European Review for Medical and Pharmacological Sciences
2016; 20: 4950-4954
Diagnosis and treatment of acute
pharyngitis/tonsillitis: a preliminary
observational study in General Medicine
F. DI MUZIO, M. BARUCCO, F. GUERRIERO
Azienda Sanitaria Locale Roma 4, Rome, Italy
Abstract. – OBJECTIVE: According to recent observations, the insufficiently targeted
use of antibiotics is creating increasingly resistant bacterial strains. In this context, it seems
increasingly clear the need to resort to extreme
and prudent rationalization of antibiotic therapy, especially by the physicians working in primary care units. In clinical practice, actually the
general practitioner often treats multiple diseases without having the proper equipment. In
particular, the use of a dedicated, easy to use
diagnostic test would be one more weapon for
the correct diagnosis and treatment of acute
pharyngo-tonsillitis. The disease is a condition
frequently encountered in clinical practice but
its optimal management remains a controversial topic. In this context, the observational
study is intended to demonstrate the usefulness of the rapid test (RAD: Rapid antigen detection) against group A beta-hemolytic streptococcus (GABHS) in everyday clinical practice
to identify individuals with acute streptococcal
pharyngo-tonsillitis needing antibiotic therapy
and to pursue the following objectives: (1) Getting the answer to an unmet medical need; (2)
Promoting the appropriateness of the use of
antibiotics; (3) Provide a means of containment
in pharmaceutical spending.
PATIENTS AND METHODS: 50 patients presenting sore throat associated with erythema
and/or pharyngeal tonsillar exudate with or without scarlatiniform rash, fever and malaise had
been subjected to perform a rapid test (RAD:
Rapid antigen detection) for the search of the
beta-hemolytic Streptococcus Group A (GABHS).
Pharyngeal-tonsillar swabs were tested using
Immunospark (relative sensitivity 97.6%, relative
specificity 97.5%) according to manufacturer's
instructions (runtime/reading response < 10
min).
RESULTS: Of the 50 tests, 45 provided a negative response while 5 were positive for the
search of the beta-hemolytic Streptococcus
group A. No test result has been invalid.
CONCLUSIONS: Based on the results obtained, only patients with a positive rapid test
were subjected to targeted antibiotic therapy.
This has resulted in a significant cost savings in
4950
pharmaceutical expenditure, without neglecting
the more important and correct application of
the Guidelines with performing of a clinically validated test that carries advantages for reducing
the use of unnecessary and potentially harmful
antibiotics and the consequent lower prevalence
and incidence of antibiotic-resistant bacterial
strains.
Key Words:
Acute pharyngitis, Tonsillitis, Strep throat, Beta-hemolytic streptococcus Group A (GABHS), Rapid antigen detection test, Appropriateness use of antibiotics,
Cost savings in pharmaceutical spending.
Introduction
Physical examination of the oropharynx is the
best method for making a diagnosis of strep
throat but rarely provides sufficient evidence to
secure its etiology. Usually, there is a widespread
hyperemia of the mucosa of the tonsils, more or
less extended to the pharynx, which may be associated with other signs such as tonsillar exudate,
petechiae on the soft palate or, more rarely, sores.
The tonsillar exudates – whitish or frankly purulent – is often considered the only element related to the etiology of GABHS (Beta Hemolytic
Streptococcus Group A). Many viruses, in particular adenovirus, and Epstein-Barr virus, may determine a comparative exudative tonsillitis, if not
even more accentuated than what would be expected to be a typical GABHS. Petechiae are often associated with a streptococcal etiology,
while ulcerative lesions are most often associated
with viral forms.
Some epidemiological data and symptoms associated with local signs of strep throat may contribute to an etiologic diagnosis1,2. Typical indications of the onset of the disease from GABHS
have been: its acute onset, the absence of other
Corresponding Author: Flavio Di Muzio, MD; e-mail: flaviodimuzio@yahoo.it
Diagnosis and treatment of acute pharyngitis/tonsillitis
acute respiratory tract illnesses in the patients’
households, the onset in late winter or early
spring, the age of 3-4 years, the high fever, the
sore throat, intense headache and sore laterocervical lymphadenopathy.
The viral forms, however, were thought to be
characterized by more modest acute systemic
symptoms, with less febrile temperature, but
concomitant involvement of the upper airways,
the presence of family members with a similar
disease, more gradual onset, usually in the summer, and elective involvement of the very first
years of life.
The symptoms of streptococcal pharyngo-tonsillitis and non-streptococcal varieties overlap
and merge so widely that an accurate diagnosis
made only on the basis of clinical signs is virtually impossible, although some have been proposed as clinical scores, such as the Mc Isaac3.
Considering that the acute pharyngo-tonsillitis
is one of the diseases that pediatricians and general practitioners most frequently encounter (15 million visits per year in the US alone), only a relatively small percentage of patients (20%-30% of
pediatric patients, even less in adults) are actually
suffering from pharyngo-tonsillitis by GABHS.
With the exception of other rare bacterial infections of the pharynx (caused by Corynebacterium diphtheriae and Neisseria gonorrhoeae),
antibiotic therapy is unnecessary for the acute
pharyngo-tonsillitis caused by other microorganisms than GABHS even more so because most
cases are caused by viruses and in particular adenovirus, influenza and parainfluenza viruses. It is
extremely important to make the diagnosis accurately to avoid unnecessary and potentially harmful antibiotic prescriptions4-6.
At present, it is recommended to obtain a pharyngeal tonsillar swab for rapid antigen testing
(RAD: Rapid antigen detection) in children or
adolescents with a history, signs and/or symptoms of suspected infection by GABHS. If RAD
test response is negative in subjects where there
is strong evidence or suspicion of infection, a
bacterial culture should be performed. In the case
of a positive RAD test response, the bacterial
culture is not necessary for the high reliability
and specificity of the tests7-9.
Bacterial culture is not necessary for the routine diagnosis of an acute pharyngitis by GABHS
in consideration of the correlation of the rapid
test with culture. The dosage of the anti streptococcus antibodies ASO (Anti-streptolysin O) is
not recommended in the routine diagnosis of
streptococcal pharyngitis because the presence of
these antibodies reflects past infections and not
ongoing infections10.
Once diagnosed, patients with streptococcal
pharyngo-tonsillitis should be treated with an
appropriate antibiotic, in the correct dosage for
the duration necessary for the eradication of
GABHS from the pharynx. Baseline antibiotics
for not allergic patients are penicillins, in particular amoxicillin. Treatment of streptococcal
pharyngo-tonsillitis in patients allergic to penicillin should include (except cross-reactions) a
first-generation cephalosporin/second generation for 10 days (5-6 days for a third-generation
cephalosporin in case of dubious compliance to
10-days therapy) or clarithromycin for 10 days
or azithromycin for 5 days: recommended for
patients with demonstrated IgE-mediated allergy to β-lactam because of reporting macrolides
resistant bacterial strains11-15.
Patients and Methods
Patient
From November 2014 to April 2015, 50 adult
patients (mean age 27.48 years) with signs and
symptoms of acute pharyngo-tonsillitis were observed, in a study of general medicine. These patients, who in the absence of diagnostic tests
(rapid test for GABHS), and even applying EBM
(Evidence Based Medicine), may be treated with
oral antibiotics (penicillin/cephalosporin or
macrolide if allergic). Informed consent was
signed and reported in medical records.
Inclusion criteria (Figures 1 and 2): Major:
sore throat associated with erythema and/or pha-
Figure 1.
4951
F. Di Muzio, M. Barucco, F. Guerriero
Figure 2.
ryngeal/tonsillar exudate with or without scarlatiniform rash. Minor: fever, general malaise. Major criteria must always be present.
Materials and Costs
Rapid Test Detection Kits for Beta hemolytic
Streptococcus group A of Immunospark (relative
sensitivity 97.6%, relative specificity 97.5%)
were used: the average price for each test being
about €2.00. Total cost (figurative) €100.00.
The tests were provided “free of charge” by the
S.D. srl (Servizi Diagnostici Srl, Rome, Italy)
and administered to patients without charge. No
test result was invalid.
Methodology
Carrying out of pharyngeal-tonsillar swab according to manufacturer’s instructions (runtime/reading result < 10 min).
Results
The presence of only one band of quality control for negative response in 45 tests (90% of patients).
The presence of dual band for positive response in 5 tests (10% of patients) (Figure 3).
Based on the data obtained, only patients with
positive response to the rapid test were subjected
to antibiotic therapy. For 3 patients amoxicillin
was used for 10 days; for 2 patients Ceftibuten
was used for 6 days. Total cost of antibiotic therapy €65.56.
4952
Total amount: €100.00 (figurative total cost of
50 kits) + €65.56 (total cost of antibiotic therapy
for positive RAD patients) = €165.56 (Figure 4).
If all 50 patients were treated equally, based
only on clinical evaluation (without the administering of the rapid test), with amoxicillin (not
considering any allergies to penicillin and/or different treatment choices) the cost of antibiotics
would be: €6.54 (two pill boxes/person) x 50 =
€327.00 (Figure 4).
The cost savings from only the positive patients treated correctly (rapid test + antibiotic ad
hoc) and all 50 patients who were treated empirically based only on clinical data (only antibiotic
without rapid test) would be as follows: €100.00
(figurative total cost 50 kit) + €65.56 (total cost
of antibiotic therapy for positive RAD patients) –
€327.00 (pharmaceutical expenditure of all 50
patients treated without distinction) = –€161.44
equal to 49.4% (Figure 4).
If we consider the use of the currently more
expensive oral antibiotic (ceftibuten) for only
positive patients compared with the possible
treatment of all 50 patients with the cheapest antibiotic (amoxicillin), the cost savings will be:
€100.00 (figurative total cost 50 kit) + €114.85
(5 pill boxes of ceftibuten for the only positive
patients) – €327.00 (All patients treated with
amoxicillin) = –€112.15 equal to 34.4% (Figure
4).
Discussion
Besides the savings in pharmaceutical expenditure in comparison to a small charge for the
cost of testing (in this case figurative total cost
thanks to free delivery), we should not neglect
the more important and correct application of the
Guidelines.
The use of the rapid antigen detection test
against group A beta-hemolytic streptococcus
(GABHS) carries advantages especially in the
Figure 3.
Diagnosis and treatment of acute pharyngitis/tonsillitis
49.4%
Expenditure for antibiotics
34.4%
Amoxicillin
Only positive RAD
test treated
All treated with
Amoxicillin vs.
only positive treated
All treated with
Amoxicillin vs. all positive
treated with Ceftibuten
Figure 4. Cost savings of pharmaceutical expenditure.
sense of a significant reduction in the use of unnecessary and potentially harmful antibiotics
with a lower prevalence of drug-resistant forms
of bacteria.
This small observational study in General
Medicine demonstrates that the use of rapid tests
has been proven both feasible and desirable.
Conclusions
Rapid tests, when the Guidelines are applied,
can help curb both pharmaceutical expenditure
and the inappropriate use of antibiotics.
–––––––––––––––––-––––
Conflict of Interest
The Authors declare that there are no conflicts of interest.
References
1) Shaikh N, Leonard E, Martin JM. Prevalence of
streptococcal pharyngitis and streptococcal carriage in children: a meta-analysis. Pediatrics
2010; 126: e557-64.
2) CHIAPPINI E, REGOLI M, BONSIGNORI F, SOLLAI S, PARRETTI A, GALLI L, DE MARTINO M. Analysis of different
recommendations from international guidelines
for the management of acute pharyngitis in adults
and children. Clin Ther 2011; 33: 48-58.
3) PALLA AH, KHAN RA, GILANI AH, MARRA F. Over prescription of antibiotics for adult pharyngitis is
prevalent in developing countries but can be reduced using McIsaac modification of Centor
scores: a cross-sectional study. BMC Pulm Med
2012; 12: 70.
4) WINDFUHR JP, TOEPFNER N, STEFFEN G, WALDFAHRER F,
BERNER R. Clinical practice guideline: tonsillitis I. Diagnostics and nonsurgical management. Eur Arch
Otorhinolaryngol 2016 Jan 11. [Epub ahead of
print].
5) S UNJOO K. Optimal diagnosis and treatment of
group A streptococcal phar yngitis. Infect
Chemother 2015; 47: 202-204.
6) AGARWAL M, RAGHUWANSHI SK, ASATI DP. Antibiotic
use in sore throat: are we judicious? Indian J
Otolaryngol Head Neck Surg 2015; 67: 267270.
7) GUROL Y, AKAN H, IZBIRAK G, TEKKANAT ZT, GUNDUZ
TS, HAYRAN O, YILMAZ G. The sensitivity and the
specifity of the rapid test in streptococcal upper
respiratory tract infections. Int J Pediatr Otorhinolaryngol 2010; 74: 591-593.
8) ESCMID SORE THROAT GUIDELINE GROUP, PELUCCHI C,
GRIGORYAN L, GALEONE C, ESPOSITO S, HUOVINEN P, LITTLE P, VERHEIJ T. Guideline for the management of
acute sore throat. Clin Microbiol Infect 2012; 18
Suppl 1: 1-28.
9) TAJBAKHSH S, GHARIBI S, ZANDI K, YAGHOBI R, ASAYESH
G. Rapid detection of Streptococcus pyogenes in
throat swab specimens by fluorescent in situ hybridization. Eur Rev Med Pharmacol Sci 2011; 15:
313-317.
10) CHIAPPINI E, PRINCIPI N, MANSI N, SERRA A, DE MASI S,
CAMAIONI A, ESPOSITO S, FELISATI G, GALLI L, LANDI M,
4953
F. Di Muzio, M. Barucco, F. Guerriero
SPECIALE AM, BONSIGNORI F, MARCHISIO P, DE MARTINO
M; ITALIAN PANEL ON THE MANAGEMENT OF PHARYNGITIS
IN CHILDREN. Management of acute pharyngitis in
children: summary of the Italian National Institute
of Health guidelines. Clin Ther 2012; 34: 14421458.
11) SHULMAN ST, BISNO AL, CLEGG HW, GERBER MA, KAPLAN EL, LEE G, MARTIN JM, VAN BENEDEN C. Clinical
practice guideline for the diagnosis and management of group A streptococcal pharyngitis: 2012
update by the Infectious Diseases Society of
America. Clin Infect Dis 2012; 55: 1279-1282.
12) THE SANFORD GUIDE TO ANTIMICROBIAL THERAPY, 43th
Edition, 2013.
4954
13) GAJIC I, MIJAC V, STANOJEVIC M, RANIN L, SMITRAN A,
OPAVSKI N. Typing of macrolide resistant group A
streptococci by random amplified polymorphic
DNA analysis. Eur Rev Med Pharmacol Sci 2014;
18: 2960-2965.
14) PINTUCCI JP, CORNO S, GAROTTA M. Biofilms and infections of the upper respiratory tract. Eur Rev
Med Pharmacol Sci 2010; 14: 683-690
15) W A J I M A T, C H I B A N, M O R O Z U M I M, S H O U J I M,
SUNAOSHI K, SUGITA K, TAJIMA T, UBUKATA K; GAS SURVEILLANCE STUDY GROUP. Prevalence of macrolide resistance among group A streptococci isolated
from pharyngo-tonsillitis. Microb Drug Resist
2014; 20: 431-435.