Strep Throat-Recurrent

by Michael E. Pichichero, M.D.
Professor of Microbiology and Immunology, Pediatrics and Medicine
University of Rochester Medical Center
Elmwood Pediatric Group

If a child or a teenager has repeated episodes of streptococcal tonsillitis or pharyngitis
(“strep throat”), several possible explanations should be considered.

Are the sore throats actually caused by strep?

Many physicians diagnose strep throat infections based on a patient’s history and
an examination. However, without the aid of a throat culture or a rapid strep detection
test, recurrent strep throat infections are difficult to accurately diagnosis. The
complaint of a sore throat is frequent in the primary care practice setting. Yet,
at the peak of the strep throat infection season (late fall through early spring),
strep is the cause of a sore throat in less than 30% of children and 10% of teenagers.

Therefore, strictly on a percentage basis, physicians, who diagnose strep in the
majority of patients with a sore throat, over-diagnose 90% of teenagers and 70%
of children. Even in a patient with typical symptoms-a fever, a red throat with
yellow pus on the tonsils, swollen and tender neck lymph glands, and the absence
of a runny nose and a cough-misdiagnosis is common. In one study, an overestimate
of the probability of a positive strep culture was observed for 81% of the patients.

To accurately diagnose strep throat infections, physicians use throat cultures (the
gold standard) or rapid strep detection tests. Rapid strep detection tests improve
the accuracy of diagnosing strep throat infections. The accuracy of rapid strep
detection tests varies between products, but the main variable is in the carefulness
of performing the test. The critical factor is attention to detail and strictly
following the manufacturers’ guidelines for the test.

Table 1.

Causes of Pharyngitis

Peak Incidence (%)
Cause Children Adults
Bacterial 30 to 40 5 to 10
GAS 28 to 40 5 to 9
Group C, G, or F Streptococcus 0 to 3 0 to 18
N gonorrhoeae 0 to 0.01 0 to 0.01
A haemolyticum 0 to 0.05 0 to 10
M pneumoniae 0 to 3 0 to 10
C pneumoniae 0 to 3 0 to 9
Viral 15 to 40 30 to 60
Idiopathic 20 to 55 30 to 65
Data compiled from Reference 1.

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Did the patient finish the prescribed antibiotic?

Patients often do not finish the complete treatment of antibiotics. The symptoms
of strep throat end quickly with antibiotics; patients feel completely better within
two to three days after beginning treatment. Because of this improved well being,
parent motivation to continue the medicine diminishes.

Studies from hospital-based clinics and private practices have confirmed that as
many as 50% of patients have stopped taking penicillin for strep throat by the third
day, 70% by the sixth day, and over 80% by the ninth day. In the same populations,
over 80% of the families claimed that all of the prescribed medicine had been taken.

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Is the problem antibiotic resistance or tolerance?

The following antibiotics-penicillin, amoxicillin, and cephalosporins (i.e., Keflex,
Duricef, Ceclor, Lorabid, Ceftin, Cefzil, Vantin, Suprax, Cedax, and Omnicef)-are
effective in treating strep throat infections. Infrequently, strep throat infections
are resistant to Erythromycin, clarithromycin (Biaxin), and azithromycin (Zithromax).

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Is the patient experiencing repeated exposure to strep?

Some patients are effectively treated for a strep infection with antibiotics, only
to return to an environment where the infection continues to circulate. The patient
then becomes re-infected and returns to the physician with a recurrent strep throat
infection. Certain circumstances-crowded working conditions, schools, day care settings,
and larger families-more frequently transmit strep. One small study and one case
report have suggested that, in rare instances, dogs also may be carriers of strep;
however, other investigations have not corroborated this possibility.

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Is the patient not responding to antibiotics?

Even when all strep infections are laboratory confirmed with throat cultures or
rapid strep detection tests, and the antibiotic is finished, failure to respond
to treatment still occurs. The highest treatment failure rates observed are with
penicillin; about two-thirds of presumed strep throat infections are treated with
either penicillin or amoxicillin. Penicillin and amoxicillin treatment failures
vary geographically, and the incidence of penicillin treatment failures for strep
throat infections may be rising. Patients most likely to experience a penicillin
or amoxicillin treatment failure are those who have recently received treatment
with these drugs and are then retreated with the same antibiotic.

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Has prior antibiotic therapy eliminated protective throat bacteria?

Prominent, normal bacteria of the throat include another type of streptococci (alpha
hemolytic). These bacteria make natural antibiotic substances (to provide an advantage
for themselves) in the throat. Penicillin or amoxicillin therapy may change the
natural environment for throat bacteria by killing these alpha hemolytic streptococci;
their elimination provides an opportunity for disease-causing strep to gain access
to the throat cells. This is another reason for patients to avoid unnecessary antibiotic
use.

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Has early, prompt antibiotic treatment suppressed natural immunity?

With the availability of rapid strep detection tests and the publication of several
convincing studies that describe faster clinical improvement from prompt treatment,
many physicians have been prescribing antibiotics sooner after diagnosing strep
throat infections.

Immediate penicillin treatment has been shown to be a cause of recurrent strep infections.
Early antibiotic treatment suppresses the natural immune response to strep. Delaying
antibiotic therapy for two days after the onset of a sore throat allows an immune
response to develop, which may reduce the chance of a relapse or recurrence of strep
throat infections.

Two similar studies compared immediate penicillin treatment with treatment delayed
for 48 to 56 hours in 343 children with documented strep throats. Early antibiotic
therapy produced a three-time increase in the frequency of recurrent infections
as compared to those for whom treatment was delayed.

Table 2.

Recurrence Rates of Immediate versus Delayed Treatment of GAS Tonsillopharyngitis
with Penicillin

Treatment Group (n)(%)*

Recurrent Acute GAS Pharyngitis

Immediate Treatment(n=70)

Delayed Treatment
(48 to 56 hr)
(n=173)

Early recurrence 32 (19) 14 (8) 0.006
Late recurrence 22 (13) 5 (3) 0.001
Total recurrence 54 (32) 19 (11) <.001
*Treatment groups compared by x2 of Fisher’s exact test,
as appropriate; data compiled from References 12 and 13.

A delay in treatment does not increase the risk of rheumatic fever since a delay
of up to nine days from the onset of symptoms can be made. Nevertheless, for patients
who appear severely ill or in times when highly infectious strains of strep are
circulating, intentionally delayed treatment should not be considered.

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Is the patient a strep carrier?

A positive throat culture or a rapid strep test alone cannot distinguish between
the patient with strep throat and the patient with an acute viral sore throat who
is a chronic strep carrier. The strep carrier has a positive throat culture, but
does not show symptoms of an acute strep infection or show a rise in strep antibody
levels. In clinical practice, identifying a strep carrier is problematic.

Following treatment, the patient needs to be seen again to determine whether strep
is present when the patient does not have a sore throat. In addition, antibody levels
need to be drawn when the patient has a sore throat and then drawn again four to
six weeks later to measure strep antibodies. If antibiotic therapy has been given
to treat prior symptoms, it may suppress the antibody rise, thereby negating the
usefulness of this test.

Table 3.

Short-Course Treatment of Streptococcal Phayngitis

Bacteriologic Cure

Duration of
Rx(days)

Cephalosporin or Azithromycin

Penicillin (10 days)

Cefuroxime axetil 4 82/90 (96%) 77/80 (96%)
Cefadroxil 5 87/104 (84%) 93/105 (89%)
Cefpodoxime proxetil 5 59/61 (97%) 49/52 (94%)
Cefpodoxime proxetil 5 79/82 (96%) 64/68 (94%)
Cefuroxime axetil 4 83/97 (88%) 90/103 (87%)
Cefpodoxime proxetil 5 112/121 (93%) 101/130 (78%)
Azithromycin 5 167/176 (95%) 130/187 (77%)
Azithromycin 5 139/147 (95%) 88/127 (69%)
Data compiled from Reference 15.

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What antibiotic should be selected?

Many antibiotics—such as penicillin-can be used to treat recurrent strep throat
infections.

Clindamycin or rifampin, in combination with a second antibiotic, such as penicillin,
amoxicillin, or a cephalosporin, has been used to treat acute, recurrent, and carrier
strep throat infections. Routine use of clindamycin is not advocated because diarrhea
is a rare, but significant, side effect. Rifampin must be used with a second antibiotic
because strep will rapidly become resistant to it when it is given as a single therapy.
Patients should be advised that rifampin produces orange discoloration of the urine
and tears (permanently staining contact lenses).

Oral cephalosporins (Keflex, Duracef, Ceclor, Lorabid, Ceftin, Cefzil, Suprax, Vantin,
Omnicef, and Cedax) have gained widespread use in treating recurrent strep throat
infections. When cephalosporin antibiotics are used to treat strep throat infections,
a failure occurs less than 5% of the time; however, they are more expensive than
penicillin or amoxicillin.

Amoxicillin/clavulanic acid (Augmentin) has been evaluated to treat strep throat
with superior or equivalent results in comparison to penicillin.

Table 4.

Penicillin versus Cephalosporins in the Treatment of Streptococcal Pharyngitis

Treatment Regimen

n

Bacteriologic Failure Rate (%)

n

Clincial Failure Rate

Cephalosporins 1290 8.01 926 5.02
Penicillins 1169 16.01 865 11.02
1p = 0.0001
2p < 0.001
Data compiled from Reference 8.

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Should a tonsillectomy be performed?

If a patient has six to seven recurrent strep throat infections over a one-to two-year
time span, then a tonsillectomy should be considered after consulting with your
primary care physician. Families should be advised that the procedure reduces the
frequency of sore throats, and, specifically, strep throats, for two to three years
after surgery.

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About the Author

Dr. Michael E. Pichichero is currently a Professor of Microbiology and Immunology,
Pediatrics and Medicine at the University of Rochester in Rochester, NY.

A graduate of the University of Rochester School of Medicine, Dr. Pichichero completed
his postgraduate pediatric residency at the University of Colorado in Denver, followed
by a Chief Residency and two fellowships resulting in board certification in Pediatrics,
in Adult and Pediatric Allergy and Immunology and in Pediatric Infectious Disease.

Dr. Pichichero is a partner in the Elmwood Pediatric Group where he continues to
practice in primary care and as a subspecialist consultant.

A recipient of numerous awards and a member of most professional societies in his
fields of interest, Mike has over 300 publications in infectious diseases, immunology,
and allergy.

His major practice and research interests are in vaccine development, streptococcal
infections, and otitis media: in each of these areas he is a prominent international
authority.

Copyright 2012 Michael E. Pichichero, M.D., All Rights Reserved