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- Springer Journals
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- Copyright © The Author(s) 2023
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- 2047-2994
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- 10.1186/s13756-023-01219-x
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Abstract
Background Antimicrobial resistance threatens the ability to successfully prevent and treat infections. While hospital benchmarks regarding antimicrobial use (AMU) have been well documented among adult populations, there is less information from among paediatric inpatients. This study presents benchmark rates of antimicrobial use (AMU) for paediatric inpatients in nine Canadian acute‑ care hospitals. Methods Acute‑ care hospitals participating in the Canadian Nosocomial Infection Surveillance Program submitted annual AMU data from paediatric inpatients from 2017 and 2018. All systemic antimicrobials were included. Data were available for neonatal intensive care units (NICUs), pediatric ICUs (PICUs), and non‑ICU wards. Data were analyzed using days of therapy (DOT ) per 1000 patient days (DOT/1000pd). Results Nine hospitals provided paediatric AMU data. Data from seven NICU and PICU wards were included. Overall AMU was 481 (95% CI 409–554) DOT/1000pd. There was high variability in AMU between hospitals. AMU was higher on PICU wards (784 DOT/1000pd) than on non‑ICU (494 DOT/1000pd) or NICU wards (333 DOT/1000pd). On non‑ICU wards, the antimicrobials with the highest use were cefazolin (66 DOT/1000pd), ceftriaxone (59 DOT/1000pd) and piperacillin‑tazobactam (48 DOT/1000pd). On PICU wards, the antimicrobials with the highest use were ceftriaxone (115 DOT/1000pd), piperacillin‑tazobactam (115 DOT/1000pd), and cefazolin (111 DOT/1000pd). On NICU wards, the antimicrobials with the highest use were ampicillin (102 DOT/1000pd), gentamicin/tobramycin (78 DOT/1000pd), and cefotaxime (38 DOT/1000pd). *Correspondence: Michelle Science michelle.science@sickkids.ca Full list of author information is available at the end of the article © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creat iveco mmons. org/ licen ses/ by/4. 0/. The Creative Commons Public Domain Dedication waiver (http:// creat iveco mmons. org/ publi cdoma in/ zero/1. 0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Rudnick et al. Antimicrobial Resistance & Infection Control (2023) 12:35 Page 2 of 9 Conclusions This study represents the largest collection of antimicrobial use data among hospitalized paediatric inpatients in Canada to date. In 2017/2018, overall AMU was 481 DOT/1000pd. National surveillance of AMU among paediatric inpatients is necessary for establishing benchmarks and informing antimicrobial stewardship efforts. Keywords Antimicrobial use, Hospital, Paediatric, Surveillance Background estimates of the prevalence of paediatric patients receiv- The advent of antibiotics has saved many lives and has ing therapy from a snapshot in time [14] as well as esti- created the conditions for much of modern medicine mates of days of therapy [13]. To address these data gaps, [1]. However, overuse of antibiotics has led to the emer- the Canadian Nosocomial Infection Surveillance Pro- gence of antimicrobial resistant organisms [2], currently gram (CNISP) developed a paediatric AMU surveillance threatening our ability to prevent and treat infections. program for acute-care secondary and tertiary hospitals Although hospital benchmarks for antimicrobial use across Canada with the following three objectives: (1) (AMU) have been well documented among adult popu- estimate national paediatric AMU in secondary and ter- lations [3], less attention has been paid to paediatric tiary care hospitals; (2) provide AMU benchmarks for inpatients. On an individual patient level, paediatric anti- paediatric wards; and (3) estimate AMU by ward-type. biotic exposure may lead to negative repercussions for child and adult health [4–8]. Methods Antibiotic use is very common among hospitalized Setting and participating sites children [9]. In studies from North America and Europe, CNISP is a collaboration between the Canadian Hospital 29–61% of hospitalized paediatric patients receive antibi- Epidemiology Committee, a subcommittee of the Associ- otics [10–13]. Data from our network of Canadian acute ation of Medical Microbiologists and Infectious Disease, care hospitals indicate that 56% of hospitalized children and the Public Health Agency of Canada. As of January aged 1–17 years received antibiotics in a 2017 point prev- 2022, 89 sentinel hospitals, from across 10 provinces and alence study [14]. one territory participate in the CNISP network. Forty Among hospitalized paediatric patients, it is estimated hospitals serve paediatric inpatients; nine are standalone that potentially 9–43% of prescriptions are unnecessary paediatric hospitals. or inappropriate [15–18]. Misuse of antibiotics among CNISP established a working group for antimicrobial neonatal and paediatric wards has been associated with use in 2007/08. Paediatric AMU surveillance started as adverse patient outcomes including increased risk of a pilot study among a few hospitals before transitioning infection with resistant organisms [19–27]. to routine surveillance. The results of this current study Antimicrobial stewardship programs aim to find a bal - represent the nine hospitals that participated in CNISP ance between the “potent ability of antibiotics for individ- paediatric AMU surveillance in 2017 and/or 2018. ual patients and their potentially hazardous effects” [28]. Paediatric stewardship programs optimize how and when Data variables and collection antimicrobials are used and have been shown to reduce Paediatric inpatients inappropriate prescriptions [29] and to reduce antibiotic Paediatric patients were defined as those < 18 years of age consumption [30–33]. Paediatric antimicrobial steward- or those patients on wards where the majority of patients ship programs can improve patient outcomes and reduce are < 18 years of age. Surveillance included all acute costs [34, 35]. In 2013, implementing an antimicrobial care inpatient units (including intensive care units) and stewardship program became a requirement of accredita- admissions in emergency departments. Non-admitted tion for all Canadian acute-care hospitals [36]; in 2018, patients in emergency departments were excluded. Par- 93% of surveyed academic paediatric hospitals in Canada ticipating sites provided corresponding paediatric inpa- had a formal antimicrobial stewardship program [37]. tient-day denominators by ward. Estimates of national Antimicrobial use (AMU) surveillance can identify inpatient days by year and age group were obtained from opportunities for interventions, enable evaluation of anti- the Canadian Institute for Health Information [41]. microbial stewardship programs and help garner political will for successful stewardship campaigns [38]. Antimicrobial use There are published AMU data from a paediatric hos - Participating hospitals provided total paediatric inpatient pital [39] and from five NICU wards [40] in Alberta, oth - AMU separated by type of antimicrobial and ward category erwise data on paediatric AMU in Canadian hospitals are (NICU, PICU and non-ICU wards). Hospitals were asked limited. National point prevalence studies have provided to submit either dispensed or administered antimicrobials Rudnick et al. Antimicrobial Resistance & Infection Control (2023) 12:35 Page 3 of 9 and to separate their data by administration route (paren- calendar years; one hospital provided data only for 2018. teral and oral) if possible. All systemic antibacterial use was Total inpatient days included in surveillance (507 583 included in the surveillance using Anatomical Therapeu - patient days) represented about a quarter of paediatric tic Chemical (ATC) codes: J01s, P01AB01 (metronidazole inpatient days in Canada in 2017/18. Three participating oral) and A07AA09 (oral vancomycin) [42]. Quantity of hospitals were in western Canada, four in central Canada antimicrobials were submitted as days of therapy (DOT), (Ontario/Quebec), and two in eastern Canada. Five of the defined as the number of days that a patient receives an hospitals were paediatric acute care centres with ≤ 200 antimicrobial agent regardless of dose. The DOT for a given beds and four hospitals were mixed adult/paediatric patient on multiple antibiotics is the sum of DOTs for each hospitals with 201–500 beds. Seven PICUs and seven antibiotic that the patient is receiving. NICUs were included in surveillance. PICUs and NICUs represented 9% and 23% of included patient days, respec- Data analysis tively. Participating site characteristics are summarized Participating hospitals submitted annual data files. The in Table 1. WHO ATC/DDD Index [42] was adapted in order to group antimicrobials by drug class. AMU data were used Antimicrobial use to rank the most frequently prescribed antimicrobial From January 2017 to December 2018, total AMU agents by drug class and by ward type. Relative differ - was 481 (95% CI 409–554) DOT/1000 patient days ences were calculated by taking the difference between (/1000pd). AMU varied substantially between hospitals; two rates and dividing the difference by the smaller rate. the interquartile range (IQR) for total AMU spanned National rates of AMU were calculated and standard- 217 DOT/1000pd: 352–569 DOT/1000pd and there was ized per 1000 inpatient days (pd): rates were calculated 17-fold variability between hospitals’ rates of overall as (total DOTs / total pd) * 1000. Bootstrapped stand- AMU (Fig. 1). Among the eight hospitals that provided ard errors with 10,000 replications were used to calcu- two years of data, overall AMU rates differed on average late 95% confidence intervals (95% CI). All analyses were by 10% between the two years (range < 1% to 24%); three done using SAS (version 9.4) software. hospitals had higher rates in 2018 than 2017 and five hos - pital had lower rates in 2018. Overall, AMU declined by Results 9% between 2017 and 2018, however, this was not statis- Participating sites tically significant (difference: − 44 DOT/1000pd; 95% CI: Nine CNISP hospitals provided paediatric AMU data. − 101–13 DOT/1000pd). Eight hospitals provided data for both 2017 and 2018 Table 1 Characteristics of hospitals and intensive care units (ICUs) participating in surveillance of paediatric antimicrobial use, 2017– Characteristic Hospitals non-ICU wards Neonatal ICUs Paediatric ICUs* Number of hospitals submitting data 9 9 7 7 Hospital sites Paediatric hospitals 5 5 5 5 Mixed (adult/paediatric) hospitals 4 4 2 2 Paediatric Inpatient Days 507,583 344,073 118,949 44,561 Total days of therapy 244,373 169,830 39,592 34,951 Regions West 3 3 2 2 Central 4 4 4 3 East 2 2 1 2 Hospital bed size 201–500 beds 4 4 2 2 ≤ 200 beds 5 5 5 5 Hospital type Teaching 9 9 7 7 Community 0 0 0 0 *Includes one paediatric cardiovascular ICU Rudnick et al. Antimicrobial Resistance & Infection Control (2023) 12:35 Page 4 of 9 Fig. 1 Rate of antimicrobial use among paediatric inpatients overall and by ward type with bootstrapped 95% confidence intervals, 2017–2018 The classes of antimicrobials with the highest use PICUs were ceftriaxone (115 DOT/1000pd), pipera- (Fig. 2) were the third-generation cephalosporins (84 cillin-tazobactam (115 DOT/1000pd), cefazolin (111 DOT/1000pd), penicillins with extended spectrum DOT/1000pd), vancomycin (98 DOT/1000pd oral and (80 DOT/1000pd; including amoxicillin, ampicillin, parenteral combined), meropenem (44 DOT/1000pd), piperacillin and ticarcillin), first-generation cephalo - ampicillin (42 DOT/1000pd), azithromycin (41 sporins (67 DOT/1000pd), piperacillin-tazobactam (46 DOT/1000pd), trimethoprim-sulfamethoxazole (35 DOT/1000pd), and aminoglycosides (40 DOT/1000pd DOT/1000pd), cefotaxime (32 DOT/1000pd) and gen- including amikacin, tobramycin, and gentamicin). tamicin/tobramycin (25 DOT/1000pd). These ten antimi - Including all clinical units from the participating crobials represented 84% of total AMU among PICUs. sites, the most frequently used antimicrobials (Fig. 3) Among the 20 most frequently used antimicrobi- were cefazolin (57 DOT/1000pd), ampicillin (55 als, antimicrobials with the largest relative differences DOT/1000pd), ceftriaxone (50 DOT/1000pd), piper- between rates of use among PICUs and among non- acillin-tazobactam (46 DOT/1000pd), tobramycin/ ICU wards were vancomycin, meropenem and azithro- gentamicin (39 DOT/1000pd), vancomycin (oral and mycin; for these antimicrobials, use was 2–3 × higher parenteral combined, 35 DOT/1000pd), trimethoprim- on PICUs compared to non-ICUs. Although the rate sulfamethoxazole (28 DOT/1000pd), cefotaxime (27 of vancomycin use was much higher on PICU wards DOT/1000pd), amoxicillin (24 DOT/1000pd), and met- from seven hospitals (98 DOT/1000pd) compared to ronidazole (19 DOT/1000pd). These 10 antimicrobials non-ICU wards from nine hospitals (30 DOT/1000pd), represented 79% (379/481 DOT) of total AMU. At the among the three hospitals with available data, the rate three hospitals where oral vancomycin use could be sepa- of oral vancomycin use was higher among non-ICU rated from parenteral use, 8% of vancomycin use was oral wards (5 DOT/1000pd) than among PICU wards (3 (3 DOT/1000pd). DOT/1000pd). Only cephalexin, metronidazole, cef- Although AMU among PICUs represented only a small tazidime and amoxicillin were used substantively more proportion of the total AMU (14% of overall DOTs), the frequently among non-ICU wards compared with PICU rate of AMU was more than 50% higher among PICUs wards; cephalexin use was 65% higher on non-ICU (784 DOT/1000pd) than among non-ICU wards (494 wards, metronidazole use was 40% higher, ceftazidime DOT/1000pd, p-value < 0.01). Among the seven PICUs use was 28% higher and amoxicillin use was 22% higher. included in surveillance, the interquartile range (IQR) The rate of total AMU among the seven NICUs (333 for total AMU spanned from 502 to 900 DOT/1000pd. DOT/1000pd) was lower than on non-ICU wards (494 The ten most frequently used antimicrobials among DOT/1000pd). Among the seven NICUs included in Rudnick et al. Antimicrobial Resistance & Infection Control (2023) 12:35 Page 5 of 9 Fig. 2 Rate of antimicrobial use among paediatric inpatients by drug class with bootstrapped 95% confidence intervals, 2017–2018. Presented antimicrobials represent 98% of reported antimicrobials used at participating hospitals surveillance, the interquartile range (IQR) for total AMU data from hospitalized paediatric populations AMU spanned from 296 to 437 DOT/1000pd. The five are limited and differences in methods (eg. metrics antimicrobials used most often on NICUs were ampi- to express AMU), services, and patient populations cillin (103 DOT/1000pd), gentamicin/tobramycin (78 make national and international comparisons diffi - DOT/1000pd), cefotaxime (38 DOT/1000pd), van- cult. However, there are studies that report paediatric comycin (IV, 26 DOT/1000pd), and meropenem (16 AMU rates similar to those in this study (IQR: 352–569 DOT/1000pd). These five antimicrobials represented 78% DOT/1000pd). A study of 20 hospitals in the United of AMU among NICUs. States reported an overall annual paediatric AMU rate of 540 DOT/1000pd in 2007 [43]. A four-hospital point Discussion prevalence study in Italy estimated an overall paediatric To date, these surveillance results represent the largest AMU rate of 305 DOT/1000pd in 2016 [44]. collection of dispensed or administered antibiotic use There are also Canadian and international studies that data from hospitalized paediatric patients in Canada. report higher rates of paediatric AMU than those found From January 2017 to December 2018, among hospital- in our study. Our AMU rate among non-ICU wards (494 ized paediatric patients, the rate of overall AMU was DOT/1000pd) is 55% of the median-adjusted AMU rate 481 DOT/1000pd with substantial variation between found among non-ICU wards from 41 hospitals in the hospitals and between ward types. United States (893 DOT/1000pd from billing data) [45]. Rudnick et al. Antimicrobial Resistance & Infection Control (2023) 12:35 Page 6 of 9 Fig. 3 Rate of antimicrobial use among paediatric inpatients for the 10 most used antimicrobials with bootstrapped 95% confidence intervals, 2017–2018. Presented antimicrobials represent 80% of reported antimicrobials used at the participating hospitals A Canadian study conducted at one of the hospitals needed to identify the reasons for this variability and how included in this study using a similar methodology found to optimize interventions in light of this variation. an AMU rate of 757 DOT/1000pd in 2013/14 [39]. Dif- In our study, the rate of AMU among PICU wards was ferences in case mixes and included time periods may about 1.5 times as high as the rate of AMU among non- explain or partially explain the differences in rates; nota - ICU wards. Higher rates of AMU among PICU wards are bly, the Canadian study found that rates of AMU were expected due to the higher prevalence of infection among decreasing at their centre [39]. Among our nine hospi- critically ill patients. Perioperative antibiotic prophylaxis, tals, there was high variability in overall AMU rates with suspected ventilator-associated pneumonia and sepsis are a 17-fold variability between hospitals and an interquar- drivers of AMU on PICU wards [47–49]. In addition, guide- tile range spanning 217 DOT/1000pd. The high varia - lines for antimicrobial use often involve recommendations tion between AMU rates at paediatric hospitals is not for empiric use of more than one antimicrobial agent among surprising given that paediatric AMU rates within the PICU patients [50, 51]. Although our absolute rates of AMU same jurisdiction have been found to vary widely [44, 46]. were lower, a study from a hospital in Oregon reported The variation observed in our study is likely at least par - about a twofold difference in AMU on a PICU ward com - tially attributable to differences in hospital services, clini - pared to their non-ICU wards [32]. Some studies have found cal specialties and the presence of ICUs. Further study is smaller differences in rates between PICU and non-ICU Rudnick et al. Antimicrobial Resistance & Infection Control (2023) 12:35 Page 7 of 9 wards [45, 52] likely resulting in part from differences in ser - specialized care have been found to have higher rates of vices and clinical specialties at these institutions. Estimates AMU than lower levels reflecting the underlying condi - of inappropriate antimicrobial use on PICUs vary widely tions (e.g. higher rates of surgical complications), severity ranging from 17 to 62% [47, 53]. It is notable that, despite of illness and risk of infection in more premature neo- the high rates of AMU on PICU wards, interventions in the nates, especially those with very low birth weight [40]. PICU will impact only a small portion of total antibiotic use; We acknowledge the limitations of our work including the PICUs represented 14% of total DOTs in our study. risk of selection bias due to hospitals voluntarily opting to Our rate of AMU among PICU wards (784 participate. The majority of the hospitals included had well- DOT/1000pd) was lower than most rates reported by developed antimicrobial stewardship programs, which may others possibly due to the state of stewardship programs not reflect all paediatric hospitals in Canada. Data were col - at these centres. A large study of billing data from 41 lected only from teaching hospitals and were not collected PICUs in the United States reported a median-adjusted from every province so are not representative of all Cana- rate of 1043/1000pd in 2010–2014 [45]. Studies from dian hospitals. We did not identify which hospitals or wards Saudi Arabia in the mid-2010s found AMU rates among had patient groups with higher expected levels of AMU. PICUs between 697 and 849 DOT/1000pd [54, 55]. A Our surveillance system does not capture data on indication German intervention study found an AMU rate of 1226 for use or appropriateness of use. There are also shortcom - DOT/1000pd [49]. A 2015 study of AMU among a PICU ings to using DOTs to measure aggregate antibiotic use [62]. in South Africa reported a rate of 1336 DOT/1000pd Interpretation of DOT data can be challenging given that it [52]. A study of German and Brazilian PICUs found rates is not possible to separate monotherapy from combination of 888 and 1441 DOT/1000pd, respectively; patients therapy. The use of dispensed data may not represent what with < 24 h of AMU were excluded in this study [56]. antibiotics were administered to the patients [63]. Glycopeptide use among PICUs (98 DOT/1000pd) was more than three-times higher than glycopeptide use among non-ICU wards (30 DOT/1000pd); this is Conclusions likely due in part to more frequent use of central lines Our study describes Canadian paediatric AMU data from and coverage for coagulase negative staphylococci on nine hospitals and represents the largest collection of dis- PICUs. Glycopeptide use among PICUs in this study pensed/administered antibiotic use data from paediatric was similar to use on a German PICU (90 DOT/1000pd) inpatients in Canada to date. In 2017/2018, overall AMU [56], but lower than Brazilian, Saudi Arabian and South was 481 DOT/1000pd. There is need for high-quality, African PICUs (151 to 263 DOT/1000pd) [52, 54–56]. hospital-based AMU surveillance to support antimicro- Differences in glycopeptide use may be partially due to bial stewardship efforts. differences in rates of methicillin-resistant Staphylococ - cus aureus across jurisdictions [56]. Vancomycin has also Abbreviations been found to represent a high percentage of inappropri- AMU Antimicrobial use ate use in some jurisdictions [55, 57–59].ATC Anatomical therapeutic chemical CI Confidence interval Our rate of overall AMU among NICUs (333 CNISP Canadian nosocomial infection surveillance program DOT/1000pd) is similar to some reports from Can- DOT Days of therapy ada and the United States. Among five NICUs in DDD Defined daily dose ICU Intensive care unit Alberta, Canada, rates of AMU ranged from 155 to 624 NICU Neonatal intensive care unit DOT/1000pd in 2011–2014 [40]. In the United States, PICU Paediatric intensive care unit Cantey et al. found a decline from 343 DOT/1000pd PD Patient days in 2012 to 252 DOT/1000pd in 2014 after implement- Acknowledgements ing a stewardship program [60]. Our rate was similar to We are thankful for all the dedicated work of the pharmacists, clinicians, epide‑ that reported on a Saudi Arabian NICU in 2012–2015 miologists, and infection control practitioners who participate in CNISP. (325 DOT/1000pd) [54] and was slightly lower than Author contributions rates reported on two German NICUs (373–486 WR, JC, DJGT, KC, LP, JB, LB, JLC, BD, JD, RD, JE, YÉ, GE, CF, SF, JH, KK, PK, JML, BEL, DOT/1000pd) in 2018 [56]. Much higher rates of AMU MAL, JAL, AM, SM, HLN, KS, KSN, ATC, KW, and MS contributed to the concep‑ tion of this work. All authors contributed to the acquisition of these data. WR, among NICU wards have been reported from other JC, KC, and LP initially analyzed the AMU data. WR, JC, DJGT, LP, JC and MS jurisdictions. Surveillance of a Brazilian NICU and five contributed to the initial interpretation of the AMU data and all authors sub‑ Russian NICUs found overall rates of AMU to be 1336 sequently contributed to the revision of the AMU data interpretation. MS and WR prepared the initial draft of the manuscript. JC and DJGT revised the initial and 1423 DOT/1000pd, respectively [56, 61]. These dif - draft. Oversight of the work was done by WR, JC, MS, DT, LP and KC. All authors ferences may partially be due to differences in levels of read and approved the final manuscript. NICUs; higher levels of NICU wards that provide more Rudnick et al. Antimicrobial Resistance & Infection Control (2023) 12:35 Page 8 of 9 Funding References The Canadian Nosocomial Infection Surveillance Program is funded by the 1. Aminov RI. A brief history of the antibiotic era: Lessons learned and chal‑ Public Health Agency of Canada. 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Journal
Antimicrobial Resistance and Infection Control – Springer Journals
Published: Apr 18, 2023
Keywords: Antimicrobial use; Hospital; Paediatric; Surveillance