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Abstract

Background:

This study evaluated the impact of a drug utilization evaluation (DUE) program on vancomycin prescribing appropriateness and examined clinical factors, including infectious disease (ID) consultation, associated with appropriate use in a pediatric setting.

Methods:

A historical-control study was conducted among hospitalized children under 18 years who received intravenous vancomycin from January 2020 to January 2022. Prescriptions before DUE implementation were retrospectively reviewed (non-DUE group). From February 2021, a voluntary DUE program was introduced (DUE group). Demographic and clinical data were collected.

Results:

Among 423 prescriptions (232 non-DUE; 191 DUE), appropriateness was significantly higher in the DUE group (87.9% vs 72.0%; P < .001). DUE implementation (adjusted OR 2.96: 95% CI 1.44-6.10; P = .003) and ID consultation (adjusted OR 3.87: 95% CI 1.95-7.67; P < .001) were independently associated with appropriate vancomycin prescribing.

Conclusion:

Implementation of a DUE program improved vancomycin prescribing appropriateness, with ID consultation serving as an additional contributor to appropriate use.

Keywords

drug utilization evaluation,vancomycin stewardship infectious disease consultation antibiotic appropriateness antibiotic stewardship

Introduction

Antibiotic resistance is a global public health concern that significantly contributes to morbidity, mortality, and healthcare expenditures.^1,2 Antibiotic misuse is a major driver of antibiotic resistance, resulting in heightened morbidity and mortality.^3-6 Vancomycin, a glycopeptide antibiotic, remains a cornerstone in treatment of infections caused by multidrug-resistant gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant Staphylococcus coagulase negative (MRSCN).⁷ However, its widespread and inappropriate use has contributed to the emergence of vancomycin-intermediate Staphylococcus aureus (VISA) and vancomycin-resistant Staphylococcus aureus (VRSA), as well as vancomycin-resistant enterococci (VRE).⁸ Additionally, adverse effects such as renal toxicity further complicate vancomycin use in clinical practice.^9-12

Guidelines from the Hospital Infection Control Practices Advisory Committee (HICPAC)¹³ and the British Society for Antimicrobial Chemotherapy (BSAC) emphasize the judicious use of vancomycin,¹⁴ as inappropriate prescribing has been associated with increased colonization and infection with vancomycin-resistant organisms.¹⁵ In Thailand, the National Antimicrobial Resistant Surveillance Center has reported a substantial decline in MRSA prevalence from 28% in 2006 to 8.3% in 2021,¹⁶ yet vancomycin remains commonly prescribed, underscoring the need for targeted stewardship to minimize unnecessary exposure, resistance, and adverse effects.

Drug Utilization Evaluation (DUE) is a systematic, criterion-based approach designed to improve the quality and appropriateness of prescribing practices, including for antibiotics.^17-19 By promoting adherence to established guidelines, DUE optimizes antimicrobial use, reduces the development of resistance, and improves patient care. Through continuous monitoring and intervention, DUE has demonstrated its effectiveness in enhancing prescribing quality and cost-efficiency. While previous studies have demonstrated the effectiveness of DUE in improving vancomycin prescribing practices, most of these studies were conducted in regions with high MRSA prevalence, where vancomycin use is often clinically justified. In such settings, 75% to 95% of vancomycin prescriptions are considered appropriated when MRSA prevalence exceeded 50%.^14,20-23 In contrast, in areas with lower MRSA prevalence, vancomycin use tends to be less consistent, leading to overprescription in many cases.^24,25

In addition to DUE, infectious disease (ID) consultation is another key intervention that has shown to enhance the appropriateness of antibiotic prescribing and improve patient outcomes, particularly in complex cases.²⁶ ID consultations provide tailored recommendations based on pathogen susceptibility, host factors, and resistance patterns, ensuring precise antibiotic selection and dosing. Therefore, ID consultations play a crucial role in preventing the overuse of broad-spectrum antibiotics, mitigating the risk of antimicrobial resistance.^27,28

To date, there is limited data on the impact of DUE on vancomycin use in regions with low MRSA prevalence, particularly in pediatric populations. To address this gap, this study evaluated the effect of implementing a vancomycin DUE program on the appropriateness of vancomycin prescribing practices in pediatric patients at a tertiary care hospital in Thailand, where MRSA prevalence remains low, and also examined clinical factors associated with appropriate use, including ID consultation.

Methods

Study Design and Setting

The study was conducted at a tertiary-care pediatric department in Thailand, which includes general pediatric units (56 beds), hemato-oncology unit (12 beds), pediatric surgery unit (20 beds), semi-intensive care unit (9 beds), neonatal intensive care unit (NICU; 8 beds), and intensive care unit (ICU; 8 beds). All patients aged less than 18 years who received at least one dose of intravenous vancomycin between January 2020 and January 2022 were included in this study.

For the first period, the appropriateness of vancomycin prescriptions between January 2020 and December 2020 was retrospectively reviewed via the DUE criteria. For the second period (February 2021-January 2022), the DUE form was implemented. The DUE form included a list of indications for vancomycin use in empirical treatment, definitive treatment, and prophylaxis, as detailed in Supplemental Material 1. All patients were followed from the date of prescription until the cessation of medication. For patients with repeated vancomycin prescriptions, an interval of less than 72 hours was considered a single administration. Patients with incomplete medical records were excluded from the study.

Drug Utilization Evaluation

Pediatric infectious disease staff reviewed and established a set of criteria for the appropriate use of vancomycin. The DUE form was subsequently developed and distributed to pediatric physicians. If the reasons for prescribing vancomycin align with one of the predefined criteria for empirical treatment, definitive treatment, or prophylaxis, the prescription was considered appropriate. On the other hand, if the reasons did not match the established criteria, physicians could still prescribe vancomycin, while also completing the DUE form to provide the rationale for the prescription.

Criteria for Appropriate Vancomycin Prescription

Criteria for appropriate vancomycin use were established on the basis of international guidelines, including those from the HICPAC,¹³ BSAC,¹⁴ National Comprehensive Cancer Network,²⁹ and Infectious Disease Society of America.³⁰ The DUE form was based on these guidelines and then tailored using institutional antibiograms, local practice guidelines, and local expert consensus to reflect our microbiology and prescribing context. Vancomycin prescriptions were categorized into 3 categories: empirical treatment, definitive treatment, and prophylaxis, with predefined indications considered appropriate within each category. Appropriateness was determined according to these established criteria.

Empirical treatment

- Gram-positive bacteremia (while waiting for definite culture identification)

- Suspected catheter-related bloodstream infection with hemodynamic instability

- History of MRSA colonization

- Suspected healthcare-associated ventriculitis and meningitis

- Severe pneumonia: pneumonia requiring intensive care (eg, respiratory failure, mechanical ventilation, or hemodynamic instability), or occurring in patients suspected cephalosporin-resistant Streptococcus pneumoniae

Definitive therapy

- A pathogen isolated from the site of infection reveals MRSA, MRSCN or Enterococcus spp. and not susceptible to narrower-spectrum antibiotics

- Catheter-related bloodstream infection with hemodynamic instability, and the catheter cannot be removed

- Prosthetic valve endocarditis

- Foreign body or post-surgical meningitis with inconclusive investigations

Prophylaxis

- Bacterial endocarditis with a history of penicillin allergy

- Prosthetic cardiac valves: transcatheter-implanted prosthesis and homograft

- Prosthetic material used for cardiac valve repair: annuloplasty rings and chords

- Previous infective endocarditis

- Unrepaired or repaired cyanotic congenital heart diseases with residual shunts or valvular regurgitation

Infectious Disease Specialist Consultation (ID Consultation)

Infectious disease (ID) consultations remained voluntary throughout the study period. Physicians could consult with pediatric ID specialists whenever they required expert opinions regarding the diagnosis or management of infectious diseases. The ID consultation process functioned independently of the DUE form, and the use of the DUE form did not necessitate an ID consultation.

Data Collection

Demographic data collected from medical records included age, sex, underlying diseases, ID consultations, length of hospital stay, previous antibiotics used, indications for vancomycin prescriptions, microbiological data prior to initiating vancomycin, type of infection, culture and susceptibility results (if available), initial laboratory investigations, vancomycin levels for therapeutic drug monitoring (TDM), and imaging studies. TDM for vancomycin was performed voluntarily, depending on clinical judgment and individual patient factors, following institutional guidelines, but it was not a mandatory component of the DUE intervention.

Statistical Analysis

Statistical analysis was performed using PASW Statistics for Windows, Version 18.0. (Chicago: SPSS Inc., 2009). Descriptive statistics were presented as frequencies and percentages for categorical data. Comparative analyses of categorical variables were performed using the Chi-square test or Fisher’s exact test, as appropriate, and the Mann‒Whitney U test was employed for nonparametric continuous variables. Determinants of appropriate vancomycin use were assessed using multiple logistic regression, with appropriateness of vancomycin prescriptions defined as the dependent variable. All covariates with P < .1 in univariate analyses, together with clinically relevant variables identified a priori, were included in the multivariable logistic regression model. A P-value <.05 in the multivariable analyses was considered statistically significant.

Ethical Approval and Inform Consent

The study was approved by the Institutional Review Board (IRB) (COA. No. MURA 2021/112). The requirement for informed consent was waived because the study used de-identified data from medical records and posed minimal risk. The study was conducted in accordance with the principles outlined in the Declaration of Helsinki.

Results

Study Population and Demographic Data

During the study period, a total of 423 vancomycin prescriptions were included, with 232 prescriptions (109 patients) in the non-DUE group and 191 prescriptions (118 patients) in the DUE group. The median duration of vancomycin use was 3 days in both groups. The 2 groups were not significantly different in terms of age, underlying disease, length of hospital stay, therapeutic drug monitoring, or adverse effects. However, the non-DUE group had a lower proportion of patients requiring intensive care (39.2% vs 49.2%, P = .04).

Regarding indications for vancomycin prescriptions, the majority were for empirical therapy, followed by definitive treatment, with no prophylactic vancomycin use in this study. In the non-DUE group, 198 prescriptions (85.3%) were for empirical therapy, and 34 (14.7%) were for definitive treatment. Similarly, in the DUE group, 168 prescriptions (88%) were for empirical therapy, and 23 (12%) were for definitive treatment. In addition, ID consultations were significantly more frequent in the DUE group, occurring in 151 patients compared to 141 patients in the non-DUE group (79.1% vs 60.8%, P < .001). TDM was performed in 88 patients (37.9%) in the non-DUE group and 113 patients (59.2%) in the DUE group, with no statistically significant difference between the 2 groups. Vancomycin trough levels within the target range of 15-20 mcg/mL were achieved in 43% to 54% of patients in both groups. Demographic data and clinical characteristics are shown in Table 1.

Table 1.

Demographic and clinical characteristics of pediatric patients receiving vancomycin in the non-DUE and DUE groups.

Clinical and demographic characteristics	Non-DUE (N = 232)	DUE (N = 191)	P-value
Age (year, IQR)	5 (0.8-9.0)	4.3 (0.7-9.6)	.91
Female gender (N, %)	159 (68.5)	118 (61.8)	.06
Immunocompromised host (N, %)	119 (51.3)	119 (62.3)	.09
Critical care patients (N, %)	91 (39.2)	94 (49.2)	.04
Length of stay (days), (median, IQR)	34 (15.5-73)	39 (16-72)	.37
Duration of vancomycin used (days), (median, IQR)	3 (2-5)	3 (2-6)	.93
Indications for prescriptions (N, %)			.92
- Empirical treatment	198 (85.3)	168 (88.0)
- Definite treatment	34 (14.7)	23 (12.0)
Infectious diseases consultation (N, %)	141 (60.8)	151 (79.1)	<.001
Therapeutic drug monitoring (N, %)	88 (37.9)	113 (59.2)	.64
Vancomycin through level (N, %)	135 (58.2)	109 (57.1)	.12
- <15 mcg/mL	42 (31.1)	22 (20.2)
- 15-20 mcg/mL	58 (43.0)	59 (54.1)
- >20 mcg/mL	35 (25.9)	28 (25.7)
Adverse effects (N, %)	12 (5.2)	6 (3.1)	.30
- Acute kidney injury	2 (16.7)	1 (16.7)
- Redman syndrome	8 (66.7)	3 (50)

Abbreviations: DUE, drug utilization evaluation; IQR, interquartile range.

Compliance with the Established DUE Criteria

Physicians voluntarily completed the DUE form throughout the implementation phase before vancomycin was prescribed. The DUE form was completed for 169 out of 191 prescriptions, accounting for a compliance rate of 88.5%.

Drug Utilization Evaluation of Vancomycin Prescriptions

In total, 335 out of 423 vancomycin prescriptions (77.5%) were considered appropriate. According to the established criteria, 167 out of 232 prescriptions (72%) in the non-DUE group were considered appropriate, whereas 168 out of 191 prescriptions (87.9%) in the DUE group were considered appropriate. The appropriateness of vancomycin prescriptions was significantly higher in the DUE group than in the non-DUE group (87.9% vs 72%, P < .001). Regarding empirical treatment, vancomycin was prescribed more appropriately in the DUE group than in the non-DUE group (72.3% vs 59.1%, P < .001). However, no statistically significant difference was observed in the appropriateness of vancomycin prescriptions between the 2 groups for definitive treatment (12.9% vs 15.7%, P = .12).

The indications for vancomycin prescriptions were comparable between the DUE and non-DUE groups. The most common reasons for empirically prescribing vancomycin included suspected catheter-related bloodstream infections (CRBSIs) and gram-positive bacteremia pending definitive microbiological identification. For definitive treatment, vancomycin was primarily prescribed for microbiologically confirmed infections where vancomycin was indicated. The details of the indications for vancomycin prescriptions and their appropriateness are shown in Table 2.

Table 2.

Comparison of vancomycin indications and appropriateness of prescriptions between the non-DUE and DUE groups.

Indications and appropriateness of vancomycin use	Non-DUE (N = 232)	DUE (N = 191)	P-value
Overall appropriateness (N, %)	167 (72.0)	168 (87.9)	<.001
Appropriate for empirical treatment (N, %)	137 (59.1)	138 (72.3)	<.001
- Suspected catheter-related bloodstream infection	97	85
- Gram-positive bacteremia (pending for definite microbiological results)	29	32
- Suspected healthcare-associated ventriculitis and meningitis	5	10
- History of MRSA colonization	4	7
- Severe pneumonia	2	4
Appropriate for definitive treatment (N, %)	30 (12.9)	30 (15.7)	.12
- Culture proven MRSA, MRSCN, Enterococcus spp.	21	24
- Catheter-related bloodstream infection	2	3
- Healthcare-associated ventriculitis and meningitis	5	3
- Prosthetic valve endocarditis	2	–

Abbreviations: MRSA, methicillin-resistant Staphylococcus aureus; MRSCN, methicillin-resistant Staphylococcus coagulase negative.

Factors Associated with Appropriate Vancomycin Prescriptions

Logistic regression analyses were performed to identify factors associated with appropriate versus inappropriate vancomycin prescriptions. In univariate analysis, use of the DUE form was significantly associated with a higher likelihood of appropriate vancomycin use (odds ratio [OR] 3.74: 95% confidence interval [CI] 1.65-4.69; P < .001), and ID consultation was also strongly associated with appropriateness (OR 4.58: 95% CI 2.20-5.82; P < .001). After adjusting for potential confounders in the multivariable logistic regression model, both use of the DUE form (adjusted OR 2.96: 95% CI 1.44-6.10; P = .003) and ID consultation (adjusted OR 3.87: 95% CI 1.95-7.67; P < .001) remained independently associated with appropriate vancomycin administration. Table 3 summarizes the univariate and multivariable analyses of factors associated with appropriate vancomycin prescriptions.

Table 3.

Factors associated with appropriate vancomycin prescription.

Factors	Univariate analysis		Multivariate analysis
Factors	OR (95% CI)	P-value	Adjusted OR (95% CI)	P-value
Using DUE form	3.74 (1.65-4.69)	<.001	2.96 (1.44-6.10)	.003
ID consultation	4.58 (2.20-5.82)	<.001	3.87 (1.95-7.67)	<.001
Critical care patient	1.19 (0.74-1.94)	.46	1.38 (0.26-0.91)	.82

Abbreviations: OR, odds ratio; CI, confidence interval; DUE, drug utilization evaluation; ID, infectious diseases.

Discussion

Vancomycin is a key antibiotic in the treatment of MRSA infections, particularly in settings with high MRSA prevalence. However, excessive and inappropriate use in such regions can lead to the emergence of vancomycin-resistant organisms and increased adverse events. This study demonstrates that the implementation of DUE, alongside with ID consultations, significantly improved the appropriateness of vancomycin prescriptions in a pediatric population with low MRSA prevalence.

Before the introduction of DUE, 72% of vancomycin prescriptions met the established criteria for appropriate use, which is slightly higher than the 65% reported in a previous study conducted in an area with low MRSA prevalence. Previous studies conducted in high MRSA prevalence areas have shown a broader range of appropriateness, from 35% to 95%,^20-23,31,32 where vancomycin use is often more clinically justified. In contrast, our findings reveal that in a low MRSA prevalence area, inappropriate use remains as high as in high-prevalence regions, highlighting the need for targeted stewardship interventions to prevent overprescription and resistance development.

With the implementation of DUE, the overall appropriateness of vancomycin prescriptions increased to 88%, even when its use was voluntary and no additional interventions were applied. This improvement can be attributed to the explicit criteria and indications outlined in the DUE form, which likely facilitated and assisted physicians in making more informed antibiotic selection decisions.³³ These results underscore the value of structured interventions like DUE in promoting appropriate of vancomycin use, even in settings with low MRSA prevalence, and emphasize the role of antimicrobial stewardship across various epidemiological contexts.

The compliance rate with the DUE form was 88.5%, indicating strong adherence to the implementation of the evaluation system. However, complete compliance was not achieved, likely due to practical challenges such as time constraints and the voluntary nature of the form.³⁴ Addressing these barriers through streamlining processes, integrating reminders, or embedding mandatory form completion into electronic medical records could improve compliance in future implementations.

Most patients in this study received vancomycin empirically, consistent with previous findings.^35,36 The implementation of DUE associated with a significant increase in the appropriateness of empirical vancomycin prescriptions, rising from 59% to 72%. The most common justifications for appropriate empirical use were catheter-related bloodstream infections in patients with hemodynamic instability and gram-positive bacteremia pending organism identification. These finding likely reflects the characteristics of the study population, which included a large number of immunocompromised patients with retained catheters or devices.

ID consultations were independently associated with more appropriate vancomycin use, underscoring the crucial role of ID specialists in optimizing antimicrobial therapy.^26-28 However, access to ID specialists may be limited in many healthcare institutions, particularly in smaller or provincial hospitals. In such settings, a standardized vancomycin DUE form can serve as a practical and effective alternative stewardship tool. Pediatrician- or pharmacist-led DUE programs using the same structured, criterion-based forms, adapted to local epidemiology and institutional guidelines, can support appropriate vancomycin use even in the absence of on-site ID expertise. Regular review of vancomycin prescribing patterns, accompanied by periodic audit and feedback to prescribers, may further strengthen prescribing quality and facilitate the ongoing refinement of DUE criteria in resource-limited settings.

With respect to TDM, vancomycin levels were obtained in 37.9% of patients in the non-DUE group and 59.2% of patients in the DUE group. However, because TDM was not incorporated into the appropriateness assessment, suboptimal vancomycin exposure or vancomycin-related toxicity may have been underestimated, particularly in more complex or prolonged treatment courses. Incorporating structured TDM guidance into future iterations of the DUE form could further strengthen its impact by optimizing vancomycin efficacy and minimize adverse effects.³⁷

This study has some limitations. First, it was conducted at a single tertiary-care center with ready access to ID consultation, which may limit the generalizability of the findings. Multicenter studies in similar low-MRSA settings, particularly those without on-site ID specialists, would help validate these results. Second, the historical-control design may be subject to secular trends. Although no major changes in MRSA prevalence or vancomycin-related policies occurred during the study period, the observed association between DUE implementation and improved appropriateness should be interpreted with caution. In addition, although both DUE use and ID consultation remained independently associated with appropriate vancomycin prescribing and their correlation was modest, ID consultations were more frequent during the DUE period, and some residual overlap between these interventions cannot be excluded. Finally, DUE was implemented on a voluntary basis and, although compliance was high, it was not complete, which may introduce selection bias. Despite these limitations, this study provides evidence that a DUE program is a practical and effective approach to improving vancomycin prescribing practices. In settings without access to ID specialists, integrating a structured DUE tool into routine care may help ensure appropriate vancomycin use and strengthen antimicrobial stewardship efforts.

Conclusion

DUE and ID consultations significantly improved the appropriateness of vancomycin use in pediatric patients. These findings underscore the utility of DUE as a stewardship tool, particularly in settings with limited access to ID specialist, and suggest that broader implementation may help mitigate inappropriate vancomycin prescribing across diverse healthcare settings.

Supplemental Material

sj-docx-1-gph-10.1177_30502225261417259 – Supplemental material for Enhancing the Appropriate Use of Vancomycin in Pediatric Patients: The Impact of Drug Utilization Evaluation and Infectious Disease Consultation

Supplemental material, sj-docx-1-gph-10.1177_30502225261417259 for Enhancing the Appropriate Use of Vancomycin in Pediatric Patients: The Impact of Drug Utilization Evaluation and Infectious Disease Consultation by Chanya Pongpatipat, Sophida Boonsathorn, Sujittra Chaisavaneeyakorn, Pitak Santanirand, Chonnamet Techasaensiri and Nopporn Apiwattanakul in Sage Open Pediatrics

Footnotes

Acknowledgements

The authors would like to thank their colleagues at Ramathibodi Hospital, particularly the pediatric infectious diseases fellows, pediatric resident trainees, and pediatric clinical pharmacists from the Department of Pediatrics, Ramathibodi Hospital, Mahidol University, Thailand, for their valuable assistance in patient care.

ORCID iD

Sophida Boonsathorn

Ethical Considerations

The study was approved by the Institutional Review Board (IRB) of the Faculty of Medicine Ramathibodi Hospital, Bangkok, Thailand, and the requirement for informed consent was waived (COA. No. MURA 2021/112). The study was conducted in accordance with the principles outlined in the Declaration of Helsinki.

Author Contributions

S.B. and C.P. conceptualized the study, conducted the investigation, and curated the data. C.P. performed the analysis and drafted the manuscript. P.S. provided key resources. S.B., N.A., S.C., and C.T. provided patient care. S.B. reviewed and edited the manuscript. S.B. and N.A. supervised the project. All authors approved the final version of the manuscript.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Declaration of Conflicting Interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Supplemental Material

Supplemental material for this article is available online.

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Supplementary Material

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