Neonatal sepsis is a severe condition with high morbidity and mortality. Early diagnosis and appropriate use of antimicrobials are essential, but indiscriminate use is associated with dysbiosis and bacterial resistance. In this regard, antimicrobial stewardship programs are necessary to reduce excessive consumption and improve therapeutic efficacy. This review aims to assess antimicrobial consumption measures in neonates, focusing on the treatment of neonatal sepsis. The review was registered on Protocols.io and followed the PRISMA-ScR guidelines for systematic reviews. Original observational studies involving neonates, addressing sepsis or healthcare-associated infections, and presenting antimicrobial consumption metrics were included. Studies on reviews, prophylactic antimicrobial use, use for less than three days, pharmacokinetic or pharmacodynamic studies, and those with mixed populations without separate analysis of neonates were excluded. The search was conducted in Scopus, PubMed, LILACS, Cochrane, and BVS databases, using MeSH and Emtree descriptors. The final analysis included 14 studies, totaling 37,214 patients, and found that the main metrics used were Days of Therapy (DOT) and Defined Daily Dose (DDD). Although the results show variations in consumption practices, most studies emphasize reducing the use of broad-spectrum antimicrobials and the need for stewardship programs to rationalize use. Standardizing these metrics, through new studies and guidelines, is essential to improving neonatal care and preventing excessive antimicrobial use, thereby mitigating long-term adverse effects.

• Neonatal sepsis • Neonatal Population • Antimicrobials • PRISMA-ScR guidelines • Neonatal care

Romanelli R, Araújo V, Sobreira L, Neumann H, Tavares H, et al. (2026) Consumption of Antimicrobial on Neonatal Population - Scoping Review. Pediatr Child Health 14(1): 1364.

Neonatal sepsis is a condition secondary to a systemic infection with dysregulation of the immune response, resulting in a high morbidity and mortality in neonates, especially those very preterm infants [1,2]. Early-onset neonatal sepsis is typically caused by pathogens transmitted through the maternal genital tract, while late sepsis occurs due to colonization and subsequent dissemination by hospital environment organisms [3-5]. The significant morbidity and mortality justify concerns about early diagnosis and antibiotic therapy, as well as appropriate management of secondary hemodynamic, respiratory, metabolic, and inflammatory disorders [6,7].

The nonspecificity of clinical and laboratory signs in neonates and the difficulty in establishing criteria for defining sepsis in this population can lead to the inappropriate antibiotic exposure, which is linked to long-term outcomes (e.g., necrotizing enterocolitis, altered microbiome), and bacterial resistance to these drugs [8-10]. Rational use through antimicrobial stewardship programs is essential for reducing the consumption of these medications. Antimicrobial stewardship programs in hospital settings aim to reduce indiscriminate use, seeking therapeutic efficacy while reducing side effects, selective pressure for drug resistance, and costs related to suboptimal use. These programs are based on five fundamental principles of clinical use: correct choice of antimicrobial, correct duration and dosage for treatment, consideration of de-escalation whenever possible, and correct diagnosis of the patient’s condition [11-13].

Consumption measures are rarely used for the neonatal population, as the dose depends on weight and days of life; some attempts at standardizing measures are described in the literature, such as Days of Therapy (DOT) and Defined Daily Dose (DDD) adapted [14,15]. However, studies are needed to evaluate these and other consumption indicators in neonates. The objective of this scoping review is to assess the antimicrobial consumption measures used in the neonatal population.

The guiding question posed was “ What antimicrobial consumption measures are used in neonates in the NICU?” followed by the acronym PCC: Population (P) - Neonates in the Neonatal Intensive Care Unit; Concept (C) - Antimicrobial Consumption Measures; Context (C) - Neonatal Infection/Sepsis treatment.

Protocol

This review was registered on Protocols.io [16], with DOI registration link: dx.doi.org/10.17504/protocols. io.j8nlk9erxv5r/v1, and was designed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews (PRISMA-ScR) guidelines [17].

Study Eligibility

Considering the focus on studies containing antimicrobial consumption metrics, inclusion criteria were: (1) Original observational studies; (2) Population: neonatal in UTIN or hospital settings; (3) Context: neonatal sepsis, infection, or healthcare-associated infections (HAI); (4) Studies containing antimicrobial consumption metrics. Exclusion criteria were: (1) Review studies; (2) Prophylactic antimicrobial use; (3) Antimicrobial use for less than three days; (4) Pharmacokinetic or pharmacodynamic studies of antimicrobials; (5) Intervention studies; (6) Studies that do not include the neonatal population, with overlap of patients from other age groups, without subgroup analysis. There were no restrictions regarding the date or language of publication or inclusion based on the size of the studied population.

All identified articles were systematically evaluated using the inclusion and exclusion criteria, according to defined PCC. Duplicate identification and screening of articles by title and abstract were performed by RAYYAN tool [18].The final selection of articles and extraction data was conducted by blind peers at RAYAAN tool [18], and any discrepancies were resolved by an independent author in a blind manner.

Search Strategy

A systematic search was conducted in the databases Scopus, PubMed (MEDLINE), LILACS (Latin American and Caribbean Literature in Health Sciences), Cochrane, and BVS (Virtual Health Library). For the construction of search descriptors, the Medical Subject Headings (MeSH) and Emtree databases were researched, and the final search across all databases was as follows: Neonatal AND (Antibiotic OR Antibiotics) AND Consumption.

Data Extraction

The following data were extracted: (1) First author; (2) Year of publication; (3) Study country; (4) Sample size; (5) Patient characteristics in the study (gestational age and birth weight); (6) Antimicrobial consumption metric used; (7) Consumption by metric. Data extraction was performed independently by six reviewers, and discrepancies were resolved by a seventh author.

The collected data will be grouped according to the consumption measure used and presented in tables, as well as detailed narratively.

Quality Assessment

The Joanna Briggs Institute’s critical appraisal tools (JBI’s) [19], were used for quality assessment. The checklist for cross sectional was used to evaluate each article, as data extraction and analysis of included articles considered the descriptive analysis within the study period. Two authors independently assessed the quality of the studies included in the analysis, and discrepancies were resolved through discussion between the two authors or by a third independent expert. When applying the respective checklist, each included article received a final score, and a higher number of “Yes” responses indicates a lower risk of bias and higher quality. A score of ≥ 70% was considered low risk of bias, a score between 50% and 69% indicated moderate risk of bias, and a score of < 49% was considered high risk of bias.

Selection of Sources of Evidence

As shown in Figure 1, a total of 1,829 studies were identified. After the removal of 275 duplicate records, 1,542 studies were screened by title and abstract, of which 37 remained for full-text reading, and two of these were not fully accessible. Then, 35 were thoroughly reviewed for inclusion and exclusion criteria, and finally, 14 manuscripts [20-33], were eligible for inclusion in this scoping review for addressing antimicrobial consumption measures in the target population. One study [34], which initially met the inclusion criteria, was excluded from the final selection due to the inability to extract data on antimicrobial consumption from the published information.

Figure 1: PRISMA flowchart for article selection.

Characteristics of Sources of Evidence

This review included observational studies published between 2010 [29], and 2024 [30]. Of the 14 studies analyzed, 11 used a retrospective design for data analysis, while three studies [23,25,33], performed prospective surveillance. The observation periods varied considerably, ranging from short-term analyses of 12 months [26], to longitudinal studies spanning 10 years [30].

Regarding geographical scope, three studies adopted a multicenter approach: Silva et al. [22], conducted a comparative analysis between units in Brazil and Germany, Villanueva-Bueno et al. [31, included 26 Spanish hospitals, and Huncikova et al. [30], analyzed data from 18 Norwegian neonatal units. The other studies were conducted in single centers, with eight of them carried out in developed countries [20,23,24,27-29,32,33], and three in developing countries [21,25,26].

Five studies conducted trend analyses of antimicrobial consumption over time [26-30]. Four studies analyzed correlations between antimicrobial consumption and specific outcomes: Karimi et al. [21], investigated the relationship with bacterial resistance in neonatal sepsis, while Romaniszyn et al. [27], Ró?a?ska et al. [24], and Wójkowska-Mach et al. [33], analyzed the association with specific infections in very low birth weight neonates. One retrospective study [20], evaluated the impact of implementing a hospital antimicrobial policy, comparing pre- and post-intervention periods.

The studies employed descriptive statistics as the primary method of analysis, presenting measures of central tendency and dispersion to characterize antimicrobial consumption.

Regarding antimicrobial consumption metrics, five studies assessed exclusively Days of Therapy (DOT) [22,23,28,30,32], five assessed only Defined Daily Dose (DDD) [18,19,24,27,29], and three included both measures [24,27,33]. The DDD definition followed the WHO’s Anatomical Therapeutic Chemical (ATC) classification [35], for each antimicrobial, while DOT was defined as the number of days on which at least one dose of an antimicrobial was administered, regardless of dose or frequency. The detailed individual characteristics of each study are presented in Table 1.

Table 1: Basic Characteristics of Selected Studies

Synthesis of Results

This review included 14 studies, totaling 37,214 patients, excluding the study by Balkhy et al. [23], for not providing these data. Studies on temporal trends in antimicrobial consumption revealed significant variations in prescribing patterns. Zingg et al. [28], demonstrated a reduction in the consumption of broad-spectrum antibiotics over eight years, with a 9.5% annual decrease in the prescription of third-generation cephalosporins (p<0.001). In contrast, Huncikova et al. [30], identified a progressive increase in total antimicrobial consumption in preterm infants under 32 weeks, from 404 to 648 DOT/1000 patient-days between 2012 and 2021 (p=0.03). In the analysis of institutional interventions, Nitsch-Osuch et al. [20], reported a significant reduction in total antimicrobial consumption after the implementation of a hospital antimicrobial policy, with a 15.3% decrease in average annual consumption (252.4 to 213.8 DDD/100 patient-days, p<0.01). Similarly, Jiménez et al. [25], showed a 22% reduction in overall consumption after the implementation of a rational antimicrobial use program. Comparative studies between different healthcare settings revealed significant heterogeneity. Silva et al. [22], identified greater consumption of third-generation cephalosporins in the Brazilian unit compared to the German one (25.3 vs 12.7 DOT/100 patient-days, p<0.001), while aminoglycosides were more frequently prescribed in the German unit (18.4 vs 10.2 DOT/100 patient-days, p<0.001). Liem et al. [29], documented up to a threefold variation in total consumption between different Dutch units (range: 116-412 DDD/100 patient-days).Regarding specific populations, Ró?a?ska et al. [24], demonstrated twice as much antimicrobial consumption in very low birth weight neonates with laboratory-confirmed bloodstream infections compared to non-confirmed cases (245.6 vs 122.3 DDD/100 patient-days, p<0.001). Wójkowska-Mach et al. [33], analyzing cases of necrotizing enterocolitis, identified an average consumption of 2.3 DDD per case, with aminoglycosides predominating (48% of prescriptions).

Karimi et al. [21], established a positive correlation between aminoglycoside consumption and the development of bacterial resistance in neonatal sepsis (r=0.78, p<0.001). Romaniszyn et al. [27], identified an association between higher consumption of glycopeptides and the isolation of methicillin-resistant Staphylococcus aureus (odds ratio: 1.45; 95% CI: 1.23-1.72).

In the Spanish multicenter setting, Villanueva-Bueno et al. [31], reported an average consumption of 56.4 DDD/100 patient-days, with ampicillin and gentamicin accounting for 65% of the total. Galankin et al. [32], documented the predominance of aminoglycosides (42%) and penicillins (38%) in total consumption in Russian units, with an average of 87.3 DDD/100 patient-days.

Balkhy et al. [23], in a 33-month prospective surveillance, identified a growing trend in carbapenem consumption (8.2 to 12.4 DOT/100 patient-days, p=0.02) and stability in vancomycin consumption. Salehifar et al. [26], reported ceftriaxone as the most consumed antimicrobial in their unit (26.4% of the total), followed by vancomycin (18.7%) and ampicillin (15.3%). Among the most used antimicrobials in the studies, aminoglycosides (amikacin and gentamicin), beta-lactams (ampicillin and amoxicillin), glycopeptides (vancomycin), and cephalosporins (ceftazidime, cefepime) were highlighted. Some studies also included antifungals in their analyses [24,31-33], with fluconazole and itraconazole being the most frequently mentioned.

Critical Appraisal within Sources of Evidence

The critical appraisal of the included sources of evidence, according to the JBI Critical Appraisal Tools [19], is presented in Table 2.

Table 2: Quality assessment by JBI Critical Appraisal for the included cross-sectional studies

A score of ≥70% was considered as a low risk of bias, a score between 50%–69% as moderate risk of bias, and a score of <49% as high risk of bias. Y = yes; N = no; NA = Not Applicable; U = unclear

Based on the presented data, the studies by Silva et al. [21], Ró?a?ska et al. [24], and Zingg et al. [28], were robust in all the evaluated criteria, including the use of appropriate statistical analyses, indicating a strong and reliable methodology. On the other hand, studies like Nitsch-Osuch et al. [20], showed gaps in the detailed description of subjects and in the declaration of strategies to identify and handle confounding factors, areas that had the most variability. Strategies were declared in only some of the studies, with notable omissions in Karimi et al. [21], Jiménez et al. [25], and Salehifar et al. [26]. Studies like Balkhy et al. [23], and Jiménez et al. [25], presented uncertainties in the identification of confounding factors and in the use of objective and standardized criteria for measuring the condition. The reliability in outcome measurement was high across the studies, as well as the application of appropriate statistical analyses, except for Nitsch-Osuch et al. [20], who did not use an adequate statistical analysis. This landscape suggests a high degree of methodological rigor in most studies, although some methodological limitations should be considered when interpreting the results.

Summary of Evidence

Main strategies of measurement of antimicrobial consumption: The consumption measures used in the studies were DOT, DDD, and Usage Rate. Of the 14 studies evaluated, eight used DDD as the consumption measure, eight used DOT, and one used the usage rate (in days) per 100 hospitalized patients, which corresponds to DOT. Two studies [27,33], used both DOT and DDD together, totaling 16 measures across the 14 studies. It is important to highlight the difficulty of comparison due to the different standardizations among the studies.

Comparative utility of DOT and DDD: DDD is defined as the average daily dose assumed for the maintenance of a medication used for its primary indication in adults. It can be assigned by ATC code and route of administration but has limited use in pediatrics and neonatology due to dose variability, which is based on body weight and different dosing intervals (adults) [36,37]. In the studies by Nitsch Osuch et al. [20], Karimi et al. [21], Ró?a?ska et al. [24], Salehifar et al. [26], Romaniszyn et al. [27], Liem et al. [29], and Wójkowska-Mach et al. [33], the DDD used considered the standard daily dose following ATC recommendations, which can lead to bias since the profile of the Neonatal Unit may present variations according to the neonatal population treated, which may vary in terms of gestational age, weight, and other clinical conditions such as malformations that require different dose adjustments. The study by Villanueva-Bueno et al. [31], used a different DDD measure, without using the doses recommended by the ATC, and based its measure on its own criteria.

DOT is the sum of the exposure days for each antibiotic used, adjusted with the denominator corresponding to the time under risk of exposure (patient-days). Therefore, evaluating DOT is more suitable for the neonatal and pediatric population when compared to DDD, as it reflects the time the patient is exposed to antimicrobials [38]. The Center for Diseases Control and Prevention defines consumption as the Standardized Antimicrobial Administration Ratio (SAAR), which is the number of observed antimicrobial use days (DOT) divided by the expected days of use per antimicrobial, also adjusted for risk when divided by the patient-day denominator [39,40]. Definitions for Calculations of Antimicrobial Days per antimicrobial assess the main antimicrobials by sector, including Neonatal Units [41]. The studies by Silva et al. [22], Balkhy et al. [23], Ró?a?ska et al. [24], Romaniszyn et al. [27], Zingg et al. [28], Huncikova et al. [30], Galankin et al. [32], and Wójkowska-Mach et al. [33], used this measure.

The usage rate, used by Jiménez et al. [25], was described as the sum of the number of days a newborn was exposed to one or more drugs, for every 100 days of hospitalized patients. This definition is closer to that used for DOT, although adapted.

It is important to emphasize the exposure time to antimicrobials, which has long-term negative impacts such as dysbiosis and changes in the flora of the digestive and respiratory tracts, promoting healthcare-associated infections, enterocolitis, longer hospital stays, costs, and mortality, as well as chronic diseases such as obesity, metabolic diseases, allergies, and immunological disorders42. Thus, stewardship programs aim for rational use of antimicrobial, with reduced treatment time, considering the shortest possible time based on clinical and laboratory responses [11,43-46].

Implications for Stewardship Programs,Antimicrobial Consumption: A systematic review published in 2020 identified six studies that showed a reduction in antimicrobial use, with a decrease in DOT for antimicrobials and a reduction in the consumption of specific antimicrobials such as vancomycin, meropenem, and cefotaxime, as well as global reductions in broad-spectrum antimicrobials and treatment time [14]. Another systematic review published in 2023 identified 16 studies evaluating the impact of stewardship programs for antimicrobial use in neonatology, which showed a reduction in the use of these medications in a generalized manner after the implementation of these programs [15]. The main consumption measure evaluated was the time in days/ patient-day, referred to in different ways. Consumption was called DOT in 12 studies, Antibiotic Use Rate (AUR) was defined in two studies, and Days of Use/Patient-day was used in one study. Only one study mentioned DDD as the average dose used during the period, in addition to evaluating density/month. In all studies, there was a reduction in the evaluated consumption, although two of them did not show statistically significant results. While there are few studies evaluating antimicrobial use in the neonatal population, the evaluation by days of use/ patient under risk is more commonly used and suitable for the neonatal population, which should be included in stewardship programs for interventions aiming for rational use of medications.

In four studies [20,22,26,31], penicillins (ampicillin, amoxicillin, and piperacillin) were the most commonly used antibiotics, while aminoglycosides (amikacin and gentamicin) were the most recorded in another four studies [21,23,25,28].The most commonly used antimicrobials for neonates with early-onset sepsis were aminopenicillins (such as ampicillin and amoxicillin) associated with aminoglycosides (such as amikacin and gentamicin), which align with the empirical treatment recommendations for early-onset sepsis, covering the main etiological agents described in these infections (Streptococcus agalactiae, Listeria monocytogenes, and Gram-negative flora from maternal sources, such as E. coli, Klebsiella sp, and Proteus sp) [6,47-52]. In cases of healthcare associated infections (HAIs) of hospital origin, there was a higher description of consumption of fourth-generation cephalosporins (cefepime), glycopeptides (vancomycin), and carbapenems, indicating the use of broad-spectrum antimicrobials, which may suggest a higher resistance profile to the antimicrobials most commonly used in cases of late-onset sepsis. These antibiotics were the most used in two studies [24,27]. In three studies [29,32,33], it was not possible to identify the most used antimicrobials since only general usage rates were provided.

Relevance of SAAR: Regarding SAAR, considering observed days over expected days of use, O’Lery et al. [53], described the consumption of seven categories in levels of NICU care for the 2018 database, aiming to be a U.S. national standard for consumption based on percentiles corresponding to the observed time over the expected time of use. The 50th percentile for Ampicillin and Aminoglycosides, used for early-onset sepsis, was 0.94 for both in NICU level II and 0.87 and 0.85 for level III/IV, respectively. The 50th percentile for vancomycin, used for covering resistant Gram-positives, was 0.36, 0.68, and 0.92 for levels II, II/III, and III/IV, respectively. The 50th percentile for Broad-Spectrum Antimicrobials for Hospital-acquired Infections ranged from 0.27 to 0.63. For all antimicrobials, the 50th percentile was 0.92 across all NICU levels. This study demonstrates that the time of use tends to be shorter than the expected time, generally estimated by the recommended treatment time in the literature based on infection topography and microbiological agent [51,54-56].

Need for Standardization: It is important to highlight that the trend is to reduce treatment time to the shortest possible period, considering clinical and laboratory response, as prolonged exposure increases morbidities and mortality in neonates. Even for newborns with risk factors who initiate empirical antimicrobials, the duration of treatment should be reduced. A study conducted by Kumar et al. [57], in a level IV NICU implemented an intervention to reduce antimicrobial use in high-risk preterm infants from 48 to 24 hours, based on clinical and laboratory evolution. A total of 57% of the newborns who started antimicrobials and had negative blood cultures used antimicrobials for less than 24 hours, which corresponds to 77% of all newborns with empirical treatment for early-onset sepsis. Current guidelines and studies recommend shorter treatments and early suspension of antimicrobials in stable neonates with 24 to 36 hours of negative blood culture, avoiding unnecessary use of antimicrobial use [10,11,50 52,56,57]. However, little evidence is concerned about consumption measurements. However, little evidence is concerned about consumption measurements. In Brazil, recent guideline the recent national guideline proposes consumption measurement by DOT, by antimicrobial days and by antimicrobial-free days [58].

Limitations

This review has some limitations, mainly related to the absence of international standardization of the measures, which prevents comparisons between values. Another important limitation is the low number of studies on the topic, which hinders a more in-depth analysis aimed at better understanding what would be an ideal measure to assess antimicrobial use. The different objectives of the included studies also made analysis difficult, leading to a preference for a descriptive process rather than an analytical one.

Through this review, we found that the main antimicrobial consumption measures used in neonatology are DOT and DDD, with some variations based on them (LOT, DID, etc.), but there is no consensus on which is superior or preferred over the other, at least in terms of prevalence in the literature.

This work indicates the importance of guidelines for standardization of this process are needed, which will facilitate the implementation of stewardship programs and the exchange of knowledge in the healthcare assistance and academic communities.

Avoiding unnecessary use of antimicrobials in newborns and minimizing exposure time to these medications is extremely important for neonatal health.

This work was supported by Federal University of Minas Gerais (Pró-reitoria de Pesquisa) and National Council for Scientific and Technological Development (CNPq) Brazil, through the Institutional Scientific Initiation Scholarships (Volunteers and PIBIC).

1. The Global Maternal and Neonatal Sepsis Iniciative Working Group. The Global Maternal and Neonatal Sepsis Initiative: a call for collaboration and action by 2030. UNDP/UNFRA/UNICEF/WHO.
2. Flanerry DD, Edwards EM, Coggins SA, Horbar JD, Puopolo KM. Late-Onset sepsis among very preterm infants. Pediatrics. 2022; 150: e2022058813.
3. Shane AL, Sánchez PJ, Stoll BJ. Neonatal sepsis. The Lancet. 2017; 390: 1770-1780.
4. Russel N, Barday M, Okomo U, Dramowski A, Sharland M, Bekker A. Early-versus late-onset sepsis in neonates - time to shift the paradigm? Clin Microbiol Infect. 2024; 30: 38-43.
5. Strunk T, Molloy EJ, Misha A, Bhutta ZA. Neonatal bacterial sepsis. The Lancet. 2024; 404: 277-293.
6. Flanerry DD, Puopolo KM. Neonatal Early-Onset Sepsis. Neoreviews. 2022; 23: 756-770.
7. Shlapback LJ, Watson RS, Sorce LR, Argent AC, Menon K, Hall MW, et al. International Consensus Criteria for Pediatric Sepsis and Septic Shock. JAMA. 2024; 21: 1-10.
8. Wynn JL, Polin RA. A Neonatal Sequential Organ Failure Assessment Score Predicts Mortality to Late-Onset Sepsis in Preterm Very Low Birth Weight Infants. Pediatr Res. 2020; 88: 85-90.
9. Sociedade Brasileira de Pediatria (SBP). Departamento Científico de Neonatologia. Diretrizes para Uso Racional de Antibióticos em Unidades Neonatais. 2025.
10. Stocker M, Klingenberg C, Navér L, Nordberg V, Berardi A, Salhab el Helou, et al. Less is more: Antibiotics at the beginning of life. Nat Commun. 2023: 14: 2423.
11. Katz S, Banerjee R, Schwenk H. Antibiotic Stewardship for the Neonatologist and Perinatologist Clin Perinatol. 2021; 48: 379-391.
12. McPherson C, Liviskie C, Zeller B, Nelson MP, Newland JG. Antimicrobial Stewardship in Neonates: Challenges and Opportunities. Neonatal Netw. 2018; 37: 2.
13. Cantey JB, Patel SJ. Antimicrobial Stewardship in the NICU. Infect Dis Clin N Am. 2014: 28: 247-261
14. Araujo da Silva AR, Marques A, Di Biase C. Effectiveness of antimicrobial stewardship programmes in neonatology: a systematic review. Arch Dis Child Epub 2020; 105: 563-568.
15. Lima DMD, Rezende RV, Diniz LMO, Anchieta LM, Romanelli RMC. Evaluation of antimicrobial consumption in the neonatal population undergoing to stewardship programs: A systematic review. J Hosp Infect. 2023; 135: 106-118.
16. Neumann HN, Sobreira L, Araújo B, Lima G, Araújo V, Bacelete H, Anchieta LM, Romanelli R. ATM in neonate population use - Protocols. io.
17. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021; 372: n71
18. Ouzzani M, Hammady H, Fedorowicz Z, Elmagarmid A. Rayyan—a Web and Mobile App for Systematic Reviews. Systematic Reviews. 2016; 5.
19. Munn Z, Tufanaru C, Aromataris E. JBI?s Systematic Reviews. Data Extration and Synthesis. AJN. 2014; 114: 49-54.
20. Nitsch-Osuch A, Kurpas D, Kuchar E, Zyci?ska K, Zielonka T, Wardyn K. Antibiotic consumption pattern in the neonatal special care unit before and after implementation of the hospital’s antibiotic policy. Adv Exp Med Biol. 2015; 835: 45-51.
21. Karimi F, Lewis LE, Thunga G, Najmi A, Sahu P, Kunhikatta V. Relationship between antibiotic consumption pattern and antibiotic resistance in neonatal sepsis. Med Pharm Rep. 2023; 96: 35-40.
22. Silva AR, Jaszkowski E, Schober T, von Both U, Meyer-Buehn M, Marques AF, et al. Patterns of antimicrobial consumption in neonatal and pediatric intensive care units in Germany and Brazil. Eur J Clin Microbiol Infect Dis. 2020; 39: 249-255.
23. Balkhy HH, El-Saed A, AlShehri A, Alshaalan M, Hijazi O, El-Metwally A, et al. Antimicrobial consumption in three pediatric and neonatal intensive care units in Saudi Arabia: 33-month surveillance study. Ann Clin Microbiol Antimicrob. 2019; 18:20.
24. Ró?a?ska A, Wójkowska-Mach J, Adamski P, Borszewska-Kornacka M, Gulczy?ska E, Nowiczewski M, et al. Antibiotic consumption in laboratory confirmed vs. non-confirmed bloodstream infections among very low birth weight neonates in Poland. Ann Clin Microbiol Antimicrob. 2017; 16: 20.
25. Jiménez E, Valls N, Astudillo P, Valls C, Cavada G, Sandoval A, et al. Evaluation of antimicrobial consumption in a Neonatology Unit: a team work to promote the rational use of antibiotics. Rev Chilena Infectol. 2017; 34: 544-552.
26. Salehifar E, Nasehi M, Eslami G, Sahraei S, Alizadeh Navaei R. Determination of Antibiotics Consumption in Buali-Sina Pediatric Hospital, Sari 2010-2011. Iran J Pharm Res. 2014; 13: e125474.
27. Romaniszyn D, Ró?a?ska A, Wójkowska-Mach J, Chmielarczyk A, Pobiega M, Adamski P, et al. Epidemiology, antibiotic consumption and molecular characterisation of Staphylococcus aureus infections-- data from the Polish Neonatology Surveillance Network, 2009-2012. BMC Infect Dis. 2015; 15: 169.
28. Zingg W, Pfister R, Posfay-Barbe KM, Huttner B, Touveneau S, Pittet D. Secular trends in antibiotic use among neonates: 2001-2008: 2001-2008. Pediatr Infect Dis J. 2011; 30: 365-370.
29. Liem TBY, Krediet TG, Fleer A, Egberts TCG, Rademaker CMA. Variation in antibiotic use in neonatal intensive care units in the Netherlands. J Antimicrob Chemother. 2010; 65: 1270-1275.
30. Huncikova Z, Stensvold HJ, Øymar KAA, Vatne A, Lang AM, Støen R, et al. Variation in antibiotic consumption in very preterm infants—a 10 year population-based study. J Antimicrob Chemother. 2024; 79:143-150.
31. Villanueva-Bueno C, Montecatine-Alonso E, Jiménez-Parrilla F, Fernández-Llamazares CM, Manrique-Rodríguez S, Zamora-Flores E, et al. Antimicrobial defined daily dose in neonatal population. Enferm Infecc Microbiol Clin. 2021; 40: 59-65.
32. Galankin TL, Kolbin AS, Sidorenko SV, Kurylev AA, Malikova EA, Lobzin YV, et al. Retrospective surveillance of antibiotic use in maternity wards and neonatal intensive care units in Saint Petersburg, Russia. Eur J Clin Microbiol Infect Dis. 2018; 37: 1531-1537.
33. Wójkowska-Mach J, Ró?a?ska A, Borszewska-Kornacka M, Doma?ska J, Gadzinowski J, Gulczy?ska E, et al. Necrotising enterocolitis in preterm infants: epidemiology and antibiotic consumption in the Polish neonatology network neonatal intensive care units in 2009. PLoS One. 2014; 9: e92865.
34. Rendón LM, Agudelo E, Echavarría AM, Atehortúa S. Medición del consumo de antibióticos en unidades neonatales de tres instituciones de alto nivel de complejidad en Antioquia, Colombia. Revista Colombiana de Ciencias Químico Farmacéuticas. 2023; 52.
35. World Health Organization (WHO). Anatomical Therapeutic Chemical (ATC) Classification. WHO, 2025.
36. World Health Organization * (WHO) - Defined Daily Dose (DDD).
37. World Health Organization * (WHO) The ATC/DDD Methodology
38. Fundação Oswaldo Cruz. Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira. Portal de Boas Práticas em Saúde da Mulher, da Criança e do Adolescente. Postagens: Principais Questões sobre Stewardship de Antimicrobianos: da teoria à prática. Rio de Janeiro, 23 mar. 2023.
39. Center for Diseases Control and Prevention. The Nhsn Standardized Antimicrobial Administration Ratio (SAAR). A Guide to the SAAR. National Healthcare Safety Network Antimicrobial Use Option (NHSN.AU). National Healthcare Safety network antimicrobial use option.
40. O’Leary EN, Edwards JR, Srinivasan A. National Healthcare Safety Network standardized antimicrobial administration ratios (SAARs): a progress report and risk modeling update using 2017 data. Clin Infect Dis. 2020; 71: e702-e709.
41. Center for Diseases Control and Prevention (CDC). Antimicrobial Use and Resistance (AUR) Module.
42. Fundação Oswaldo Cruz. Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira. Portal de Boas Práticas em Saúde da Mulher, da Criança e do Adolescente. Uso de Antibióticos em Neonatologia: menos é mais! De: 13/08/2021.Disponível
43. Ho T, Buus- Frank M, Edwards EM, Morrow KA, Ferrelli K, Srinivassan A, et al. Adherence of Newborn-Specific Antibiotic Stewardship Programs to CDC Recommendations. Pediatrics. 2018; 142: e20174322.
44. Akinboyo IC, Gerber JS. Principles, Policy and Practice of Antibiotic Stewardship. Seminars in Perinatology. 2020; 44: 151324.
45. Aleem S, Wohlfarth M, Cotton M, Greenberg RG. Infection control and other stewardship strategies in late onset sepsis, necrotizing enterocolitis, and localized infection in the neonatal intensive care unit. Semin Perinatol. 2020; 44: 151326.
46. Rub DM, Dhudasia MB, Healy T, Mukhopadhyay S. Role of microbiological tests and biomarkers in antibiotic stewardship. Semin Perinatol. 2020; 44: 151328.
47. American College of Obstretricians and Gynecologists (ACOG). Prevention of Group B Streptococcal Early-Onset Disease in Newborns. Number 797.
48. Center for Diseases Control and Prevention (CDC). Early-Onset Neonatal Sepsis Surveillance and Trends.
49. Courtney Briggs-Steinberg 1 2 , Philip Roth 1 2Pediatr Rev. 2023 Early-Onset Sepsis in Newborns. 2023; 44: 14-22.
50. Puopolo KM, Benitz WE, Zaoutis TE. American Academy of Pediatrics (AAP) Committee on Fetus and Newborn, AAP Committee on Infectious Diseases. Management of Neonates Born at ≤34 6/7 Weeks’ Gestation with Suspected or Proven Early-Onset Bacterial Sepsis. Pediatrics. 2018; 142: e20182896.
51. Fleiss N, Schwabenbauer K, Randis TM, Polin RA. What’s new in the management of neonatal early onset sepsis? Arch Dis Child Fetal Neonatal Ed. 2023; 108: F10-F14.
52. O’Leary EN, Edwards JR, Srinivasan A, Neuhauser MM, Soe MM. National Healthcare Safety Network 2018 Baseline Neonatal Standardized Antimicrobial Administration Ratios. Hosp Pediatr. 2022; 12: 2154-1663.
53. Sarah A. Coggins, Kirsten Glaser. Updates in Late-Onset Sepsis: Risk Assessment, Therapy and Outcomes Neoreviews. 2022; 23: 738-755.
54. Stocker M, Mangeret FR, Agyeman FKA, McDougall J, Berger C, Giannoni E. Management of neonates at risk of early onset sepsis: a probability-based approach and recent literature appraisal. Eur J Pediatr. 2024; 183: 5517-5529
55. National Institute of HealthCare Excellence. Neonatal infection: antibiotics for prevention and treatment NICE guideline [NG195]. 2021.
56. Kumar R, Setiady I, Bultmann CR, Kaufman DA, Swanson JR, Sullivan BA. Implementation of a 24-hour empiric antibiotic duration for negative early-onset sepsis evaluations to reduce early antibiotic exposure in premature infants. Infect Control Hosp Epidemiol. 2022: 1-6.
57. Brasil. Agência Nacional de Vigilância Sanitária (ANVISA). Diretriz Nacional para Implantação de Programa de Gerenciamento de Antimicrobianos em Serviços de Neonatologia e Pediatria - 2025.es