Introduction

Upper respiratory tract infections (URTIs) are common and pose a major health challenge, especially in developing countries. While most are viral, some may present with bacterial involvement or subsequent superinfection, often requiring antibacterial treatment. Azithromycin is preferred for its convenient dosing, low resistance risk, and good tolerability, but real-world evidence from India on its use in such cases is limited.

Aim

To evaluate the real-world effectiveness and safety of azithromycin in the management of moderate to severe URTIs.

Patient Profile

• N=427
• Adult patients (>18 years) with moderate to severe URTIs

Methods

• Subgroup analysis of a retrospective, multicenter, observational real-world study
• Duration: 12 weeks across 184 ENT centers in India.

Intervention: Azithromycin 500 mg once daily for five days

Study endpoints

Primary: Effectiveness of azithromycin measured by:

• Change in cumulative clinical score (six parameters: pharyngeal erythema, tonsillar erythema, tonsillar exudates, sore throat/swallowing pain, fever, interference with daily activities) from baseline to day 5
• Clinical Global Impression (CGI) scale rating on day 5

Secondary:

• Proportion of patients showing improvement in individual signs and symptoms from baseline to day 5
• Resolution of fever and reduction in work absenteeism by day 5
• Safety assessment

Results

Day 5 of Treatment:

By day 5, there was a highly significant improvement in all clinical parameters (p < 0.001). The total clinical score dropped from 9.7 ± 2.02 at baseline to 0.59 ± 1.24.

Table 1: Effectiveness Outcomes: Changes in Mean Clinical Score

Clinical Parameter	Baseline Mean ± SD	Day 5 Mean ± SD	Mean Difference ± SD	p-value
Pharyngeal erythema/swelling (n=421)	1.6 ± 0.49	0.17 ± 0.38	1.43 ± 0.57	<0.001
Tonsillar erythema/swelling (n=421)	1.64 ± 0.48	0.12 ± 0.32	1.52 ± 0.55	<0.001
Exudates/plugs in tonsils (n=420)	1.48 ± 0.50	0.08 ± 0.28	1.40 ± 0.53	<0.001
Sore throat/swallowing pain (n=422)	1.74 ± 0.44	0.11 ± 0.32	1.63 ± 0.50	<0.001
Fever (n=419)	1.56 ± 0.50	0.03 ± 0.18	1.53 ± 0.51	<0.001
Interfering with daily activities (n=422)	1.72 ± 0.45	0.09 ± 0.32	1.63 ± 0.51	<0.001
Total score (n=427)	9.7 ± 2.02	0.59 ± 1.24	9.10 ± 2.23	<0.001

 

This table presents the percentage of patients with moderate or severe symptoms at baseline compared to Day 5. There was a dramatic reduction in severity across all parameters.

Table 2: Symptom Severity Reduction

Clinical parameter	Severity	Baseline (%)	Day 5 (%)	P value (change from baseline)
Pharyngeal erythema	Moderate	40.7%	16.6%	<0.001
	Severe	59.3%	0.2%
Tonsillar erythema	Moderate	37%	11.9%	NA
	Severe	63%	0%
Presence of exudates/plugs in tonsils	Moderate	52.9%	7.6%	<0.001
	Severe	47.1%	0.2%
Sore throat/swallowing pain	Sore but can swallow	26.5%	10.2%	<0.001
	Difficult to swallow	73.5%	0.2%
Fever in °C	37.6-38.5	44.5%	3.3%	<0.001
	≥38.6	55.5%	0%
Interfering with daily activities	Annoying but can work	28.8%	7.3%	<0.001
	Absent from work	71.2%	0.9%

 

Most patients were rated as “very much improved” or “much improved” by investigators, reflecting strong clinical effectiveness.

Table 3: Clinical Global Impression (Day 5)

Rating	% Patients
Very much improved	50.8%
Much improved	44.8%
Minimally improved	4.1%
No change / worse	<1%

 

Safety: 2.1% reported adverse events

Conclusion

• A five-day azithromycin regimen was effective and safe for treating moderate to severe URTIs, including tonsillitis and pharyngitis, while minimizing complications
• Rapid symptom relief reduced disruption to daily life and enabled early return to work in Indian patients
• Azithromycin was well-tolerated with few adverse events, and high investigator ratings reinforced its efficacy and safety
• Further randomized prospective studies are needed to confirm these findings

Reference

Cureus. 2025 Aug 5;17(8):e89403