Monitoring of pediatric antibiotic consumption using electronic medical records in an Italian tertiary care hospital

Abstract

Investigation of antibiotic use in the pediatric population is crucial, in particular in the hospital setting. Measures of antibiotic consumption, such as Duration-Of-Therapy (DOT) and Length-Of-Therapy (LOT) are recommended as indicators of use in pediatrics. This study is aimed to estimate DOT and LOT in hospitalized children using data from electronic medical records (EMRs). We included all patients hospitalized in a tertiary care children’s hospital in Italy, from January to December 2022. Measures DOT and LOT were derived from data recorded in patient EMRs. DOT/1000 patient-days was estimated by patient characteristics, antibiotic molecule prescribed and type of inpatient ward. The time trend of antimicrobial consumption in hospitalized children was also estimated. At least one antibiotic was prescribed in 8,518 out of 21,787 children (39.1%). Overall, DOT and LOT/1000 patient-days were 539 and 354, with a DOT/LOT ratio of 1.5. The molecule with the highest DOT/1000 patient-days was piperacillin/tazobactam followed by meropenem (81.3 and 59.6 DOT/1000 patient-days). Oncohematology and Intensive Care Units were the type of wards with highest DOT/1000 patient-days (1112 and 944, respectively) and LOT/1000 patient-days (591 and 547, respectively). EMRs enhances data accessibility to measure antibiotic use in hospitalized children and their integration into pediatric antibiotic stewardship programs.

Introduction

Improving antibiotic use is a core strategy to optimize patient safety and combat antimicrobial resistance¹. Investigation of antibiotic use in the pediatric population is crucial, in particular in the hospital setting, where the risk of the bacterial resistance development and transmission has dramatically increased².

In the hospital setting, the use of antibiotic for treatment or prophylaxis can be measured by prevalence surveys. In addition to prevalence surveys, several indicators have been used to measure antibiotic use. The most commonly used metric is the defined daily dose (DDD), as proposed by the World Health Organization (WHO), generally expressed as DDDs per 100,000 inhabitants (for outpatient use) and DDDs per 1000 patient-days (for inpatient use)³. The DDD is the standard daily dose that a 70-kg adult should take for the main indication of that drug and whose value the WHO Collaborating Centre for Drug Statistics Methodology updates³. This measure allows standardized comparisons between institutions or countries. However, DDD does not consider that the prescribed dose of a drug could vary significantly according to the weight or age of the subject, so in children DDDs are not applicable to quantify antibiotic use since there is large variation in body weight⁴. For pediatric hospitals, the metrics Duration-Of-Therapy (DOT) and Length-Of-Therapy (LOT) combined with a suitable denominator, such as patient-days, appears to be a superior alternative to DDDs⁵.

Bambino Gesù Children’s Hospital (hereafter OPBG) has estimated DOT and LOT in inpatients children using data collected during antimicrobial use prevalence surveys⁶; the implementation of electronic medical records (EMRs) throughout the hospital and the availability of an automated prescribing system offer the possibility of calculating these indicators automatically and routinely in the current setting.

This study is aimed to estimate DOT and LOT of antibiotics prescribed in children hospitalized in different types of wards using data extracted by EMRs.

Results

Study population

We included 21,787 children with 29,342 hospitalizations and 234,733 inpatient days. Admissions mainly related to males patients (n = 16,360; 55.7%) with a median age of 97 months (interquartile range: 31–167). Out of 21,787 children, 8,518 (39.1%) were treated with at least one antibiotic during the study period. Overall, 18,986 antibiotic therapies had been prescribed with an average of 2.2 molecules per patient (Table 1).

Table 1.

Characteristics of patients included in the study; OPBG, January–December 2022

N. of hospitalizations (total)	29,342
N. of hospitalizations by sex
Male	16,360
Female	12,982
N. of patients	21,787
N. of patient-days	234,733
Median age of patients (IQR* range)	97 months (31–167)
N. of antibiotic therapies prescribed	18,986
N. patients on antibiotic treatment	8,518

*Interquartile range

Estimation of DOTs and LOTs by patient characteristics

Overall, DOT and LOT per 1000 patient-days were 539 and 354, respectively, with a DOT/LOT ratio of 1.5. Antibiotic consumption was higher in males (555 DOT/1000 patient-days and 362 LOT/1000 patient-days) with respect to females (521 DOT/1000 patient-days and 343 LOT/1000 patient-days, p < 0.001) and in patients aged 5–9 years (600 DOT/1000 patient-days and 377 LOT/1000 patient-days) with respect to other age classes (p < 0.001; Table 2). Antibiotic consumption was higher for patient with a length of hospital stay ≥ 30 days (809 DOT/1000 patient-days and 470 LOT/1000 patient-days) with respect to patients hospitalized > 7 and < 30 days (598 DOT/1000 patient-days and 395 LOT/1000 patient-days; p < 0.001). Patients hospitalized for less than 7 days had the lowest antibiotic consumption (242 DOT/1000 patient-days and 210 LOT/1000 patient-days; p < 0.001). Duration of antibiotic therapy and the DOT/LOT ratio was proportional to the increase of patient-days (Table 2).

Table 2.

DOT and LOT per 1000 patient-days and DOT/LOT ratio calculated by sex, age classes and length of hospital stay

	Number of patient days	DOT/1000 patient-days	P-value DOT	LOT/1000 patient-days	P-value LOT	DOT/LOT
Sex
Male	128,353	555	< 0.001	362	< 0.001	1.5
Female	106,380	521		343		1.5
Age classes
0–11 months	46,675	505	< 0.001	340	< 0.001	1.5
12–23 months	17,498	433		317		1.4
2–4 years	38,980	495		323		1.5
5–9 years	43,758	600		377		1.6
≥ 10 years	87,822	569		370		1.5
Length of hospital stay (days)
≤ 7	81,511	242	< 0.001	210	< 0.001	1.2
> 7 –<30	81,047	598		395		1.5
≥ 30	72,175	809		470		1.7
Total	234,733	539		354		1.5

Estimation of DOTs per single antibiotic molecule

Cefazolin was the most prescribed drug (3,342 prescriptions), followed by sulfamethoxazole/ trimethoprim (1,838 prescriptions, Table 3). Piperacillin/tazobactam had the highest DOT/1000 patient-days (81.3 DOT/1000 patient-days), followed by meropenem (59.6 DOT/1000 patient-days), sulfamethoxazole/trimethoprim (53.4 DOT/1000 patient-days) and cefazolin (51.3 DOT/1000 patient-days).

Table 3.

DOT/1000 patient-days and number of therapies for single antibiotic molecules

Antibiotic molecules	Number of prescriptions	DOT/1000 patient-days
Piperacillin/tazobactam	1,615	81.3
Meropenem	1,034	59.6
Sulfamethoxazole/ trimethoprim	1,838	53.4
Cefazolin	3,342	51.3
Teicoplanin	1,092	32.2
Amoxicillin/clavulanic acid	1,504	30.0
Metronidazole	810	27.2
Amikacin	895	26.6
Levofloxacin	385	21.3
Ceftazidime	572	16.4
Vancomycin	306	15.0
Cefixime	1,417	13.4
Ceftazidime/avibactam	211	12.3
Tigecycline	261	12.1
Ampicillin	360	10.7
Ceftriaxone	518	10.5
Cefoxitin	712	9.4
Gentamicin	351	7.9
Netilmicin	302	7.5
Ciprofloxacin	267	7.4
Clarithromycin	295	6.5
Linezolid	88	6.3
Daptomycin	90	4.6
Azithromycin	196	4.1
Colistin	94	4.4
Cefotaxime	195	3.0
Amoxicillin	125	1.9
Oxacillin	37	1.0
Cefiderocol	15	0.6
Fosfomycin	11	0.5
Clindamycin	11	0.3
Tobramycin	7	0.2
Ceftolozane/tazobactam	4	0.1
Penicillin	2	0.1
Ceftaroline	2	0.1
Ofloxacin	4	0.1
Moxifloxacin	5	0.1
Streptomycin	1	0.05
Piperacillin	5	0.04
Imipenem	2	0.03
Benzylpenicillin	4	0.02
Cefpodoxime	1	0.004
Total	18,986	539

Estimation of DOTs by ward type

DOT/1000 patient-days was highest in oncohematology unit (1,112 DOT/1000 patient-days; 591 LOT/1000 patient-days), followed by Intensive Care Units (ICUs) (944 DOT/1000 patient-days; 547 LOT/1000 patient-days), neonatal surgery (471 DOT/1000 patient-days; 320 LOT/1000 patient-days), pediatric surgery (374 DOT/1000 patient-days; 309 LOT/1000 patient-days), neonatal medical wards (334 DOT/1000 patient-days; 210 LOT/1000 patient-days) and pediatric medical wards (320 DOT/1000 patient-days; 225 LOT/1000 patient-days; Fig. 1). Oncohematology was the ward with the highest use of polypharmacy (DOT/LOT ratio 1.9), followed by ICUs with a DOT/LOT ratio of 1.7.

Fig. 1.

DOT and LOT/1000 patient-days stratified by hospital ward type

In oncohematology, piperacillin/tazobactam and sulfamethoxazole/trimethoprim were the most frequently used (335 and 272 DOT/1000 patient-days, respectively), followed by meropenem (176 DOT/1000 patient-days) and levofloxacin (119 DOT/1000 patient-days; Fig. 2). In ICUs, meropenem was the drug with the highest consumption (128 DOT/1000 patient-days), followed by vancomycin (91 DOT/1000 patient-days) and piperacillin/tazobactam (88 DOT/1000 patient-days). Cefoxitin was the drug with the highest consumption (64 DOT/1000 patient-days) in neonatal surgery followed by ampicillin (49 DOT/1000 patient-days) and amoxicillin clavulanic acid (46 DOT/1000 patient-days). Pediatric surgery had the highest DOT/1000 patient-days for cefazolin (138 DOT/1000 patient-days), metronidazole (29 DOT/1000 patient-days) and amoxicillin clavulanic acid (28 DOT/1000 patient-days). Pediatric medical wards recorded higher use of piperacillin/tazobactam (45 DOT/1000 patient-days), meropenem (40 DOT/1000 patient-days) and teicoplanin (30 DOT/1000 patient-days). Lastly, neonatal medicine had the highest consumption for ampicillin and netilmicin (106 and 84 DOT/1000 patient-days, respectively).

Fig. 2.

DOT/1000 patient-days by antibiotic molecules (≥ 3 DOT/1000 patient-days) and hospital ward type

Estimated trend of DOT/1000 ad LOT/1000 patient-days in inpatients from January to December 2022

Antibiotic consumption was highest in the first quarter of the year (January–March) with an average DOT/1000 patient-days and LOT/1000 patient-days of 542 e 349, respectively. DOT/1000 patient-days decreased in the second quarter (April–June) with an average of 540 and reached its lowest level in the fourth quarter (October–December) with an average DOT/1000 patient-days of 469 (p < 0.05). LOT/1000 patient-days did not show a statistically significant decreasing trend over time (p = 0.06). The DOT/LOT ratio remained constant at approximately 1.5 throughout the months (Fig. 3).

Fig. 3.

Monthly trend of DOT/1000 and LOT/1000 patient-days; January – December 2022

Discussion

Our analysis of antibiotic consumption administered in an Italian tertiary care academic children hospital in 2022 showed a DOT and LOT/1000 patient-days equal to 539 and 354, respectively; the DOT/LOT ratio was equal to 1.5. Antibiotic consumptions were the highest in oncohematology and ICU wards with a DOT/1000 patient-days of 1,112 and 944 and a LOT/1000 patient-days of 591 and 547, respectively.

A small number of studies used data on antibiotic prescriptions dispensed to hospitalized pediatric patients to estimate their consumption using DOT/1000 patient-days as an indicator. A study conducted in a tertiary care children hospital in London from 2010 to 2018 estimated a median antibiotic consumption of 617 DOT/1000 patient-days in non-ICUs and 1,413 DOT/1000 patient-days in pediatric ICU⁵. Our results were lower than that reported in the literature; nonpharmaceutical interventions for controlling COVID-19 spread were still in place in 2022 affecting the transmission of many respiratory viruses, and reducing Emergency Department visits and hospitalizations due to acute respiratory infections⁷ that are frequently treated with unnecessary antibiotics. However, comparisons between institutions are challenging, being influenced by the patient population and the range of interventions undertaken in each setting⁵.

As we documented in a previous multicenter study⁶, DOT and LOT/1000 patient-days were higher in males with respect to females. Prevalence of antibiotic use in Italy in 2022 was slightly higher in males than females in all age classes, in particular in the 0–1 year age group (35.7% vs. 32.3%). In terms of consumption, in the age group 2–5 years, there are more marked differences between males and females than in the other age groups, with males exceeding 938 packs per 1000 children compared to 879 packs/1000 in females^8,9. Analysis by single antibiotic molecule showed that piperacillin/tazobactam, meropenem and sulfamethoxazole/trimethoprim were the drugs with the highest DOT, although they were not the most prescribed; this could be due to the use of these molecules for long periods either for treatment of severe infections (e.g. meropenem; piperacillin/tazobactam)¹⁰ or for medical prophylaxis in immunocompromised children (e.g. sulfamethoxazole/trimethoprim)¹¹. Meropenem had a high DOT (59.6 DOT/1000 patient-days); it is frequently used to treat serious infections, such as bloodstream infections, especially in patients with chronic underlying diseases⁶. This may be one reason why meropenem resulted to be widely used in oncohematology (176 DOT/1000 patient-days) and in ICU (128 DOT/1000 patient-days). In contrast, cefazolin represented the molecule with the highest number of prescriptions but had a lower DOT of 51.3 DOT/1000 patient-days. Cefazolin is the most commonly used antibiotic for perioperative prophylaxis because of its efficacy, low cost, duration of action, and spectrum of activity¹². Surgical prophylaxis represents one of the main indication for antibiotic prescription in hospitalised children⁶, and the administration of only one preoperative dose is recommended¹³. This can explain the high number of cefazolin prescriptions observed in our study, and its low DOT. With regard to the use of AWaRe antibiotics according to the WHO classification¹⁴, we reported consumptions related to molecules belonging to the “Reserve group”, meaning antibiotics that should be reserved for treatment of confirmed or suspected infections due to multi-drug-resistant organisms (e.g. ceftazidime/avibactam). This result could be due to the higher prevalence of multidrug-resistant microorganisms in Italy compared to other European countries¹⁵.

The analysis by type of ward showed that oncohematology had a DOT/1000 patient-days equal to 1,121, higher than other clinical wards; this is in line with what was observed from a study conducted in Italy on antibiotic prescriptions and prophylaxis in Italian children in 2016¹⁶. Children with oncologic or hematologic diseases are at particularly high risk for severe infections, especially while on chemotherapeutic treatment, radiation, or after stem cell transplantation^17,18. Among children treated in pediatric cancer centers, the high prevalence of and risk for adverse outcomes related to severe bacterial and fungal infections lead to a high level of antimicrobial prescribing, for both treatment and prophylaxis¹⁸. Our data confirmed that oncologic and hematologic patients were responsible for a large proportion of antibiotic consumption with the highest use of polypharmacy (DOT/LOT ratio 1.9).

With respect to studies that are based on information collected manually from patients’ medical clinical records, we had no need to restrict the sample size. Moreover, the data useful for the study derived from patients’ EMRs which provide the most detailed information of patient clinical and demographical characteristics and of the prescribed treatments. Our study has some limitations. Firstly, it was a monocentric study, therefore results cannot be considered representative of the whole country. The analysis focused on inpatient prescribing alone and did not includes corresponding clinical data regarding the indications for antimicrobial use, or the complexity and acuity of patient population.

In conclusion, our results indicate that the availability of EMRs can greatly improve the accessibility of data to calculate DOT and LOT of antibiotics with the ability to calculate these indicators in an automated and routine manner and use them as part of antibiotic stewardship programs.

Materials and methods

Study setting

This study was conducted at OPBG, a 627-bed tertiary care academic hospital in the Lazio Region, Italy. OPBG has a long experience in prevalence surveys on antibiotic use that are done annually in the same period of the year according to the standard protocol published by European Centre for Disease Prevention and Control^19,20.

Starting from 2008, a series of actions have been undertaken to promote the appropriate use of antibiotics, namely: (a) dissemination of results of annual prevalence surveys on antibiotic use by posting reports on the hospital intranet website, presenting data in hospital meetings, and discussing actions to be undertaken within the hospital infection control team (from 2008); (b) production and dissemination of hospital guidelines on antibiotic surgical prophylaxis (from 2009); (c) production and dissemination of hospital guidelines on antibiotic medical prophylaxis (from 2011); (d) restriction of use of third-generation cephalosporins for surgical prophylaxis (from 2012)¹⁹; (e) production and dissemination of hospital guidelines on use for antibiotic therapy recommending antibiotic prescriptions review after 48–72 hours and de-escalation whenever appropriate; (f) implementation of formulary restriction and preauthorization requirements for specific antibiotic molecules; (g) implementation of clinical pathways on management of pharyngitis²¹, acute otitis media, community-acquired pneumonia and sepsis. Moreover, in the ICUs, multidisciplinary meetings are conducted to discuss antibiotic therapies of individual patients.

Study design and data collection

We conducted an observational, retrospective, descriptive study including all patients hospitalized in OPBG from January to December 2022. Demographic and clinical data of these patients were collected from EMRs. Information collected for each patient included: age, sex, dates of hospital admission and discharge, and ward type. In case of antibiotic prescriptions, we collected information on antibiotic type according to the Anatomical Therapeutic Chemical Classification code (ATC: J01), the start date and the end date of administration, and the hospital ward of administration.

Statistical analysis

Patients were described according to demographic factors (age and sex), length of stay and ward of hospitalization. Collected data were presented as count and proportions (categorical data). Age was categorized into five groups (0–11 months; 12–23 months; 2–4 years; 5–9 years; ≥ 10 years). Length of stay was expressed in days and categorized as ≤ 7 days, > 7 and < 30 days and ≥ 30 days. Hospital ward units were grouped into six categories: oncohematology, neonatal medical ward, pediatric medical ward, neonatal surgery, pediatric surgery and ICUs (including neonatal and pediatric ICUs).

For each patient, DOTs were computed summing up the duration (in days) of each antibacterial drug received. Days of antibiotic therapy in patients transferred to different types of wards were counted twice for each type of ward in which the patient was admitted and treated on that day. LOTs were the number of days that a patient received an antibacterial drug irrespective of the number of different drugs⁶.

DOTs/1000 patient-days and LOTs/1000 patient-days were computed stratifying by sex, age classes and length of stay. DOT/1000 patient-days was calculated stratifying by single antibiotic molecules and ward type. Groups comparisons were performed using Student’s t-test and one-way ANOVA test. Use of antibiotic polytherapy was estimate with the DOT/LOT ratio. The monthly time trend of antimicrobial consumption in hospitalized children was tested with linear regression. All statistical analyses were performed using STATA, Statistical Software: Release 17 (StataCorp LP, College Station, TX).

Author contributions

MCDA and MR developed the concept; CDA and CNG performed the data analysis and wrote the draft of the manuscript; MCDA, MR, CDA, CNG, MDL, LL interpreted the data. All authors reviewed the final manuscript.

Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

Declarations

Competing interests

The authors declare no competing interests.

Ethical approval

This study is part of a protocol approved by the Ethical Committee of the Bambino Gesù Children’s Hospital (N° 3203_OPBG_2023) and all methods were performed following relevant guidelines and regulations. Since data were obtained by EMRs and were analyzed anonymously, informed consent was not deemed necessary. The need for informed consent was waived by the Ethical Committee of the Bambino Gesù Children’s Hospital.