Вы находитесь на странице: 1из 14

Group A Streptococcal Infections

Group a Streptococci

I. History - organism first described by Billroth in 1874, hemolytic


classification by Brown in 1919, serogrouping by Lancefield in early
1930s

II. Epidemiology - streptococcal pharyngitis most common treatable cause


of pharyngitis, streptococcal impetigo most common bacterial skin
infection, rheumatic heart disease most common form of acquired
heart disease worldwide, poststreptococcal AGN most common form of
AGN

Group a Streptococci
Classification

I. Hemolytic classes

A. Beta-hemolytic: clear zone of complete hemolysis around colony


on blood agar, all group A strains 1. Two beta-hemolysins

2. Streptolysin O-oxygen-labile, subsurface hemolysis, gives


rise to antibodies (ASO) that neutralize its action

3. Streptolysin S-oxygen-stabile, surface hemolysis

4. Both hemolysins can damage cell membranes


other than RBCs

B. AIpha-hemolytic: partial hemolysis producing green zone around


colony on blood agar

C. Gamma-hemolytic: no surface or deep hemolysis

Group a Streptococci
Classification

II. Serologic grouping:

specific grouping (A to O) based on presence of group-specific C


carbohydrate antigen, most important human pathogens are group A,
extract out carbohydrate antigen and react with hyperimmune rabbit
sera

Group a Streptococci
Classification

Ill. Serologic typing at GABHS:

A. M typing - over 70 immunologic types that differ in their cell wall M


protein, M protein extracted out and reacted with hyperimmune
rabbit sera in precipitin test, M protein extends out as fimbriae
from surface of cell, most important virulence factor -
antiphagocytic properties, antibodies to M protein are protective

B. T typing - another cell wall protein found in a number of


immunologically distinct antigenic forms, also designated by
numbers

Group a Streptococci
Metabolism

1. Growth - optimal at 37EC, complex nutritional requirements,


promoted by blood serum

2. Lactic acid bacteria

3. Catalase - negative, nonmotile, facultative anaerobes

Group a Streptococci
Cellular Antigens

1. C carbohydrate, M protein, T protein

2. Hyaluronic acid capsule - mucoid, matt, and glossy colonies;


possible virulence factor
3. Lipoteichoic acid - adherence to mucosal surfaces

4. Peptidoglycan, other surface proteins, cytoplasmic membrane

Group a Streptococci
Extracellular Products

1. Streptolysin O and streptolysin S

2. Erythrogenic toxin - responsible for rash in scarlet fever,


production mediated by temperate bacteriophage, at least three
immunologically distinct forms (A, B, C), streptococcal TSS

3. Streptokinase - promotes lysis of clots by catalyzing conversion of


plasminogen to plasmin, used commercially as thrombolytic
agent, uncertain role as virulence factor

4. Deoxyribonucleases - four immunologically distinct types (A, B, C,


D), antibodies to DNase B (ADB) are used in conjunction with
ASO for serodiagnosis of GABHS infection

5. Others - NADase, hyaluronidase, proteinase

Case

3 year old male has had rhinorrhea, cough, and conjunctivitis for 2
days. At a Fourth of July picnic he begins to complain about a sore
throat with marked pain on swallowing. His mother looks into his mouth
and notices that his throat is bright red and his tonsils are very
enlarged. He has also begun to have some loose watery stools.

Case

Diagnosis

Would you perform a rapid strep test? Would you perform a throat
culture?

Would you perform a rapid strep test and a confirmatory throat culture
only if the rapid strep test were negative?

Clinical Diagnosis of GABHS


Pharyngitis

Features suggestive of GABHS as the etiology:

Sudden onset

Sore throat

Fever

Headache

Nausea, vomiting, abdominal pain

Marked inflammation of pharynx and tonsils

Patchy discrete exudate

Tender, enlarged anterior cervical nodes

Features suggestive of a viral etiology:

Conjunctivitis, coryza, cough, diarrhea

Clinical Diagnosis of GABHS


Pharyngitis

Predictive value of single findings or combinations of findings

Clinical scoring systems

Stillerman and Bernstein

Breese

At best, clinical diagnoses correlate with throat culture results 80% of the
time
Throat Culture on Bap

Accuracy

Most important factor is quality of specimen

Atmosphere of incubation

Media

Duration of incubation

Bacitracin disc, serogrouping

Properly performed office culture probably around 90% sensitivity

Recommendations

If rapid test is positive,

initiate antimicrobial therapy,

no need to perform throat culture

If rapid test is negative, perform throat culture to confirm results

Use of Throat Cultures and ADTs by Responding Pediatricians


(n = 510)*

Throat cultures alone 38%

ADT with throat culture backup 42%

for negative results only

ADT alone 13%

Throat culture and ADT for all 5%

Clinical criteria alone 2%

*Hofer C., Binns H J, Tanz RR. Unpublished Data

Rapid ADT for GABHS

Latex agglutination (LA)

Least sensitive

Endpoints indistinct

Enzyme immunoassay (EIA)

More sensitive

More distinct endpoints

Optical immunoassay (OIA)

Newest methodology Clear endpoints

More time, more steps

Accuracy incompletely evaluated

Comparison of Rapid Tests And Blood Agar Cultures

Rapid Sensitivity Specificity


Study Year Method (%) (%)

Gerber 1984 LA 83 99

Campos 1985 LA 62 100

Roddey 1986 LA 72 98

Schwabe 1987 EIA 90 97


Gerber 1990 EIA 91 83

Roddey 1995 OIA 91 96

Fries 1995 OIA 95 99

Gerber 1997 OIA 94 86

Evaluation of Strep a OIA


Results
2114 throat swabs processed at 6 sites

1009 (47.7%) were positive for GABHS by THB and/or BAP in reference lab

Chicago sites

659 (58.3%) of 1131 were positive

Connecticut sites

342 (35.6%) of 983 were positive

Results

Sites

Sensitivities* I 2 3 4 5 6

OIA 97% 94% 91% 83% 77% 70%

BAP 94% 86% 89% 74% 73% 64%

* Comparisons with "Gold Standard" of THB and/or BAP in reference lab


yielding GABHS

Case

AG is an 8 year old male, who, during the first week of March, has the
sudden onset of a severe sore throat with an oral temperature of
102EF. He has nausea, abdominal pain, and enlarged, tender anterior
cervical nodes. On examination he has marked inflammation of the
pharynx and tonsils, considerable enlargement of both tonsils with
patchy exudate, and numerous petechiae on the uvula and soft palate.
A rapid strep test is performed and is positive.

Reasons for diagnosing and treating GABHS pharyngitis

1. Prevention of acute rheumatic fever

2. Prevention of suppurative complications

3. Reduction of morbidity

4. Prevention of spread

Group A Streptococci
Transmission

Direct contact between infected and susceptible persons-important


extrahuman or animal reservoirs do not exist

GABHS recovered from dried barracks dust for months


but not infectious

Pharyngitis - large airborne droplets, M-typeable and large number enhance


spread, in military barracks risk is inversely proportional to distance
between beds, food-borne and milk-borne epidemics are uncommon

Diagnosis of Initial Attack of Rheumatic Fever


(Jones Criteria, Updated 1992)

Major manifestation Minor manifestation

Carditis Clinical findings

Polyarthritis Arthralgia

Chorea Fever
Erythema marginatum Laboratory findings

Subcutaneous nodules Elevated acute phase


reactants(ESR, CRP)

Prolonged PR interval

Supporting evidence of antecedent group A streptococcal infection

Positive throat culture or rapid strep antigen test

Elevated or rising strep antibody titer

Group A Streptococci
Nonsuppurative Diseases

1. Acute glomerulonephritis and rheumatic fever

2. Comparison of AGN and RF

A. AGN after impetigo or pharyngitis, RF after


pharyngitis only

B. AGN after latent period of 10 days, RF after


latent period of 18 days

C. Second attacks of AGN rare, second attacks of RF common

D. AGN not prevented by antibiotics, RF prevente by


antibiotics

Treatment of GABHS

Benz Pen G IM <27 kg: 600,000 units


> 27 kg: 1,200,000 units

Pen V Oral Children: 250 mg, 2 - 3 times


daily x 10 days

Adolescents and adults: 500 mg,


2 - 3 times daily for 10 days

Erythromycin Oral 20 - 40 mg/kg/d, 2 - 4 rimes daily


Estolate for 10 days

Erythromycin Oral 40 mg/kg/d, 2 - 4 times daily


Ethylsuccinate for 10 days

Treatment of GABHS Pharyngitis

Amoxicillin

Narrow-spectrum cephalosporins

Broader-spectrum cephalosporins

New macrolides

5 - day course with selected cephalosporins

5 - day course with azithromycin

Cephalosporins Should Replace Penicillin as the Drug of Choice for


Treatment of Acute GABHS Pharyngitis

1. Penicillin is less effective than in the past

2. Cephalosporin therapy results in fewer clinical and bacteriologic


treatment failures

Effectiveness of Penicillin in the Treatment of GABHS Pharyngitis

Indirectly

1. Incidence of GABHS pharyngitis

2. Incidence of suppurative complications


of GABHS pharyngitis
3. Incidence of nonsuppurative complications
of GABHS pharyngitis

Directly

1. Clinical response

2. Bacteriologic response

Clinical Treatment Failures with GABHS Pharyngitis

1. Inconsistent reporting of clinical findings

2. Unblinded reporting of subjective findings

3. Clinical significance of persistent or recurrent


signs or symptoms in the absence of a positive culture

4. Clinical significance of persistent or recurrent


signs or symptoms of a disease that is self-limited even without therapy

Bacteriologic Treatment Failures


(True)

1. Resistance to penicillin

2. Tolerance to penicillin

3. Bacteriocin production by normal


pharyngeal flora

4. Beta-lactamase production by normal


pharyngeal flora

Bacteriologic Treatment Failures


(Apparent)

1. GABHS carriers

Present with intercurrent vital pharyngitis

Loose entry criteria

Substantial number of carriers

Penicillin is ineffective

Cephalosporins are effective

2. Follow-up isolates are either improperly or inadequately identified

3. Noncompliance

4. Reacquisition of GABHS

Group A Streptococci Antimicrobial Resistance

Penicillin - No significant change in the in vitro susceptibility


over past 40 years
Resistance has never been reported among
clinical isolates

Erythromycin:

Japan: 1970 - 2%, 1974 - 60%, 1982 - 22%, 1990 - 1%

Finland: 1988 - 4%, 1990 - 24%

United States: < 5%

Tetracycline: 5% - 25% of isolates in U.S.

Sulfonamides: no recent data


do not eradicate GABHS or prevent ARF

Cephalosporins: no resistance

Clindamycin:
Italy: 1995- 18%

United States: < 5%

Advantages of Ceph Vs. Pen in the Treatment of Gabhs Pharyngitis

Lower clinical failure rate

Lower bacteriologic failure rate

Once daily regimen

Five day regimen

Treatment of GABHS Pharyngitis with Oral Cephalosporins

Cefixime qD > Pen V rid (clin and bact)

Loracarbef bid > Pen V qid (bact)

Ceftibuten qD >Pen v rid (Clin and bact)

Cefadroxil qD >Pen v tid (Clin and bact)

Cefuroxime bid >Pen v tid (Clin and bact)

Cefuroxime bid (x4) >Pen v rid (Clin and bact)

Cefpodoxime qD >Pen v rid (bact)

Cefpodoxime bid (x5) >Pen v tid (bact)

Disadvantages of Ceph Vs. Pen in the Treatment of GABHS Pharyngitis

Cost

Broader spectrum of activity

Cost of Treatment for 30 Kg Child

Average wholesale Price - Red Book

Pen v susp 250 mg/5 ml $ 2.95

Amoxicillin susp 250 mg/5 ml $ 6.13

Benzathine Pen G 1.2 million units $10.93

Cefixime susp 100 mg/5 ml $77.89

Ceftibuten susp 90 mg/5 ml $74.73

Cefpodoxime proxetil susp 100 mg/5 ml $58.26/$29.13

Cefuroxime axetil susp 125mg/Sml $53.59/$21.44

Loracarbef susp 200mg/5ml $37.79

Cefadroxil susp 50mg/5m! $33.28

Treatment of GABHS Pharyngitis


With New Macrolides

Clarithromycin bid > PenV tid (bact)

Azithromycin qD (x5) > PenV qid (clin and bact)

Cost of Treatment For 30 Kg Child

Average wholesale Price - Red Book

PenV susp 250mg/5ml $ 2.95

Amoxicillin susp 250mg/5ml $ 6.13

Benzathine PenG 1.2 million units $10.93

Clarithromycin susp 250mg/5ml $51.05


Azithromycin susp 200mg/5ml $102,16/$51.08

Relapses And Recurrences in Two Treatment Groups (Rochester Study)

Penicillin Placebo P
(n = 59) (n = 55)

Relapse 17% 15% NS

Early recurrence 24% 15% NS

Late recurrence 14% 2% <0.05

Early and late recurrence 37% 16% <0.05

Bacteriologic Responses to Immediate or Delayed Therapy (Conn Study)

Immediate Delay P
(N = 50) (N = 63)

Recurrences 12% 14% NS

New Acquisitions 24% 27% NS

Total 36% 41% NS

Streptococcal Carrier

Definition: a person with GABHS in the upper respiratory tract with no


evidence of a serologic response to that organism

Clinical Significance: At low risk for spreading GABHS to their contacts,


suppurative and nonsuppurative complications are not encountered

Eradication: Antimicrobials are frequently less effective in eradicating


GABHS from a streptococcal carrier than from someone with acute
GABHS pharyngitis

Identification and Treatment of Streptococcal Carriers

Family history of rheumatic fever

"Ping-Pong" spread of GABHS within family

Inordinate amount of anxiety about GABHS

Outbreaks of GABHS pharyngitis in closed or semi-closed


communities

Tonsillectomy is being considered only because of chronic


carriage of GABHS

Outbreaks of acute rheumatic fever or poststreptococcal


acute glomerulonephritis

Regimens for Eradicating Streptococcal Carrier State

Oral rifampin (20 mg/kg every 24 hrs x 4) during last 4


days of a 10-day course of oral penicillin

Oral rifampin (10 mg/kg every 12 hrs. x 8) given with one


dose of IM benzathine penicillin G

Oral clindamycin (20 mg/kg/day in 3 doses) for 10 days

Management of Repeated Episodes of Acute Gabhs Pharyngitis

Prophylactic oral penicillin - no evidence of benefit, resistance

Tonsillectomy

Benefit only for those meeting stringent criteria:

7 episodes within I year

5 episodes in each of 2 years

3 episodes in each of 3 years clinical findings


Relatively small group

Statistically significant difference only over the subsequent 2


years

Group a Streptococci

Severe Invasive Disease

Definition: An infection associated with the isolation of GABHS from a


normally sterile body site.

Includes three overlapping clinical syndromes:

1. Group A streptococcal TSS


shock and multi-organ system failure early in course 1993 CDC case
definition

2. Necrotizing fasciitis
extensive local necrosis of subcutaneous soft tissue
and skin

3. Group of infections not meeting the criteria for streptococcal TSS or


necrotizing fasciitis (e.g., meningitis, pneumonia, peritonitis, puerperal
sepsis, osteomyelitis, septic arthritis, myositis, and surgical wound
infections)

Group a Streptococci
Case Definition for the Streptococcal Toxic Shock Syndrome

I. Isolation of GABHS

A. From a normally sterile site (eg, blood, cerebrospinal fluid,


peritoneal fluid, tissue biopsy, etc.)

B. From a non-sterile site (e.g., throat, sputum, vagina, etc.)

II. Clinical signs of severity

A. Hypotension: Systolic blood pressure <90 mm Hg for adults or < 5th


percentile for age in children

AND

Group a Streptococci
Case Definition for the Streptococcal Toxic Shock Syndrome

B. > 2 of the following signs

1. Renal impairment: creatinine > 2 mg/dl for adults or_> twice


the upper limit of normal for age

2. Coagulopathy: platelets < 100,000 or


disseminated intravascular coagulation

3. Liver involvement: alanine aminotransferase (SGPT), aspartate


aminotransferase (SGOT), or total bilirubin levels > twice the
upper limit of normal for age

Group a Streptococci
Case Definition for the Streptococcal Toxic Shock Syndrome

4. Adult respiratory distress syndrome

5. A generalized erythematous macular rash that may


desquamate

6. Soft-tissue necrosis, including necrotizing fasciitis or myositis,


or gangrene

Definite case - IA and II (A and B)


Possible case - IB and Ii (A and B)

Group a Streptococci

Epidemiology of Severe Disease

May 27,1994 report of 6 cases (3 deaths) of necrotizing


fasciitis in Gloucestershire, England
Exaggerated reporting:

Not new

No evidence of an epidemic

Relatively rare, sporadic

No evidence of antibiotic resistance

Group a Streptococci
Epidemiology of Severe Disease

No data on precise incidence in U.S.

CDC estimates:

4 to 5 cases per 100,000 persons

10,000 cases annually in U.S.

10% TSS, 5% NF

Mortality rates: in adults 30 to 80%

in children 5 to 10%

Group a Streptococci
Epidemiology of Severe Disease

Decline in incidence following WWll

Improved standard of living

Antibiotic therapy

Disappearance of virulent strains

Increase in incidence in 1980s

U.S., Canada, Great Britain, Europe, Australia

Reason For Increase in Invasive


GABHS Infections

Epidemiologic shifts in strains over time, increased prevalence of certain M


serotypes (eg, M-I and M-3) and increase in the number of strains
producing SPE-A

Outbreaks of streptococcal toxic shock syndrome and other forms of severe,


invasive disease may be related to cyclic variations in prevalent strains
and/or delay in development of protective immunity to specific M types
or SPEs

Of M-I strains isolated from patients, 91% had a common RFLP and
contained the SPE-A toxin gene: virulent clone theory
However, other serotypes also associated with severe, invasive GABHS
infections, in some areas strains have been very heterogenous

Streptococcal Pyrogenic
Exotoxins (SPEs)

SPE - A, B, C - previously known as erythrogenic or scarlet fever toxins

SPE-F - mitogenic factor

SSA - streptococcal superantigen

Belong to a family of pyrogenic toxins that includes the


staphylococcal toxic shock toxin - 1

Superantigens that stimulate T cells without regard to antigen


specificity - massive release of cytokines (interleukin 1 and 2, TNF - a
and [B, ¥ interferon) from both T cells and macrophages

Evidence for a causative role of SPE's (particularly SPE-A although others


have been implicated) in the pathogenesis of streptococcal toxic shock
syndrome
Group a Streptococci
Epidemiology of Severe Disease

85% - sporadic

10% - hospital acquired

4% - residents of long-term care facilities

1% - close contact with a case

Outbreaks at military bases, nursing homes, hospitals

Cases in children at school or out-of-home child care but no


secondary cases

Secondary cases tend to mimic index cases

Population-based active surveillance in Ontario, Canada rate of 2.9


cases/1000 household contacts 200 - times baseline risk in community
95% confidence limits of 0.8 to 7.5 per 1000

Group a Streptococci
Risk Factors for Severe Disease

Incidence highest among young children and elderly Diabetes, chronic


cardiac or pulmonary disease, HIV/AIDS, intravenous drug use, alcoholism

Not usually associated with acute pharyngitis - usually skin or soft tissue
infection

Varicella should be considered with localized skin findings of erythema,


warmth, swelling, or induration - temp > 39EC beyond the third day of illness
or any fever beyond the fourth day

very painful, pain out of proportion to clinical findings

Group a Streptococci
Risk Factors for Severe Disease

Suggested relationship with use of NSAIDs


impair granulocyte function, enhance production of
cytokines, mask signs and symptoms

causal relationship has not been established

insufficient data on which to base a clinical decision


regarding either the use or restriction of NSAIDs in children with
varicella

Group a Streptococci
Diagnosis of Severe Disease

Course is often precipitous requiring rapid diagnosis and


initiation of appropriate therapy

Initial signs and symptoms are nonspecific

High index of suspicion in patients at increased risk: more localized or severe


pain than is typical with flu absence of respiratory signs or contact
history presence of skin lesions or history of blunt trauma

Culture of focal lesion if present

Blood cultures

Monitor blood pressure frequently


If necrotizing fasciitis is suspected, MRI may be helpful

Group a Streptococci
Management of Severe Disease

I. Hemodynamic stabilization - fluid resuscitation, inotropic agents

2. Necrotizing fasciitis suspected - drainage, debridement, fasciotomy,


amputation

3. Antimicrobial therapy
Initial parenteral antimicrobial therapy to cover GABH and S. aureus

Once GABHS has been identified, intravenous penicillin G (200,000 u


to 400,000 u/kg/day in 4 - 6 divided doses

Eagle phenomenon - failure of penicillin to eradicate GABHS when a large


inoculum is present

Group a Streptococci
Management of Severe Disease

Clindamycin - No Eagle phenomenon


inhibits synthesis of M protein and SPEs long post-antibiotic
effect

can not use alone because of resistance


Some experts recommend clindamycin (25 - 40 mg/kg/day in 3 or 4
divided doses) in addition to penicillin, no controlled clinical studies
demonstrating benefit

IVIG: 150 - 400 mg/kg/d for 5 days or I - 2 gm/kg given


once may be beneficial but no controlled clinical studies

Hyperbaric oxygen for necrotizing fasciitis - no controlled


clinical studies demonstrating benefit

Group a Streptococci
Prevention of Severe Disease

Immunization against varicella

Improving infection control practices for surgical procedures, obstetrics, and


placement or care of intravenous catheters

Chemoprophylaxis for close contacts

no data about which agents would be effective

no data about identifying contacts at increased risk

limited data about risk of secondary cases

Group a Streptococci
Prevention of Severe Disease

No recommendations for the routine use of chemoprophylaxis can be made


at this time

If contemplating for household contacts, consider the severity of disease in


index case, the extent of contact, underlying conditions in contacts, cost and
potential adverse effects of chemoprophylaxis

Not recommended in schools or child care facilities no reported secondary


cases low risk of invasive GABHS infection in children

Group a Streptococci
Impetigo

Most common skin infection in children

Most superficial skin infection

Indolent, well-tolerated infection, regional adenopathy but no systemic signs


or symptoms Most often on legs; arms > face > trunk

Importance of insults to integrity of skin

Group a Streptococci
Transmission

Pyoderma - direct contact, enhanced by crowding, poor living conditions, and


poor hygiene; does not invade normal skin - areas of trauma (bites,
abrasions, burns); flies may act as a mechanical vector; environmental
reservoirs (clothes, bedding, dust) - not important.

Group a Streptococci
Impetigo

Antimicrobial therapy:
minimize spread to others

prevent local extension does not prevent AGN


Two basic forms:

1. Thick crusted - common, begins as an erythematous papule in a


traumatized area, small transient vesicles, thick crusted lesions

2. Bullous - much less common, superficial bullae arising from normal


appearing skin

Group a Streptococci
Impetigo

Microbiology
Bullous - exclusively S. aureus

Thick crusted:

1960s and 1970s - GABHS, mixed, S. aureus


GABHS primary pathogen

1980s - S. aureus, mixed, GABHS


S. aureus primary pathogen, 100% res to
pen, 10% - 15% res to eryth
Therapy

Systemic oral more effective than topical


1960s and 1970s: bullous - treat for S. aureus
thick crusted - penicillin

1980s: either form - treat for S. aureus and GABHS

Potential agents: semisynthetic penicillin, erythromycin,cephalexin,


cefadroxil, clindamycin x 10 days

Group A Streptococci
Vulvovaginitis

GABHS was isolated from 18% of vaginal swabs submitted to a district


microbiology lab in London from girls with vulvovaginitis

Boisvert 1948
Usually prepubertal

Irritation and profuse greenish or serous discharge

Often associated with GABHS elsewhere but not always

Systemic penicillin

Group a Streptococci Perianal Cellulitis

12 of 22 (55%) children seen in pediatric surgery practice in NSW with


perianal cellulitis had GABHS

Amren 1966

Intense erythema, tender, boggy, cracking, superficial fissuring

Often associated with GABHS elsewhere but not always Systemic penicillin
Recurrences common

Bibliography

Gerber MA, Markowitz M. Streptococcal pharyngitis: cleaning up the


controversies. Contemp Pediatr 9: 118-1431, 1992.

Shulman ST. Streptococcal pharyngitis: diagnostic considerations. Pediatr


Infect Dis J. 13: 567-571, 1994.

Shulman ST, Gerber MA, Tanz RR, Markowitz M. Streptococcal pharyngitis:


the case for penicillin therapy. Pediatr Infect Dis J 13: 1-7, 1994.

Markowitz M, Gerber MA. Treatment of streptococccal pharyngotonsillitis:


reports of penicillin's demise are premature. J Pediatr 123: 679-685, 1993.

Pichichero ME. Cephalosporins are superior to penicillin for treatment of


streptococcal tonsillopharyngitis: is the difference worth it? Pediatr Infect Dis
J 12: 268-274, 1993.

Dajani A, Taubert K, Ferrieri P, et al. Treatment of acute streptococcal


pharyngitis and prevention of rheumatic fever: a statement for health
professionals Pediatrics 96:758764, 1995.

Gerber MA. Treatment failures and carriers: perception or problems? Pediatr


Infect Dis J. 13: 576-579, 1991.

Paradise JL, Bluestone CD, Bachman RZ, et al. Efficacy of tonsillectomy for
recurrent throat infection in severely affected children: results of parallel
randomized and nonrandomized clinical trials. N Engl J Med 310: 674-683,
1984.

Gerber MA, Tanz RR, Kabat W, et al. Optical immunoassay test for group A
beta-hemolytic streptococcal pharyngitis: an office-based, multicenter
investigation. JAMA 277: 899-903, 1997.

Gerber MA. Antibiotic resistance in group A streptococci. Pediatr Clin N. Am


42: 539551, 1995.

Gerber MA, Randolph MF, DeMao KK, Kaplan EL. Lack of impact of early
antibiotic therapy for streptococcal pharyngitis on recurrence rates. J Pediatr
117: 853-858, 1990.

Stevens DL. Streptococcal toxic-shock syndrome: spectrum of disease,


pathogenesis, and new concepts in treatment. Emerging Inf Dis 1: 69-78,
1995.

Davies HD, McGeer A, Schwartz B, et al. Invasive group A streptococcal


infections in Ontario, Canada. N. Engl J Med 335: 547-554, 1996.

Bisno AL. Group A streptococcal infections and acute rheumatic fever. N.


Engl J Med 325: 783-793, 1991.

Bisno AL, Stevens DL. Streptococcal infections of skin and soft tissues. N
Engl J Med 334:240-245, 1996.

Вам также может понравиться