Acute Upper Respiratory Tract Infections: Clinical Review and Therapeutic Scope for Using Clarithromycin

Written By :  Dr. Kamal Kant Kohli
Published On 2024-01-12 06:52 GMT   |   Update On 2024-01-12 11:02 GMT

Upper respiratory tract infections (URTIs) are among the most commonly encountered diseases in primary care settings, accounting for 17.2 billion cases annually. Adults typically experience two to four episodes of acute URTI per year, but preschool children suffer six to ten episodes in the same period. Most acute URTIs are of short duration and have moderate symptoms; however, they can cause serious complications such as pneumonia, rhinosinusitis, otitis media, and exacerbation of asthma or chronic obstructive pulmonary disease [COPD] in certain groups of the patient population. (1)

Although viruses cause the majority of URTIs but there is a risk of secondary bacterial infections. The clinical manifestations of URTIs vary from person to person. Acute URTI symptoms can be divided into two categories: early and late symptoms. Early symptoms include sniffling, sneezing, throat pain with intermittent chills, headache, and malaise; these may appear and disappear within 24-48 hours of infection. Late signs include nasal discharge/obstruction, throat pain caused by swollen tonsils/adenoids, and a cough that develops over many days and lasts for a week or more after infection. (1)

Management of Upper Respiratory Tract Infections (URTI):

Management strategies aim to reduce symptoms. Early care can lower the chance of developing a full-blown acute URTI and the severity of symptoms. (1) Antibiotic medications can be started if symptoms worsen in appropriate cases. (2)

Choice of Antibiotics:

The rising burden of beta-lactamase-positive, Hemophilus influenzae and Moraxella catarrhalis, as well as penicillin-resistant Streptococcus pneumoniae, has necessitated the development of alternatives to amoxicillin. Similarly, the growing problem of bacteriologic failure in roughly 30% of patients, associated with significant clinical recurrence rates, limits the use of penicillin in treating group A hemolytic streptococcus (GABHS) pharyngitis. (3) Due to extended-spectrum β-lactamases (ESBL) production, multi-resistant Enterobacteriaceae have become very common in India. (4) Macrolide therapy, including clarithromycin, is a viable option for the treatment of uncomplicated URTIs (3)

For common URTI, such as acute otitis media and acute bacterial rhinosinusitis, the use of clarithromycin is indicated at the dose 15-30 mg/ kg/d, every 12 hours for 5 days. For acute pharyngotonsillitis, clarithromycin is suggested for 500 mg every 12 hours or 500 mg once daily for 10 days in adults or 15 mg/kg/d every 12 hours for 10 days in children. (2)

Applicability of Clarithromycin in Acute Upper Respiratory Infections: Guidelines’ Glance

The Indian Council for Medical Research (ICMR) guideline for Treatment Guidelines for Antimicrobial Use in Common Syndrome (2022) recommends Clarithromycin for treating URTI, including streptococcal pharyngitis, bacterial sinusitis, and acute otitis media at 500 mg twice daily in adults or 7.5 mg/kg twice daily in paediatrics. (5)

Clarithromycin in Acute Upper Respiratory Infections: Review of Clinical Evidences Clarithromycin Effective in Acute Rhinosinusitis: A single-blind randomised clinical trial examined the efficacy of clarithromycin and amoxicillin/clavulanate for the treatment of acute rhinosinusitis in relation to the patient’s quality of life. The study enrolled 22 patients and evaluated quality of life using SSS-6* and Rhinoconjunctivitis quality of life Questionnaire** showed significant improvement for all patients at week 4 (P=0.002 and P=0.003, respectively). The SSS-6 demonstrated significant improvement for clarithromycin at 14 days (P=0.02) and 28 days (P=0.029), whereas amoxicillin/clavulanate patients demonstrated significant improvement in symptoms only at 28 days (P=0.046). This suggests that clarithromycin effectively treats acute rhinosinusitis and supports rapid symptom improvement. (6)

*SSS-6=symptom severity score, a six-item survey designed to evaluate ARS-specific symptomology, the severity of the patient group’s symptoms relative to each other and relative to the patient’s progress)

**Rhinoconjunctivitis quality of life Questionnaire=a 28-question survey, measures seven domains related to the functioning of patients with rhinoconjunctivitis: sleep, non–hay-fever symptoms, practical problems, nasal symptoms, eye symptoms, and emotions.

Clarithromycin Reduces Fever Duration in Influenza: A randomised, prospective, open-label study examined the effects of clarithromycin on symptoms of influenza. The study enrolled 79 patients with fever and other symptoms, including rhinorrhea, cough, sore throat, arthralgia or myalgia, and general malaise who received either neuraminidase inhibitor or clarithromycin plus neuraminidase inhibitors (clarithromycin group) for 5 days. Fever duration was approximately 42% shorter in patients with temperatures ≥38.5°C (P=0.02), decreasing from 42 h to 24 h in the clarithromycin group. Patients with body temperatures of ≥38.5 °C diagnosed with influenza who received clarithromycin also had shorter fever duration than the control group (P=0.06), and the rhinorrhea improvement rate was higher in the clarithromycin group (p=0.03; 88% vs. 20%). This study revealed the additional clinical benefit of clarithromycin in improving fever in influenza patients. (7)

Clinical Takeaways
  • Upper respiratory tract infections (URTIs) are among the most common diagnoses in primary care worldwide.
  • Acute URTIs are of short duration with mild symptoms; however, they can lead to severe complications such as pneumonia, rhinosinusitis, and otitis media.
  • Antibiotic therapy reduces symptom severity and chances of secondary infections and decreases the risk of morbidity in appropriate cases.
  • Macrolide therapy, including clarithromycin, could be a reasonable option for the treatment of uncomplicated URTIs.
  • Clarithromycin is effective in acute rhinosinusitis with rapid symptom improvement, streptococcal pharyngitis with a high biological cure rate, and the additional clinical benefit of improving fever among influenza patients.
  • Clarithromycin use is recommended by guidelines, including the Indian Council for Medical Research for managing upper respiratory tract infections, including streptococcal pharyngitis, bacterial sinusitis, acute otitis media.
References:
1. Wang Y, Eccles R, Bell J, et al. Management of acute upper respiratory tract infection: the role of early intervention. Expert Rev Respir Med. 2021;15(12):1517-1523. doi:10.1080/17476348.2021.1988569
2. van Eyk, A.. "Treatment of bacterial respiratory infections." South African Family Practice [Online], 61.2 (2019): 8-15. Web. 23 Dec. 2023
3. Wierzbowski AK, Hoban DJ, Hisanaga T, DeCorby M, Zhanel GG. The use of macrolides in treatment of upper respiratory tract infections. Curr Allergy Asthma Rep. 2006;6(2):171-181. doi:10.1007/s11882-006-0056-x
4. Kumar SG, Adithan C, Harish BN, Sujatha S, Roy G, Malini A. Antimicrobial resistance in India: A review. J Nat Sci Biol Med. 2013;4(2):286-291. doi:10.4103/0976-9668.116970
5. Indian Council on Medical Research. Treatment Guidlines for Antimicrobial Use in Common Syndrome 2022. Accessed on 22nd December 2023 from https://main.icmr.nic.in/content/guidelines-0
6. Rechtweg JS, Moinuddin R, Houser SM, Mamikoglu B, Corey JP. Quality of life in treatment of acute rhinosinusitis with clarithromycin and amoxicillin/clavulanate. Laryngoscope. 2004;114(5):806-810. doi:10.1097/00005537-200405000-00003
7. Higashi F, Kubo H, Yasuda H, Nukiwa T, Yamaya M. Additional treatment with clarithromycin reduces fever duration in patients with influenza. Respir Investig. 2014;52(5):302-309. doi:10.1016/j.resinv.2014.05.001
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