Drug-related problems, or DRPs, are defined as events or circumstances involving drug therapy that actually or potentially interfere with a patient’s desired health outcome. They span prescribing errors, monitoring failures, adverse drug reactions, and non-adherence, and they are a leading cause of preventable harm in hospitalized children. Children are particularly vulnerable because pediatric dosing is weight-based, drug distribution and excretion change with age, and clinicians frequently resort to off-label prescribing. Reported prevalence in pediatric wards ranges from 5 to 68 percent, with dose-related problems consistently the most common category. In Pakistan, where community-acquired infections such as enteric fever, pneumonia, and gastroenteritis account for an estimated 60 to 70 percent of pediatric admissions at tertiary centers, the stakes are especially high.

The research team, led by investigators from Dow University of Health Sciences in Karachi with collaborators in Iraq, enrolled children aged two months to 14 years admitted to the pediatric medical ward or pediatric high-dependency unit with confirmed community-acquired infections, including enteric fever, gastroenteritis, pneumonia, dengue, malaria, meningitis, urinary tract infections, viral hepatitis, bronchitis, and skin and soft tissue infections. Children in intensive care or neonatal units were excluded, as were patients discharged within 24 hours. A trained pharmacist stationed on the ward during morning shifts reviewed every medication order daily, classifying each problem using the Pharmaceutical Care Network Europe classification version 9.1 and grading severity with the NCC MERP criteria, which distinguish errors unlikely to cause harm from those with the potential to require increased monitoring or to cause serious harm, permanent damage, or death.

The scale of the problem was considerable. Of the 400 children enrolled, 372, or 93 percent, had at least one drug-related problem, and the average patient carried 5.03 problems. The mean age was 4.79 years, nearly two-thirds were boys, and enteric fever was the most common diagnosis at 29.5 percent, followed by acute gastroenteritis at 21.3 percent and pneumonia at 12 percent. Nearly three-quarters of the children were receiving more than five medications, and 96 percent were febrile on admission. Every order was checked against reference standards including the Lexicomp Online pediatric dosing database, the Sanford Guide to Antimicrobial Therapy, World Health Organization treatment guidelines, and the British National Formulary for Children.

Dose selection errors dominated the landscape, accounting for 58.13 percent of all problems. Within that category, over-dosing made up 43.7 percent and under-dosing 40.2 percent, with the remainder involving incorrect dosing frequency. Antibiotics were implicated in 67.3 percent of dose-related problems, followed by antipyretics and analgesics at 18 percent. The examples the authors cite are sobering: ceftriaxone prescribed at 50 mg/kg/day instead of the 80 to 100 mg/kg/day required for meningitis, paracetamol ordered at 20 mg/kg/dose when 10 to 15 mg/kg/dose is appropriate, and vancomycin given without any therapeutic drug monitoring. Inappropriate drug form accounted for 15.01 percent of problems, a figure the authors attribute partly to the scarcity of pediatric-friendly formulations, while drug selection errors, driven largely by excessive polypharmacy, made up 13.08 percent.

Severity grading revealed that 9 percent of the 2,010 problems, 184 in total, had the potential to cause serious harm, permanent damage, or death. These included vancomycin prescribed without therapeutic drug monitoring, which carries a nephrotoxicity risk; co-administration of intravenous ceftriaxone and calcium, which risks precipitation; high-dose aminoglycosides without renal monitoring; contraindicated drug combinations; and tenfold dosing errors in low-weight infants. Roughly half of all problems were classified as minor and nearly 39 percent as moderate. The inter-rater reliability of the classification was high, with Cohen’s kappa of 0.85 for PCNE coding and 0.82 for severity grading, based on independent review of a 10 percent random sample by a second pharmacist.

The intervention workflow was systematic. When a problem was identified, the pharmacist verified it against reference standards, formulated an evidence-based recommendation, communicated it to the prescribing physician, usually face to face during ward rounds, and documented the outcome using PCNE codes. Complex antimicrobial cases were discussed with an infectious diseases specialist. Of the 2,010 problems, 1,986 received interventions, and the acceptance rate was remarkable: 98.7 percent of pharmacist recommendations were accepted, with 89.1 percent fully implemented. Ultimately, 81.1 percent of problems were completely resolved and another 13.9 percent partially resolved. Only 26 interventions, 1.3 percent, were rejected, most often because the prescriber disagreed.

The economic analysis was grounded in actual drug acquisition costs drawn from the Drug Regulatory Authority of Pakistan’s 2023 price list and hospital pharmacy records, not estimates. Cost savings totaled PKR 363,184 over ten months, with a positive-to-negative cost ratio of 23:1, meaning that for every rupee spent on therapeutically necessary cost increases, 23 rupees were saved through error correction. Dose corrections delivered the largest share of savings at 50.5 percent, while eliminating duplicated therapy yielded the highest savings per intervention at an average of PKR 1,888. The cost per problem prevented was just PKR 241, about USD 0.86, and after deducting the estimated PKR 150,000 cost of 600 hours of pharmacist time, the net return on investment stood at 142 percent. Sensitivity analyses varying pharmacist salary, time, and drug costs confirmed the findings remained positive across all scenarios. Notably, the authors emphasize that these figures exclude indirect benefits such as reduced length of stay, prevented adverse events, and long-term gains from curbing antimicrobial resistance, making the estimates conservative.

Statistical modeling identified four independent predictors of drug-related problems. Each additional prescribed medication raised the odds by 32 percent, fever at admission nearly tripled the risk, and a hospital stay longer than seven days increased it by 76 percent. Most intriguingly, complete past immunization was protective, cutting the odds by 49 percent. The authors suggest this may be indirect: vaccinated children may present with less severe illness or different infection profiles requiring less complex treatment, rather than immunization directly preventing prescribing errors. The finding, they note, adds a medication-safety dimension to the already strong case for childhood vaccination programs.

The study is the first prospective application of the PCNE V9.1 classification to hospitalized children with community-acquired infections in South Asia, and the first from Pakistan to link such classification with a rigorous economic analysis using real acquisition costs. The authors acknowledge limitations: the single-center design, the absence of a control group, the exclusion of ICU patients, and the fact that the primary investigator was not blinded, which may have inflated detection rates. The Hawthorne effect, in which prescribers modify behavior when they know they are being observed, also cannot be ruled out. Still, the authors argue the implications are clear. Hospital administrators in Pakistan and comparable settings should treat clinical pharmacy services as a net investment rather than a cost, policymakers should mandate such services in tertiary hospitals and adopt standardized DRP classification in quality indicators, and clinicians should prioritize daily pharmacist review for high-risk patients, particularly those on five or more medications, those who are febrile, and those with prolonged stays. In a field where only 14.1 percent of pediatric antimicrobial stewardship studies have evaluated cost outcomes, this study provides rare, concrete evidence that a single pharmacist on a pediatric ward can intercept hundreds of potentially dangerous errors while paying for itself many times over.

Subject of Research: Drug-related problems and pharmacist-led interventions in pediatric community-acquired infections in Pakistan

Article Title: Drug-related problems and their predictors in pediatric community-acquired infections: the role of pharmacist-led interventions in Pakistan

Article References: Ali, S., Zehra, A., Anjum, F., Shah, S. S. A. M., Abro, F., Shakeel, S., & Ali, M. (2026). Drug-related problems and their predictors in pediatric community-acquired infections: the role of pharmacist-led interventions in Pakistan. Journal of Pharmacy & Pharmaceutical Sciences, 29, Article 16612. https://doi.org/10.3389/jpps.2026.16612

Image Credits: AI Generated

DOI: 10.3389/jpps.2026.16612

Keywords: drug-related problems, pediatric medication safety, pharmacist interventions, community-acquired infections, Pakistan, PCNE classification, NCC MERP, cost savings, polypharmacy, antimicrobial stewardship, low- and middle-income countries, immunization