1. INTRODUCTION:

Acute pharyngotonsillitis (APT), as one of the upper respiratory tract infections (URTIs), is a very common illness among adult and pediatric patients for which emergency facilities and other primary care physicians and pharmacists are consulted in our setting.

APT may be caused by viral or bacterial infections, notwithstanding most APT are viral in etiology, which in most cases will resolve spontaneously within one to two week^1,2.

With rare exceptions, group A β-hemolytic streptococcus (GABHS) is the main bacterial cause for APT, counting for approximately 15-30% of APT cases in children and teenagers, and 5-15% of the adult cases. Only these cases of GABHS caused infections have formal indication for antibiotic treatment^3,4. Nonetheless, a high percentage of patients with APT, vary between studies but often exceed 50%, are treated with antibiotics^3,5. Unnecessary use of antibiotics in non-streptococcus cases can expose patients to unnecessary expenses, lead to side effects, and emergence of bacterial resistance⁶.

The main reason for antibiotic over prescription in APT is the difficulty to obtain a rapid and correct diagnosis of APT viral or bacterial origin. In Syria, pharmacists could sell antibiotics over the counter, a fact that has been reported as common practice in different countries^7,8. Moreover, pharmacists and physicians still rely on the clinical signs and symptoms, such as fever, sore throat, tonsillar exudates, anterior cervical adenitis, and/or absence of cough, for the diagnosis of APT and prescribing antibiotic therapy. However, due to the variability in streptococcus APT clinical presentation and the similarity of signs and symptoms produced by other agents, a clinical diagnosis of GABHS caused APT is not always reliable^3,9. Throat swab culture is the gold standard for the diagnosis of streptococcal APT. However, the delay in obtaining results makes its performance useless in clinical practice. During the 80’s, quick tests to detect GABHS antigen were introduced in the market aiming at diagnosing them in minutes. These tests are easy to handle and interpret methods that may be used in the doctor’s office and pharmacy. Recent studies in different countries showed that the use of these tests can help in the etiological diagnosis of streptococcal APT, and thus reduce the prescribing of antibiotics for APT in children and adults^10,11. However, in Syria rapid antigen detection test (RADT) is not used in public health care facilities, where it is most important, and no studies have been carried out to know the impact of RADT on the pattern of how general practitioners prescribe antibiotics for patients with APT.

The main objective of this study was to determine the percentage of antibiotics prescribing in patients with APT depending on clinical signs and symptoms, and to assess the necessity of RADT usage to guide the rational antibiotics treatment of APT, by ruling out GABHS caused APT, in different primary care facilities in Latakia, Syria.

The second objective was to determine the influence of some factors such as age and sex of patient, clinical signs and symptoms, place of consultation (urban pharmacies, rural pharmacies, and otolaryngology clinic and emergency units in University Tishreen hospital) and McIsaac score on the antibiotics prescribing rate. The type of antibiotics the most prescribed for patients with APT were also determined.

2. MATERIALS AND METHODS:

2.1. Study population and data collection:

The study was performed in three different places of consultation: urban pharmacies, rural pharmacies and University Tishreen hospital (otolaryngology clinic, and emergency unit). Eighty patients (40 patients in hospital, 20 in urban pharmacies and 20 in rural pharmacies) diagnosed only with clinical APT, seen from October 2018 to March 2019, were selected as long as they agreed to participate in the study and they fulfilled the inclusion criteria and were not within the exclusion criteria.

Inclusion criteria included male and female aged of 5 years or more, having more than one symptom of APT, such as fever, sore throat, tonsillar exudates, anterior cervical adenitis and/or absence of cough. Patients were excluded from the study if having one at least of the following criteria: Patients who did not consent to participate, having more than five episodes of pharyngitis over the last year, immunosuppressed condition (such as reception of chemotherapy, radiotherapy, corticosteroids and/ or immunosuppressive therapy), heart valve disease, rheumatic fever, episode of pharyngitis treated with antibiotics in the previous fifteen days, or tonsillectomy.

All patients who agreed to participate in the study were asked to fill a personal file with information such as age, sex, previous infection disease, and previous antibiotic treatment.

Patients included in this study were diagnosed by physicians or pharmacists depending on clinical signs and symptoms, and treatment was decided upon without having any knowledge about the RADT result. The treatment, including anti thermic drugs, non-steroidal anti-inflammatory drugs, corticosteroids, antibiotic therapy or none were recorded in patient file, the name, dose, and duration of the antibiotic therapy were also recorded.

All throat swabs were taken by the same person who was previously trained to perform the technique correctly, with vigorous rotation of the tonsils and over the posterior pharynx without touching the tongue, teeth or gums. RADT was undertaken with all the swabs within 5 minutes with the StrepA (Certest, Spain) kit following the manufacturer’s instructions.

Because of logistic difficulties in transporting the samples, the throat swab culture was done only for patients seen in the hospital. For those patients, when the first swab had given a negative RADT, a second swab was taken and sent to the laboratory of Microbiology in University Tishreen hospital. The swab was cultured on a blood agar plate and incubated at 37°C in an atmosphere of CO₂ at 5% during 48 hours.

No positive cultures were seen in our samples. The culture was considered negative after 48 hours of incubation with the absence of β-hemolytic colonies. The negative quick test results were compared to the culture results as the gold standard method.

2.2. Calculation of McIsaac score (modified Centor criteria):

One point is added for each of the following signs and symptoms (temperature ≥38˚c, absence of cough, anterior cervical adenitis and tonsillar exudate) and according to the patient’s age, as listed in table 1¹².

Table 1: McIsaac score.

Criteria	point
Temperature ≥38˚c	1
Absence of cough	1
Anterior cervical adenitis	1
Tonsillar exudate	1
Age 5-14 years old	1
Age 15-44 years old	0
Age ≥ 45 years old	-1

3. STATISTICAL ANALYSIS:

Data were entered into a Microsoft excel spreadsheet and exported for analysis using the statistical package for social sciences (SPSS, version 20). Chi-square test was used to investigate the differences in antibiotic prescription by patient age, sex, place of consultation, clinical signs and symptoms of APT, and McIsaac score, and to compare categorical variables according to RADT results. Statistical significance was set at P˂0.05.

4. RESULTS:

4.1. The percentage of inappropriate antibiotic prescribing:

The study population included a total of 80 patients who were seen in the different three places of consultation (urban pharmacies, rural pharmacies and University Tishreen hospital), in the city of Latakia, Syria. They all matched the inclusion specified criteria and were diagnosed with APT by physicians or pharmacists depending only on clinical signs and symptoms. Among them 34 patients (42.5%) were males and 46 (57.5%) were females. Fifteen specimens (18.75%) were collected from children (≤ 18 years old), and 65 (81.25%) were collected from adults (>18 years old). Average age was 29.9±13.6 year, varying from 5 to 68 years.

Depending on clinical diagnosis, antibiotics were prescribed for 59 patients (74%) and were used at almost the same rate in children (73.33%) and in adults (73.84%). The rest 21 patients (26%) received a symptomatic treatment (analgesic, antipyretic agent …etc.) without antibiotic treatment. However, from 80 analyzed throat swabs, only 9 (11.25%) had a positive RADT result, 2 from children (13.33%) and 7 from adults (10.76%) (Figure 1). All positive RADT swabs were among patients who received antibiotic therapy. In other words, from 59 patients with antibiotic prescribing only 9 (15.25%) had a positive RADT result, included 7 adults (14.58%) and 2 children (18.18%). So, the percent of the inappropriate antibiotic prescribing in our population was 84.75%, (85.42% in adults and 81.82% in children) (figure 1).

Throat culture were done only for patients who were seen in the hospital and their throat swabs gave a negative RADT result (34 swabs). All of them had also negative GABHS culture confirming the negative results of RADT.

Figure 1: percentage of patients treated with antibiotics depending on clinical diagnosis, Percentage of patients with positive RADT results. Percentage of positive RADT results in patients receiving antibiotic treatment depending on clinical diagnosis.

Percentage of inappropriate antibiotic prescribing in all patients (total), children, and adults.

4.2. Factors influencing antibiotic prescribing for clinically diagnosed APT:

We studied the effect of some factors (age and sex of patient, place of consultation, clinical signs and symptoms, and McIsaac score) on the decision of prescribing an antibiotic for clinically diagnosed APT. As shown in table 2, patients were classified into tow age brackets (≤18 and >18 years). Statistical analysis indicated that the age of patients did not influence the prescribing of antibiotics (P=0.967). Similarly, concerning the sex of patients, there was no difference in antibiotics prescribing between male and female among patients seen in our study (P=0.969).

Table 2: Factors influencing antibiotic prescribing for clinically diagnosed APT

		Number of patients N=80 (100%)	Antibiotic prescribing N=59 (74%)	No antibiotic prescribing N=21 (26%)	X2 statistic	P value
Age bracket (years)	≤18	15 (18.75)	11 (73.3)	4 (26.7)	0.0017	0.967
	>18	65 (81.25)	48 (73.8)	17 (26.2)
Sex	male	34 (42.5)	25 (73.5)	9 (26.5)	0.0015	0.969
	Female	46 (57.5)	34 (73.9)	12 (26.1)
Clinical Signs and Symptoms	Fever (≥38ºC)	Yes56 (70)	45 (80)	11 (20)	4.156	0.041
		No 24 (30)	14 (58.33)	10 (41.67)
	Absence of cough	Yes 38 (47.5)	28 (73.7)	10 (26.3)	0.0002	0.989
		No 42 (52.5)	31 (73.81)	11 (26.19)
	anterior cervical adenitis	Yes 30 (37.5)	29 (96.6)	1 (4.4)	12.858	0.0003
		No 50 (62.5)	30 (60)	20 (40)
	Tonsillar exudate	Yes 8 (10)	8 (100)	0 (0)	3.124	0.077
		No 72 (90)	51 (70.83)	21 (29.17)
	Difficult to swallow	Yes 57 (71.25)	42 (73.7)	15 (26.3)	0.0004	0.983
		No 23 (28.75)	17 (73.91)	6 (26.09)
McIsaac score	≥4	Yes 3 (3.75)	3 (100)	0 (0)	1.0955	0.2952
		No 77 (96.25)	56 (72.72)	21 (27.28)
	3	Yes 15 (18.75)	13 (86.6)	2 (13.4)	1.5711	0.210
		No 65 (81.25)	46 (70.77)	19 (29.23)
	2	Yes 26 (32.5)	21 (80.7)	5 (19.3)	0.9680	0.3252
		No 54 (67.5)	38 (70.37)	16 (29.63)
	1	Yes 18 (22.5)	15 (83.3)	3 (16.7)	1.0881	0.2969
		No 62 (77.5)	44 (70.96)	18 (29.04)
	≤0	Yes 18 (22.5)	7 (38.8)	11 (61.2)	14.397	0.0001
		No 62 (77.5)	52 (83.87)	10 (16.13)
Place of consultation	Hospital	40 (50)	32 (80)	8 (20)	1.7433	0.418
	urban pharmacies	20 (25)	13 (65)	7 (35)
	rural pharmacies	20 (25)	14 (70)	6 (30)

Table 3: Association of clinical signs and symptoms with RADT results.

P value	X² statistic	Total n=80 (100%)	RADT		Signs and symptoms
			Negative n=71 (88.75%)	Positive n=9 (11.25%)
0.192	1.701	(70) 56	(85.72) 48	(14.28) 8	yes	Fever (≥38ºC)
		(30) 24	23 (95.84)	1 (4.16)	no
0.609	0.260	(47.5) 38	(86.85) 33	(13.15) 5	yes	Absence of cough
		(52.5) 42	(90.48) 38	(9.52) 4	no
0.056	3.634	(37.5) 30	(80) 24	(20) 6	yes	anterior cervical adenitis
		(62.5) 50	(94) 47	(6) 3	no
0.013	6.057	(10) 8	(62.5) 5	(37.5) 3	yes	Tonsillar exudate
		(90) 72	(91.67) 66	(8.33) 6	no
0.748	0.102	(71.25) 57	(89.47) 51	(10.53) 6	yes	Difficult to swallow
		23 (28.75)	20 (86.96)	3 (13.04)

Table 4: Association between McIsaac score and RADT results.

P value	X² statistic	Total n=80 (100%)	RADT		McIsaac score
			Negative n=71 (88.75%)	Positive n=9 (11.25%)
0.002	9.467	3 (3.75)	1 (25)	2 (75)	yes	≥4
		77 (96.25)	70 (90.9)	7 (9.1)	no
0.778	0.079	15 (18.75)	13 (86.67)	2 (13.33)	yes	3
		65 (81.25)	58 (89.23)	7 (10.77)	no
0.419	0.651	26 (32.5)	22 (84.7)	4 (15.3)	yes	2
		54 (67.5)	49 (90.74)	5 (9.26)	no
0.388	0.744	18 (22.5)	17 (94.5)	1 (5.5)	yes	1
		62 (77.5)	54 (87.1)	8 (12.9)	no
0.088	2.907	18 (22.5)	18 (100)	0 (0)	yes	≤0
		62 (77.5)	53 (85.48)	9 (14.52)	no

We also analyzed the effect of specified signs and symptoms on the decision to prescribe an antibiotic. As shown in table 2, all patients (100%) presented with tonsillar exudate, (96.6%) with anterior cervical adenitis, (80%) with fever, and (73.7%) with difficulty of swallow or absence of cough were prescribed antibiotics. However, only anterior cervical adenitis and fever, was shown to significantly influence antibiotic prescribing (p=0.0001, p=0.041 respectively). When patients were classified according to McIsaac score, no significance difference was observed in percentage of antibiotic prescription according to patient score, except for patients not having any sign or symptom of McIsaac criteria (score ≤0), These patients were treated with antibiotics less than the others (p=0.0001), (table 2).

We also investigated whether the percentage of prescribing an antibiotic for clinically diagnosed APT can differ according to the place of primary care, where the patient was seen. Table 2 shows that physicians in hospital were more likely to prescribe antibiotics for patient presented with signs and symptoms of APT (80%) compared to the pharmacists in rural pharmacies (70%), and the pharmacists in urban pharmacies (65%), but the difference was not statistically significant (P=0.418).

4.3. Association of clinical signs and symptoms with RADT results:

The analysis of association between clinical findings and RADT results demonstrated that only tonsillar exudate was significantly associated with the results of RADT. Patients with tonsillar exudate were RADT positive more often (37.5%, 3 of 8) than those not having this criteria (8.33%, 6 of 72), (p=0.013). Anterior cervical adenitis came in the second place after tonsillar exudate with higher rate of RADT positive (20%, 6 of 30) than patients not having this criteria 6% (3 of 50), but the difference was at the limit of significance (P=0.056). For other signs and symptoms, there was no significant difference in positive RADT frequency.

4.4. Association between McIsaac score and RADT results:

The patients were divided into categories according to McIsaac score. The prevalence of positive RADT results with a McIsaac score of ≤0, 1, 2, 3, or ≥4 was 0%, 5.5%, 15.3%, 13.3 and 75%, respectively. The statistical analysis revealed that the association between positive RADT results and McIsaac score was significant only when the score was ≥4 (P=0.002) (Table 4).

4.5. Choice of antibiotics prescribed for clinically diagnosed APT according to place of consultation:

The choice of antibiotics prescribed for clinically diagnosed APT according to place of consultation is presented in table 5. Overall, azithromycin was the most commonly prescribed antibiotic (50.8%) in total, and it was the most frequently prescribed antibiotic for APT in all places of consultation, hospital (40.6%), urban pharmacies (77%) and rural pharmacies (50%). The second choice was the combination of amoxicillin/clavulanic acid with (32.2%) of all cases, (37.5%) in hospital, (23%) in urban pharmacies and (29%) in rural pharmacies. Ceftriaxone IM injection was the third choice with (15.3%) of patients, and distributed between hospital (21.9%) and rural pharmacies (14%), while we did not record any prescription of ceftriaxone IM injection in urban pharmacies. There was only one patient (1.7%) for whom Cefuroxime was prescribed. This patient was seen in a rural pharmacy (7%).(Table-5)

5. DISCUSSION:

APT is a very prevalent infection that results in numerous visit to primary care facilities¹³^,¹⁴. Despite the viral cause of most cases of APT, the usage of antibiotics to treat this condition was noted to be inappropriately high on a worldwide scale³^,⁵. So, the accurate and timely diagnosis of GABHS caused APT is a reasonable clinical goal, yet many factors affect a clinician’s ability to achieve it.

In our country, many patients with symptoms of APT visit physicians in search of antibiotic prescription, often contrary to doctor’s assessment that there is no indication. In other cases, patients could go directly to the pharmacy to obtain medication to alleviate the symptoms of APT. In other words, in Syria, pharmacists, especially in rural communities, play an integral role in provision of medical treatment to patients, including prescribing of antibiotics in some common infections like APT. Primary care physicians and pharmacists are aware that when patients visit with APT symptoms, what they want is often treatment with antibiotics. Furthermore, the prescribing behavior among physicians and pharmacists could be influenced by education, the doctor/pharmacist-patient personal relationship, the fear of developing a secondary bacterial infection or complications. These are probably the main reasons why physicians and pharmacists in our country prescribe these medications, together with the fact that is clinically difficult to distinguish streptococcal from viral etiology and in case of doubt they are more prone to prescribe antibiotics. These reasons could explain the very high percentage (74%) founded in our study of antibiotics prescribing for clinically diagnosed APT, without difference between children (73.3%) and adults (73.8%). This percentage comes in accordance with results of many previous studies^3,5,15,17, confirming the high rates of unnecessary antibiotic use.

The 2012 updated guidelines by the Infection Disease Society of America (IDSA) for the diagnosis and management of GABHS APT states that swabbing the throat and testing for GABHS APT by RADT and/or culture should be performed because the clinical features alone do not reliably discriminate between GABHS and viral APT except when overt viral features like rhinorrhea, cough, oral ulcers, and/or hoarseness are present⁴.

The throat swab culture is until now the gold standard test for GABHS diagnosis, with a sensitivity between 90% and 95%. However, the results of this test may take an additional 24 to 48 hours, leaving clinicians to make treatment decision without complete diagnosis results^9,18. Patients either receive antibiotics empirically, which may or may not be warranted, or must wait 1 to 2 days, during which they may have untreated symptoms, and antibiotic therapy would lose its power in alleviating APT symptoms and reducing GABHS transmission to other people¹⁹, along with the additional resources needed to follow-up culture results and report these results to patients. Moreover, Rao et al. (2019) showed that bacterial culture had much lower sensitivity rates than expected that were lower than those observed with RADT²⁰.

The RADT has the advantage that the results could be obtained at the time of initial visit¹¹. These immunological tests targeting the detection of GABHS antigens, demonstrated high specificity (>95%) making the probability of obtaining false positive results very low^20,22. The sensitivity of the RADT varies from 68% to 97% in the literature^16,23,24. However, this variability has been attributed to several factors, including the severity of clinical symptoms, the knowledge of the RADT results during the culture colonies count, inoculum size used for culture, lack of technical training and personnel conducting the test^3,22,25.

Thus, we believe that our study is of great importance to know how the utilization of RADT could improve the antibiotic prescribing by physicians and pharmacists for patients with APT. We founded that among 74% of patients who received treatment with antibiotics the incidence of GABHS APT, diagnosed by RADT, was only 15.25%, which means that the use of RADT could have prevented inappropriate antibiotics prescribing for APT treatment in 84.75% of cases. Many studies indicated that RADT reduce inappropriate antibiotic prescription for non-GABHS APT^10,21,26. In the study of Kose et al (2016), RADT use had an influence in decreasing the frequency of unnecessary antibiotic prescription by 53% in patients with non-GABHS APT¹⁶.

The 2012 update of IDSA guidelines for GABHS caused APT state that in children and adolescents, negative RADT test should be ensured by a throat culture. However, positive RADTs do not necessitate a back-up culture because they are highly specific. In addition, routine use of back-up throat cultures for those with a negative RADT is not necessary for adults in usual circumstances, because the risk of subsequent acute rheumatic fever or rheumatic carditis is generally exceptionally low in adults with APT⁴. In our study, for reasons mentioned above, and for logistic issues concerning the difficulty to transport the throat swabs from the pharmacies in rural or urban area to the laboratory of microbiology in University Tishreen hospital, we performed cultures only for patients with negative RADT result seen in the hospital. We used the blood agar culture medium in an aerobic environment, because studies that compared different culture mediums showed this medium to be as good as other more selective methods^18,27,28. All these throat cultures, among them only 5.88% were from children or adolescents (between 5-15 years), were negative for GABHS, confirming the results of RADT.

In the study of Filho et al (2006), the quick test negative predictive value was 94.2% alerting them for possibility of 6% of negative test having positive culture. Nonetheless, they explained that this represent a small fraction of the population and complications would be very rare, especially among adults, where rheumatic fever development is exceptional²⁹. In addition, RADTs currently available are highly speciﬁc, when compared with blood agar plate cultures^20,21. Thus, false-positive test results are highly unusual, and therefore therapeutic decisions can be made with conﬁdence on the basis of a positive RADT result²⁶. Thus, we could understand that in negative RADT result, we neither order a culture, nor use antibiotic treatment, because it is a very reliable test. In positive tests, it is worth to use antibiotic treatment. In other words, RADT could give a correct diagnosis at the time of visit with a high sensitivity and specificity that could have a significant impact on the overuse of antimicrobial therapy for APT seen in our study.

It is interesting that another diagnostic strategy has been proposed in the literature. In 2017 three nucleic acid amplification tests (NAAT) assay, that amplify targeted regions of GABHS DNA, received clearance from the Food and Drug Administration (FDA). These 3 tests have a high specificity and sensitivity when compared with bacterial culture for detection of GABHS with rapid turnaround time and ease to use²⁵. However, current GABHS APT guidelines do not yet provide guidance on the use of NAAT⁴. Moreover, the cost of these tests may limit their widespread use, and their high sensitivity may result in the detection of GABHS carriers and consequently in unnecessary treatment²⁵.

In our country, we still lack a cost-benefit study about the use of RADT. Notwithstanding, in other countries like the USA, despite the higher cost of RADT when compared to culture, there are great savings in the prevention of injudicious use of antibiotic and additional medical visits for reasons triggered by antibiotics side effects^18,21,30. Similarly, the study of Kose et al (2016) in Turkey showed that the antibiotic cost per patient decreased by 60.6% using RADT rather than empirical treatment¹⁶.

APT is primarily a disease of children 5–15 years of age. and prevalence rates of GABHS APT among school-age children (37%) is higher compared to children <5 years. (24%)³¹. Therefore, we chose our population to be ≥5 years old, and it was interested to study the influence of age on antibiotic prescribing, as this idea has been discussed by previous studies and the results was variable. In our study we found that the age did not influence the antibiotic prescribing when divided into two age brackets (children ≤18 years and adults>18 years). Similarly, in a Malaysian study, Teng et al. (2011) found no difference between the antibiotic prescribing rates for children and adults³². However, in India, antibiotics were more frequently prescribed for URTI including APT in children aged between 6 and 18 years compared to adults³³. This may be due to pressure from accompanying parents, as a local study by Chan and Tang (2006) reported that nearly 30% of parents requested for their children to be given antibiotics for URTI symptoms. Prescribers may also feel that children and teenagers have a higher risk of post URTI complications³⁴.

In our study, the inappropriate antibiotic prescribing rates by all the prescribers, pharmacists in rural or urban pharmacies and physicians in the hospital (otolaryngology clinic or emergency units), were found to be high and not significantly different. This result alerts to the presence of the problem of injudicious prescribing of antibiotics in many places of primary care in our country. Moreover, prescribers based their decision for antibiotic treatment on certain clinical criteria of patients, like the presence of tonsillar exudate or fever, which means that they believed that most of these cases were bacterial in etiology. However, McIsaac score of ≥1 did not significantly affect the decision of prescribing antibiotic. It was effective in decreasing antibiotic prescribing only for patients under very low risk of GABHS APT (score ≤0). In a similar context, the study of Mehta et al (2017) showed that the antibiotic prescription significantly associated with the presence of fever and absence of cough³⁵.

From other side, among clinical criteria we found that only tonsillar exudate was significantly associated with positive RADT results suggesting the bacterial origin. While Gieseker et al (2003), found that anterior cervical adenitis, scarlatina rash, and presence of tonsillar exudate were the clinical symptoms significantly associated with GABHS APT³⁶. Furthermore, in the study of Kose et al (2016), the absence of cough, enlarged cervical nodes and tender cervical nodes were found to be more frequent in the GABHS positive group¹⁶. However, given the association between McIsaac score and RADT results in our study, GABHS APT was suggested only by the score of ≥4, but the small number of patients in this category (only 3 patients) may give results that cannot be accurately judged on the reliability of these criteria. Shih et al (2012), found that Patients with a McIsaac score ≥4 points were 2.72 times more likely to have positive GABHS cultures than those with a McIsaac score < 4 points; but this was not significant³⁷. In McIsaac study (1998), a score of ≥4 would have the probability of 51% of detecting GABHS³⁸. In another study by Walker et al (2006), they found that a score of ≥4 would have only a 40% chance of detecting GABHS³⁹. Centor himself concluded through a logistic regression analysis that the prevalence of GABHS with a Centor score of 1, 2, 3, or 4 was 6.5%, 15%, 32%, and 56%, respectively¹⁹. According to the American College of Physicians-American Society of Internal Medicine (ACP/ASIM) guidelines, the empiric treatment for GABHS is recommended for a Centor score of ≥4; RADT or throat culture should be performed with a score of 2 or 3; and no treatment for a score of ≤1².

Overall, we can conclude that it is important to carefully classify patients based on appropriate clinical signs and symptoms for GABHS APT, but GABHS testing is still essential in making a precise diagnosis because practitioners often greatly overestimate the probability that GABHS is the cause of APT. Therefore, the generally high speciﬁcity of RADT should minimize overprescribing of antibiotics for treatment of ATP.

The 2012 update of IDSA guidelines for the treatment of patients diagnosed with GABHS APT recommend penicillin or amoxicillin for 10 days as the drug of choice for treatment of non-allergic patients, based on their efficacy, narrow spectrum of activity, infrequency of adverse reactions and modest cost. Treatment of GABHS APT in penicillin-allergic individuals may include a first generation cephalosporin (for those not anaphylactically sensitive) for 10 days, clindamycin or clarithromycin for 10 days, or azithromycin for 5 days⁴. In our study, azithromycin and amoxicillin/clavulanic acid, were prescribed for 83% of total patients who received antibiotics. The prescribers, especially the pharmacists highly favored the somewhat broad-spectrum macrolide azithromycin. These results may indicate that prescribers chose antibiotics based on the cost and ease of dosing. Azithromycin which made up to 50.8% of total antibiotics prescribed, has the advantage of once daily dosing versus three or twice daily dosing of amoxicillin or cefuroxime, which improve patient compliance, but also the price of drug and offers of marketing groups from the pharmaceutical industry, could influence this choice. In the study of teratani et al in Japan (2019), although penicillin was more likely to be prescribed for cases with streptococcal APT, the penicillin selection rate is still only 37.6%, which implies that patients with streptococcal APT are treated using broader-spectrum antibiotics⁴⁰. Similarly in the study of Ayranci et al in Turkey (2005), sixteen different antibiotics were given, with oral and intramuscular penicillins, as a drug of choice, prescribed in 46.5% of cases, but most of the antibiotics (53.5%) in this study consisted of the most expensive ones such as the new macrolides and third-generation cephalosporins⁴¹. Amoxicillin in our study is often used as combination with clavulanic acid, probably because of general increasing rate of resistance to amoxicillin alone due to the wide spread use of this antibiotic⁴². It is prescribed at the rate of 32.2% only. This finding in turn comes in line with other studies showing that the rate of prescribed antibiotics, apart from penicillins, was more than 50% ^43,44.

Finally, our results confirm that if the injudicious use of antibiotics in Syria continues in this way, the prevalence of antimicrobial resistance will ever increase. This resistance will threaten the efficacy of important bacterial antibiotics such as penicillin, cephalosporines and macrolides. For this reason, Multi-faceted interventions are necessary to reduce the prescribing rate of antibiotics. These strategies include interactive educational meetings of physicians, pharmacists and patients consisting of academic detailing and information about the necessity to use RADT for APT diagnosis that help to avoid the inappropriate prescribing of antibiotic and thereby decreasing the antimicrobial resistance. Another possible educational intervention would be strengthening the knowledge about the importance of appropriate antibiotic prescribing for medicine and pharmacy students during their years in university. Moreover, educational campaigns for the public to increase their awareness about the existence and importance of bacterial resistance should be a part of any attempt to improve rational use of antibiotics.

The strength of the study is that this is the first study that confirm the possibility and necessity of routine use of RADT in clinical practice for antibiotics treatment in the different places of medical care facilities in Syria. Some limitations of our study should also be mentioned, first, the relatively small sample size. Second, culture results were not assessed for all RADT test, so we could not calculate the positive and negative predictive value of RADT test in our study. Further, patients follow up was not performed to assess clinical symptoms and treatment decision with RADT results.

6. CONCLUSION:

This study showed that antibiotics were prescribed widely and inconsistently for treating APT in pharmacies but also in university Tishreen hospital in Latakia. Antibiotic prescribing was influenced by patient’s signs and symptoms, without significant difference whether the prescriber was a physician in hospital or a pharmacist in urban or rural pharmacy.

The RADT but also the new NAAT consist an important adjuvant tool in APT diagnosis and could be effective in reducing the percentage of antibiotic prescribing and so limiting of bacterial resistance in our setting. We believe that new studies should be made in order to determine the cost-benefit of these detection kits and their impact on the health care economy. Moreover, there is a need for further studies to elucidate the causes and motivations for this high prescription rate of antibiotics, as well as establishing of multifaceted interventions to improve antibiotic prescribing rate and choice.

7. CONFLICT OF INTEREST:

There is no conflict of interest in publication of this manuscript.

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Received on 26.05.2020 Modified on 28.07.2020

Research J. Pharm. and Tech. 2021; 14(6):2962-2970.

DOI: 10.52711/0974-360X.2021.00519

Antibiotic	Total n=59 (74%)	Prescribed in hospital n=32 (80%)	Prescribed in urban pharmacy n=13 (65%)	Prescribed in rural pharmacy n=14 (70%)
Azithromycin	30 (50.8%)	13 (40.6%)	10 (77%)	7 (50%)
Amoxicillin/clavulanic acid	19 (32.2%)	12 (37.5%)	3 (23%)	4 (29 %)
Ceftriaxone (IM)	9 (15.3%)	7 (21.9%)	0 (0%)	2 (14%)
Cefuroxime	1 (1.7%)	0 (0%)	0 (0%)	1 (7%)