Exploring the Role of Cefuroxime in Treatment of Upper Respiratory Tract Infections within ENT Outpatient Settings

Understanding the Impact and Epidemiology of Upper Respiratory Tract Infections: Upper respiratory tract infections (URTIs) are inflammation of the upper airways resulting from infections; encompassing the nose, sinuses, pharynx, larynx, and large airways characterized by localized symptoms of sore throat, nasal obstruction, headache, and cough without a history of chronic obstructive pulmonary disease, emphysema, or chronic bronchitis (1,2). URTIs impose a considerable burden on the healthcare system and economy by significantly impairing the quality of life.

The global incidence of URTIs accounted for 42.83% of all diseases and injuries as per the Global Burden of Diseases data. Male gender, children under 5 years, and the elderly have higher disability-adjusted life years and mortality rates attributed to URTIs. Furthermore, URTIs are also associated with complications like pneumonia, otitis media, glomerulonephritis, and myocarditis (1).

In India, URTIs account for 87.5% of total infections (3), with a regional Indian study detecting 747 positive detections for URTI among 2085 reported infections (4). Acute Otitis media, Acute rhinosinusitis, Epiglottitis, Influenza, and Pharyngitis are some of the commonly detected URTIs (5).

Optimizing Management Approaches for Upper Respiratory Tract Infections (URTIs): Respiratory infections often arise from viral or bacterial interaction and may be symptomatic or asymptomatic. The upper respiratory tract contains diverse bacteria, including commensals and potential pathogens, forming a complex microbial community. Viral infestation renders the epithelium more susceptible to bacterial colonization, causes bacterial adhesion to host cells, and impairs host immune system components increasing susceptibility to bacterial infections (6). Antimicrobial therapy is recommended depending on patient factors such as temperature >380c, swollen and tender nodes, tonsillar exudate, age, and other co-morbidities to prevent complications (7).

Management of URTIs includes antihistamines, antipyretics or anti-inflammatory agents, cough suppressants, expectorants, and decongestants (8). However, certain cases of URTI require antibiotics when clinically indicated (9).

Guideline Recommendations for Antibiotics in Upper Respiratory Tract Infections(URTIs): Several prominent societies have issued guidelines on the appropriate use of antibiotics for URTIs. They are:

• The Infectious Diseases Society of America (IDSA) has released guidelines for the management of acute bacterial rhinosinusitis in children and adults stating that empiric antimicrobial therapy should be initiated in acute bacterial rhinosinusitis at the time of diagnosis. (10)
• As per the guidelines by The Indian Council of Medical Research (ICMR), antibiotics should be prescribed for bacterial pharyngitis, acute bacterial sinusitis, and Acute Otitis Media infections (11).

Among the various antibiotics prescribed by healthcare providers, cefuroxime is a broad-spectrum second-generation cephalosporin that stands out with swift hydrolysis to the active parent compound. This leads to a similar antibacterial spectrum as a parenterally administered drug.

Cefuroxime for Upper Respiratory Tract Infections(URTIs) (12): 

• Cefuroxime demonstrates a broad spectrum of activity against both Gram-positive and Gram-negative bacteria encompassing pathogens like Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, S. pyogenes and methicillin-sensitive Staphylococcus aureus (MSSA).
• The minimum inhibitory concentration (MIC90) values for S.pnuemonia are ≤0.06 to ≤0.25 mg/L, for H. influenzae mean MIC90 ranges from 1 to 2 and 2 to 4 mg/L, and M. catarrhalis is 2 and 0.5 mg/L. Cefuroxime concentrations for these pathogens exceed 50% of the dosage interval most of the times.
• Upon administration of 125 to 1000mg dosages, the peak plasma concentration (Cmax) ranges from 2.1 to 13.6 mg/L. Cefuroxime exhibits an elimination half-life (t=1 ⁄2) of 2.2 to 3 hours, with a time (tmax) to reach peak plasma concentration (Cmax) of 1.2 to 1.3 hours, and an area under the plasma concentration time-curve (AUC) ranging from 6.7 to 50 mg/L • h.
• Notably, cefuroxime demonstrates the highest levels of tissue penetration in sinus tissues.
• The Clinical Laboratory Standards Institute has established the susceptibility breakpoints for Cefuroxime against various microorganisms like Hemophilus Influenza (≤ 4), Streptococcus pnuemoniae (≤ 1), and Moraxella catarrhalis (≤ 4) indicating its broad spectrum of activity (13).

Review of Literature on Cefuroxime for Different Upper Respiratory Infections(URTIs):

• Cefuroxime- Effective First Line in URTIs: A study was carried out to assess the clinical effectiveness and tolerability of oral cefuroxime axetil in 369 patients having acute URTIs by prescribing 250 mg cefuroxime axetil twice daily for 7 days. The URTIs included tonsillitis, pharyngitis, sinusitis, and otitis media. Their clinical symptoms reported were pain, sinus tenderness, and reddening of the eardrum. The results demonstrated that 67% of patients had complete resolution of clinical symptoms, and 22% had improvement. Eighty-one percent of patients expressed immense satisfaction post-treatment. About 98% of tonsillitis cases were completely resolved. Thus, the study concluded that cefuroxime is clinically effective and well-tolerated and should be used as the first-line treatment of URTIs (14).
• Cefuroxime Effective & Better Tolerated than Amox-Clav in Bacterial Sinusitis: Another randomized, investigator-blinded, parallel-group study evaluated the clinical efficacy of oral cefuroxime axetil (250 mg twice daily) with oral amoxicillin/clavulanate (500 mg three times daily) among 317 patients with clinical and radiologic evidence of acute maxillary sinusitis for 10 days. About 85% of the cefuroxime group and 82% of the amox-clav group showed a satisfactory clinical outcome assessed based on resolution, improvement, failure, and recurrence of symptoms. The number of adverse events was less in the cefuroxime group than in the amox-clav group. The study concluded that cefuroxime axetil twice a day is as effective as amoxicillin-clavulanate three times a day in the treatment of acute bacterial maxillary sinusitis (15).
• Cefuroxime Short Course in Tonsillopharyngitis: A phase IV randomized, open-label, comparative, multicentre study was carried out at 137 pediatric centers on culture-positive tonsillopharyngitis cases comparing 50,000 IU of penicillin V in three divided doses with a short course of 250 mg cefuroxime twice a day on post-streptococcal sequelae with Group A β hemolytic streptococci (GABHS) infection. The study found that though the efficacy and carriage rates were similar between the two drug groups, cefuroxime (90%) was more effective in eradicating GABHS than penicillin V (84%) 2-4 days post-treatment. The study concluded that short-course (4-5 days) treatment with cefuroxime was effective and comparable to standard oral penicillin V in preventing post-streptococcal sequelae (16).

A cross-sectional, questionnaire-based study conducted among Indian physicians reported that cefuroxime and cefuroxime + clavulanic acid are among the listed preferred oral antibiotics in treating URTI. (17)

Guidelines on Cefuroxime in Upper Respiratory Tract Infections (URTIs):

The Indian Council of Medical Research has mentioned antibiotics including Cefuroxime 500 mg twice daily orally/1.5 gm twice daily IV for the treatment of URTIs (11).

The United States Food and Drug Administration (U.S F.D.A) mentions the dosages of cefuroxime 250mg every 12 hours for a duration of 10 days in mild to moderate cases of pharyngitis/tonsillitis and acute bacterial maxillary sinusitis (18).

Take-Home Points:

• Upper respiratory tract infections (URTIs) are inflammation of the upper airways, resulting from infections (1).
• Upper respiratory tract infections (URTIs) are very common in India. Acute Otitis media, Acute rhinosinusitis, Epiglottitis, Influenza, and Pharyngitis are some of the commonly detected URTIs (5).
• Guidelines suggest using Antibiotics for bacterial URTIs like tonsilitis, acute bacterial rhinosinusitis, and Group A Streptococcal Pharyngitis (11).
• Cefuroxime is a second-generation, broad-spectrum antibiotic administered at dosages from 125 to 1000 mg daily. Cefuroxime is an effective, safe, and well-tolerated anti-microbial agent (12).

References:

‌1. Jin X, Ren J, Li R, Gao Y, Zhang H, Li J, et al. Global burden of upper respiratory infections in 204 countries and territories, from 1990 to 2019. EClinicalMedicine. 2021 Jul;37:100986. Doi: https://doi.org/10.1016/j.eclinm.2021.100986.

2. Thomas M, Bomar PA. Upper respiratory tract infection [Internet]. National Library of Medicine. StatPearls Publishing; 2022. Available from: https://www.ncbi.nlm.nih.g ov/books/NBK532961/.

3. Jain N, Lodha R, Kabra SK. Upper respiratory tract infections. Indian Journal of Pediatrics [Internet]. 2001 Dec 1;68(12):1135–8. Doi: 10.1007/BF02722930.

4. Waghmode R, Jadhav S, Nema V. The Burden of Respiratory Viruses and Their Prevalence in Different Geographical Regions of India: 1970–2020. Frontiers in Microbiology. 2021 Aug 31;12. Doi: 10.3389/fmicb.2021.723850.

‌5. Sur DKC, Plesa ML. Antibiotic Use in Acute Upper Respiratory Tract Infections. American Family Physician [Internet]. 2022 [cited 2024 Apr 18];106(6):628–36. Available from: https://www.aafp.org/pubs/afp/issues/2022/1200/antibiotics-upper-respiratory-tract-infections.html#afp20221200p628-b48.

6‌. Bosch AATM, Biesbroek G, Trzcinski K, Sanders EAM, Bogaert D. Viral and Bacterial Interactions in the Upper Respiratory Tract. Hobman TC, editor. PLoS Pathogens [Internet]. 2013 Jan 10;9(1):e1003057. Doi: 10.1371/journal.ppat.1003057.

7. Yoon YK, Park CS, Kim JW, Hwang K, Lee SY, Kim TH, et al. Guidelines for the Antibiotic Use in Adults with Acute Upper Respiratory Tract Infections. Infection & Chemotherapy. 2017;49(4):326.

8‌. Cotton M, Innes S, Jaspan H, Madide A, Rabie H. Management of upper respiratory tract infections in children. South African family practice: official journal of the South African Academy of Family Practice/Primary Care [Internet]. 2008;50(2):6–12. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3098742/.

9‌. Yoon YK, Park CS, Kim JW, Hwang K, Lee SY, Kim TH, et al. Guidelines for the Antibiotic Use in Adults with Acute Upper Respiratory Tract Infections. Infection & Chemotherapy. 2017;49(4):326. Doi: 10.3947/ic.2017.49.4.326.

1‌0. Lambert M. IDSA Releases Guidelines for Management of Acute Bacterial Rhinosinusitis. American Family Physician [Internet]. 2013 Mar 15;87(6):445–9. Available from: https://www.aafp.org/pubs/afp/issues/2013/0315/p445.html.

11. Treatment Guidelines for Antimicrobial Use in Common Syndromes 2022 New Delhi, India [Internet]. Available from: https://main.icmr.nic.in/sites/default/files/guidelines/Treatment_Guidelines_2022_Final.pdf

12. Scott LJ, Ormrod D, Goa KL. Cefuroxime Axetil. Drugs. 2001;61(10):1455–500. Doi: 10.2165/00003495-200161100-00008

13. Chow AW, Benninger MS, Brook I, Brozek JL, Goldstein EJC, Hicks LA, et al. IDSA Clinical Practice Guideline for Acute Bacterial Rhinosinusitis in Children and Adults. Clinical Infectious Diseases. 2012 Apr 15;54(8):e72–112.

1‌4. Griffiths GK, Vanden Burg MJ, Wight LJ, Gudgeon AC, Kelsey M. Efficacy and tolerability of cefuroxime axetil in patients with upper respiratory tract infections. Current Medical Research and Opinion. 1987 Jan;10(8):555–61.

1‌5. Camacho AE, Cobo R, Otte J, Spector SL, Lerner CJ, Garrison NA, et al. Clinical comparison of cefuroxime axetil and amoxicillin/clavulanate in the treatment of patients with acute bacterial maxillary sinusitis. The American Journal of Medicine [Internet]. 1992 Sep 1 [cited 2021 Nov 30];93(3):271–6. Available from: https://pubmed.ncbi.nlm.nih.gov/1524078/.

‌16. Adam D, Scholz H, Helmerking M. Comparison of short-course (5-day) cefuroxime axetil with a standard 10-day oral penicillin V regimen in the treatment of tonsillopharyngitis. Journal of Antimicrobial Chemotherapy. 2000 Feb;45(suppl_1):23–30.

17. Manjula, S. and Krishna Kumar, M. 2024. Expert Opinion on the Use of Oral Antibiotics with A Special Focus on Amoxicillin-Clavulanate and Cefuroxime for the Management of Respiratory Tract Infections and Otitis Media in Indian Settings. Int.J.Curr.Microbiol.App.Sci. 13(01): 33-41. doi: https://doi.org/10.20546/ijcmas.2024.1301.004

18. Enforcement Reports [Internet]. www.accessdata.fda.gov. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/050605s048.Upper respiratory tract infections