A study by French experts has found the prescribing of inappropriate antibiotics for children is extensive in the three low- and middle-income countries (LMICs) in which they carried out their research, with more than three quarters of consultations resulting in an unnecessary antibiotic script for children under two.
The authors of the study, published in PLOS Medicine, and which was carried out in Madagascar, Senegal and Cambodia, said factors tied to the increased risk of an inappropriate prescription included being older than three months and living in rural settings.
“These inappropriate scripts, despite providing little or no benefit – or even harm to the patients – could contribute to the emergence of antibiotic resistance,” they wrote.
Scarce data
For the study, a team led by researchers from Université Paris-Saclay used data from a prospective, community-based mother-and-child cohort known as the BIRDY study, which followed children from birth to 24 months across rural and urban sites in Madagascar, Senegal and Cambodia from 2012 to 2018.
Data from the cohort have been used for multiple studies aimed at assessing the incidence of childhood infections caused by antibiotic-resistant bacteria in three representative LMICs, reports CIDRAP.
The authors note that although young children in LMICs bear the greatest share of global infectious disease burden and are heavily exposed to antibiotics in the first few years of life, there are few studies describing the magnitude and determinants of inappropriate prescribing, particularly in outpatient settings.
“Such data are necessary to quantify potential for prescribing reductions, to describe which populations are potentially overexposed to antibiotics, and ultimately to inform interventions targeting prevention of inappropriate prescribing,” they wrote.
They examined data on children from the BIRDY cohort who had at least one outpatient consultation during the time they were followed. Using a classification algorithm developed according to World Health Organisation guidelines, they defined inappropriate antibiotic prescriptions as those prescribed for a condition that does not require antibiotic therapy.
They used mixed logistics analyses to investigate risk factors for inappropriate prescriptions.
Overall, there were 11 762 outpatient consultations in the three countries over the follow-up period, 3 448 of which (29.3%) resulted in an antibiotic prescription. Of those prescriptions, 2 639 (76.5%) were associated with diagnoses the researchers determined did not require an antibiotic.
The proportion of consultations involving a diagnosis that didn’t require an antibiotic but still received one ranged from 15.5% in Madagascar to 57% in Cambodia and 57.2% in Senegal.
In Cambodia and Madagascar, the diagnoses that accounted for the greatest share of inappropriate prescriptions were the common cold (59% of associated consultations in Cambodia, 7.9% in Madagascar), and gastroenteritis (vomiting and diarrhoea) without evidence of blood in the stool (61.6% and 24.6%, respectively).
In Senegal, inappropriate prescribing was primarily driven by uncomplicated bronchiolitis, a lung infection (84.4% of associated consultations).
Analysis of risk factors found that children aged three months and older had a higher risk of an inappropriate prescription than children under three months in all three countries, ranging from an adjusted odds ratio (aOR) of 1.91 (95% confidence interval [CI], 1.63 to 2.25) in Senegal to 3.65 (95% CI, 2.96 to 4.28) in Madagascar to 5.25 (95% CI, 3.85 to 7.15) in Cambodia.
Children in rural areas had a higher rate of inappropriate prescription, with aORs of 1.83 (95% CI, 1.57 to 2.14) in Madagascar, 4.07 (95% CI, 3.12 to 5.31) in Cambodia, and 4.40 (95% CI, 2.34 to 8.28) in Senegal.
Consultations during the rainy season and children with a higher clinical severity score were also linked to a higher risk of an inappropriate prescription.
Improving prescribing at community level
The authors say that while the findings are limited by the lack of bacteriologic documentation, the rigorous documentation of patient symptoms and diagnoses suggests the results represent a reliable estimate of local antibiotic prescribing practices. They said this indicates the need for interventions in LMICs to improve prescribing at community level.
They suggest training prescribers using validated paediatric clinical guidelines, and increasing access to rapid diagnostic tests that can distinguish between viral and bacterial infections, especially in remote areas.
They also note that further research is needed in these settings to better understand prescribers’ motivations and the perceived necessity of antibiotics among patients.
“The decision-making process underlying antibiotic prescription is complex, particularly in the absence of robust microbiological information and given challenging socioeconomic contexts, requiring the implementation of locally adapted multimodal strategies,” they wrote.
Study details
Inappropriate antibiotic prescribing and its determinants among outpatient children in 3 low- and middle-income countries: A multicentric community-based cohort study
Antoine Ardillon, Lison Ramblière, Perlinot Herindrainy, et al.
Published in PLOS Medicine on 6 June 2023
Abstract
Background
Antibiotic resistance is a global public health issue, particularly in low- and middle-income countries (LMICs), where antibiotics required to treat resistant infections are not affordable. LMICs also bear a disproportionately high burden of bacterial diseases, particularly among children, and resistance jeopardises progress made in these areas. Although outpatient antibiotic use is a major driver of antibiotic resistance, data on inappropriate antibiotic prescribing in LMICs are scarce at the community level, where the majority of prescribing occurs. Here, we aimed to characterise inappropriate antibiotic prescribing among young outpatient children and to identify its determinants in 3 LMICs.
Methods and findings
We used data from a prospective, community-based mother-and-child cohort (BIRDY, 2012 to 2018) conducted across urban and rural sites in Madagascar, Senegal, and Cambodia. Children were included at birth and followed-up for 3 to 24 months. Data from all outpatient consultations and antibiotics prescriptions were recorded. We defined inappropriate prescriptions as antibiotics prescribed for a health event determined not to require antibiotic therapy (antibiotic duration, dosage, and formulation were not considered). Antibiotic appropriateness was determined a posteriori using a classification algorithm developed according to international clinical guidelines. We used mixed logistic analyses to investigate risk factors for antibiotic prescription during consultations in which children were determined not to require antibiotics. Among the 2,719 children included in this analysis, there were 11,762 outpatient consultations over the follow-up period, of which 3,448 resulted in antibiotic prescription. Overall, 76.5% of consultations resulting in antibiotic prescription were determined not to require antibiotics, ranging from 71.5% in Madagascar to 83.3% in Cambodia. Among the 10,416 consultations (88.6%) determined not to require antibiotic therapy, 25.3% (n = 2,639) nonetheless resulted in antibiotic prescription. This proportion was much lower in Madagascar (15.6%) than in Cambodia (57.0%) or Senegal (57.2%) (p < 0.001). Among the consultations determined not to require antibiotics, in both Cambodia and Madagascar the diagnoses accounting for the greatest absolute share of inappropriate prescribing were rhinopharyngitis (59.0% of associated consultations in Cambodia, 7.9% in Madagascar) and gastroenteritis without evidence of blood in the stool (61.6% and 24.6%, respectively). In Senegal, uncomplicated bronchiolitis accounted for the greatest number of inappropriate prescriptions (84.4% of associated consultations). Across all inappropriate prescriptions, the most frequently prescribed antibiotic was amoxicillin in Cambodia and Madagascar (42.1% and 29.2%, respectively) and cefixime in Senegal (31.2%). Covariates associated with an increased risk of inappropriate prescription include patient age greater than 3 months (adjusted odds ratios (aOR) with 95% confidence interval (95% CI) ranged across countries from 1.91 [1.63, 2.25] to 5.25 [3.85, 7.15], p < 0.001) and living in rural as opposed to urban settings (aOR ranged across countries from 1.83 [1.57, 2.14] to 4.40 [2.34, 8.28], p < 0.001). Diagnosis with a higher severity score was also associated with an increased risk of inappropriate prescription (aOR = 2.00 [1.75, 2.30] for moderately severe, 3.10 [2.47, 3.91] for most severe, p < 0.001), as was consultation during the rainy season (aOR = 1.32 [1.19, 1.47], p < 0.001). The main limitation of our study is the lack of bacteriological documentation, which may have resulted in some diagnosis misclassification and possible overestimation of inappropriate antibiotic prescription.
Conclusion
In this study, we observed extensive inappropriate antibiotic prescribing among paediatric outpatients in Madagascar, Senegal, and Cambodia. Despite great intercountry heterogeneity in prescribing practices, we identified common risk factors for inappropriate prescription. This underscores the importance of implementing local programmes to optimise antibiotic prescribing at the community level in LMICs.
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