EURASIAN JOURNAL OF

FAMILY MEDICINE

AVRASYA AİLE HEKİMLİĞİ DERGİSİ

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The Efficacy and Safety of Rapid Antigen Detection Test in Adults: A Retrospective Study

Erişkinlerde Hızlı Antijen Testinin Etkinliği ve Güvenirliği- Retrospektif Bir Çalışma

Guzin Zeren Ozturk, Dilek Toprak

 

How to cite / Atıf için: Toprak D, Ozturk GZ. The Efficacy and Safety of Rapid Antigen Detection Test in Adults: A Retrospective Study. Euras J Fam Med 2018;7(2):47-52

 

Original Research / Orijinal Araştırma


ABSTRACT

Aim: Acute respiratory infections are one of the diseases in which antibiotics are inappropriately used.Our study aim was to define the efficacy and safety of the rapid antigen detection test in decreasing the inappropriate use of antibiotics in adults.

Methods: This was a retrospective study on patients over 15 years of age who came to our clinic because of sore throat from September 2016 to 2017. Data on culture, rapid antigen detection test results, and the prescribed drugs were recorded from their filesand were expressed as frequencies. Statistical analyses were performed by the Chi-square test and Student’s t-test, with p

Results: Among a total of 2426 patients, the rapid antigen detection test and culture results had a perfect fit (κ=0.911) and had no statistically significant differences (p=0.125). Using culture as the standard, the rapid antigen detection test had a sensitivity of 86.4%, specificity of 99.9%, positive predictive value of 97.4%, negative predictive value of 99.2%, and correct awareness rate of 99.1%. 

Conclusion: The use of rapid antigen detection test in cases with pharyngitis could make antibiotic prescription safe and appropriate.

Keywords: respiratory tract infections, antibiotics, antibacterial drug resistance

ÖZET

Amaç: Akut solunum yolu enfeksiyonları, antibiyotiklerin uygunsuz şekilde kullanıldığı hastalıklardan biridir. Çalışmamızın amacı, yetişkinlerde uygun olmayan antibiyotik kullanımını azaltmada hızlı antijen saptama testinin etkinliğini ve güvenilirliğini araştırmaktır. 

Yöntem: Bu çalışma Eylül 2016- 2017 tarihleri arasında kliniğimize boğaz ağrısı nedeniyle gelen 15 yaş üstü hastaların retrospektif olarak tarandığı bir çalışmadır. Kültür, hızlı antijen tespit testisonuçları ve reçete edilen ilaçlarla ilgili veriler dosyalarından kaydedildi. Gerekli olan istatistiksel analizler yapıldı (Ki-kare testi ve Student's t-testi). p<0,05 istatistiksel olarak anlamlı kabul edildi. 

Bulgular: Toplam 2426 hasta arasında hızlı antijen tespit testive kültür sonuçları mükemmel uyum sağlamış (κ=0,911) ve istatistiksel olarak anlamlı fark (p=0,125) göstermedi. Hızlı antijen tespit testinin duyarlılığı %86,4, özgüllüğü %99,9, pozitif prediktif değeri %97,4, negatif prediktif değeri %99,2 ve doğru farkındalık oranı %99,1 idi. 

Sonuç: Boğaz ağrısı ile gelen olgularda hızlı antijen tespit testinin kullanımı ve sonuca göre antibiyotik reçetelemesi uygunsuz antibiyotik kullanımını azaltacaktır.

Anahtar kelimeler:solunum yolu enfeksiyonları, antibiyotikler, antibakteriyel ilaç direnci


 

Introduction

Anti-microbial resistance (AMR) is the ability of microorganisms, such as bacteria, viruses and some parasites to stop an antimicrobial, such as antibiotics, anti-virals and anti-malarials from working against them. As a result, standard treatments become ineffective and infections can persist and spread to others (1). Inappropriate antibiotic use is one of the reasons for developing AMR.

Acute respiratory infection (ARIs), which is most commonly caused by viruses, is one of the diagnoses for which antibiotics are inappropriately used (2). For example, pharyngitis is mostly caused by viruses and only 5% to 10% are caused by Group A beta-hemolytic streptococcus (GAS). Majority of ARIs are treated at primary care centers (3). According to the Centers for Disease Control and Prevention treatment guidelines for ARI, patients who meet two or more Centor criteria (e.g., fever, tonsillar exudates, tender cervical lymphadenopathy and absence of cough) should undergo a rapid antigen detection test (RADT). Antibiotic treatment is not recommended for patients with negative RADT results (4). In our daily practice, false-negative or false-positive test results can sometimes occur. 

Our study aim was to define the efficacy and safety of RADT in adults.

Methods

Patients more than 15 years old who came to our clinic from September 2016 to 2017 for sore throat were included in this retrospective study. According to our clinical procedures, only the patients who fulfilled two or more Centor criteria were simultaneously cultured and tested by RADT. Data on culture, RADT results and the prescribed drugs were recorded by 
scanning the files retrospectively. A total of 2426 patients with sore throat came to our polyclinics between September 2016 and 2017 (Fig. 1); 1242 (51.2%) were men and the mean age was 34.40 ± 15.6 years (range, 15–92 years).   

Figure 1. Study design

The socio-demographic features of the study group are shown in Table 1. According to the Centor criteria, 71.8% (n=1613) of the patients scored 0, 1 and were treated as viral infection, whereas 28.2% (n=813) underwent simultaneous culture and RADT. Of the 2426 patients, only 1.6% (n=39) were RADT-positive and 1.81% (n=44) were culture-positive.

Table 1. Sociodemographic features of patients and associations between RADT and Culture

The study was approved by the ethics committee of Sisli Hamidiye Etfal Training and Research Hospital on 3thOctober 2017 (Number:1700).

Measures

Centor criteria: The Centor criteria were developed to trace patients with streptococcal tonsillitis and comprise fever, tonsillar exudate, tender cervical nodes and absence of cough (5). Patients who score 0–1 points are diagnosed to have viral pharyngitis, whereas those who score 2 or more points are recommended to undergo RADT to determine the need for drug therapy.

Rapid Antigen Detection Test: Rapid antigen testing to detect GAS infection provides important information for decision-making on antibiotic use for patients with acute pharyngitis.The Infectious Diseases Society of America guidelines on streptococcal pharyngitis recommended using a rapid test in patients with a modest probability of GAS infection (6). Antibiotics are prescribed to those with a positive rapid test and withheld in those with negative rapid test.

Culture: Throat swab samples were submitted to our laboratory for culture. Samples were seeded on a blood agar plate and incubated at 37 °C in a 5% CO2atmosphere for 48 hours. Culture growth of any number of beta-haemolytic colonies was considered positive for group A beta-haemolytic streptococcus (GABHS).

Statistical analyses were performed using SPSS software version 20 (IBM SPSS, Chicago, IL, USA). Aside from the socio-demographic features, such as age and gender, results of RADT and culture and treatments were recorded. Frequencies were calculated. Chi-square and Student’s t-tests were used and p

Results

Among the 813 patients who underwent simultaneous culture and RADT, the mean age was 27.8 ± 10 years (range, 15–63 years). The associations of the socio-demographic features of the patients with the RADT and culture results are shown in Table 1. Female gender and the age group 35–49 years were significantly associated with RADT and culture positivity (p<0.001). 

As shown in Table 2, there was a perfect fit between the rapid test and the culture results (κ=0.911). There was no statistically significant difference between the rapid test and the culture results (p=0.125). Using culture as the standard, the RADT had a sensitivity of 86.4%, specificity of 99.9%, positive predictive value of 97.4%, negative predictive value of 99.2%, and correct awareness rate of 99.1%.

Table 2. The relation between Culture and RADT

A total of 9.3% (n=76) of patients were prescribed antibiotics according to the RADT and culture results (Table 3). Of these, 6.6% (n=51) were prescribed antibiotics, most commonly amoxicillin/clavulanate, despite RADT negativity, and 35.9% (n=14) were not prescribed antibiotics despite RADT positivity. Similarly, 6.5% (n=50) were prescribed antibiotics, most commonly amoxicillin/clavulanate, despite culture negativity and 40.9% (n=18) were not prescribed antibiotics despite culture positivity. There were 6.5% (n=50) patients who were prescribed antibiotics despite negative RADT and culture results (i.e., inappropriateantibiotic use). The most commonly prescribed antibiotics were trimethoprim/sulfamethoxazole at 45.5% (n=20) for culture-positive cases and penicillin at 48.7% (n=19) for RADT-positive cases.

Table 3. The prescribed antibiotics according to RADT results and culture

Discussion

About 80% of cases with sore throat are diagnosed in the primary care setting (7); and most of them are caused by viruses. In adults, GABHS infection accounts for approximately 5% to 15% (8); in this study, GABHS infection was detected 1.85%. In general, antibiotics are overprescribed for pharyngitis, which is commonly caused by viruses. In Turkey, according to the Prescription Information System, 55.51% of patients are prescribed antibiotics for pharyngitis. Similarly, in Europe, most antibiotics continue to be prescribed in the primary care setting and mainly for patients with ARIs (9). Even among experienced physicians, not more than 75% of the cases can be accurately diagnosed as streptococcal pharyngitis based on clinical findings alone (10). Therefore, both clinical criteria and diagnostic tests should be used.

Throat culture has a sensitivity of 90% to 95% in diagnosing GABHS infections, whereas lateral flow RADT has a wide variability in sensitivity (59% to 96%) (6). Optical immunoassays are 86% sensitive for diagnoses and molecular RADT models are even more sensitive (89% to 96%) in children (11). In our study, there was a perfect fit between the rapid test and the culture results (κ = 0.911). There was no statistically significant difference between the rapid test and culture results (p = 0.125). The sensitivity of the rapid test, using culture as the gold standard, was 86.4% in our study. In some studies, the high specificity (>95%) of RADT decreases the probability of obtaining false-positive results (12–14). The good diagnostic performance of RADT in this study implied that the prescription of antibiotics for RADT-positive cases were appropriate. These results were consistent with the results of a clinical trial, which found that the use of the RADT in primary care offices was associated with a significant reduction in the prescription of antibiotics among adults with a clinical diagnosis of acute pharyngitis (15). However, some cases with negative RADT may have positive culture results. In this situation, there was a question about this may cause or increase complications. One study showed that there were no differences among cases that were given immediate, delayed and no antibiotics for several symptoms and complications (16). Therefore, waiting for the culture result does not increase complications; moreover, antimicrobial therapy should be prescribed only for proven cases of GAS pharyngitis because of the generally increasing rate of resistance to antibiotics (17).

Patients with acute GAS pharyngitis should be treated with an appropriate antibiotic at an appropriate dose for a duration (usually 10 days) that is likely to eradicate the organism from the pharynx. The choice of antibiotic should be based on a narrow spectrum of activity, infrequent adverse reactions and modest cost (18). According to a Cochrane study, the first drug of choice remains to be penicillin (19), probably because β-lactam antibiotic resistance has not been reported (20). In our study, the trend for the most commonly prescribed antibiotics according to RADT and culture results implied that there remains inappropriateantibiotic use. The rate of inappropriateantibiotic use for pharyngitisin primary care was reported to be 14.7% in Iceland, 5.7% in Denmark (21) and 6.5% in our study. This may be because our clinic was in a training and research hospital, where educations are held about daily practice and the Centor criteria are applied using a computer program. 

There remains considerable misuse of antibiotics. The reasons for prescribinginappropriateantibiotics for sore throat could be uncertainty about the microbial etiology, influence of patient demand and other non-clinical factors (21). According to a study, limited time, poor doctor-patient communication and diagnostic uncertainty were major causes of inappropriateantibiotic use in ARIs (22). We suggest the use of the Centor criteria and RADT for diagnosis, an application to policlinic computer program that remember the Centor criteria and test and educations post graduate and in university training programs about antibiotic resistance and inappropriate antibiotic.

Inappropriateantibiotic prescription is not solely because of doctors, but also of patient knowledge on antibiotics and ARIs. In a study, the main reason of patients for expecting antibiotic prescriptions was the belief that antibiotics are effective for the common cold or influenza and that antibiotics can shorten the duration and prevent deterioration of their illness (23). Educational programs must be held in order to break these incorrect perceptions.

Conclusion

The rapid test had a perfect fit with the culture results, with sensitivity of 86.4%, specificity of 99.9%, positive predictive value of 97.4%, negative predictive value of 99.2%, and correct awareness rate of 99.1%. The use of computer applications and training the physicians about the Centor criteria and RADT for pharyngitis could reduce the rate of antibiotic prescription.Informing patients by media about inappropriate antibiotic use may reduce AMR.

Conflict of Interest 

No conflict of interest was declared by the authors.

References

1. World Health Organization [internet]. Antimicrobial resistance [cited 2017 Oct 18]. Available from: http://www.who.int/antimicrobial-resistance/en/

2. Barnett ML, Linder JA. Antibiotic prescribing for adults with acute bronchitis in the United States 1996–2010. JAMA2014;311(19):2020-2.

3. Centers for Disease Control and Prevention [internet]. Adult treatment recommendations [cited 2017 Oct 18]. Available from: https://www.cdc.gov/getsmart/community/for-hcp/outpatient-hcp/adult-treatment-rec.html

4. Cooper RJ, Hoffman JR, Bartlett JG, Besser RE, Gonzales R, Hickner JM, et al. Principles of appropriate antibiotic use for acute pharyngitis in adults: background. Ann Intern Med 2001;134(6):509-17.

5. Centor RM, Whitherspoon JM, Dalton HP, Brody CE, Link K. The diagnosis of strep throat in adults in the emergency room. Med DecisMaking1981;1(3):239-46.

6. Shulman ST, Bisno AL, Clegg HW, Gerber MA, Kaplan EL, Lee G, et al. 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(10):1279-82.

7. Kalra MG, Higgins KE, Perez ED. Common questions about streptococcal pharyngitis. Am Fam Physician 2016;94(1):24-31.

8. Centers for Disease Control and Prevention [internet]. Pharyngitis (strep throat) [cited 2017 Oct 18]. Availabe from: https://www.cdc.gov/groupastrep/diseases-hcp/strep-throat.html

9. Goossens H, Ferech M, Vander Stichele R, Elseviers M; ESAC Project Group. Outpatient antibiotic use in Europe and association with resistance: a cross-national database study. Lancet 2005;365(9459):579-87.

10. Gerber MA, Shulman ST. Rapid diagnosis of pharyngitis caused by group A streptococci. Clin Microbiol Rev 2004:17(3):571-80.

11. Lean WL, Arnup S, Danchin M, Steer AC. Rapid diagnostic tests for group A streptococcal pharyngitis: a meta-analysis.Pediatrics2014;134(4):771-81.

12. Joslyn SA, Hoekstra GL, Sutherland JE. Rapid antigen detection testing in diagnosing group A beta-hemolytic streptococcal pharyngitis. J Am Board Fam Pract 1995;8(3):177-82. 

13. Roe M, Kishiyama C, Davidson K, Schaefer L, Todd J. Comparison of BioStar Strep A OIA optical immune assay, Abbott TestPack Plus Strep A, and culture with selective media for diagnosis of group A streptococcal pharyngitis. J Clin Microbiol 1995;33(6):1551-3. 

14. Kaplan EL. Rapid detection of group A streptococcal antigen for the clinical and the epidemiologist: accurate? cost-effective? useful?N Z Med J 1988;101(847 Pt 2):401-2.

15. Llor C, Madurell J, Balagué-Corbella M, Gomez M, Cots JM. Impact on antibiotic prescription of rapid antigen detection testing in acute pharyngitis in adults: a randomised clinical trial. Br J Gen Pract 2011;61(586):e244-51.

16. Spurling GK, Del Mar CB, Dooley L, Foxlee R, Farley R.Delayed antibiotic prescriptions for respiratory infections.Cochrane Database Syst Rev 2017;9:CD004417. doi: 10.1002/14651858.CD004417.pub5.

17. Snow V, Mottur-Pilson C, Cooper RJ, Hoffman JR, American Academy of Family Physicians, American College of Physicians-American Society of Internal Medicine, et al. Principles of appropriate antibiotic use for acute pharyngitis in adults. Ann Intern Med 2001;134(6):506-8.

18. Shulman ST, Bisno AL, Clegg HW, et al. 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(10):e86-102. doi: 10.1093/cid/cis629.

19. Van Driel ML, De Sutter AI, Habraken H, Thorning S, Christiaens T. Different antibiotic treatments for group A streptococcal pharyngitis. Cochrane Database Syst Rev 2016;9:CD004406. doi: 10.1002/14651858.CD004406.pub4.

20. Chochua S, Metcalf BJ, Li Z, Rivers J, Mathis S, Jackson D, et al. Population and whole genome sequence based characterization of invasive group a streptococci recovered in the United States during 2015. MBio 2017;8(5):e01422-17. doi: 10.1128/mBio.01422-17.

21. Rún Sigurðardóttir N, Nielsen AB, Munck A, Bjerrum L. Appropriateness of antibiotic prescribing for upper respiratory tract infections in general practice: comparison between Denmark and Iceland. Scand J Prim Health Care 2015;33(4):269-74.

22. Fletcher-Lartey S, Yee M, Gaarslev C, Khan R. Why do general practitioners prescribe antibiotics for upper respiratory tract infections to meet patient expectations: a mixed methods study. BMJ Open 2016;6(10):e012244. doi: 10.1136/bmjopen-2016-012244.

23. Gaarslev C, Yee M, Chan G, Fletcher-Lartey S, Khan R. A mixed methods study to understand patient expectations for antibiotics for an upper respiratory tract infection. Antimicrob Resist Infect Control 2016;5:39. doi: 10.1186/s13756-016-0134-3.

 


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