European Review for Medical and Pharmacological Sciences

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Abstract. – OBJECTIVE: According to re-cent observations, the insufficiently targeteduse of antibiotics is creating increasingly resis-tant bacterial strains. In this context, it seemsincreasingly clear the need to resort to extremeand prudent rationalization of antibiotic thera-py, especially by the physicians working in pri-mary care units. In clinical practice, actually thegeneral practitioner often treats multiple dis-eases without having the proper equipment. Inparticular, the use of a dedicated, easy to usediagnostic test would be one more weapon forthe correct diagnosis and treatment of acutepharyngo-tonsillitis. The disease is a conditionfrequently encountered in clinical practice butits optimal management remains a controver-sial topic. In this context, the observationalstudy is intended to demonstrate the useful-ness of the rapid test (RAD: Rapid antigen de-tection) against group A beta-hemolytic strep-tococcus (GABHS) in everyday clinical practiceto identify individuals with acute streptococcalpharyngo-tonsillitis needing antibiotic therapyand to pursue the following objectives: (1) Get-ting the answer to an unmet medical need; (2)Promoting the appropriateness of the use ofantibiotics; (3) Provide a means of containmentin pharmaceutical spending.

PATIENTS AND METHODS: 50 patients pre-senting sore throat associated with erythemaand/or pharyngeal tonsillar exudate with or with-out scarlatiniform rash, fever and malaise hadbeen subjected to perform a rapid test (RAD:Rapid antigen detection) for the search of thebeta-hemolytic Streptococcus Group A (GABHS).Pharyngeal-tonsillar swabs were tested usingImmunospark (relative sensitivity 97.6%, relativespecificity 97.5%) according to manufacturer'sinstructions (runtime/reading response < 10min).

RESULTS: Of the 50 tests, 45 provided a nega-tive response while 5 were positive for thesearch of the beta-hemolytic Streptococcusgroup A. No test result has been invalid.

CONCLUSIONS: Based on the results ob-tained, only patients with a positive rapid testwere subjected to targeted antibiotic therapy.This has resulted in a significant cost savings in

Diagnosis and treatment of acutepharyngitis/tonsillitis: a preliminaryobservational study in General Medicine

F. DI MUZIO, M. BARUCCO, F. GUERRIERO

Azienda Sanitaria Locale Roma 4, Rome, Italy

Corresponding Author: Flavio Di Muzio, MD; e-mail: flaviodimuzio@yahoo.it

pharmaceutical expenditure, without neglectingthe more important and correct application ofthe Guidelines with performing of a clinically val-idated test that carries advantages for reducingthe use of unnecessary and potentially harmfulantibiotics and the consequent lower prevalenceand incidence of antibiotic-resistant bacterialstrains.

Key Words:Acute pharyngitis, Tonsillitis, Strep throat, Beta-he-

molytic streptococcus Group A (GABHS), Rapid anti-gen detection test, Appropriateness use of antibiotics,Cost savings in pharmaceutical spending.

Introduction

Physical examination of the oropharynx is thebest method for making a diagnosis of strepthroat but rarely provides sufficient evidence tosecure its etiology. Usually, there is a widespreadhyperemia of the mucosa of the tonsils, more orless extended to the pharynx, which may be asso-ciated with other signs such as tonsillar exudate,petechiae on the soft palate or, more rarely, sores.The tonsillar exudates – whitish or frankly pu-

rulent – is often considered the only element re-lated to the etiology of GABHS (Beta HemolyticStreptococcus Group A). Many viruses, in partic-ular adenovirus, and Epstein-Barr virus, may de-termine a comparative exudative tonsillitis, if noteven more accentuated than what would be ex-pected to be a typical GABHS. Petechiae are of-ten associated with a streptococcal etiology,while ulcerative lesions are most often associatedwith viral forms.Some epidemiological data and symptoms as-

sociated with local signs of strep throat may con-tribute to an etiologic diagnosis1,2. Typical indica-tions of the onset of the disease from GABHShave been: its acute onset, the absence of other

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acute respiratory tract illnesses in the patients’households, the onset in late winter or earlyspring, the age of 3-4 years, the high fever, thesore throat, intense headache and sore laterocer-vical lymphadenopathy.The viral forms, however, were thought to be

characterized by more modest acute systemicsymptoms, with less febrile temperature, butconcomitant involvement of the upper airways,the presence of family members with a similardisease, more gradual onset, usually in the sum-mer, and elective involvement of the very firstyears of life.The symptoms of streptococcal pharyngo-ton-

sillitis and non-streptococcal varieties overlapand merge so widely that an accurate diagnosismade only on the basis of clinical signs is virtual-ly impossible, although some have been pro-posed as clinical scores, such as the Mc Isaac3.Considering that the acute pharyngo-tonsillitis

is one of the diseases that pediatricians and gener-al practitioners most frequently encounter (15 mil-lion visits per year in the US alone), only a rela-tively small percentage of patients (20%-30% ofpediatric patients, even less in adults) are actuallysuffering from pharyngo-tonsillitis by GABHS.With the exception of other rare bacterial in-

fections of the pharynx (caused by Corynebac-terium diphtheriae and Neisseria gonorrhoeae),antibiotic therapy is unnecessary for the acutepharyngo-tonsillitis caused by other microorgan-isms than GABHS even more so because mostcases are caused by viruses and in particular ade-novirus, influenza and parainfluenza viruses. It isextremely important to make the diagnosis accu-rately to avoid unnecessary and potentially harm-ful antibiotic prescriptions4-6.At present, it is recommended to obtain a pha-

ryngeal tonsillar swab for rapid antigen testing(RAD: Rapid antigen detection) in children oradolescents with a history, signs and/or symp-toms of suspected infection by GABHS. If RADtest response is negative in subjects where thereis strong evidence or suspicion of infection, abacterial culture should be performed. In the caseof a positive RAD test response, the bacterialculture is not necessary for the high reliabilityand specificity of the tests7-9.Bacterial culture is not necessary for the rou-

tine diagnosis of an acute pharyngitis by GABHSin consideration of the correlation of the rapidtest with culture. The dosage of the anti strepto-coccus antibodies ASO (Anti-streptolysin O) isnot recommended in the routine diagnosis of

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Diagnosis and treatment of acute pharyngitis/tonsillitis

Figure 1.

streptococcal pharyngitis because the presence ofthese antibodies reflects past infections and notongoing infections10.Once diagnosed, patients with streptococcal

pharyngo-tonsillitis should be treated with anappropriate antibiotic, in the correct dosage forthe duration necessary for the eradication ofGABHS from the pharynx. Baseline antibioticsfor not allergic patients are penicillins, in partic-ular amoxicillin. Treatment of streptococcalpharyngo-tonsillitis in patients allergic to peni-cillin should include (except cross-reactions) afirst-generation cephalosporin/second genera-tion for 10 days (5-6 days for a third-generationcephalosporin in case of dubious compliance to10-days therapy) or clarithromycin for 10 daysor azithromycin for 5 days: recommended forpatients with demonstrated IgE-mediated aller-gy to β-lactam because of reporting macrolidesresistant bacterial strains11-15.

Patients and Methods

PatientFrom November 2014 to April 2015, 50 adult

patients (mean age 27.48 years) with signs andsymptoms of acute pharyngo-tonsillitis were ob-served, in a study of general medicine. These pa-tients, who in the absence of diagnostic tests(rapid test for GABHS), and even applying EBM(Evidence Based Medicine), may be treated withoral antibiotics (penicillin/cephalosporin ormacrolide if allergic). Informed consent wassigned and reported in medical records.Inclusion criteria (Figures 1 and 2): Major:

sore throat associated with erythema and/or pha-

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F. Di Muzio, M. Barucco, F. Guerriero

ryngeal/tonsillar exudate with or without scarla-tiniform rash. Minor: fever, general malaise. Ma-jor criteria must always be present.

Materials and CostsRapid Test Detection Kits for Beta hemolytic

Streptococcus group A of Immunospark (relativesensitivity 97.6%, relative specificity 97.5%)were used: the average price for each test beingabout €2.00. Total cost (figurative) €100.00.The tests were provided “free of charge” by theS.D. srl (Servizi Diagnostici Srl, Rome, Italy)and administered to patients without charge. Notest result was invalid.

MethodologyCarrying out of pharyngeal-tonsillar swab ac-

cording to manufacturer’s instructions (run-time/reading result < 10 min).

Results

The presence of only one band of quality con-trol for negative response in 45 tests (90% of pa-tients).The presence of dual band for positive re-

sponse in 5 tests (10% of patients) (Figure 3).Based on the data obtained, only patients with

positive response to the rapid test were subjectedto antibiotic therapy. For 3 patients amoxicillinwas used for 10 days; for 2 patients Ceftibutenwas used for 6 days. Total cost of antibiotic ther-apy €65.56.

Total amount: €100.00 (figurative total cost of50 kits) + €65.56 (total cost of antibiotic therapyfor positive RAD patients) = €165.56 (Figure 4).If all 50 patients were treated equally, based

only on clinical evaluation (without the adminis-tering of the rapid test), with amoxicillin (notconsidering any allergies to penicillin and/or dif-ferent treatment choices) the cost of antibioticswould be: €6.54 (two pill boxes/person) x 50 =€327.00 (Figure 4).The cost savings from only the positive pa-

tients treated correctly (rapid test + antibiotic adhoc) and all 50 patients who were treated empiri-cally based only on clinical data (only antibioticwithout rapid test) would be as follows: €100.00(figurative total cost 50 kit) + €65.56 (total costof antibiotic therapy for positive RAD patients) –€327.00 (pharmaceutical expenditure of all 50patients treated without distinction) = –€161.44equal to 49.4% (Figure 4).If we consider the use of the currently more

expensive oral antibiotic (ceftibuten) for onlypositive patients compared with the possibletreatment of all 50 patients with the cheapest an-tibiotic (amoxicillin), the cost savings will be:€100.00 (figurative total cost 50 kit) + €114.85(5 pill boxes of ceftibuten for the only positivepatients) – €327.00 (All patients treated withamoxicillin) = –€112.15 equal to 34.4% (Figure4).

Discussion

Besides the savings in pharmaceutical expen-diture in comparison to a small charge for thecost of testing (in this case figurative total costthanks to free delivery), we should not neglectthe more important and correct application of theGuidelines.The use of the rapid antigen detection test

against group A beta-hemolytic streptococcus(GABHS) carries advantages especially in the

Figure 2.

Figure 3.

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Diagnosis and treatment of acute pharyngitis/tonsillitis

sense of a significant reduction in the use of un-necessary and potentially harmful antibioticswith a lower prevalence of drug-resistant formsof bacteria.This small observational study in General

Medicine demonstrates that the use of rapid testshas been proven both feasible and desirable.

Conclusions

Rapid tests, when the Guidelines are applied,can help curb both pharmaceutical expenditureand the inappropriate use of antibiotics.

–––––––––––––––––-––––Conflict of InterestThe Authors declare that there are no conflicts of interest.

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Figure 4. Cost savings of pharmaceutical expenditure.

All treated withAmoxicillin vs.

only positive treated

All treated withAmoxicillin vs. all positivetreated with Ceftibuten

Amoxicillin

Only positive RADtest treated

Exp

enditure

foran

tibiotics

49.4% 34.4%

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