Data Show Amoxicillin Therapy Resistance for Invasive Pneumococcal Disease

Amoxicillin therapy had not been associated with an increased risk of resistance for patients with a nonfatal McCabe score who had invasive pneumococcal disease (IPD). However, investigators of study data published in Antimicrobial Agents and Chemotherapy found amoxicillin was associated with increased resistance for patients who were in the ultimately fatal or rapidly fatal groups.¹

New research data reveal amoxicillin's effectiveness varies in treating invasive pneumococcal disease, highlighting the importance of patient-specific factors in antibiotic therapy. | Image Credit: Maksym Yemelyanov - stock.adobe.com

“Amoxicillin is one of the most commonly used antibiotics to treat pneumococcal pneumonia,” the study authors said.¹ “Furthermore, it is also employed in stewardship programs to reduce the antimicrobial spectrum and switch to oral administration.”

Pneumococcal disease is caused by Streptococcus pneumoniae and can cause infections such as sinusitis, pneumonia, and sepsis. The bacteria can also cause bacterial meningitis and otitis media, according to the CDC. Treatment typically includes antibiotics, but prescribers might try several kinds, as the infection can become resistant to these agents. For mild infections, prescribers might also recommend pain relievers.^2,3

Vaccination is the best way to prevent IPD, with the CDC recommending vaccination for all children younger than 5 years, patients aged 5 through 49 years with certain risk factors, and adults 50 years and older. There are 2 types of vaccination: pneumococcal conjugate vaccines (PCVs) and pneumococcal polysaccharide vaccines. Pneumococcal disease is common in young children, but older adults are at the greatest risk of severe illness and death, according to the CDC.^3,4

Investigators aimed to determine the potential impact of elevated minimum inhibitory concentrations (MICs) in antibiotics, specifically regarding epidemiology, molecular basis, and clinical impact. Further, they will explore the potential role of amoxicillin in treatment and antibiotic de-escalation in the context of IPD, noted the study authors.¹

The study was observational in nature and included a hospital with 700 beds that admitted patients 18 years and older in the Barcelona, Spain, metropolitan area. Data included sex, age, origin of infection, acquisition, comorbidities, severity of underlying diseases, treatment, and 30-day mortality. From 1994 to 2020, 1663 S pneumoniae isolates were collected, and approximately 98% of isolates had data on serotypes, with 7 serotypes accounting for over half of cases: 3, 14, 19A, 1, 8, 7F, and 9V.¹

The proportion of isolates susceptible to amoxicillin increased over time from 72.9% from 1994 to 2001 to 91.4% from 2016 to 2020. For MICs greater than 0.5 to 2 mg/L, there was a drastic reduction of isolates from 22.3% to 3.3%, respectively, according to the study authors. For those with isolates greater than 2 mg/L, the numbers remained relatively stable at 4.8% and 5.3%, respectively. For nonsusceptible isolates, the most common vaccine serotypes were 14, 9V, and 23F before PCVs were introduced and 19A and 11A after the introduction of PCVs.¹

As for clinical outcomes, 1527 cases were included for analysis, with patients having a median age of 62.4 years and 36.7% being women. Patients who were older and had a worse prognosis (an ultimately/rapidly fatal McCabe score) were more likely to have amoxicillin-resistant isolates. Furthermore, patients with malignancies (38.5%) and those receiving immunosuppressive therapy (29.7%) were more likely to be amoxicillin resistant.¹

“Amoxicillin therapy was independently associated with increased mortality in patients in the McCabe ultimately/rapidly fatal groups, but not in patients in the nonfatal group. These data are interesting as they indicate variations in antimicrobial efficacy based on the host’s status,” the authors stated.¹ “Taken together, these results highlight that prescribing a specific antimicrobial should always be accompanied by a thorough evaluation of the host’s comorbidities and the severity of the infection.”

READ MORE: Pneumococcal Resource Center

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REFERENCES

1. Càmara J, Grau I, González-Díaz A, et al. Amoxicillin-non-susceptible Streptococcus pneumoniae causing invasive pneumonia: serotypes, clones, and clinical impact. Antimicrob Agents Chemother. Published online July 8, 2025. doi:10.1128/aac.00237-25

2. About pneumococcal disease. CDC. Updated October 21, 2024. Accessed July 16, 2025. https://www.cdc.gov/pneumococcal/about/index.html

3. Pneumococcal disease. Cleveland Clinic. Updated September 27, 2022. Accessed July 16, 2025. https://my.clevelandclinic.org/health/diseases/24231-pneumococcal-disease

4. Pneumococcal vaccination. CDC. Updated October 26, 2024. Accessed July 16, 2025. https://www.cdc.gov/pneumococcal/vaccines/index.html