cost*

  Primary treatment (recommended by current guidelines)
  Penicillin V (Veetids;        Penicillin              Oral               Children: 250 mg two to three times per day           10 days       $4
    brand no longer                                                        Adolescents and adults: 250 mg three to four
    available in the                                                        times per day
    United States)                                                             or
                                                                            500 mg two times per day

  Amoxicillin                   Penicillin (broad       Oral               Children (mild to moderate GABHS pharyngitis):        10 days       $4
                                  spectrum)                                 12.25 mg per kg two times per day
                                                                               or
                                                                            10 mg per kg three times per day
                                                                           Children (severe GABHS pharyngitis):
                                                                            22.5 mg per kg two times per day
                                                                               or
                                                                            13.3 mg per kg three times per day
                                                                               or
                                                                            750 mg (not FDA approved) once per day†
                                                                           Adults (mild to moderate GABHS pharyngitis):
                                                                            250 mg three times per day
                                                                               or
                                                                            500 mg two times per day
                                                                           Adults (severe GABHS pharyngitis): 875 mg
                                                                            two times per day

  Penicillin G benzathine       Penicillin              Intramuscular      Children: < 60 lb (27 kg): 6.0 × 105 units            One dose      Varies
    (Bicillin L-A)                                                         Adults: 1.2 × 106 units

  Treatment for patients with penicillin allergy (recommended by current guidelines)
  Erythromycin             Macrolide             Oral          Children: 30 to 50 mg per kg per day in two                       10 days       $4
    ethylsuccinate                                              to four divided doses
                                                               Adults: 50 mg per kg per day in three to four
                                                                divided doses

  Erythromycin estolate         Macrolide               Oral               Children: 20 to 40 mg per kg per day in two           10 days       $4
                                                                            to four divided doses
                                                                           Adults: not recommended‡

  Cefadroxil (Duricef; brand    Cephalosporin           Oral               Children: 30 mg per kg per day in two                 10 days       $45
   no longer available in        (first generation)                         divided doses
   the United States)                                                      Adults: 1 g one to two times per day

  Cephalexin (Keflex)           Cephalosporin           Oral               Children: 25 to 50 mg per kg per day in two           10 days       $4
                                 (first generation)                         to four divided doses
                                                                           Adults: 500 mg two times per day

  NOTE:The following medications are FDA approved, but are not recommended by guidelines for primary GABHS therapy: azithromycin (Zithro-
  max), clarithromycin (Biaxin), cefprozil (Cefzil; second-generation cephalosporin), cefpodoxime (Vantin; third-generation cephalosporin), ceftibuten
  (Cedax; third-generation cephalosporin), and cefdinir (Omnicef; third-generation cephalosporin).
  FDA = U.S. Food and Drug Administration; GABHS = group A beta-hemolytic streptococcus.
  *—Average price of generic based on http://www.pharmacychecker.com.
  †—Children four to 18 years of age.
  ‡—Adults receiving erythromycin estolate may develop cholestatic hepatitis; the incidence is higher in pregnant women, in whom the drug is
  contraindicated.
  Information from references 2, 17 through 20, and 28 through 34.




March 1, 2009   ◆   Volume 79, Number 5	                         www.aafp.org/afp	                                American Family Physician  387
Streptococcal Pharyngitis




results	 may	 be	 skewed	 because	 cephalosporins	 more	                    positive	 predictive	 value	 with	 higher	 scores	 (approxi-
effectively	 eradicate	 GABHS	 carriage	 than	 penicillin	                  mately	 50	 percent)	 and	 the	 risk	 of	 overtreatment.36	
does.	 Although	 cephalosporins	 are	 effective,	 the	 shift	               The	 ACP	 guidelines	 attempt	 to	 prevent	 inappropriate	
toward	 expensive,	 broad-spectrum	 second-	 and	 third-	                   antibiotic	use	while	avoiding	unnecessary	testing.	Dif-
generation	 cephalosporin	 use	 is	 increasing.	 Whether	                   ferences	 in	 guidelines	 are	 best	 explained	 by	 whether	
cephalosporins	 will	 replace	 penicillin	 as	 primary	                     emphasis	is	placed	on	avoiding	inappropriate	antibiotic	
GABHS	therapy	remains	to	be	seen.                                           use	 or	 on	 relieving	 acute	 GABHS	 pharyngitis	 symp-
                                                                            toms.	Several	U.S.	guidelines	recommend	confirmatory	
Guidelines for Treatment                                                    throat	culture	for	negative	RADT	in	children	and	ado-
Although	 GABHS	 pharyngitis	 is	 common,	 the	 ideal	                      lescents.2,18,19	This	approach	is	100	percent	sensitive	and	
approach	 to	 management	 remains	 a	 matter	 of	 debate.	                  99	to	100	percent	specific	for	diagnosing	GABHS	phar-
Numerous	 practice	 guidelines,	 clinical	 trials,	 and	 cost	              yngitis	 in	 children.37	 However,	 because	 of	 improved	
analyses	 give	 divergent	 opinions.	 U.S.	 guidelines	 differ	             RADT	sensitivity,	the	IDSA	and	ACP	recently	omitted	
in	 whether	 they	 recommend	 using	 clinical	 prediction	                  this	recommendation	for	adults.	A	similar	recommen-
models	versus	diagnostic	testing	(Table 4).	Several	inter-                  dation	to	omit	confirmatory	throat	culture	after	nega-
national	guidelines	recommend	not	testing	for	or	treat-                     tive	RADT	is	likely	for	children.
ing	GABHS	pharyngitis	at	all.35
  The	AAFP,	the	American	College	of	Physicians	(ACP),	                      Management of Recurrent GABHS Pharyngitis
and	the	Centers	for	Disease	Control	and	Prevention	rec-                     RADT	 is	 effective	 for	 diagnosing	 recurrent	 GABHS	
ommend	using	a	clinical	prediction	model	to	manage	                         infection.	 In	 patients	 treated	 within	 the	 preceding	   	
suspected	 GABHS	 pharyngitis.18	 Guidelines	 from	 the	                    28	 days,	 RADT	 has	 similar	 specificity	 and	 higher	 sen-
IDSA,	conversely,	state	that	clinical	diagnosis	of	GABHS	                   sitivity	 than	 in	 patients	 without	 previous	 streptococ-
pharyngitis	 cannot	 be	 made	 with	 certainty,	 even	 by	                  cal	infection	(0.91	versus	0.70,	respectively;	P	<	.001).38	
experienced	 physicians,	 and	 that	 diagnostic	 testing	 is	               Recurrence	 of	 GABHS	 pharyngitis	 within	 one	 month	
required.2	 Whereas	 the	 Centor	 algorithm	 effectively	                   may	be	treated	using	the	antibiotics	listed	in	Table 3.2,17-
identifies	 low-risk	 patients	 in	 whom	 testing	 is	 unnec-               20,28-34
                                                                                     	Intramuscular	penicillin	G	injection	is	an	option	
essary,	 the	 IDSA	 is	 concerned	 about	 its	 relatively	 low	             when	oral	antibiotics	were	initially	prescribed.



  Table 4. Comparison of GABHS Guidelines

  Recommendation               ACP (endorsed by the CDC and AAFP)         AAP                 IDSA                            UKNHS

  Screening for acute          Use Centor criteria (see Figure 1)         Use clinical and epidemiologic findings to assess   History and physical
    pharyngitis                                                            patient’s risk of GABHS (e.g., sudden onset          examination to
                                                                           of sore throat, fever, odynophagia, tonsillar        establish risk
                                                                           erythema, exudates, cervical lymphadenitis, or
                                                                           history of streptococcal exposure)
  Diagnostic testing           RADT with Centor score of 2 or 3           RADT or throat culture in all patients at risk      None
                                only
  Back-up culture needed if    Adults: No                                 Adults: NA          Adults: No                      —
   RADT result negative?       Children: Yes                              Children: Yes       Children: Yes
  Who requires antibiotic      Empiric antibiotics for Centor score       Positive RADT result or throat culture              Only high-risk and
   treatment?                   of 3 or 4; treat patients with                                                                 very ill patients
                                positive RADT result
  Antibiotic of choice         Oral penicillin V (Veetids; brand no longer available in the United States); intramuscular     Oral penicillin V
                                penicillin G benzathine (Bicillin L-A); oral amoxicillin with equal effectiveness and
                                better palatability in children
  Penicillin allergy           Oral erythromycin; cephalosporin (first generation)                                            Oral erythromycin

  AAFP = American Academy of Family Physicians; AAP = American Academy of Pediatrics; ACP = American College of Physicians; CDC = Centers for
  Disease Control and Prevention; GABHS = group A beta-hemolytic streptococcus; IDSA = Infectious Diseases Society of America; NA = not applicable;
  RADT = rapid antigen detection testing; UKNHS = United Kingdom National Health Service.




388  American Family Physician                                  www.aafp.org/afp	                             Volume 79, Number 5    ◆   March 1, 2009
Streptococcal Pharyngitis




Chronic Pharyngeal Carriage
                                                                   The Author
Chronic	 pharyngeal	 carriage	 is	 the	 persistent	 pres-
ence	of	pharyngeal	GABHS	without	active	infection	or	              BETH A. CHOBY, MD, FAAFP, is a board-certified family physician and direc-
                                                                   tor of research and procedural training in the Department of Family Medicine,
immune/inflammatory	 response.	 Patients	 may	 carry	              University of Tennessee–Chattanooga. She received her medical degree from
GABHS	 for	 one	 year	 despite	 treatment.	 Chronic	 car-          West Virginia University School of Medicine in Morgantown, and completed
riers	 are	 at	 little	 to	 no	 risk	 of	 immune-mediated	 post-   a family medicine residency at the University of Tennessee–Memphis, and
streptococcal	complications	because	no	active	immune	              a fellowship in advanced women’s health and obstetrics at the University
                                                                   of Tennessee–St. Francis Hospital, Memphis. She also completed a faculty
response	occurs.39	Risk	of	GABHS	transmission	is	very	             development fellowship at the Waco (Tex.) Faculty Development Center.
low	and	is	not	linked	to	invasive	group	A	streptococcal	
                                                                   Address correspondence to Beth A. Choby, MD, FAAFP, UT Family
(GAS)	infections.	Unproven	therapies	such	as	long-term	            Practice Center, 1100 E. 3rd St., Chattanooga, TN 37403 (e-mail: beth.
antibiotic	 use,	 treatment	 of	 pets,	 and	 exclusion	 from	      choby@erlanger.org). Reprints are not available from the author.
school	 and	 other	 activities	 have	 proved	 ineffective	 and	
                                                                   Author disclosure: Dr. Choby is an assistant editor of The Core Content
are	best	avoided.39	Carriage	of	one	GABHS	serotype	does	           Review of Family Medicine.
not	preclude	infection	by	another;	therefore,	throat	cul-
ture	or	RADT	is	appropriate	when	GABHS	pharyngitis	                REFERENCES  
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gone	tonsillectomies	(odds	ratio	=	3.1;	P	<	.001).42                   health outcomes. Pediatrics. 2006;117(3):609-619.


March 1, 2009   ◆   Volume 79, Number 5	                www.aafp.org/afp	                                American Family Physician  389
Streptococcal Pharyngitis




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    group A beta-hemolytic streptococci to thirteen antibiotics: examination        Laryngoscope. 2006;116(11):1946-1950.




390  American Family Physician                                      www.aafp.org/afp	                             Volume 79, Number 5       ◆   March 1, 2009

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Faringitis

  • 1. Diagnosis and Treatment of Streptococcal Pharyngitis BETH A. CHOBY, MD, University of Tennessee College of Medicine–Chattanooga, Chattanooga, Tennessee Common signs and symptoms of streptococcal pharyngitis include sore throat, temperature greater than 100.4°F (38°C), tonsillar exudates, and cervical adenopathy. Cough, coryza, and diarrhea are more common with viral phar- yngitis. Available diagnostic tests include throat culture and rapid antigen detection testing. Throat culture is consid- ered the diagnostic standard, although the sensitivity and specificity of rapid antigen detection testing have improved significantly. The modified Centor score can be used to help physicians decide which patients need no testing, throat culture/rapid antigen detection testing, or empiric antibiotic therapy. Penicillin (10 days of oral therapy or one injec- tion of intramuscular benzathine penicillin) is the treatment of choice because of cost, narrow spectrum of activity, and effectiveness. Amoxicillin is equally effective and more palatable. Erythromycin and first-generation cephalospo- rins are options in patients with penicillin allergy. Increased group A beta-hemolytic streptococcus (GABHS) treatment failure with peni- cillin has been reported. Although current guidelines recommend first-generation cephalosporins for persons with penicillin allergy, some advocate the use of cephalosporins in all nonallergic patients because of better GABHS eradication and effectiveness against chronic GABHS carriage. Chronic GABHS colonization is common despite appropriate use of antibiotic therapy. Chronic carriers are ILLUSTRATION BY MICHAEL KRESS-RUSSICK at low risk of transmitting disease or developing invasive GABHS infections, and there is generally no need to treat carriers. Whether tonsillectomy or adenoidectomy decreases the incidence of GABHS pharyngitis is poorly understood. At this time, the benefits are too small to outweigh the associated costs and surgical risks. (Am Fam Physician. 2009;79(5):383-390. Copyright © 2009 American Acad- emy of Family Physicians.) P Patient information: haryngitis is diagnosed in 11 mil- is transmitted via respiratory secretions, and ▲ A handout on strep throat, lion patients in U.S. emergency the incubation period is 24 to 72 hours. written by the author of departments and ambulatory set- this article, is available at http://www.aafp. tings annually.1 Most episodes are Diagnosis of Streptococcal Pharyngitis org/afp/20090301/383-s1. viral. Group A beta-hemolytic streptococcus CLINICAL DIAGNOSIS (GABHS), the most common bacterial etiol- Because the signs and symptoms of GABHS ogy, accounts for 15 to 30 percent of cases of pharyngitis overlap extensively with other acute pharyngitis in children and 5 to 20 per- infectious causes, making a diagnosis based cent in adults.2 Among school-aged children, solely on clinical findings is difficult. In the incidences of acute sore throat, swab- patients with acute febrile respiratory illness, positive GABHS, and serologically confirmed physicians accurately differentiate bacterial GABHS infection are 33, 13, and eight per from viral infections using only the history 100 child-years, respectively.3 Thus, about and physical findings about one half of the one in four children with acute sore throat time.4 No single element of the patient’s his- has serologically confirmed GABHS phar- tory or physical examination reliably con- yngitis. Forty-three percent of families with firms or excludes GABHS pharyngitis.5 Sore an index case of GABHS pharyngitis have a throat, fever with sudden onset (temperature secondary case.3 Late winter and early spring greater than 100.4° F [38° C]), and exposure are peak GABHS seasons. The infection to Streptococcus within the preceding two Downloaded from the American Family Physician Web site at www.aafp.org/afp. Copyright © 2009 American Academy of Family Physicians. For the private, noncommercial use of one individual user of the Web site. All other rights reserved. Contact copyrights@aafp.org for copyright questions and/or permission requests.
  • 2. Streptococcal Pharyngitis SORT: KEY RECOMMENDATIONS FOR PRACTICE Evidence Clinical recommendation rating References Use of clinical decision rules for diagnosing GABHS pharyngitis improves quality of care while reducing A 5-8, 18, 37, 38 unwarranted treatment and overall cost. Penicillin is the treatment of choice for GABHS pharyngitis in persons who are not allergic to penicillin. A 2, 18-20 Treatment is not typically indicated in chronic carriers of pharyngeal GABHS. C 39 GABHS = group A beta-hemolytic streptococcus. A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to http://www.aafp.org/afpsort.xml. weeks suggest GABHS infection. Cervical node lymph- at very low risk for streptococcal pharyngitis and do not adenopathy and pharyngeal or tonsillar inflammation require testing (i.e., throat culture or rapid antigen detec- or exudates are common signs. Palatal petechiae and tion testing [RADT]) or antibiotic therapy. Patients with a scarlatiniform rash are highly specific but uncommon; a score of 2 or 3 should be tested using RADT or throat cul- swollen uvula is sometimes noted. Cough, coryza, con- ture; positive results warrant antibiotic therapy. Patients junctivitis, and diarrhea are more common with viral with a score of 4 or higher are at high risk of streptococcal pharyngitis. The diagnostic accuracy of these signs and pharyngitis, and empiric treatment may be considered. symptoms is listed in Table 1.5 LABORATORY DIAGNOSIS CLINICAL DECISION RULES With correct sampling and plating techniques, a single- The original Centor score uses four signs and symptoms swab throat culture is 90 to 95 percent sensitive.10 RADT to estimate the probability of acute streptococcal phar- allows for earlier treatment, symptom improvement, and yngitis in adults with a sore throat.6 The score was later reduced disease spread. RADT specificity ranges from modified by adding age and validated in 600 adults and 90 to 99 percent. Sensitivity depends on the commer- children.7,8 The cumulative score determines the likeli- cial RADT kit used and was approximately 70 percent hood of streptococcal pharyngitis and the need for anti- with older latex agglutination assays.11,12 Newer enzyme- biotics (Figure 19). Patients with a score of zero or 1 are linked immunosorbent assays, optical immunoassays, Table 1. History and Physical Examination Findings Suggesting GABHS Pharyngitis Factor Sensitivity (%) Specificity (%) Positive likelihood ratio Negative likelihood ratio Absence of cough 51 to 79 36 to 68 1.1 to 1.7 0.53 to 0.89 Anterior cervical nodes swollen or enlarged 55 to 82 34 to 73 0.47 to 2.9 0.58 to 0.92 Headache 48 50 to 80 0.81 to 2.6 0.55 to 1.1 Myalgia 49 60 1.2 0.84 Palatine petechiae 7 95 1.4 0.98 Pharyngeal exudates 26 88 2 0.85 Streptococcal exposure in past two weeks 19 91 2 0.9 Temperature ≥ 100.9° F (38.3° C) 22 to 58 53 to 92 0.68 to 3.9 0.54 to 1.3 Tonsillar exudates 36 85 2.3 0.76 Tonsillar or pharyngeal exudates 45 75 1.8 0.74 GABHS = group A beta-hemolytic streptococcus. Adapted with permission from Ebell MH, Smith MA, Barry HC, Ives K, Carey M. The rational clinical examination. Does this patient have strep throat? JAMA. 2000;284(22):2915. 384  American Family Physician www.aafp.org/afp Volume 79, Number 5 ◆ March 1, 2009
  • 3. Streptococcal Pharyngitis recommends that negative RADT results Clinical Decision Rule for Management   in children be confirmed using throat cul- of Sore Throat   ture unless physicians can guarantee that RADT sensitivity is similar to that of throat Patient with sore throat Apply streptococcal score culture in their practice.13 False-negative RADT results may lead to misdiagnosis and GABHS spread and, very rarely, to Criteria Points increased suppurative and nonsuppurative Absence of cough 1 complications. Other studies suggest that Swollen and tender anterior 1 the sensitivity of newer optical immunoas- cervical nodes says approaches that of single-plate throat Temperature > 100.4° F (38° C) 1 culture, obviating the need for back-up cul- Tonsillar exudates or swelling 1 ture.14,15 In many clinical practices, confir- Age 3 to 14 years 1 matory throat culture is not performed in 15 to 44 years 0 children at low risk for GABHS infection. 45 years and older –1 The precipitous drop in rheumatic fever in Cumulative score: the United States, significant costs of addi- tional testing and follow-up, and concerns about inappropriate antibiotic use are valid reasons why back-up cultures are not rou- Score ≤ 0 Score = 1 Score = 2 Score = 3 Score ≥ 4 tinely performed.16 Streptococcal antibody titers are not use- ful for diagnosing streptococcal pharyn- Risk of Risk of Risk of Risk of Risk of GABHS GABHS GABHS GABHS GABHS gitis and are not routinely recommended. pharyngitis pharyngitis pharyngitis pharyngitis pharyngitis They may be indicated to confirm previous 1 to 2.5% 5 to 10% 11 to 17% 28 to 35% 51 to 53% infection in persons with suspected acute Option poststreptococcal glomerulonephritis or Consider empiric rheumatic fever. They may also help distin- treatment with guish acute infection from chronic carrier No further Perform throat culture or RADT antibiotics testing or status, although they are not routinely rec- antibiotics ommended for this purpose. indicated Negative Positive Treatment of GABHS Pharyngitis  JUSTIFICATION FOR TREATMENT GABHS pharyngitis is self-limited and No antibiotics indicated Treat with antibiotics resolves within a few days, even without treatment.17 Arguments for antibiotic treat- Figure 1. Modified Centor score and management options using clini- ment include acute symptom relief, preven- cal decision rule. Other factors should be considered (e.g., a score of 1, tion of suppurative and nonsuppurative but recent family contact with documented streptococcal infection). complications, and reduced communicabil- (GABHS = group A beta-hemolytic streptococcus; RADT = rapid anti- gen detection testing.) ity (Table 2).2,18-21 Antibiotics shorten symp- Adapted with permission from McIsaac WJ, White D, Tannenbaum D, Low DE. A clinical score tom duration by about 16 hours; the number to reduce unnecessary antibiotic use in patients with sore throat. CMAJ. 1998;158(1):79. needed to treat (NNT) for symptom relief at 72 hours is four in those with positive throat and chemiluminescent DNA probes are 90 to 99 percent swabs.22 In addition, rates of suppurative peritonsillar sensitive.11,12 However, newer tests may be more expen- and retropharyngeal abscesses are reduced (approxi- sive, and not all tests are waived by the Clinical Labora- mately one in 1,000 cases).23 tory Improvement Act of 1988. Antibiotics also reduce the incidence of acute rheu- Whether negative RADT results in children and ado- matic fever (relative risk reduction = 0.28).24 Although lescents require confirmatory throat culture is contro- rheumatic heart disease is a major public health versial. The American Academy of Pediatrics (AAP) issue in low- and middle-income countries (annual March 1, 2009 ◆ Volume 79, Number 5 www.aafp.org/afp American Family Physician  385
  • 4. Table 2. Complications of GABHS Pharyngitis  Suppurative Nonsuppurative Bacteremia Poststreptococcal glomerulonephritis Cervical lymphadenitis injection (Bicillin C-R) lessens injection-associated dis- Endocarditis Rheumatic fever comfort. Over the past 50 years, no increase in minimal Mastoiditis inhibitory concentration or resistance to GABHS has Meningitis been documented for penicillins or cephalosporins.28 Otitis media Oral amoxicillin suspension is often substituted for Peritonsillar/retropharyngeal penicillin because it tastes better. The medication is abscess also available as chewable tablets. Five of eight trials Pneumonia (1966 to 2000) showed greater than 85 percent GABHS GABHS = group A beta-hemolytic streptococcus. eradication with the use of amoxicillin.29 Ten days of Information from references 2, and 18 through 21. therapy is standard; common dosages are provided in Table 3.2,17-20,28-34 Amoxicillin taken once per day is likely as effective as a regimen of three times per day. One ran- incidence of five per 100,000 persons), it has largely been domized controlled trial (RCT) demonstrated compa- controlled in industrialized nations since the 1950s.25 It rable symptom relief with once-daily dosing, although is estimated that 3,000 to 4,000 patients must be given like almost all studies of pharyngitis treatment, the trial antibiotics to prevent one case of acute rheumatic fever was not powered to detect nonsuppurative complica- in developed nations.18 Rates of acute rheumatic fever tions.30 A recent study of children three to 18 years of and retropharyngeal abscess have not increased fol- age showed that once-daily dosing of amoxicillin was not lowing more judicious antibiotic use in children with inferior to twice-daily dosing; both regimens had failure respiratory infections.26 Children with GABHS phar- rates of about 20 percent.31 It should be noted that once- yngitis may return to school after 24 hours of antibiotic daily therapy is not approved by the U.S. Food and Drug therapy.27 Administration (FDA). Non–group A beta-hemolytic streptococci (groups C Current U.S. treatment guidelines recommend and G) also can cause acute pharyngitis; these strains erythromycin for patients with penicillin allergy. Gas- are usually treated with antibiotics, although good clini- trointestinal side effects of erythromycin cause many cal trials are lacking. Fusobacterium necrophorum causes physicians to instead prescribe the FDA-approved endemic acute pharyngitis, peritonsillar abscess, and second-generation macrolides azithromycin (Zith- persistent sore throat. Untreated Fusobacterium infec- romax) and clarithromycin (Biaxin). Azithromycin tions may lead to Lemierre syndrome, an internal jugular reaches higher concentrations in pharyngeal tissue vein thrombus caused by inflammation. Complications and requires only five days of treatment. Macrolide occur when septic plaques break loose and embolize. resistance is increasing among GABHS isolates in the Empiric antibiotic therapy may reduce the incidence of United States, likely because of azithromycin overuse.32 complications. Reported GABHS resistance in certain areas of the United States and Canada approaches 8 to 9 percent.33 ANTIBIOTIC SELECTION Most guidelines recommend reserving erythromycin Effectiveness, spectrum of activity, safety, dosing sched- for patients who are allergic to penicillin. ule, cost, and compliance issues all require consider- First-generation oral cephalosporins are recom- ation. Penicillin, penicillin congeners (ampicillin or mended for patients with penicillin allergy who do amoxicillin), clindamycin (Cleocin), and certain cepha- not have immediate-type hypersensitivity to beta- losporins and macrolides are effective against GABHS. lactam antibiotics. Bacteriologic failure rates for Based on cost, narrow spectrum of activity, safety, and penicillin-treated GABHS pharyngitis increased from effectiveness, penicillin is recommended by the Ameri- about 10 percent in the 1970s to more than 30 percent can Academy of Family Physicians (AAFP),18 the AAP,19 in the past decade.29 Several studies suggest that cepha- the American Heart Association,20 the Infectious Dis- losporins are more effective against GABHS than peni- eases Society of America (IDSA),2 and the World Health cillin. Higher rates of GABHS eradication and shorter Organization for the treatment of streptococcal phar- courses of therapy that are possible with cephalosporins yngitis.25 Options for penicillin dosing are listed in may be beneficial. One meta-analysis of 35 trials com- Table 3.2,17-20,28-34 When patients are unlikely to complete paring various cephalosporins against penicillin noted the entire course of antibiotics, a single intramuscu- significantly more bacteriologic and clinical cures in the lar dose of penicillin G benzathine (Bicillin L-A) is an cephalosporin group (NNT = 13).34 However, the poor option. A premixed penicillin G benzathine/procaine quality of included studies limited these findings, and 386  American Family Physician www.aafp.org/afp Volume 79, Number 5 ◆ March 1, 2009
  • 5. Streptococcal Pharyngitis Table 3. Antibiotic Options for GABHS Pharyngitis Class of Route of Duration Drug antimicrobial administration Dosage of therapy Cost* Primary treatment (recommended by current guidelines) Penicillin V (Veetids; Penicillin Oral Children: 250 mg two to three times per day 10 days $4 brand no longer Adolescents and adults: 250 mg three to four available in the times per day United States) or 500 mg two times per day Amoxicillin Penicillin (broad Oral Children (mild to moderate GABHS pharyngitis): 10 days $4 spectrum) 12.25 mg per kg two times per day or 10 mg per kg three times per day Children (severe GABHS pharyngitis): 22.5 mg per kg two times per day or 13.3 mg per kg three times per day or 750 mg (not FDA approved) once per day† Adults (mild to moderate GABHS pharyngitis): 250 mg three times per day or 500 mg two times per day Adults (severe GABHS pharyngitis): 875 mg two times per day Penicillin G benzathine Penicillin Intramuscular Children: < 60 lb (27 kg): 6.0 × 105 units One dose Varies (Bicillin L-A) Adults: 1.2 × 106 units Treatment for patients with penicillin allergy (recommended by current guidelines) Erythromycin Macrolide Oral Children: 30 to 50 mg per kg per day in two 10 days $4 ethylsuccinate to four divided doses Adults: 50 mg per kg per day in three to four divided doses Erythromycin estolate Macrolide Oral Children: 20 to 40 mg per kg per day in two 10 days $4 to four divided doses Adults: not recommended‡ Cefadroxil (Duricef; brand Cephalosporin Oral Children: 30 mg per kg per day in two 10 days $45 no longer available in (first generation) divided doses the United States) Adults: 1 g one to two times per day Cephalexin (Keflex) Cephalosporin Oral Children: 25 to 50 mg per kg per day in two 10 days $4 (first generation) to four divided doses Adults: 500 mg two times per day NOTE:The following medications are FDA approved, but are not recommended by guidelines for primary GABHS therapy: azithromycin (Zithro- max), clarithromycin (Biaxin), cefprozil (Cefzil; second-generation cephalosporin), cefpodoxime (Vantin; third-generation cephalosporin), ceftibuten (Cedax; third-generation cephalosporin), and cefdinir (Omnicef; third-generation cephalosporin). FDA = U.S. Food and Drug Administration; GABHS = group A beta-hemolytic streptococcus. *—Average price of generic based on http://www.pharmacychecker.com. †—Children four to 18 years of age. ‡—Adults receiving erythromycin estolate may develop cholestatic hepatitis; the incidence is higher in pregnant women, in whom the drug is contraindicated. Information from references 2, 17 through 20, and 28 through 34. March 1, 2009 ◆ Volume 79, Number 5 www.aafp.org/afp American Family Physician  387
  • 6. Streptococcal Pharyngitis results may be skewed because cephalosporins more positive predictive value with higher scores (approxi- effectively eradicate GABHS carriage than penicillin mately 50 percent) and the risk of overtreatment.36 does. Although cephalosporins are effective, the shift The ACP guidelines attempt to prevent inappropriate toward expensive, broad-spectrum second- and third- antibiotic use while avoiding unnecessary testing. Dif- generation cephalosporin use is increasing. Whether ferences in guidelines are best explained by whether cephalosporins will replace penicillin as primary emphasis is placed on avoiding inappropriate antibiotic GABHS therapy remains to be seen. use or on relieving acute GABHS pharyngitis symp- toms. Several U.S. guidelines recommend confirmatory Guidelines for Treatment throat culture for negative RADT in children and ado- Although GABHS pharyngitis is common, the ideal lescents.2,18,19 This approach is 100 percent sensitive and approach to management remains a matter of debate. 99 to 100 percent specific for diagnosing GABHS phar- Numerous practice guidelines, clinical trials, and cost yngitis in children.37 However, because of improved analyses give divergent opinions. U.S. guidelines differ RADT sensitivity, the IDSA and ACP recently omitted in whether they recommend using clinical prediction this recommendation for adults. A similar recommen- models versus diagnostic testing (Table 4). Several inter- dation to omit confirmatory throat culture after nega- national guidelines recommend not testing for or treat- tive RADT is likely for children. ing GABHS pharyngitis at all.35 The AAFP, the American College of Physicians (ACP), Management of Recurrent GABHS Pharyngitis and the Centers for Disease Control and Prevention rec- RADT is effective for diagnosing recurrent GABHS ommend using a clinical prediction model to manage infection. In patients treated within the preceding suspected GABHS pharyngitis.18 Guidelines from the 28 days, RADT has similar specificity and higher sen- IDSA, conversely, state that clinical diagnosis of GABHS sitivity than in patients without previous streptococ- pharyngitis cannot be made with certainty, even by cal infection (0.91 versus 0.70, respectively; P < .001).38 experienced physicians, and that diagnostic testing is Recurrence of GABHS pharyngitis within one month required.2 Whereas the Centor algorithm effectively may be treated using the antibiotics listed in Table 3.2,17- identifies low-risk patients in whom testing is unnec- 20,28-34 Intramuscular penicillin G injection is an option essary, the IDSA is concerned about its relatively low when oral antibiotics were initially prescribed. Table 4. Comparison of GABHS Guidelines Recommendation ACP (endorsed by the CDC and AAFP) AAP IDSA UKNHS Screening for acute Use Centor criteria (see Figure 1) Use clinical and epidemiologic findings to assess History and physical pharyngitis patient’s risk of GABHS (e.g., sudden onset examination to of sore throat, fever, odynophagia, tonsillar establish risk erythema, exudates, cervical lymphadenitis, or history of streptococcal exposure) Diagnostic testing RADT with Centor score of 2 or 3 RADT or throat culture in all patients at risk None only Back-up culture needed if Adults: No Adults: NA Adults: No — RADT result negative? Children: Yes Children: Yes Children: Yes Who requires antibiotic Empiric antibiotics for Centor score Positive RADT result or throat culture Only high-risk and treatment? of 3 or 4; treat patients with very ill patients positive RADT result Antibiotic of choice Oral penicillin V (Veetids; brand no longer available in the United States); intramuscular Oral penicillin V penicillin G benzathine (Bicillin L-A); oral amoxicillin with equal effectiveness and better palatability in children Penicillin allergy Oral erythromycin; cephalosporin (first generation) Oral erythromycin AAFP = American Academy of Family Physicians; AAP = American Academy of Pediatrics; ACP = American College of Physicians; CDC = Centers for Disease Control and Prevention; GABHS = group A beta-hemolytic streptococcus; IDSA = Infectious Diseases Society of America; NA = not applicable; RADT = rapid antigen detection testing; UKNHS = United Kingdom National Health Service. 388  American Family Physician www.aafp.org/afp Volume 79, Number 5 ◆ March 1, 2009
  • 7. Streptococcal Pharyngitis Chronic Pharyngeal Carriage The Author Chronic pharyngeal carriage is the persistent pres- ence of pharyngeal GABHS without active infection or BETH A. CHOBY, MD, FAAFP, is a board-certified family physician and direc- tor of research and procedural training in the Department of Family Medicine, immune/inflammatory response. Patients may carry University of Tennessee–Chattanooga. She received her medical degree from GABHS for one year despite treatment. Chronic car- West Virginia University School of Medicine in Morgantown, and completed riers are at little to no risk of immune-mediated post- a family medicine residency at the University of Tennessee–Memphis, and streptococcal complications because no active immune a fellowship in advanced women’s health and obstetrics at the University of Tennessee–St. Francis Hospital, Memphis. She also completed a faculty response occurs.39 Risk of GABHS transmission is very development fellowship at the Waco (Tex.) Faculty Development Center. low and is not linked to invasive group A streptococcal Address correspondence to Beth A. Choby, MD, FAAFP, UT Family (GAS) infections. Unproven therapies such as long-term Practice Center, 1100 E. 3rd St., Chattanooga, TN 37403 (e-mail: beth. antibiotic use, treatment of pets, and exclusion from choby@erlanger.org). Reprints are not available from the author. school and other activities have proved ineffective and Author disclosure: Dr. Choby is an assistant editor of The Core Content are best avoided.39 Carriage of one GABHS serotype does Review of Family Medicine. not preclude infection by another; therefore, throat cul- ture or RADT is appropriate when GABHS pharyngitis REFERENCES   is suspected. Testing is unnecessary if clinical symptoms 1. Hing E, Cherry DK, Woodwell DA. National Ambulatory Medical Care suggest viral upper respiratory infection. Survey: 2003 Summary. Adv Data. 2005;365:1-48. Antibiotic treatment may be appropriate in the fol- 2. 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Efficacy of tonsillectomy in treat- 28. Kaplan EL, Johnson DR, Del Rosario MC, Horn DL. Susceptibility of ment of recurrent group A beta-hemolytic streptococcal pharyngitis. group A beta-hemolytic streptococci to thirteen antibiotics: examination Laryngoscope. 2006;116(11):1946-1950. 390  American Family Physician www.aafp.org/afp Volume 79, Number 5 ◆ March 1, 2009