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Home , Pharyngitis, Tonsillitis

Eur opean Rev iew for Med ical and Pharmacol ogical Sci ences 2016; 20: 4950-4954 Diagnosis and treatment of /: 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 re - pharmaceutical expenditure, without neglecting cent observations, the insufficiently targeted the more important and correct application of use of is creating increasingly resis - the Guidelines with performing of a clinically val - tant bacterial strains. In this context, it seems idated test that carries advantages for reducing increasingly clear the need to resort to extreme the use of unnecessary and potentially harmful and prudent rationalization of thera - antibiotics and the consequent lower prevalence py, especially by the physicians working in pri - and incidence of antibiotic-resistant bacterial mary care units. In clinical practice, actually the strains. general practitioner often treats multiple dis - eases without having the proper equipment. In Key Words: particular, the use of a dedicated, easy to use Acute pharyngitis, Tonsillitis, Strep , Beta-he - diagnostic test would be one more weapon for molytic Group A (GABHS), Rapid anti - the correct diagnosis and treatment of acute gen detection test, Appropriateness use of antibiotics, pharyngo-tonsillitis. The disease is a condition Cost savings in pharmaceutical spending. frequently encountered in clinical practice but its optimal management remains a controver - sial topic. In this context, the observational study is intended to demonstrate the useful - ness of the rapid test (RAD: Rapid antigen de - Introduction tection) against group A beta-hemolytic strep - tococcus (GABHS) in everyday clinical practice Physical examination of the oropharynx is the to identify individuals with acute streptococcal pharyngo-tonsillitis needing antibiotic therapy best method for making a diagnosis of strep and to pursue the following objectives: (1) Get - throat but rarely provides sufficient evidence to ting the answer to an unmet medical need; (2) secure its etiology. Usually , there is a widespread Promoting the appropriateness of the use of hyperemia of the mucosa of the , more or antibiotics; (3) Provide a means of containment less extended to the , which may be asso - in pharmaceutical spending. ciated with other signs such as tonsillar , PATIENTS AND METHODS: 50 patients pre - senting associated with petechiae on the soft palate or, more rarely, sores . and/or pharyngeal tonsillar exudate with or with - The tonsillar – whitish or frankly pu - out scarlatiniform rash, and had rulent – is often considered the only element re - been subjected to perform a rapid test (RAD: lated to the etiology of GABHS (Beta Hemolytic Rapid antigen detection) for the search of the Streptococcus Group A ). Many , in partic - beta-hemolytic Streptococcus Group A (GABHS). ular adenovirus, and Epstein-Barr , may de - Pharyngeal-tonsillar swabs were tested using termine a comparative exudative tonsillitis, if not Immunospark (relative sensitivity 97.6%, relative specificity 97.5%) according to manufacturer's even more accentuated than what would be ex - instructions (runtime/reading response < 10 pected to be a typical GABHS. Petechiae are of - min). ten associated with a streptococcal etiology, RESULTS: Of the 50 tests, 45 provided a nega - while ulcerative lesions are most often associated tive response while 5 were positive for the with viral forms. search of the beta-hemolytic Streptococcus Some epidemiological data and symptoms as - group A. No test result has been invalid. sociated with local signs of strep throat may con - CONCLUSIONS: Based on the results ob - 1,2 tained, only patients with a positive rapid test tribute to an etiologic diagnosis . Typical indica - were subjected to targeted antibiotic therapy. tions of the onset of the disease from GABHS This has resulted in a significant cost savings in have been: its acute onset, the absence of other

4950 Corresponding Author: Flavio Di Muzio, MD; e-mail: [email protected] Diagnosis and treatment of acute pharyngitis/tonsillitis acute illnesses in the patients’ streptococcal pharyngitis because the presence of households, the onset in late winter or early these antibodies reflects past and not spring, the age of 3-4 years, the high fever, the ongoing infections 10 . sore throat, intense and sore laterocer - Once diagnosed, patients with streptococcal vical . pharyngo-tonsillitis should be treated with an The viral forms, however, were thought to be appropriate antibiotic, in the correct dosage for characterized by more modest acute systemic the duration necessary for the eradication of symptoms, with less febrile temperature, but GABHS from the pharynx. Baseline antibiotics concomitant involvement of the upper airways, for not allergic patients are , in partic - the presence of family members with a similar ular . Treatment of streptococcal disease, more gradual onset, usually in the sum - pharyngo-tonsillitis in patients allergic to peni - mer, and elective involvement of the very first cillin should include (except cross-reactions) a years of life. first-generation /second genera - The symptoms of streptococcal pharyngo-ton - tion for 10 days (5-6 days for a third-generation sillitis and non-streptococcal varieties overlap cephalosporin in case of dubious compliance to and merge so widely that an accurate diagnosis 10-days therapy) or clarithromycin for 10 days made only on the basis of clinical signs is virtual - or for 5 days: recommended for ly impossible, although some have been pro - patients with demonstrated IgE-mediated aller - 3 posed as clinical scores, such as the Mc Isaac . gy to β-lactam because of reporting Considering that the acute pharyngo-tonsillitis resistant bacterial strains 11-15 . 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 - Patients and Methods tively small percentage of patients (20%-30% of pediatric patients, even less in adults) are actually Patient suffering from pharyngo-tonsillitis by GABHS. From November 2014 to April 2015, 50 adult With the exception of other rare bacterial in - patients (mean age 27.48 years) with signs and fections of the pharynx (caused by Corynebac - symptoms of acute pharyngo-tonsillitis were ob - terium diphtheriae and ), served, in a study of general medicine. These pa - antibiotic therapy is unnecessary for the acute tients, who in the absence of diagnostic tests pharyngo-tonsillitis caused by other microorgan - (rapid test for GABHS), and even applying EBM isms than GABHS even more so because most (Evidence Based Medicine) , may be treated with cases are caused by viruses and in particular ade - oral antibiotics (/cephalosporin or novirus, and parainfluenza viruses. It is if allergic). Informed consent was extremely important to make the diagnosis accu - signed and reported in medical records. rately to avoid unnecessary and potentially harm - Inclusion criteria (Figures 1 and 2): Major: ful antibiotic prescriptions 4-6 . sore throat associated with erythema and/or pha - At present , it is recommended to obtain a pha - ryngeal tonsillar swab for rapid antigen testing (RAD: Rapid antigen detection) in children or adolescents with a history, signs and/or symp - toms of suspected 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 tests 7-9 . Bacterial culture is not necessary for the rou - tine diagnosis of an acute pharyngitis by GABHS in consideration of the correlation of the rapid test with culture. The dosage of the anti strepto - coccus antibodies ASO (Anti-streptolysin O) is not recommended in the routine diagnosis of Figure 1.

4951 F. Di Muzio, M. Barucco, F. Guerriero

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 adminis - tering of the rapid test), with amoxicillin (not considering any to penicillin and/or dif - ferent 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 pa - tients treated correctly (rapid test + antibiotic ad hoc) and all 50 patients who were treated empiri - cally 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 Figure 2. of antibiotic therapy for positive RAD patients ) – €327.00 (pharmaceutical expenditure of all 50 patients treated without distinction) = –€161.44 ryngeal/tonsillar exudate with or without scarla - equal to 49 .4% ( Figure 4). tiniform rash. Minor: fever, general malaise. Ma - If we consider the use of the currently more jor criteria must always be present. expensive oral antibiotic () for only positive patients compared with the possible Materials and Costs treatment of all 50 patients with the cheapest an - Rapid Test Detection Kits for Beta hemolytic tibiotic (amoxicillin) , the cost savings will be: Streptococcus group A of Immunospark (relative €100.00 (figurative total cost 50 kit) + €114.85 sensitivity 97.6%, relative specificity 97.5%) (5 pill boxes of ceftibuten for the only positive were used : the average price for each test being patients ) – €327.00 ( All patients treated with about €2.00. Total cost (figurative) €100.00. amoxicillin ) = – €112.15 equal to 34 .4% ( Figure The tests were provided “free of charge” by the 4). S.D. srl (Servizi Diagnostici Srl , Rome, Italy) and administered to patients without charge. No test result was invalid . Discussion

Methodology Besides the savings in pharmaceutical expen - Carrying out of pharyngeal-tonsillar swab ac - diture in comparison to a small charge for the cording to manufacturer’s instructions (run - cost of testing (in this case figurative total cost time/reading result < 10 min). 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 Results against group A beta-hemolytic streptococcus (GABHS) carries advantages especially in the 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 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 ther - apy €65.56. Figure 3.

4952 Diagnosis and treatment of acute pharyngitis/tonsillitis

49.4% 34.4% Amoxicillin s c

i Only positive RAD t

o test treated i b i t n a r o f e r u t i d n e p x E

All treated with All treated with Amoxicillin vs . Amoxicillin vs . all positive only positive treated treated with Ceftibuten

Figure 4. Cost savings of pharmaceutical expenditure.

sense of a significant reduction in the use of un - 3) PALLA AH, K HAN RA, G ILANI AH, M ARRA F. Over pre - necessary and potentially harmful antibiotics scription of antibiotics for adult pharyngitis is prevalent in developing countries but can be re - with a lower prevalence of drug-resistant forms duced using McIsaac modification of Centor of bacteria . scores: a cross-sectional study. BMC Pulm Med This small observational study in General 2012; 12: 70. Medicine demonstrates that the use of rapid tests 4) WINDFUHR JP, T OEPFNER N, S TEFFEN G, W ALDFAHRER F, has been proven both feasible and desirable. BERNER R. Clinical practice guideline: tonsillitis I. Di - agnostics and nonsurgical management. Eur Arch Otorhinolaryngol 2016 Jan 11. [Epub ahead of print]. Conclusions 5) SUNJOO K. Optimal diagnosis and treatment of group A streptococcal pharyngitis. Infect Rapid tests, when the Guidelines are applied, Chemother 2015; 47: 202-204. can help curb both pharmaceutical expenditure 6) AGARWAL M, R AGHUWANSHI SK, A SATI DP . Antibiotic and the inappropriate use of antibiotics. use in sore throat: are we judicious? Indian J Otolaryngol Head Surg 2015; 67: 267- 270. –––––––––––––––– –-– –– 7) GUROL Y, A KAN H, I ZBIRAK G, T EKKANAT ZT, G UNDUZ Conflict of Interest TS, H AYRAN O, Y ILMAZ G. The sensitivity and the The Authors declare that there are no conflicts of interest. specifity of the rapid test in streptococcal upper respiratory tract infections. Int J Pediatr Otorhino - laryngol 2010; 74: 591-593. 8) ESCMID S ORE THROAT GUIDELINE GROUP , P ELUCCHI C, References GRIGORYAN L, G ALEONE C, E SPOSITO S, H UOVINEN P, L IT - TLE P, V ERHEIJ T. Guideline for the management of 1) Shaikh N, Leonard E, Martin JM. Prevalence of acute sore throat. Clin Microbiol Infect 2012; 18 streptococcal pharyngitis and streptococcal car - Suppl 1: 1-28. riage in children: a meta-analysis. Pediatrics 9) TAJBAKHSH S, G HARIBI S, Z ANDI K, Y AGHOBI R, A SAYESH 2010; 126: e557-64. G. Rapid detection of in 2) CHIAPPINI E, R EGOLI M, B ONSIGNORI F, S OLLAI S, P ARRET - throat swab specimens by fluorescent in situ hy - TI A, G ALLI L, DE MARTINO M. Analysis of different bridization. Eur Rev Med Pharmacol Sci 2011; 15: recommendations from international guidelines 313-317. for the management of acute pharyngitis in adults 10) CHIAPPINI E, P RINCIPI N, M ANSI N, S ERRA A, D E MASI S, and children. Clin Ther 2011; 33: 48-58. CAMAIONI A, E SPOSITO S, F ELISATI G, G ALLI L, L ANDI M,

4953 F. Di Muzio, M. Barucco, F. Guerriero

SPECIALE AM, B ONSIGNORI F, M ARCHISIO P, DE MARTINO 13) GAJIC I, M IJAC V, S TANOJEVIC M, R ANIN L, S MITRAN A, M; I TALIAN PANEL ON THE MANAGEMENT OF PHARYNGITIS OPAVSKI N. Typing of macrolide resistant group A IN CHILDREN . Management of acute pharyngitis in streptococci by random amplified polymorphic children: summary of the Italian National Institute DNA analysis. Eur Rev Med Pharmacol Sci 2014; of Health guidelines. Clin Ther 2012; 34: 1442- 18: 2960-2965. 1458. 14) PINTUCCI JP, C ORNO S, G AROTTA M. Biofilms and in - 11) SHULMAN ST, B ISNO AL, C LEGG HW, G ERBER MA, K A- fections of the upper respiratory tract. Eur Rev PLAN EL, L EE G, M ARTIN JM, V AN BENEDEN C. Clinical Med Pharmacol Sci 2010; 14: 683-690 practice guideline for the diagnosis and manage - 15) WAJIMA T, C HIBA N, M OROZUMI M, S HOUJI M, ment of group A streptococcal pharyngitis: 2012 SUNAOSHI K, S UGITA K, T AJIMA T, U BUKATA K; GAS S UR - update by the Infectious Diseases Society of VEILLANCE STUDY GROUP . Prevalence of macrolide re - America. Clin Infect Dis 2012; 55: 1279-1282. sistance among group A streptococci isolated 12) THE SANFORD GUIDE TO ANTIMICROBIAL THERAPY , 43th from pharyngo-tonsillitis. Microb Drug Resist Edition, 2013. 2014; 20: 431-435.

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