Amoxicillin In Review - Standing the Test of Time since Five Decades

Amoxicillin is regarded as one of the most widely and frequently used antibiotics, especially in primary healthcare settings (1). Owing to its spectrum of action against a diverse variety of micro-organisms (1), including both gram-positive and gram-negative species, this drug has cemented its position as a 'first line' antimicrobial against an array of diseases.

This article puts together the use of amoxicillin in various diseases, highlights its significance in low resource countries, and focuses on the current guidelines on its use.

Major indications of using amoxicillin as has been approved by the FDA (1) are summarised below.

1. Ear, nose, and throat infections-adults and pediatric patients ≥ 12 years of age suffering from upper respiratory tract infections like tonsillitis, pharyngitis, and otitis media are to be treated with amoxicillin.

2. Lower respiratory tract infections- beta-lactamase-negative Streptococcus species (alpha- and beta-hemolytic strains only), pneumococcus, Staphylococcus species, or Haemophilus influenza are mainly responsible for such infections and are regarded to be vulnerable to amoxicillin. For community-acquired pneumonia, a combination of amoxicillin and macrolide is generally recommended.

3. FDA advocates a triple therapy for Helicobacter pylori with clarithromycin, amoxicillin, and lansoprazole as well as a Dual treatment therapy with amoxicillin and lansoprazole to eradicate Helicobacter pylori and reduce the risk of duodenal ulcer recurrence.

4. Treating Acute Bacterial Sinusitis infections due to beta-lactamase-negative Streptococcus species (alpha-beta-hemolytic isolates only), Streptococcus species, or Haemophilus influenza.

5. Skin and skin structure infections due to beta-lactamase-negative Streptococcus species (alpha and beta-hemolytic strains only), Staphylococcus species, or Escherichia coli are to be treated with amoxicillin.

6. Urinary tract infection: Treatment of the genitourinary tract infections. Organisms include beta-lactamase-negative Escherichia coli, Proteus mirabilis, or Enterococcus faecalis.

7. Centers for Disease Control and Prevention (CDC) recommends using amoxicillin for post-exposure prophylaxis for anthrax(second-line agent) (2)

   Clinical Use of amoxicillin includes Infectious endocarditis prophylaxis, Periodontitis in combination with metronidazole, and Actinomycosis.

   Clinical Relevance of Amoxicillin in Low-Resource Settings

Research has revealed that huge healthcare disparities exist in low to middle-income countries, commonly known as developing nations. (3)Such low resource settings call for a drug that is not only easily available to the masses and active against common infections but also cost-effective.

Evidence supporting the potency of amoxicillin under such scenarios has been listed below.

A study by Abdul Bari et al aimed to assess whether community case management with oral amoxicillin in children with severe pneumonia was equivalent to the current standard of care. The results indicated that treatment failure rates by day 6 were significantly reduced in the intervention clusters, suggesting that amoxicillin therapy was non-inferior to the current standard of care practice. (4) These findings are consistent with those of previous studies in which oral amoxicillin and facilities-based parenteral treatment for severe pneumonia were compared. The NO-SHOTS study and APPIS study reported an equivalence in in-hospital parenteral treatment and home-based amoxicillin, and a relatively high failure rate in the ambulatory group. (5,6)

In a breakthrough study, Mehta S et al (7) in 2020 investigated the susceptibility patterns of Azithromycin, Cefuroxime, Doxycycline, and Amoxicillin against common bacteriological isolates through a diagnostic laboratory-based retrospective study. The results confirmed that only amoxicillin was more active (95.8 %) than doxycycline, azithromycin, and cefuroxime against Streptococcus spp and this was consistent across all tested clinical specimens – sputum, pus, blood, and urine.

Yet another study (8) examining the efficacy of amoxicillin versus cefixime, a third-generation cephalosporin, conducted on 114 patients with sinusitis inferred that the cure rate was 96% in the amoxicillin group as compared to 94% in the cefixime group. Such findings highlight the fact that amoxicillin was at par in efficacy with cefixime, in mixed bacteriological infections.

In an observational study, conducted to evaluate the bacteriological and clinical efficacy of amoxicillin among 137 children suffering from beta-hemolytic streptococcal (GABHS)  tonsillopharyngitis, researchers observed that the bacteriological and clinical cure rates were high-76% and 84% respectively. (9)

Amoxicillin – Strongly holding the testimony of Global Guidelines

The WHO has recommended the use of amoxicillin in the ACCESS category of antibiotics, thus rationalizing its potency in a wide range of infections, while exhibiting minimal resistance. (10)

According to the 2019 ICMR guidelines, amoxicillin has been recommended as a first-line agent for mild bacterial sinusitis and acute otitis media. Amoxicillin is also one of the preferred choices for pediatric community-acquired pneumonia in outpatient settings. (11)

Summary & Way Forward - Amoxicillin is here to stay!

Take home message-

Amoxicillin holds a special place as the go-to antibiotic in low-income countries, where primary healthcare settings play a crucial role in managing the disease burden of the country.

Being effective against a range of diseases, both global and Asian evidence confirms that this drug has been in use successfully, for a long time.

Amoxicillin has been listed in the WHO list of essential medicines in the ACCESS group (9). ACCESS group drugs are the ones that can be made available at all times as empiric, first, or second choice treatments of common infections and should be widely available, at an affordable cost, inappropriate formulations, and of assured quality.

Conclusion-

Amoxicillin is a common antimicrobial often advocated by medical professionals (1). Being backed up by decades of scientifically affirmed research, this drug has proven its efficacy, safety, and tolerability over and again across various study populations. Withstanding the test of time, amoxicillin leads the way as one of the most preferred antibiotic drugs among medical professionals and will continue to reign in years to come.

References

1. Akhavan BJ, Khanna NR, Vijhani P. Amoxicillin. [Updated 2021 Aug 17]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK482250/

2. Katherine A Hendricks, Mary E Wright, Sean V Shadomy, et.al. Centers for Disease Control and Prevention Expert Panel Meetings on Prevention and Treatment of Anthrax in Adults. Center for Disease Control and Prevention. 2014. PMCID: PMC3901462 PMID: 24447897

3. van Zyl C, Badenhorst M, Hanekom S, et al Unravelling 'low-resource settings': a systematic scoping review with qualitative content analysis BMJ Global Health 2021;6:e005190.

4. Abdul Bari; Salim Sadruddin; Attaullah Khan; Ibad ul Haque Khan; Amanullah Khan; Iqbal A Lehri; William B Macleod; Matthew P Fox; Donald M Thea; Shamim A Qazi (2011). Community case management of severe pneumonia with oral amoxicillin in children aged 2–59 months in Haripur district, Pakistan: a cluster randomised trial. , 378(9805), 0–1803. doi:10.1016/s0140-6736(11)61140-9

5. Addo-Yobo E, Chisaka N, Hassan M, et al, for the Amoxicillin Penicillin Pneumonia International Study (APPIS) group. Oral amoxicillin versus injectable penicillin for severe pneumonia in children aged 3 to 59 months: a randomised multicentre equivalency study. Lancet 2004; 364: 1141–48

6. Hazir T, Fox LM, Nasir YB, et al, for the New Outpatient Short-Course Home Oral Therapy for Severe Pneumonia (NO-SHOTS) Study Group. Ambulatory short-course high-dose amoxicillin for treatment of severe pneumonia in children: a randomised equivalency trial. Lancet 2008; 371: 49–5

7. Suyog C Mehta et al, Susceptibility Pattern of Doxycycline in Comparison toAzithromycin, Cefuroxime and Amoxicillin against Common Isolates: ARetrospective Study Based on Diagnostic Laboratory Data, Journal of The Associationof Physicians of India 2020;68:59-63

8. Edelstein DR, Avner SE, Chow JM, Duerksen RL, Johnson J, Ronis M, RybakLP, Bierman WC, Matthews BL, Kohlbrenner VM. Once-a-day therapy for sinusitis: acomparison study of cefixime and amoxicillin. Laryngoscope. 1993 Jan;103(1 Pt1):33-41. doi: 10.1288/00005537-199301000-00008. PMID: 8421417.

9. Murphy ML, Francis AB, Pichichero ME. Efficacy of penicillin vs. amoxicillin inchildren with group A beta hemolytic streptococcal tonsillopharyngitis. Clin Pediatr(Phila). 2003 Apr;42(3):219-25. doi: 10.1177/000992280304200305. PMID:12739920.

10. World Health Organization. (‎2017)‎. WHO model list of essential medicines, 20th list (‎March 2017, amended August 2017)‎. World Health Organization. https://apps.who.int/iris/handle/10665/273826

11. Treatment Guidelines for Antimicrobial Use in Common Syndromes, IndianCouncil of Medical Research 2019, 2nd edition, Pages 1-206