Amoxicillin outperforms penicillin V in treating pediatric pneumonia, study finds

In a recent study published in the journal Clinical Microbiology and Infection, researchers conducted a population-based emulated trial to evaluate the clinical efficacy of penicillin V (PcV) and amoxicillin in treating pediatric pneumonia. Specifically, they compared the two antimicrobial agents' risk of treatment failure and severe complications. Their findings support the global trend of amoxicillin use by verifying its lower risk of treatment failure than penicillin V. It further debunks the Scandinavian practice of penicillin V use, highlighting that despite its narrower antimicrobial range than amoxicillin, the risk of severe complications was statistically identical between the two.

Study: Penicillin V versus amoxicillin for pneumonia in children – a Swedish nationwide emulated target trial. Image Credit: Michelle Lee Photography / ShutterstockStudy: Penicillin V versus amoxicillin for pneumonia in children – a Swedish nationwide emulated target trial. Image Credit: Michelle Lee Photography / Shutterstock

A brief history of pediatric pneumonia treatment

Pneumonia is the single most significant transmissible cause of childhood mortality in the world today, estimated to have accounted for 740,180 children dying in 2019 alone (14% of all childhood deaths; World Health Organisation [WHO]). Pediatric pneumonia is an upper respiratory tract infection caused by viruses, fungi, or bacteria, with Streptococcus pneumoniae and Haemophilus influenzae historically being the most common causative agents of the disease. Unfortunately, a shortage of reliable diagnostic tests combined with the commonality of bacteria-caused pneumonia results in antibiotics being the primary clinical intervention in most pediatric pneumonia cases.

Amoxicillin, an aminopenicillin popularised for its narrow microbial range and high efficacy against gram-positive bacteria (including S. pneumonia and Streptococci sp.), is the most widely used antimicrobial agent to treat pediatric pneumonia. However, some Scandinavian countries (for example, Sweden) prefer using penicillin V (PcV) due to their assumption that amoxicillin can demonstrate antimicrobial activity against beneficial gut microbiota in addition to the target pneumonia pathogen. PcV has been shown to have an even narrower microbial range than amoxicillin, notably having minimal impact on the gram-negative gut microbiome.

The debate between clinicians who favor amoxicillin and those who favor PcV has created substantial disparities in treatment practices across Sweden. Stockholm almost exclusively prescribes amoxicillin, Västra Götaland and Skåne predominantly use PcV instead. Unfortunately, these antibiotics' clinical efficacy and complication risk have never been scientifically verified.

About the study

The present study aimed to compare clinical outcomes, specifically 'treatment failure' (defined as antibiotic re-treatment within 14 days of primary course completion or, in severe cases, hospitalization) and 'severe complications' (lung complications, ICU admissions, or death within 28 days of primary course initiation) in children with laboratory-confirmed pneumonia. The age group of interest was children between one and 59 months.

Data for this emulated study was obtained from the national health and population registers between 2001 and 2021, comprising medical records and sociodemographic data. Registries queried included the National Patient Register (NPR), the Swedish Prescribed Drug Register (SPDR), the Medical Birth Register (MBR), the Longitudinal Integrated Database for Labour Market Studies (LISA), the Swedish Intensive Care Registry register (SIR), and the Cause of Death Register (CDR).

The exposure variable under consideration was the initial prescription of either antibiotic. A directed acyclic graph was used to assess and address potential confounders (literature confirmed associations between covariates and outcomes).

"Data on sex and maternal smoking during pregnancy were collected from the MBR. Educational level of parents (primary school i.e. ≤9 years, secondary school i.e. 9-12 years or university studies i.e. >12 years) was collected from LISA. Data on initial hospitalization (<2 days), age and comorbidities were collected from the NPR. Previous asthma was defined based on dispensed prescriptions of asthma medications and doctors diagnosis according to a previously validated algorithm."

Statistical analyses consisted of multivariable logistic regressions controlled for confounders. Geographical regions under investigation were categorized into three cohorts (<33%, 33-66%, and >66%) based on the number of amoxicillin prescriptions.

Study findings and conclusions

A total of 37,674 pneumonia cases were reported from 2001 to 2021, 25,332 of which met the study inclusion criteria and were included in the present analyses. Of these, 14,766 cases were prescribed PcV, while 10,566 were prescribed amoxicillin.

"Children receiving PcV were more likely to come from families with lower educational level and more prevalent maternal smoking. Further, children receiving PcV were less likely to have asthma but more likely to initially have been hospitalized during their pneumonia prior to the antibiotic prescription."

Significant regional discrepancies in antibiotic prescriptions were observed, ranging from 10% to 79% amoxicillin prescriptions across the country. 6.4% (1,627) of cases were found to be accompanied by treatment failure, while 0.3% (68) were followed by severe complications. PcV was found to result in a higher risk of treatment failure (odd ratio [OR] = 7.7%) compared to amoxicillin (OR = 4.7%). Surprisingly, contrary to historic Scandinavian belief, no differences were observed in the risk of severe complications between these antibiotic interventions.

In summary, the global recommendation of amoxicillin for treating pediatric pneumonia was found to be better than the historic Scandinavian practice of using PcV – the clinical efficacy and performance of the former were more than 3.2% better than the latter, without any increase in the risk of severe complications.

Journal reference:
  • Rhedin, S., Kvist, B., Osvald, E. C., Karte, G., Smew, A. I., Nauclér, P., Lundholm, C., & Almqvist, C. (2024). Penicillin V versus amoxicillin for pneumonia in children – a Swedish nationwide emulated target trial. In Clinical Microbiology and Infection. Elsevier BV, DOI – 10.1016/j.cmi.2024.06.008, https://www.sciencedirect.com/science/article/pii/S1198743X2400288X
Hugo Francisco de Souza

Written by

Hugo Francisco de Souza

Hugo Francisco de Souza is a scientific writer based in Bangalore, Karnataka, India. His academic passions lie in biogeography, evolutionary biology, and herpetology. He is currently pursuing his Ph.D. from the Centre for Ecological Sciences, Indian Institute of Science, where he studies the origins, dispersal, and speciation of wetland-associated snakes. Hugo has received, amongst others, the DST-INSPIRE fellowship for his doctoral research and the Gold Medal from Pondicherry University for academic excellence during his Masters. His research has been published in high-impact peer-reviewed journals, including PLOS Neglected Tropical Diseases and Systematic Biology. When not working or writing, Hugo can be found consuming copious amounts of anime and manga, composing and making music with his bass guitar, shredding trails on his MTB, playing video games (he prefers the term ‘gaming’), or tinkering with all things tech.

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