Therapeutic Drug Monitoring of Vancomycin in Pediatric Patients: A Retrospective Study

Therapeutic Drug Monitoring of Vancomycin in Pediatric Patients: A Retrospective Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Therapeutic Drug Monitoring of Vancomycin in Pediatric Patients: A Retrospective Study Tao Zhang, Jingjing Yi, Hua Cheng, Xinyan Han, Yan Wang, Jiao Xie, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7050678/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 18 Nov, 2025 Read the published version in BMC Pharmacology and Toxicology → Version 1 posted 14 You are reading this latest preprint version Abstract Objective Methicillin-resistant Staphylococcus aureus (MRSA) infections among children are escalating annually. Vancomycin stands as the frontline therapeutic agent against MRSA infections. However, determining the therapeutic window for vancomycin in pediatric patients remains a challenge. Methods This retrospective study collected data from hospitalized children aged 1 month to 18 years, who underwent routine therapeutic drug monitoring for vancomycin. We analyzed the distribution patterns of vancomycin concentrations in these patients. Factors influencing clinical outcomes and adverse reaction (nephrotoxicity) were investigated. ROC analysis was used to establish the therapeutic window for vancomycin in pediatric patients. Results A comprehensive dataset encompassing 183 pediatric patients with 330 samples was analyzed. The mean trough concentration ( C min ) of vancomycin was 7.6 ± 5.5 mg/L. 74.3% of patients exhibited concentrations below the conventionally recommended therapeutic window of 10-20 mg/L. Patients responding positively to treatment exhibited significantly higher C min values (8.4 ± 5.7 mg/L) compared to those with treatment failure (5.9 ± 4.4 mg/L, P = 0.006). Similarly, patients who developed nephrotoxicity had significantly elevated C min levels (17.8 ± 5.3 mg/L) compared to those without nephrotoxicity (6.4 ± 3.9 mg/L, P < 0.001). Both univariate and multivariate logistic regressions revealed that the C min of vancomycin was the predictor of both clinical outcomes and adverse reaction. Furthermore, receiver operating characteristic curve analysis pinpointed that C min of vancomycin with 5.9 mg/L and 14.8 mg/L associated with clinical effectiveness and safety, respectively. Referring to the therapeutic window of adults, vancomycin underexposure in pediatrics is serious extremely. Conclusion Based on our findings, we propose a revised therapeutic window of 5.9-14.8 mg/L for vancomycin in pediatric patients, which could aid in optimizing treatment outcomes and minimizing adverse effects. vancomycin pediatrics therapeutic drug monitoring therapeutic window pharmacodynamics Figures Figure 1 Figure 2 Figure 3 1. Introduction Vancomycin, a water-soluble glycopeptide antibacterial agent, has been approved for treating G + bacterial infections in both adults and children. Although drugs like clindamycin, tetracycline, and trimethoprim-sulfamethoxazole are also utilized in infections by methicillin-resistant Staphylococcus aureus (MRSA), vancomycin remains the preferred choice, which has significant cost contribution among antibacterial drugs prescribed to children [1]. Vancomycin exhibits a narrow therapeutic index and significant inter-individual variations among individuals. The American Society of Health-System Pharmacists, Infectious Diseases Society of America (IDSA), and Society of Infectious Diseases Pharmacists advocate for monitoring the ratio of the 24 h area under the concentration-time curve and minimally inhibitory concentration ( AUC 24 /MIC ) of vancomycin, aiming for a target value within the range of 400–600 mg·h/L [1, 2]. However, monitoring vancomycin through pharmacokinetics/pharmacodynamics (PK/PD) exists significant challenges in clinical practice. A survey reveals that 93% of healthcare institutions still select trough concentration ( C min ) as the primary indicator in therapeutic drug monitoring (TDM). The generally recommended vancomycin C min range is 10–20 mg/L, with a narrower range of 10–15 mg/L for uncomplicated infections and 15–20 mg/L for severe infections, including endocarditis, meningitis, osteomyelitis, pneumonia, and septicemia [3]. Despite insufficient evidence, IDSA extrapolates the target ranges from adult patients to the pediatric population. Our research group has discovered that vancomycin C min exhibits a strong correlation with PK/PD target [4], which was consistent with reported evidence [5]. Specifically, achieving a C min within the ranges of 5.0-6.9 mg/L or 9.0-12.9 mg/L could meet the PK/PD target, depending on the MIC. In fact, the initial vancomycin C min target range for most infections in pediatric patients was 5–10 mg/L, while for central nervous system infections, it was 10–15 mg/L [6]. The IDSA guidelines in 2011 advocated a higher C min range, but the product insert did not introduce any new recommendations for the standard vancomycin dosing regimen accordingly [7]. Recent studies have revealed that with the current dosing of vancomycin, the rate of achieving the desired C min in pediatric patients is unexpectedly low when using 10–15 mg/L as the standard for effective therapeutic concentration, approximately 80%-90%[8]. Frankly, the IDSA recommended a vancomycin dosing of 60 mg/kg·d (15 mg/kg, q6 h) for pediatric patients with severe invasive MRSA infections. Nevertheless, several studies have indicated that even with higher dosing, it may still be inadequate to attain the desired C min [9]. Even when the target concentration is adjusted to 5–15 mg/L, the achievement rate rises to only 51% [10]. Surprisingly, a study reported a C min achievement rate of just 4% despite the included pediatric patients receiving the recommended vancomycin dose of 40–60 mg/kg/day [11]. The clearance (CL) and volume of distribution of vancomycin vary significantly in pediatric patients compared to adults, rendering it particularly difficult to attain and sustain vancomycin concentrations within the desired range for pediatrics. This challenge is further exacerbated in patients with underlying conditions, such as congenital heart disease, renal impairment, sepsis, and those undergoing fluid resuscitation [12]. A number of studies have demonstrated that standard dosing regimens often fall short of achieving the current target concentration range, indicating that applying adult concentration ranges to pediatric patients directly may not be appropriate[8]. The aim of this study is to establish the therapeutic window of vancomycin specifically for pediatric patients, minimizing the risk of treatment failure due to insufficient exposure or toxicity. A preprint has previously been published [13]. 2. Methods 2.1 Patient information and collection of clinical blood samples This study retrospectively collected hospitalized pediatric patients from two hospitals: the First Affiliated Hospital of Xi'an Jiaotong University and the Affiliated Children's Hospital of Xi'an Jiaotong University. The period spanned from January 2017 to December 2018. Inclusion criteria for the study comprised of: ① hospitalized patients aged 1 month to 18 years; ② those diagnosed or suspected with G + bacterial infection and receiving vancomycin treatment; and ③ patients able to provide at least one TDM data point. The following patients were excluded from the study: ① those receiving vancomycin through non-intravenous routes; ② patients allergic to vancomycin; ③ and patients who died within 24 hours of vancomycin administration. Demographic data, medication details, and physiological and biochemical indicators (including age, gender, weight, serum creatinine [Scr], vancomycin dosing regimen, dosage, medication dates, and indications) were retrieved from the hospital's electronic medical record system. Blood concentration data of vancomycin in patients was collected from those undergoing routine TDM (samples taken 30 minutes prior to the next dose after reaching a steady state). The blood concentration of vancomycin was determined using the previously established HPLC-MS/MS method by our research team [14]. 2.2 Therapeutic window of vancomycin in pediatric patients A univariate logistic regression analysis was conducted to investigate the correlation between various factors and both clinical outcomes and adverse reactions. Subsequently, factors exhibiting a P value less than 0.1 in the univariate analysis were subjected to multivariate logistic analysis to further identify factors potentially linked to clinical efficacy and adverse reactions Clinical outcomes were categorized into a four-level scale encompassing cured, improved, ineffective, and relapsed. For simplicity, cured and improved outcomes were jointly classified as treatment success, whereas ineffective and relapsed outcomes were grouped under treatment failure. The assessment of adverse reactions involved measuring Scr levels from the initiation of medication to 72 h post-medication. Acute kidney injury (AKI) was defined as either an elevation of Scr to 1.5 times the baseline level or a rise by 26.5 µmol/L. The therapeutic window refers to the spectrum of drug concentration levels that exhibit a significant correlation with clinical outcomes and the incidence of adverse reactions. 2.3 Statistics and analysis Continuous variables were described using mean ± standard deviation for normally distributed data and median for non-normal distributions. Categorical variables were characterized by frequencies and percentages. All statistical tests were two-sided with a significance level of α set at 0.05, and all analyses were conducted using SPSS (Version 19.0). 3. Results A total of 183 pediatric patients were included in this study and provided at least one vancomycin C min sample. A comprehensive monitoring of 330 blood drug concentrations was undertaken. Boys comprised the majority, constituting 61.2% of the total patients. The mean age of the pediatric patients was 3.4 years, with a mean weight of 15.0 kg. Acute lymphoblastic leukemia emerged as the most prevalent underlying condition, representing 15.9% of the total cases. Furthermore, 24% of the patients were admitted to the intensive care unit (ICU). Of the indications for antimicrobial therapy, 67.8% were attributed to invasive infections, encompassing pneumonia, endocarditis, as well as bone and joint infections. Subsequently, central nervous system infections comprised 29.0% of the total cases. Only 53 patients had available pathogen culture results, which revealed the presence of 23 methicillin-susceptible Staphylococcus aureus (MSSA) and 7 MRSA strains. While undergoing vancomycin therapy, 37% of patients received at least one nephrotoxic drug. Diuretics were the most commonly prescribed nephrotoxic drugs, representing 30.6% of the total administered. Additionally, 45% of patients received concurrent therapy with meropenem, as part of their antimicrobial regimen. Baseline Scr levels were measured at 28.2 ± 19.0 µmol/L, whereas creatinine clearance was calculated as 134.3 ± 81.4 mL/min. A comprehensive overview of demographic and other information are presented in Table 1 . Table 1 Patient demographics, clinical characteristics and vancomycin dose. Variable All Patients n = 183 (%) Treatment Outcomes Adverse Effects Treatment Success n = 132 (%) Treatment Failure or Death n = 51 (%) P Nephrotoxicity n = 21 (%) No Nephrotoxicity n = 162 (%) P Gender, male 112 (61.2) 84 (63.6) 28 (54.9) 0.277 14 (66.7) 98 (60.5) 0.474 Age, year a 3.4 ± 3.4 3.3 ± 3.4 3.6 ± 3.6 0.707 4.7 ± 3.6 3.2 ± 3.4 0.074 weight, kg a 15.0 ± 9.6 14.1 ± 9.8 16.4 ± 8.8 0.213 14.1 (10.3) 15.1 (9.5) 0.671 Body mass index, kg/m 2 0.6 ± 0.3 0.6 ± 0.3 0.7 ± 0.3 0.067 0.6 ± 0.3 0.6 ± 0.3 0.595 Comorbid conditions Acute lymphoblastic leukemia 29 (15.9) 21 (15.9) 8 (15.7) 0.970 6 (28.6) 23 (14.2) 0.168 Other malignant solid tumor 9 (4.9) 8 (6.1) 1 (2) 0.442 0 9 (5.6) - Liver disease 20 (10.9) 14 (10.6) 6 (11.8) 0.822 0 20 (12.3) - Anemia 22 (12.0) 16 (12.1) 6 (11.8) 0.947 1 (4.8) 21 (13.0) 0.465 Sepsis/severe sepsis/septic shock 54 (29.5) 54 (29.5) 10 (19.6) 0.068 10 (47.6) 44 (27.2) 0.053 Intensive care unit stay b 44 (24.0) 30 (22.7) 14 (27.5) 0.503 7 (33.3) 37 (22.8) 0.290 Mechanical ventilation b 40 (21.9) 27 (20.5) 13 (25.5) 0.460 7 (33.3) 33 (20.4) 0.284 Median white blood cell count, ×10 9 b 10.8 (5.9 ~ 16.4) 10.9 (6.5 ~ 16.5) 10.8 (4.0 ~ 15.3) 0.978 11.5 (2.9 ~ 14.5) 10.8 (6.3 ~ 16.7) 0.354 Blood urea nitrogen, mmol/L a 4.1 ± 4.2 4.2 ± 4.6 4.0 ± 3.0 0.742 5.3 ± 5.2 3.9 ± 3.8 0.103 Baseline creatinine, µmol/L a 28.2 ± 19.0 28.9 ± 21.4 26.5 ± 10.5 0.463 36.4 ± 37.6 27.1 ± 14.9 0.036 Baseline creatinine clearance, mL/min a* 134.3 ± 81.36 126.3 ± 55.0 154.9 ± 124.8 0.033 124.5 ± 76.7 135.6 ± 82.1 0.561 Infection type and diagnosis Skin/soft tissue infection 16 (8.7) 16 (8.7) 3 (5.9) 0.576 1 (4.8) 15 (9.3) 0.783 Bone/joint infection 23 (12.6) 23 (12.6) 6 (11.8) 0.838 1 (4.8) 22 (13.6) 0.425 Bacteremia 34 (18.6) 34 (18.6) 9 (17.6) 0.840 5 (23.8) 29 (17.9) 0.721 CNS infection 53 (29.0) 53 (29.0) 9 (17.6) 0.036 11 (52.4) 42 (25.9) 0.012 Other/unknown 19 (10.4) 19 (10.4) 5 (9.8) 0.873 1 (4.8) 18 (11.1) 0.605 Invasive infection c 124 (67.8) 129 (70.5) 33 (64.7) 0.286 14 (66.7) 115 (71.0) 0.683 Pathogens Methicillin-resistant Staphylococcus aureus 7 (3.8) 5 (3.8) 2 (3.9) 1.000 1 (4.8) 6 (3.7) 1.000 Methicillin-susceptible Staphylococcus aureus 23 (12.6) 18 (13.6) 5 (9.8) 0.483 7 (33.3) 16 (9.9) 0.007 Other Gram-positive bacteria 23 (12.6) 17 (12.9) 6 (11.8) 0.838 4 (19.0) 19 (11.7) 0.547 Concomitant nephrotoxins Diuretics 56 (30.6) 41 (31.1) 15 (29.4) 0.828 8 (37.1) 48 (29.6) 0.428 Acyclovir 10 (5.5) 10 (5.5) 1 (2.0) 0.351 1 (4.8) 9 (5.6) 1.000 Amphotericin B 6 (3.3) 2 (1.5) 4 (7.8) 0.091 1 (4.8) 5 (3.1) 1.000 No. of concomitant nephrotoxins 0 114 (62.2) 82 (62.1) 32 (62.7) 0.938 12 (57.1) 102 (63.0) 0.605 1-2 69 (37.8) 50 (37.9) 19 (37.3) 9 (42.9) 60 (37.0) Concomitant other antibiotics Meropenem 82 (44.8) 63 (47.7) 19 (37.3) 0.202 13 (61.9) 69 (42.6) 0.094 Vancomycin dose, mg/kg a 38.6 ± 5.4 38.7 ± 4.9 38.2 ± 6.6 0.539 39.0 ± 3.0 38.5 ± 5.6 0.694 Vancomycin trough concentration, mg/L a 7.6 ± 5.5 8.4 ± 5.7 5.9 ± 4.4 0.006 17.8 ± 5.3 6.4 ± 3.9 < 0.001 Treatment duration, day a 15.0 (9.0 ~ 21.0) 15.0 (10.0 ~ 21.8) 13.0 (9.0 ~ 20.0) 0.944 14 (8.8 ~ 16.8) 15.0 (10.0 ~ 22.0) 0.319 Statistically significant values are shown in bold. Abbreviations: CNS, central nervous system. a Data are presented as mean ± standard deviation. b Data are presented as median, interquartile range. * Estimated using Schwartz formula. Figure 1 A provides a distribution of vancomycin C min , encompassing both the overall picture and specific concentration groupings. The average vancomycin C min concentration was determined as 7.6 ± 5.5 mg/L. Notably, 74.3% of pediatric patients exhibited vancomycin C min levels below the recommended therapeutic window of 10–20 mg/L. Specifically, 69 patients exhibited a mean vancomycin C min concentration below 5 mg/L, whereas 67 patients had mean C min levels ranging from 5 to 10 mg/L. A mere 25.7% of patients, equating to 47 individuals, attained a C min level exceeding 10 mg/L, while 8 patients demonstrated mean C min concentrations surpassing 20 mg/L. The mean C min concentration in patients who responded successfully to treatment was significantly higher than in those who failed ( P = 0.006). In detail, the mean C min values were 8.4 ± 5.7 mg/L and 5.9 ± 4.4 mg/L, respectively (Fig. 1 B). Among patients with nephrotoxicity, the mean C min concentration was 17.8 ± 5.3 mg/L, significantly exceeding that of patients without nephrotoxicity (6.4 ± 3.9 mg/L, P < 0.001). In this study, the overall success rate of vancomycin therapy was 72.1%, while 11.5% (21 patients) developed nephrotoxicity during treatment. Table 2 compares the variables between treatment success and failure groups, as well as nephrotoxicity and non-nephrotoxicity groups. After adjusting for confounding factors, vancomycin C min alone was associated with clinical outcomes. In the analysis of nephrotoxicity, baseline Scr level, central nervous system infections, presence of MSSA, and vancomycin C min were significantly associated in univariate analysis. However, only vancomycin C min maintained significance in multivariate analysis when considering factors with P < 0.1. Table 2 Multivariate logistic regression analysis of factors influencing the effectiveness and safety of vancomycin. Variable Treatment Outcomes Adverse Effects OR (95% CI) P OR (95% CI) P Age, year - - 1.000 (1.000 ~ 1.001) 0.115 BMI, kg/m 2 0.638 (0.174 ~ 2.331) 0.496 - - Sepsis/severe sepsis/septic shock 0.663 (0.288 ~ 1.524) 0.333 0.401 (0.124 ~ 1.301) 0.128 Baseline creatinine clearance, mL/min * 0.997 (0.993 ~ 1.002) 0.232 - - CNS infection 0.185 (0.227 ~ 1.332) 0.550 0.402 (0.137 ~ 1.177) 0.096 Baseline creatinine, µmol/L - - 0.999 (0.984 ~ 1.014) 0.888 MSSA - - 1.222 (0.322 ~ 4.638) 0.769 Concomitant amphotericin B 5.118 (0.836 ~ 31.314) 0.077 - - Concomitant meropenem - - 0.531 (0.203 ~ 1.389) 0.197 Vancomycin trough concentration, mg/L 1.090 (1.007 ~ 1.179) 0.032 1.320 (1.197 ~ 1.456) < 0.001 Statistically significant values are shown in bold. Abbreviations: OR, odds ratio; CI, confidence interval; BMI, body mass index; CNS, central nervous system; MSSA, methicillin-susceptible Staphylococcus aureus. * Estimated using Schwartz formula. Additional analysis of the receiver operating characteristic (ROC) curve demonstrated that a C min concentration of 5.9 mg/L serves as a predictor for therapeutic effect, exhibiting an area under the curve (AUC) of 0.643, with a sensitivity of 70.1% and a specificity of 64.1% (Fig. 2 A). A C min level of 14.8 mg/L effectively anticipated the emergence of nephrotoxicity, displaying an AUC of 0.960, accompanied by a sensitivity of 95.2% and a specificity of 85.0% (Fig. 2 B). Taking into account the temporal influence on nephrotoxicity risk, patients were stratified into two groups based on their C min levels (< 14.8 and ≥ 14.8 mg/L) for subsequent Kaplan-Meier survival analysis. As depicted in Fig. 3 , a significant difference in the incidence of nephrotoxicity was observed between the two groups over the course of vancomycin treatment. 4. Discussion Vancomycin has been clinically utilized for more than 60 years, yet the precise therapeutic window for pediatric patients remains elusive. CL serves as a crucial PK parameter, exerting a significant influence on drug exposure levels. Nevertheless, the vancomycin CL in pediatric patients is typically much faster compared to adults, approximately 2.5 times greater [11, 15]. Limited available data indicate that the vancomycin CL in Chinese pediatric patients ranges from 0.11 to 0.17 L/h·kg, which is notably higher than that observed in adults[5, 16]. This may be attributed to physiological characteristics in pediatric patients, such as higher water content and renal clearance, which influence PK parameters and subsequently lead to lower drug concentration attainment rates. Therefore, acknowledging the PK disparities between pediatric and adult populations, this study reassessed the therapeutic window of vancomycin in pediatric patients and advocated for adjusting it to a range of 5.9–14.8 mg/L, which is similar to the findings reported previously by our research team [4]. According to the latest international guidelines, monitoring the AUC 24 /MIC for vancomycin is recommended, with a target range of 400–600 [2]. Nevertheless, the practicality of monitoring AUC 24 /MIC in clinical settings is limited due to various factors, including the necessity for secondary sampling, the scarcity of specialized personnel, and the ambiguity surrounding PK/PD standards for pediatric patients [17]. Consequently, monitoring C min remains a widely adopted practice, even in most large tertiary medical institutions, emphasizing the crucial importance of further exploring the rational use of vancomycin through C min monitoring [18]. Owing to the lack of clinical data, the reference range for target concentrations of vancomycin in special populations, including children, has historically aligned with that established for adults. When administered standard dosing regimens, only 28.9% of pediatric patients attain a vancomycin C min within the range of 10–20 mg/L, while a mere 6.9% achieve a C min of 15–20 mg/L [19]. Consistent with our findings, Tatjana et al. observed a mere 24% achievement rate of C min in pediatric patients during TDM [20]. Data indicate that pediatric patients with normal renal function need 70 mg/kg·d to attain a target C min of 10 mg/L, while younger patients aged 1–6 years may require 80–85 mg/kg·d to achieve a target C min ranging from 15–20 mg/L [21, 22]. To investigate the reasons for the low vancomycin blood concentration attainment rate in pediatric patients, we assess the appropriateness of extrapolating the therapeutic window from adults to the pediatric population. Our findings reveal that satisfactory clinical outcomes could be attained in pediatric patients when C min exceeds 5.9 mg/L, which aligns with the lower limit of the initial vancomycin therapeutic window [6]. A recent meta-analysis suggests that a vancomycin C min ranging from 10–15 mg/L in pediatric patients is associated with clinical efficacy, and exceeding 15 mg/L is not necessary [23]. The Chinese guidelines for TDM of vancomycin (2020) also recommend maintaining a vancomycin C min of 5–15 mg/L for pediatric patients. However, this recommendation is solely based on a retrospective study with a limited sample size of 100 cases [24]. By employing a nearly doubled sample size, we achieved comparable outcomes, thus providing robust evidence to support the recommended scope outlined in the guidelines. The IDSA published vancomycin TDM guidelines from 2009 to 2011, consecutively for three years, advocating a monitoring threshold of 10 mg/L to mitigate drug resistance. However, despite the persistent and significant shortfall in achieving the target C min , no change in the resistance of MRSA isolates to vancomycin has been noted [25, 26]. Over a four-year period, Faiqa et al. gathered 352 MRSA isolates and discovered no alterations in MIC 50 or MIC 90 values. [27]. Another study examining the MIC changes of 736 MRSA isolates against vancomycin revealed that all MIC values were below 2 mg/L, with the majority falling below 1 mg/L [28]. Wang et al. also conducted an analysis of 879 MRSA isolates collected from pediatric patients with bloodstream infections in China over a four-year period (2015–2018) and reported no vancomycin-resistant strains [29]. Additionally, our institution also conducted a statistical analysis spanning from 2013 to 2019, focusing on the MIC changes of MRSA isolates against vancomycin. The proportion of MRSA strains with MIC of 1 mg/L exhibited a steady decline, decreasing from 81% in 2013 to 30% in 2024. Conversely, the proportion of MRSA strains with MIC of ≤ 0.5 mg/L increased from 19% in 2013 to 70% during the same period. No vancomycin-resistant MRSA strains have been detected. Actually, since the establishment of the China Antimicrobial Resistance Surveillance Network in 2005, domestic drug resistance surveillance data indicate no reported cases of vancomycin-resistant MRSA strains. The findings from these studies suggest that while vancomycin TDM guidelines recommend specific monitoring thresholds to prevent drug resistance, the actual resistance patterns of MRSA isolates to vancomycin may not be as straightforward as initially anticipated. In other words, vancomycin has maintained a consistently low exposure level in pediatric patients for decades, without causing any significant shifts in the MIC of MRSA against vancomycin. Certainly, it is crucial to continue monitoring and evaluating these isolates to gain a deeper understanding of their resistance patterns and to ensure effective treatment strategies. A high concentration of vancomycin C min is strongly associated with the occurrence of nephrotoxicity [3]. Our findings indicate a significant increase in the risk of AKI in pediatric patients when vancomycin C min exceeds 14.8 mg/L. A large retrospective study of 859 pediatric patients found a significant association between vancomycin C min concentrations exceeding 15 mg/L and AKI (odds ratio, 2.18; 95% confidence interval, 1.21–3.92), corroborating our own observations [30]. Furthermore, a recent meta-analysis encompassing eight pediatric studies revealed that vancomycin C min concentrations exceeding 15 mg/L could elevate the risk of nephrotoxicity by a factor of 2.7 [23]. These findings highlight the need for careful monitoring of vancomycin levels in pediatric patients to mitigate the risk of nephrotoxicity. Clinicians prioritize the potential adverse effects of vancomycin over therapeutic outcomes, making it challenging to justify aiming for high-level vancomycin C min levels in pediatric patients, especially when high concentrations lack clear clinical benefits. Notably, children with sepsis frequently have a history of multiple hospitalizations and underlying diseases, potentially increasing AKI risk. This study is not without limitations. First, our study solely established a correlation between C min and AKI risk, and our assessment focused solely on the concurrent use of nephrotoxic drugs, neglecting the effects of pretreatment medications prior to hospitalization and the cumulative effects of other nephrotoxic agents. It is imperative to point out that children with sepsis frequently have a history of multiple hospitalizations and underlying diseases, and obese children might receive higher dosing regimen based on actual weight, potentially increasing AKI risk. Second, measuring the free concentration of vancomycin holds greater significance than measuring the total concentration, particularly in neonatal and pediatric intensive care units[31]. However, there remains a lack of consensus regarding the optimal concentration range of free vancomycin, necessitating further exploration in future research. Last but not least, the absence of microbial culture results for most patients precluded the comprehensive analysis of microbial susceptibility in the final analysis. In fact, given the low proportion of positive cultures, the clinical application of vancomycin is primarily empirical. Considering acceptable therapeutic outcomes of vancomycin and the concordance of previous reports with our findings, we maintain that our study holds significant guiding value, to a certain extent. Although there are limited evidences supporting specific vancomycin therapeutic windows for pediatric patients, further research with larger sample sizes and more robust methodologies is still needed to establish more definitive therapeutic windows for this vulnerable population. 5. Conclusion Based on the correlation between vancomycin C min and both clinical effectiveness and safety, a therapeutic window of 5.9–14.8 mg/L for vancomycin in pediatric patients is proposed, aiming to facilitate its rational use within this specific population. Abbreviations MRSA Methicillin-resistant Staphylococcus aureus Cmin Mean trough concentration AUC 24 /MIC The ratio of the 24 h area under the concentration-time curve and minimally inhibitory concentration PK/PD Pharmacokinetics/pharmacodynamics TDM Therapeutic drug monitoring CL Clearance Scr Serum creatinine AKI Acute kidney injury ICU Intensive care unit MSSA Methicillin-susceptible Staphylococcus aureus Declarations Acknowledgements The authors would like to acknowledge Zhenyu Pan, Yuan Li, Ziyun Duan and Jie Mi for their attribution in samples collecting and useful insights to the results. Author Contributions Conceived and designed the protocol: Yalin Dong, Tao Zhang. Determination of samples: Xinyan Han, Yan Wang, Jiao Xie, Qianting Yang, Sasa Hu. Statistical analyses: Hua Cheng, Tao Zhang. Drafting manuscript: Yalin Dong, Jingjing Yi, Tao Zhang. All authors contributed to the interpretation of data and critical revisions of the manuscript for important intellectual content. Tao Zhang had final responsibility for the decision to submit for publication. Funding This work is supported by the National Science Fund for Distinguished Young Scholars (82404762). Data Availability Statement The datasets used and analysed during the current study are available from the corresponding author on reasonable request. Consent for publication Not applicable. Competing Interests The authors declare that they have no competing interests. Ethical Approval Statement and Consent to Participate The ethics has been approved by the Ethic Committee of Stomatology College Affiliated to Xi'an Jiaotong University (2024-XJKQIEC-KY-QT-0050-001). Informed consent for the use of routinely collected data has been waived according to local requirements. All associated procedures were conducted in accordance with the approved guidelines. 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Scully PT, Lam WM, Coronado Munoz AJ, et al. Augmented Renal Clearance of Vancomycin in Suspected Sepsis: Single-Center, Retrospective Pediatric Cohort. Pediatr Crit Care Med. 2022;23(6):444 − 52. Rasmussen M. Aerococcus: an increasingly acknowledged human pathogen. Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases. 2016;22(1):22 − 7. Zhang T, Cheng H, Li Y, et al. Paediatric acute kidney injury induced by vancomycin monotherapy versus combined vancomycin and meropenem. J Clin Pharm Ther. 2019;44(3):440-6. Cao L, Li Z, Zhang P, et al. Relationship between Vancomycin Trough Serum Concentrations and Clinical Outcomes in Children: a Systematic Review and Meta-Analysis. Antimicrob Agents Chemother. 2022;66(8):e0013822. Shen X, Li X, Lu J, et al. Population pharmacokinetic analysis for dose regimen optimization of vancomycin in Southern Chinese children. CPT: pharmacometrics & systems pharmacology. 2024;13(7):1201-13. Shen K, Fan Y, Yang M, et al. Modeling Approach to Optimizing Dose Regimen of Vancomycin for Chinese Pediatric Patients with Gram-Positive Bacterial Infections. Front Pharmacol. 2021;12:648668. Alrahahleh D, Xu S, Luig M, et al. Dosing of vancomycin and target attainment in neonates: a systematic review. International journal of antimicrobial agents. 2022;59(2):106515. Geerlof LM, Boucher J. Evaluation of vancomycin dosing and corresponding drug concentrations in pediatric patients. Hospital pediatrics. 2014;4(6):342-7. Van Der Heggen T, Buyle FM, Claus B, et al. Vancomycin dosing and therapeutic drug monitoring practices: guidelines versus real-life. Int J Clin Pharm. 2021;43(5):1394 − 403. Durham SH, Simmons ML, Mulherin DW, et al. An evaluation of vancomycin dosing for complicated infections in pediatric patients. Hospital pediatrics. 2015;5(5):276 − 81. Eiland LS, English TM, Eiland EH, 3rd. Assessment of vancomycin dosing and subsequent serum concentrations in pediatric patients. The Annals of pharmacotherapy. 2011;45(5):582-9. Fiorito TM, Luther MK, Dennehy PH, et al. Nephrotoxicity With Vancomycin in the Pediatric Population: A Systematic Review and Meta-Analysis. Pediatr Infect Dis J. 2018;37(7):654 − 61. He N, Su S, Ye Z, et al. Evidence-based Guideline for Therapeutic Drug Monitoring of Vancomycin: 2020 Update by the Division of Therapeutic Drug Monitoring, Chinese Pharmacological Society. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2020;71(Suppl 4):S363-S71. Fu P, Xu H, Jing C, et al. Bacterial Epidemiology and Antimicrobial Resistance Profiles in Children Reported by the ISPED Program in China, 2016 to 2020. Microbiology spectrum. 2021;9(3):e0028321. La Vecchia A, Ippolito G, Taccani V, et al. Epidemiology and antimicrobial susceptibility of Staphylococcus aureus in children in a tertiary care pediatric hospital in Milan, Italy, 2017–2021. Ital J Pediatr. 2022;48(1):67. Arshad F, Saleem S, Jahan S, et al. Assessment of Vancomycin MIC Creep Phenomenon in Methicillin-Resistant Staphylococcus aureus isolates in a Tertiary Care Hospital of Lahore. Pakistan journal of medical sciences. 2020;36(7):1505-10. Aljohani S, Layqah L, Masuadi E, et al. Occurrence of vancomycin MIC creep in methicillin resistant isolates in Saudi Arabia. Journal of infection and public health. 2020;13(10):1576-9. Wang C, Hao W, Yu R, et al. Analysis of Pathogen Distribution and Its Antimicrobial Resistance in Bloodstream Infections in Hospitalized Children in East China, 2015–2018. Journal of tropical pediatrics. 2021;67(1). Knoderer CA, Nichols KR, Lyon KC, et al. Are Elevated Vancomycin Serum Trough Concentrations Achieved Within the First 7 Days of Therapy Associated With Acute Kidney Injury in Children? Journal of the Pediatric Infectious Diseases Society. 2014;3(2):127 − 31. Resztak M, Sobiak J, Czyrski A. Recent Advances in Therapeutic Drug Monitoring of Voriconazole, Mycophenolic Acid, and Vancomycin: A Literature Review of Pediatric Studies. Pharmaceutics. 2021;13(12). Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 18 Nov, 2025 Read the published version in BMC Pharmacology and Toxicology → Version 1 posted Editorial decision: Revision requested 27 Aug, 2025 Reviews received at journal 25 Aug, 2025 Reviews received at journal 20 Aug, 2025 Reviewers agreed at journal 16 Aug, 2025 Reviewers agreed at journal 16 Aug, 2025 Reviewers agreed at journal 15 Aug, 2025 Reviews received at journal 07 Aug, 2025 Reviewers agreed at journal 28 Jul, 2025 Reviewers agreed at journal 27 Jul, 2025 Reviewers invited by journal 25 Jul, 2025 Editor invited by journal 23 Jul, 2025 Editor assigned by journal 15 Jul, 2025 Submission checks completed at journal 15 Jul, 2025 First submitted to journal 05 Jul, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7050678","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":491606065,"identity":"2205b8e6-d676-4515-991e-1e208e234554","order_by":0,"name":"Tao Zhang","email":"","orcid":"","institution":"Key laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi’an Jiaotong University","correspondingAuthor":false,"prefix":"","firstName":"Tao","middleName":"","lastName":"Zhang","suffix":""},{"id":491606067,"identity":"7b842018-1130-4a17-9e34-c25f8ee2f358","order_by":1,"name":"Jingjing Yi","email":"","orcid":"","institution":"the Third Affiliated Hospital of Xi’an Medical University","correspondingAuthor":false,"prefix":"","firstName":"Jingjing","middleName":"","lastName":"Yi","suffix":""},{"id":491606070,"identity":"f108a196-755f-407d-bd4d-2f72f733c820","order_by":2,"name":"Hua Cheng","email":"","orcid":"","institution":"the Affiliated Children Hospital of Xi’an Jiaotong University","correspondingAuthor":false,"prefix":"","firstName":"Hua","middleName":"","lastName":"Cheng","suffix":""},{"id":491606073,"identity":"f664aa2a-f122-46bb-9ea4-9e02ca67bc66","order_by":3,"name":"Xinyan Han","email":"","orcid":"","institution":"Key laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi’an Jiaotong University","correspondingAuthor":false,"prefix":"","firstName":"Xinyan","middleName":"","lastName":"Han","suffix":""},{"id":491606076,"identity":"a7eb51f0-d3d0-4d7f-bb0a-031df7415571","order_by":4,"name":"Yan Wang","email":"","orcid":"","institution":"the Second Affiliated Hospital of Xi’an Jiaotong University","correspondingAuthor":false,"prefix":"","firstName":"Yan","middleName":"","lastName":"Wang","suffix":""},{"id":491606079,"identity":"9f9f6357-db35-4f66-9e88-ad437e378cba","order_by":5,"name":"Jiao Xie","email":"","orcid":"","institution":"the Second Affiliated Hospital of Xi’an Jiaotong University","correspondingAuthor":false,"prefix":"","firstName":"Jiao","middleName":"","lastName":"Xie","suffix":""},{"id":491606081,"identity":"18f53ba3-9c45-4a10-8869-a5d2d1e83ce4","order_by":6,"name":"Qianting Yang","email":"","orcid":"","institution":"the Second Affiliated Hospital of Xi’an Jiaotong University","correspondingAuthor":false,"prefix":"","firstName":"Qianting","middleName":"","lastName":"Yang","suffix":""},{"id":491606083,"identity":"7a9d2251-fdfb-47dc-9096-f0940a6c344c","order_by":7,"name":"Sasa Hu","email":"","orcid":"","institution":"the First Affiliated Hospital of Xi’an Jiaotong University","correspondingAuthor":false,"prefix":"","firstName":"Sasa","middleName":"","lastName":"Hu","suffix":""},{"id":491606085,"identity":"cda2b991-6e8f-40a0-a618-0e48378ffb88","order_by":8,"name":"Yalin Dong","email":"data:image/png;base64,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","orcid":"","institution":"the First Affiliated Hospital of Xi’an Jiaotong University","correspondingAuthor":true,"prefix":"","firstName":"Yalin","middleName":"","lastName":"Dong","suffix":""}],"badges":[],"createdAt":"2025-07-05 05:38:09","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7050678/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7050678/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s40360-025-01035-6","type":"published","date":"2025-11-18T15:58:06+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":87882189,"identity":"fe170087-0db6-4a50-9f44-42d691b04baa","added_by":"auto","created_at":"2025-07-30 04:28:29","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":346481,"visible":true,"origin":"","legend":"\u003cp\u003eA. Distribution of vancomycin \u003cem\u003eC\u003c/em\u003e\u003csub\u003e\u003cem\u003emin\u003c/em\u003e\u003c/sub\u003e among overall and varying concentration subgroups (n = 183, 69, 67, 28, 11, 8); B. Distribution of vancomycin \u003cem\u003eC\u003c/em\u003e\u003csub\u003e\u003cem\u003emin\u003c/em\u003e\u003c/sub\u003e among children with successful treatment, treatment failure, nephrotoxicity, and no nephrotoxicity (n = 132, 51, 21, 162，**\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.01, ***\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.001)\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7050678/v1/b69f839212c1c9f316ae85a5.jpeg"},{"id":87882193,"identity":"25b861da-623c-4678-a0c1-0fc248b62e9b","added_by":"auto","created_at":"2025-07-30 04:28:29","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":387386,"visible":true,"origin":"","legend":"\u003cp\u003eROC curves for predicting therapeutic efficacy and nephrotoxicity using vancomycin \u003cem\u003eC\u003c/em\u003e\u003csub\u003e\u003cem\u003emin\u003c/em\u003e\u003c/sub\u003e\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7050678/v1/f34fafbafbc383c8bf312085.jpeg"},{"id":87882346,"identity":"264999cc-9683-49a6-843b-3f492bbf5bf9","added_by":"auto","created_at":"2025-07-30 04:36:29","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":281333,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier survival curve illustrating the impact of vancomycin \u003cem\u003eC\u003c/em\u003e\u003csub\u003e\u003cem\u003emin\u003c/em\u003e\u003c/sub\u003e on nephrotoxicity\u003c/p\u003e","description":"","filename":"floatimage3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7050678/v1/ebd754aa1fc6b701eaea5bd4.jpeg"},{"id":96650324,"identity":"9bdd839a-4c5c-4938-822b-08da8de5d3e9","added_by":"auto","created_at":"2025-11-24 16:11:08","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2189313,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7050678/v1/0f985b84-facc-406a-8a04-9b117d543d17.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Therapeutic Drug Monitoring of Vancomycin in Pediatric Patients: A Retrospective Study","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eVancomycin, a water-soluble glycopeptide antibacterial agent, has been approved for treating G\u003csup\u003e+\u003c/sup\u003e bacterial infections in both adults and children. Although drugs like clindamycin, tetracycline, and trimethoprim-sulfamethoxazole are also utilized in infections by methicillin-resistant \u003cem\u003eStaphylococcus aureus\u003c/em\u003e (MRSA), vancomycin remains the preferred choice, which has significant cost contribution among antibacterial drugs prescribed to children [1].\u003c/p\u003e\u003cp\u003eVancomycin exhibits a narrow therapeutic index and significant inter-individual variations among individuals. The American Society of Health-System Pharmacists, Infectious Diseases Society of America (IDSA), and Society of Infectious Diseases Pharmacists advocate for monitoring the ratio of the 24 h area under the concentration-time curve and minimally inhibitory concentration (\u003cem\u003eAUC\u003c/em\u003e\u003csub\u003e\u003cem\u003e24\u003c/em\u003e\u003c/sub\u003e\u003cem\u003e/MIC\u003c/em\u003e) of vancomycin, aiming for a target value within the range of 400\u0026ndash;600 mg\u0026middot;h/L [1, 2]. However, monitoring vancomycin through pharmacokinetics/pharmacodynamics (PK/PD) exists significant challenges in clinical practice. A survey reveals that 93% of healthcare institutions still select trough concentration (\u003cem\u003eC\u003c/em\u003e\u003csub\u003e\u003cem\u003emin\u003c/em\u003e\u003c/sub\u003e) as the primary indicator in therapeutic drug monitoring (TDM).\u003c/p\u003e\u003cp\u003eThe generally recommended vancomycin \u003cem\u003eC\u003c/em\u003e\u003csub\u003e\u003cem\u003emin\u003c/em\u003e\u003c/sub\u003e range is 10\u0026ndash;20 mg/L, with a narrower range of 10\u0026ndash;15 mg/L for uncomplicated infections and 15\u0026ndash;20 mg/L for severe infections, including endocarditis, meningitis, osteomyelitis, pneumonia, and septicemia [3]. Despite insufficient evidence, IDSA extrapolates the target ranges from adult patients to the pediatric population. Our research group has discovered that vancomycin \u003cem\u003eC\u003c/em\u003e\u003csub\u003e\u003cem\u003emin\u003c/em\u003e\u003c/sub\u003e exhibits a strong correlation with PK/PD target [4], which was consistent with reported evidence [5]. Specifically, achieving a \u003cem\u003eC\u003c/em\u003e\u003csub\u003e\u003cem\u003emin\u003c/em\u003e\u003c/sub\u003e within the ranges of 5.0-6.9 mg/L or 9.0-12.9 mg/L could meet the PK/PD target, depending on the MIC. In fact, the initial vancomycin \u003cem\u003eC\u003c/em\u003e\u003csub\u003e\u003cem\u003emin\u003c/em\u003e\u003c/sub\u003e target range for most infections in pediatric patients was 5\u0026ndash;10 mg/L, while for central nervous system infections, it was 10\u0026ndash;15 mg/L [6]. The IDSA guidelines in 2011 advocated a higher \u003cem\u003eC\u003c/em\u003e\u003csub\u003e\u003cem\u003emin\u003c/em\u003e\u003c/sub\u003e range, but the product insert did not introduce any new recommendations for the standard vancomycin dosing regimen accordingly [7]. Recent studies have revealed that with the current dosing of vancomycin, the rate of achieving the desired \u003cem\u003eC\u003c/em\u003e\u003csub\u003e\u003cem\u003emin\u003c/em\u003e\u003c/sub\u003e in pediatric patients is unexpectedly low when using 10\u0026ndash;15 mg/L as the standard for effective therapeutic concentration, approximately 80%-90%[8].\u003c/p\u003e\u003cp\u003eFrankly, the IDSA recommended a vancomycin dosing of 60 mg/kg\u0026middot;d (15 mg/kg, q6 h) for pediatric patients with severe invasive MRSA infections. Nevertheless, several studies have indicated that even with higher dosing, it may still be inadequate to attain the desired \u003cem\u003eC\u003c/em\u003e\u003csub\u003e\u003cem\u003emin\u003c/em\u003e\u003c/sub\u003e [9]. Even when the target concentration is adjusted to 5\u0026ndash;15 mg/L, the achievement rate rises to only 51% [10]. Surprisingly, a study reported a \u003cem\u003eC\u003c/em\u003e\u003csub\u003e\u003cem\u003emin\u003c/em\u003e\u003c/sub\u003e achievement rate of just 4% despite the included pediatric patients receiving the recommended vancomycin dose of 40\u0026ndash;60 mg/kg/day [11].\u003c/p\u003e\u003cp\u003eThe clearance (CL) and volume of distribution of vancomycin vary significantly in pediatric patients compared to adults, rendering it particularly difficult to attain and sustain vancomycin concentrations within the desired range for pediatrics. This challenge is further exacerbated in patients with underlying conditions, such as congenital heart disease, renal impairment, sepsis, and those undergoing fluid resuscitation [12]. A number of studies have demonstrated that standard dosing regimens often fall short of achieving the current target concentration range, indicating that applying adult concentration ranges to pediatric patients directly may not be appropriate[8].\u003c/p\u003e\u003cp\u003eThe aim of this study is to establish the therapeutic window of vancomycin specifically for pediatric patients, minimizing the risk of treatment failure due to insufficient exposure or toxicity. A preprint has previously been published [13].\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003e2.1 Patient information and collection of clinical blood samples\u003c/h2\u003e\u003cp\u003eThis study retrospectively collected hospitalized pediatric patients from two hospitals: the First Affiliated Hospital of Xi'an Jiaotong University and the Affiliated Children's Hospital of Xi'an Jiaotong University. The period spanned from January 2017 to December 2018.\u003c/p\u003e\u003cp\u003eInclusion criteria for the study comprised of: ① hospitalized patients aged 1 month to 18 years; ② those diagnosed or suspected with G\u003csup\u003e+\u003c/sup\u003e bacterial infection and receiving vancomycin treatment; and ③ patients able to provide at least one TDM data point. The following patients were excluded from the study: ① those receiving vancomycin through non-intravenous routes; ② patients allergic to vancomycin; ③ and patients who died within 24 hours of vancomycin administration.\u003c/p\u003e\u003cp\u003eDemographic data, medication details, and physiological and biochemical indicators (including age, gender, weight, serum creatinine [Scr], vancomycin dosing regimen, dosage, medication dates, and indications) were retrieved from the hospital's electronic medical record system. Blood concentration data of vancomycin in patients was collected from those undergoing routine TDM (samples taken 30 minutes prior to the next dose after reaching a steady state). The blood concentration of vancomycin was determined using the previously established HPLC-MS/MS method by our research team [14].\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\u003ch2\u003e2.2 Therapeutic window of vancomycin in pediatric patients\u003c/h2\u003e\u003cp\u003eA univariate logistic regression analysis was conducted to investigate the correlation between various factors and both clinical outcomes and adverse reactions. Subsequently, factors exhibiting a \u003cem\u003eP\u003c/em\u003e value less than 0.1 in the univariate analysis were subjected to multivariate logistic analysis to further identify factors potentially linked to clinical efficacy and adverse reactions\u003c/p\u003e\u003cp\u003eClinical outcomes were categorized into a four-level scale encompassing cured, improved, ineffective, and relapsed. For simplicity, cured and improved outcomes were jointly classified as treatment success, whereas ineffective and relapsed outcomes were grouped under treatment failure. The assessment of adverse reactions involved measuring Scr levels from the initiation of medication to 72 h post-medication. Acute kidney injury (AKI) was defined as either an elevation of Scr to 1.5 times the baseline level or a rise by 26.5 \u0026micro;mol/L. The therapeutic window refers to the spectrum of drug concentration levels that exhibit a significant correlation with clinical outcomes and the incidence of adverse reactions.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003e2.3 Statistics and analysis\u003c/h2\u003e\u003cp\u003eContinuous variables were described using mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation for normally distributed data and median for non-normal distributions. Categorical variables were characterized by frequencies and percentages. All statistical tests were two-sided with a significance level of α set at 0.05, and all analyses were conducted using SPSS (Version 19.0).\u003c/p\u003e\u003c/div\u003e"},{"header":"3. Results","content":"\u003cp\u003eA total of 183 pediatric patients were included in this study and provided at least one vancomycin \u003cem\u003eC\u003c/em\u003e\u003csub\u003e\u003cem\u003emin\u003c/em\u003e\u003c/sub\u003e sample. A comprehensive monitoring of 330 blood drug concentrations was undertaken. Boys comprised the majority, constituting 61.2% of the total patients. The mean age of the pediatric patients was 3.4 years, with a mean weight of 15.0 kg. Acute lymphoblastic leukemia emerged as the most prevalent underlying condition, representing 15.9% of the total cases. Furthermore, 24% of the patients were admitted to the intensive care unit (ICU). Of the indications for antimicrobial therapy, 67.8% were attributed to invasive infections, encompassing pneumonia, endocarditis, as well as bone and joint infections. Subsequently, central nervous system infections comprised 29.0% of the total cases. Only 53 patients had available pathogen culture results, which revealed the presence of 23 methicillin-susceptible \u003cem\u003eStaphylococcus aureus\u003c/em\u003e (MSSA) and 7 MRSA strains. While undergoing vancomycin therapy, 37% of patients received at least one nephrotoxic drug. Diuretics were the most commonly prescribed nephrotoxic drugs, representing 30.6% of the total administered. Additionally, 45% of patients received concurrent therapy with meropenem, as part of their antimicrobial regimen. Baseline Scr levels were measured at 28.2\u0026thinsp;\u0026plusmn;\u0026thinsp;19.0 \u0026micro;mol/L, whereas creatinine clearance was calculated as 134.3\u0026thinsp;\u0026plusmn;\u0026thinsp;81.4 mL/min. A comprehensive overview of demographic and other information are presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003ePatient demographics, clinical characteristics and vancomycin dose.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"9\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eVariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eAll Patients\u003c/p\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;183 (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e\u003cp\u003eTreatment Outcomes\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c9\" namest=\"c7\"\u003e\u003cp\u003eAdverse Effects\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTreatment Success\u003c/p\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;132 (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTreatment Failure or Death\u003c/p\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;51 (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNephrotoxicity\u003c/p\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;21 (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003eNo Nephrotoxicity\u003c/p\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;162 (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGender, male\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e112 (61.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e84 (63.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e28 (54.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.277\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e14 (66.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e98 (60.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.474\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge, year \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e3.4\u0026thinsp;\u0026plusmn;\u0026thinsp;3.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e3.3\u0026thinsp;\u0026plusmn;\u0026thinsp;3.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3.6\u0026thinsp;\u0026plusmn;\u0026thinsp;3.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.707\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e4.7\u0026thinsp;\u0026plusmn;\u0026thinsp;3.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e3.2\u0026thinsp;\u0026plusmn;\u0026thinsp;3.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.074\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eweight, kg \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e15.0\u0026thinsp;\u0026plusmn;\u0026thinsp;9.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e14.1\u0026thinsp;\u0026plusmn;\u0026thinsp;9.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e16.4\u0026thinsp;\u0026plusmn;\u0026thinsp;8.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.213\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e14.1 (10.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e15.1 (9.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.671\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBody mass index, kg/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.067\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e0.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.595\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eComorbid conditions\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAcute lymphoblastic leukemia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e29 (15.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e21 (15.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e8 (15.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.970\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e6 (28.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e23 (14.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.168\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOther malignant solid tumor\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e9 (4.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e8 (6.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1 (2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.442\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e9 (5.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLiver disease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e20 (10.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e14 (10.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6 (11.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.822\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e20 (12.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAnemia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e22 (12.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e16 (12.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6 (11.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.947\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1 (4.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e21 (13.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.465\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSepsis/severe sepsis/septic shock\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e54 (29.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e54 (29.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e10 (19.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.068\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e10 (47.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e44 (27.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.053\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIntensive care unit stay \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e44 (24.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e30 (22.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e14 (27.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.503\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e7 (33.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e37 (22.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.290\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMechanical ventilation \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e40 (21.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e27 (20.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e13 (25.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.460\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e7 (33.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e33 (20.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.284\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMedian white blood cell count, \u0026times;10\u003csup\u003e9 b\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e10.8 (5.9\u0026thinsp;~\u0026thinsp;16.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e10.9 (6.5\u0026thinsp;~\u0026thinsp;16.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e10.8 (4.0\u0026thinsp;~\u0026thinsp;15.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.978\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e11.5 (2.9\u0026thinsp;~\u0026thinsp;14.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e10.8 (6.3\u0026thinsp;~\u0026thinsp;16.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.354\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBlood urea nitrogen, mmol/L\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e4.1\u0026thinsp;\u0026plusmn;\u0026thinsp;4.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e4.2\u0026thinsp;\u0026plusmn;\u0026thinsp;4.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4.0\u0026thinsp;\u0026plusmn;\u0026thinsp;3.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.742\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e5.3\u0026thinsp;\u0026plusmn;\u0026thinsp;5.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e3.9\u0026thinsp;\u0026plusmn;\u0026thinsp;3.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.103\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBaseline creatinine, \u0026micro;mol/L\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e28.2\u0026thinsp;\u0026plusmn;\u0026thinsp;19.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e28.9\u0026thinsp;\u0026plusmn;\u0026thinsp;21.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e26.5\u0026thinsp;\u0026plusmn;\u0026thinsp;10.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.463\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e36.4\u0026thinsp;\u0026plusmn;\u0026thinsp;37.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e27.1\u0026thinsp;\u0026plusmn;\u0026thinsp;14.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e\u003cb\u003e0.036\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBaseline creatinine clearance, mL/min\u003csup\u003ea*\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e134.3\u0026thinsp;\u0026plusmn;\u0026thinsp;81.36\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e126.3\u0026thinsp;\u0026plusmn;\u0026thinsp;55.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e154.9\u0026thinsp;\u0026plusmn;\u0026thinsp;124.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e0.033\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e124.5\u0026thinsp;\u0026plusmn;\u0026thinsp;76.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e135.6\u0026thinsp;\u0026plusmn;\u0026thinsp;82.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.561\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInfection type and diagnosis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSkin/soft tissue infection\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e16 (8.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e16 (8.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3 (5.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.576\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1 (4.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e15 (9.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.783\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBone/joint infection\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e23 (12.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e23 (12.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6 (11.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.838\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1 (4.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e22 (13.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.425\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBacteremia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e34 (18.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e34 (18.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e9 (17.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.840\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e5 (23.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e29 (17.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.721\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCNS infection\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e53 (29.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e53 (29.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e9 (17.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e0.036\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e11 (52.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e42 (25.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e\u003cb\u003e0.012\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOther/unknown\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e19 (10.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e19 (10.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5 (9.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.873\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1 (4.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e18 (11.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.605\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInvasive infection \u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e124 (67.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e129 (70.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e33 (64.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.286\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e14 (66.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e115 (71.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.683\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePathogens\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMethicillin-resistant \u003cem\u003eStaphylococcus aureus\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e7 (3.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e5 (3.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2 (3.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.000\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1 (4.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e6 (3.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e1.000\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMethicillin-susceptible \u003cem\u003eStaphylococcus aureus\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e23 (12.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e18 (13.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5 (9.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.483\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e7 (33.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e16 (9.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e\u003cb\u003e0.007\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOther Gram-positive bacteria\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e23 (12.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e17 (12.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6 (11.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.838\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e4 (19.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e19 (11.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.547\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eConcomitant nephrotoxins\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiuretics\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e56 (30.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e41 (31.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e15 (29.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.828\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e8 (37.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e48 (29.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.428\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAcyclovir\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e10 (5.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e10 (5.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1 (2.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.351\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1 (4.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e9 (5.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e1.000\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAmphotericin B\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e6 (3.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2 (1.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4 (7.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.091\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1 (4.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e5 (3.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e1.000\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo. of concomitant nephrotoxins\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e114 (62.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e82 (62.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e32 (62.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.938\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e12 (57.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e102 (63.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.605\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e1-2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e69 (37.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e50 (37.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e19 (37.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e9 (42.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e60 (37.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eConcomitant other antibiotics\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMeropenem\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e82 (44.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e63 (47.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e19 (37.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.202\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e13 (61.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e69 (42.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.094\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVancomycin dose, mg/kg \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e38.6\u0026thinsp;\u0026plusmn;\u0026thinsp;5.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e38.7\u0026thinsp;\u0026plusmn;\u0026thinsp;4.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e38.2\u0026thinsp;\u0026plusmn;\u0026thinsp;6.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.539\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e39.0\u0026thinsp;\u0026plusmn;\u0026thinsp;3.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e38.5\u0026thinsp;\u0026plusmn;\u0026thinsp;5.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.694\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVancomycin trough concentration, mg/L \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e7.6\u0026thinsp;\u0026plusmn;\u0026thinsp;5.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e8.4\u0026thinsp;\u0026plusmn;\u0026thinsp;5.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5.9\u0026thinsp;\u0026plusmn;\u0026thinsp;4.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e0.006\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e17.8\u0026thinsp;\u0026plusmn;\u0026thinsp;5.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e6.4\u0026thinsp;\u0026plusmn;\u0026thinsp;3.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTreatment duration, day \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e15.0 (9.0\u0026thinsp;~\u0026thinsp;21.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e15.0 (10.0\u0026thinsp;~\u0026thinsp;21.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e13.0 (9.0\u0026thinsp;~\u0026thinsp;20.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.944\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e14 (8.8\u0026thinsp;~\u0026thinsp;16.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e15.0 (10.0\u0026thinsp;~\u0026thinsp;22.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.319\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"9\"\u003eStatistically significant values are shown in bold.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"9\"\u003eAbbreviations: CNS, central nervous system.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"9\"\u003e\u003csup\u003ea\u003c/sup\u003e Data are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"9\"\u003e\u003csup\u003eb\u003c/sup\u003e Data are presented as median, interquartile range.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"9\"\u003e\u003csup\u003e*\u003c/sup\u003eEstimated using Schwartz formula.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eFigure \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA provides a distribution of vancomycin \u003cem\u003eC\u003c/em\u003e\u003csub\u003e\u003cem\u003emin\u003c/em\u003e\u003c/sub\u003e, encompassing both the overall picture and specific concentration groupings. The average vancomycin \u003cem\u003eC\u003c/em\u003e\u003csub\u003e\u003cem\u003emin\u003c/em\u003e\u003c/sub\u003e concentration was determined as 7.6\u0026thinsp;\u0026plusmn;\u0026thinsp;5.5 mg/L. Notably, 74.3% of pediatric patients exhibited vancomycin \u003cem\u003eC\u003c/em\u003e\u003csub\u003e\u003cem\u003emin\u003c/em\u003e\u003c/sub\u003e levels below the recommended therapeutic window of 10\u0026ndash;20 mg/L. Specifically, 69 patients exhibited a mean vancomycin \u003cem\u003eC\u003c/em\u003e\u003csub\u003e\u003cem\u003emin\u003c/em\u003e\u003c/sub\u003e concentration below 5 mg/L, whereas 67 patients had mean \u003cem\u003eC\u003c/em\u003e\u003csub\u003e\u003cem\u003emin\u003c/em\u003e\u003c/sub\u003e levels ranging from 5 to 10 mg/L. A mere 25.7% of patients, equating to 47 individuals, attained a \u003cem\u003eC\u003c/em\u003e\u003csub\u003e\u003cem\u003emin\u003c/em\u003e\u003c/sub\u003e level exceeding 10 mg/L, while 8 patients demonstrated mean \u003cem\u003eC\u003c/em\u003e\u003csub\u003e\u003cem\u003emin\u003c/em\u003e\u003c/sub\u003e concentrations surpassing 20 mg/L.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThe mean \u003cem\u003eC\u003c/em\u003e\u003csub\u003e\u003cem\u003emin\u003c/em\u003e\u003c/sub\u003e concentration in patients who responded successfully to treatment was significantly higher than in those who failed (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.006). In detail, the mean \u003cem\u003eC\u003c/em\u003e\u003csub\u003e\u003cem\u003emin\u003c/em\u003e\u003c/sub\u003e values were 8.4\u0026thinsp;\u0026plusmn;\u0026thinsp;5.7 mg/L and 5.9\u0026thinsp;\u0026plusmn;\u0026thinsp;4.4 mg/L, respectively (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB). Among patients with nephrotoxicity, the mean \u003cem\u003eC\u003c/em\u003e\u003csub\u003e\u003cem\u003emin\u003c/em\u003e\u003c/sub\u003e concentration was 17.8\u0026thinsp;\u0026plusmn;\u0026thinsp;5.3 mg/L, significantly exceeding that of patients without nephrotoxicity (6.4\u0026thinsp;\u0026plusmn;\u0026thinsp;3.9 mg/L, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003cp\u003eIn this study, the overall success rate of vancomycin therapy was 72.1%, while 11.5% (21 patients) developed nephrotoxicity during treatment. Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e compares the variables between treatment success and failure groups, as well as nephrotoxicity and non-nephrotoxicity groups. After adjusting for confounding factors, vancomycin \u003cem\u003eC\u003c/em\u003e\u003csub\u003e\u003cem\u003emin\u003c/em\u003e\u003c/sub\u003e alone was associated with clinical outcomes. In the analysis of nephrotoxicity, baseline Scr level, central nervous system infections, presence of MSSA, and vancomycin \u003cem\u003eC\u003c/em\u003e\u003csub\u003e\u003cem\u003emin\u003c/em\u003e\u003c/sub\u003e were significantly associated in univariate analysis. However, only vancomycin \u003cem\u003eC\u003c/em\u003e\u003csub\u003e\u003cem\u003emin\u003c/em\u003e\u003c/sub\u003e maintained significance in multivariate analysis when considering factors with \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.1.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eMultivariate logistic regression analysis of factors influencing the effectiveness and safety of vancomycin.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eVariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eTreatment Outcomes\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003eAdverse Effects\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eOR (95% CI)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eOR (95% CI)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge, year\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.000 (1.000\u0026thinsp;~\u0026thinsp;1.001)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.115\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBMI, kg/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.638 (0.174\u0026thinsp;~\u0026thinsp;2.331)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.496\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSepsis/severe sepsis/septic shock\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.663 (0.288\u0026thinsp;~\u0026thinsp;1.524)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.333\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.401 (0.124\u0026thinsp;~\u0026thinsp;1.301)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.128\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBaseline creatinine clearance, mL/min\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.997 (0.993\u0026thinsp;~\u0026thinsp;1.002)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.232\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCNS infection\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.185 (0.227\u0026thinsp;~\u0026thinsp;1.332)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.550\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.402 (0.137\u0026thinsp;~\u0026thinsp;1.177)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.096\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBaseline creatinine, \u0026micro;mol/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.999 (0.984\u0026thinsp;~\u0026thinsp;1.014)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.888\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMSSA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.222 (0.322\u0026thinsp;~\u0026thinsp;4.638)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.769\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eConcomitant amphotericin B\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5.118 (0.836\u0026thinsp;~\u0026thinsp;31.314)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.077\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eConcomitant meropenem\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.531 (0.203\u0026thinsp;~\u0026thinsp;1.389)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.197\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVancomycin trough concentration, mg/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.090 (1.007\u0026thinsp;~\u0026thinsp;1.179)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e0.032\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.320 (1.197\u0026thinsp;~\u0026thinsp;1.456)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"6\"\u003eStatistically significant values are shown in bold.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"6\"\u003eAbbreviations: OR, odds ratio; CI, confidence interval; BMI, body mass index; CNS, central nervous system; MSSA, methicillin-susceptible \u003cem\u003eStaphylococcus aureus.\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"6\"\u003e\u003csup\u003e*\u003c/sup\u003eEstimated using Schwartz formula.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eAdditional analysis of the receiver operating characteristic (ROC) curve demonstrated that a \u003cem\u003eC\u003c/em\u003e\u003csub\u003e\u003cem\u003emin\u003c/em\u003e\u003c/sub\u003e concentration of 5.9 mg/L serves as a predictor for therapeutic effect, exhibiting an area under the curve (AUC) of 0.643, with a sensitivity of 70.1% and a specificity of 64.1% (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA). A \u003cem\u003eC\u003c/em\u003e\u003csub\u003e\u003cem\u003emin\u003c/em\u003e\u003c/sub\u003e level of 14.8 mg/L effectively anticipated the emergence of nephrotoxicity, displaying an AUC of 0.960, accompanied by a sensitivity of 95.2% and a specificity of 85.0% (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB). Taking into account the temporal influence on nephrotoxicity risk, patients were stratified into two groups based on their \u003cem\u003eC\u003c/em\u003e\u003csub\u003e\u003cem\u003emin\u003c/em\u003e\u003c/sub\u003e levels (\u0026lt;\u0026thinsp;14.8 and \u0026ge;\u0026thinsp;14.8 mg/L) for subsequent Kaplan-Meier survival analysis. As depicted in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, a significant difference in the incidence of nephrotoxicity was observed between the two groups over the course of vancomycin treatment.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eVancomycin has been clinically utilized for more than 60 years, yet the precise therapeutic window for pediatric patients remains elusive. CL serves as a crucial PK parameter, exerting a significant influence on drug exposure levels. Nevertheless, the vancomycin CL in pediatric patients is typically much faster compared to adults, approximately 2.5 times greater [11, 15]. Limited available data indicate that the vancomycin CL in Chinese pediatric patients ranges from 0.11 to 0.17 L/h\u0026middot;kg, which is notably higher than that observed in adults[5, 16]. This may be attributed to physiological characteristics in pediatric patients, such as higher water content and renal clearance, which influence PK parameters and subsequently lead to lower drug concentration attainment rates. Therefore, acknowledging the PK disparities between pediatric and adult populations, this study reassessed the therapeutic window of vancomycin in pediatric patients and advocated for adjusting it to a range of 5.9\u0026ndash;14.8 mg/L, which is similar to the findings reported previously by our research team [4].\u003c/p\u003e\u003cp\u003eAccording to the latest international guidelines, monitoring the \u003cem\u003eAUC\u003c/em\u003e\u003csub\u003e\u003cem\u003e24\u003c/em\u003e\u003c/sub\u003e\u003cem\u003e/MIC\u003c/em\u003e for vancomycin is recommended, with a target range of 400\u0026ndash;600 [2]. Nevertheless, the practicality of monitoring \u003cem\u003eAUC\u003c/em\u003e\u003csub\u003e\u003cem\u003e24\u003c/em\u003e\u003c/sub\u003e\u003cem\u003e/MIC\u003c/em\u003e in clinical settings is limited due to various factors, including the necessity for secondary sampling, the scarcity of specialized personnel, and the ambiguity surrounding PK/PD standards for pediatric patients [17]. Consequently, monitoring \u003cem\u003eC\u003c/em\u003e\u003csub\u003e\u003cem\u003emin\u003c/em\u003e\u003c/sub\u003e remains a widely adopted practice, even in most large tertiary medical institutions, emphasizing the crucial importance of further exploring the rational use of vancomycin through \u003cem\u003eC\u003c/em\u003e\u003csub\u003e\u003cem\u003emin\u003c/em\u003e\u003c/sub\u003e monitoring [18]. Owing to the lack of clinical data, the reference range for target concentrations of vancomycin in special populations, including children, has historically aligned with that established for adults. When administered standard dosing regimens, only 28.9% of pediatric patients attain a vancomycin \u003cem\u003eC\u003c/em\u003e\u003csub\u003e\u003cem\u003emin\u003c/em\u003e\u003c/sub\u003e within the range of 10\u0026ndash;20 mg/L, while a mere 6.9% achieve a \u003cem\u003eC\u003c/em\u003e\u003csub\u003e\u003cem\u003emin\u003c/em\u003e\u003c/sub\u003e of 15\u0026ndash;20 mg/L [19]. Consistent with our findings, Tatjana et al. observed a mere 24% achievement rate of \u003cem\u003eC\u003c/em\u003e\u003csub\u003e\u003cem\u003emin\u003c/em\u003e\u003c/sub\u003e in pediatric patients during TDM [20]. Data indicate that pediatric patients with normal renal function need 70 mg/kg\u0026middot;d to attain a target \u003cem\u003eC\u003c/em\u003e\u003csub\u003e\u003cem\u003emin\u003c/em\u003e\u003c/sub\u003e of 10 mg/L, while younger patients aged 1\u0026ndash;6 years may require 80\u0026ndash;85 mg/kg\u0026middot;d to achieve a target \u003cem\u003eC\u003c/em\u003e\u003csub\u003e\u003cem\u003emin\u003c/em\u003e\u003c/sub\u003e ranging from 15\u0026ndash;20 mg/L [21, 22]. To investigate the reasons for the low vancomycin blood concentration attainment rate in pediatric patients, we assess the appropriateness of extrapolating the therapeutic window from adults to the pediatric population.\u003c/p\u003e\u003cp\u003eOur findings reveal that satisfactory clinical outcomes could be attained in pediatric patients when \u003cem\u003eC\u003c/em\u003e\u003csub\u003e\u003cem\u003emin\u003c/em\u003e\u003c/sub\u003e exceeds 5.9 mg/L, which aligns with the lower limit of the initial vancomycin therapeutic window [6]. A recent meta-analysis suggests that a vancomycin \u003cem\u003eC\u003c/em\u003e\u003csub\u003e\u003cem\u003emin\u003c/em\u003e\u003c/sub\u003e ranging from 10\u0026ndash;15 mg/L in pediatric patients is associated with clinical efficacy, and exceeding 15 mg/L is not necessary [23]. The Chinese guidelines for TDM of vancomycin (2020) also recommend maintaining a vancomycin \u003cem\u003eC\u003c/em\u003e\u003csub\u003e\u003cem\u003emin\u003c/em\u003e\u003c/sub\u003e of 5\u0026ndash;15 mg/L for pediatric patients. However, this recommendation is solely based on a retrospective study with a limited sample size of 100 cases [24]. By employing a nearly doubled sample size, we achieved comparable outcomes, thus providing robust evidence to support the recommended scope outlined in the guidelines.\u003c/p\u003e\u003cp\u003e The IDSA published vancomycin TDM guidelines from 2009 to 2011, consecutively for three years, advocating a monitoring threshold of 10 mg/L to mitigate drug resistance. However, despite the persistent and significant shortfall in achieving the target \u003cem\u003eC\u003c/em\u003e\u003csub\u003e\u003cem\u003emin\u003c/em\u003e\u003c/sub\u003e, no change in the resistance of MRSA isolates to vancomycin has been noted [25, 26]. Over a four-year period, Faiqa et al. gathered 352 MRSA isolates and discovered no alterations in MIC\u003csub\u003e50\u003c/sub\u003e or MIC\u003csub\u003e90\u003c/sub\u003e values. [27]. Another study examining the MIC changes of 736 MRSA isolates against vancomycin revealed that all MIC values were below 2 mg/L, with the majority falling below 1 mg/L [28]. Wang et al. also conducted an analysis of 879 MRSA isolates collected from pediatric patients with bloodstream infections in China over a four-year period (2015\u0026ndash;2018) and reported no vancomycin-resistant strains [29]. Additionally, our institution also conducted a statistical analysis spanning from 2013 to 2019, focusing on the MIC changes of MRSA isolates against vancomycin. The proportion of MRSA strains with MIC of 1 mg/L exhibited a steady decline, decreasing from 81% in 2013 to 30% in 2024. Conversely, the proportion of MRSA strains with MIC of \u0026le;\u0026thinsp;0.5 mg/L increased from 19% in 2013 to 70% during the same period. No vancomycin-resistant MRSA strains have been detected. Actually, since the establishment of the China Antimicrobial Resistance Surveillance Network in 2005, domestic drug resistance surveillance data indicate no reported cases of vancomycin-resistant MRSA strains. The findings from these studies suggest that while vancomycin TDM guidelines recommend specific monitoring thresholds to prevent drug resistance, the actual resistance patterns of MRSA isolates to vancomycin may not be as straightforward as initially anticipated. In other words, vancomycin has maintained a consistently low exposure level in pediatric patients for decades, without causing any significant shifts in the MIC of MRSA against vancomycin. Certainly, it is crucial to continue monitoring and evaluating these isolates to gain a deeper understanding of their resistance patterns and to ensure effective treatment strategies.\u003c/p\u003e\u003cp\u003eA high concentration of vancomycin \u003cem\u003eC\u003c/em\u003e\u003csub\u003e\u003cem\u003emin\u003c/em\u003e\u003c/sub\u003e is strongly associated with the occurrence of nephrotoxicity [3]. Our findings indicate a significant increase in the risk of AKI in pediatric patients when vancomycin \u003cem\u003eC\u003c/em\u003e\u003csub\u003e\u003cem\u003emin\u003c/em\u003e\u003c/sub\u003e exceeds 14.8 mg/L. A large retrospective study of 859 pediatric patients found a significant association between vancomycin \u003cem\u003eC\u003c/em\u003e\u003csub\u003e\u003cem\u003emin\u003c/em\u003e\u003c/sub\u003e concentrations exceeding 15 mg/L and AKI (odds ratio, 2.18; 95% confidence interval, 1.21\u0026ndash;3.92), corroborating our own observations [30]. Furthermore, a recent meta-analysis encompassing eight pediatric studies revealed that vancomycin \u003cem\u003eC\u003c/em\u003e\u003csub\u003e\u003cem\u003emin\u003c/em\u003e\u003c/sub\u003e concentrations exceeding 15 mg/L could elevate the risk of nephrotoxicity by a factor of 2.7 [23]. These findings highlight the need for careful monitoring of vancomycin levels in pediatric patients to mitigate the risk of nephrotoxicity. Clinicians prioritize the potential adverse effects of vancomycin over therapeutic outcomes, making it challenging to justify aiming for high-level vancomycin \u003cem\u003eC\u003c/em\u003e\u003csub\u003e\u003cem\u003emin\u003c/em\u003e\u003c/sub\u003e levels in pediatric patients, especially when high concentrations lack clear clinical benefits. Notably, children with sepsis frequently have a history of multiple hospitalizations and underlying diseases, potentially increasing AKI risk.\u003c/p\u003e\u003cp\u003eThis study is not without limitations. First, our study solely established a correlation between \u003cem\u003eC\u003c/em\u003e\u003csub\u003e\u003cem\u003emin\u003c/em\u003e\u003c/sub\u003e and AKI risk, and our assessment focused solely on the concurrent use of nephrotoxic drugs, neglecting the effects of pretreatment medications prior to hospitalization and the cumulative effects of other nephrotoxic agents. It is imperative to point out that children with sepsis frequently have a history of multiple hospitalizations and underlying diseases, and obese children might receive higher dosing regimen based on actual weight, potentially increasing AKI risk. Second, measuring the free concentration of vancomycin holds greater significance than measuring the total concentration, particularly in neonatal and pediatric intensive care units[31]. However, there remains a lack of consensus regarding the optimal concentration range of free vancomycin, necessitating further exploration in future research. Last but not least, the absence of microbial culture results for most patients precluded the comprehensive analysis of microbial susceptibility in the final analysis. In fact, given the low proportion of positive cultures, the clinical application of vancomycin is primarily empirical. Considering acceptable therapeutic outcomes of vancomycin and the concordance of previous reports with our findings, we maintain that our study holds significant guiding value, to a certain extent. Although there are limited evidences supporting specific vancomycin therapeutic windows for pediatric patients, further research with larger sample sizes and more robust methodologies is still needed to establish more definitive therapeutic windows for this vulnerable population.\u003c/p\u003e"},{"header":"5. Conclusion","content":"\u003cp\u003eBased on the correlation between vancomycin \u003cem\u003eC\u003c/em\u003e\u003csub\u003e\u003cem\u003emin\u003c/em\u003e\u003c/sub\u003e and both clinical effectiveness and safety, a therapeutic window of 5.9\u0026ndash;14.8 mg/L for vancomycin in pediatric patients is proposed, aiming to facilitate its rational use within this specific population.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eMRSA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eMethicillin-resistant Staphylococcus aureus\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eCmin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eMean trough concentration\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eAUC\u003csub\u003e24\u003c/sub\u003e/MIC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eThe ratio of the 24 h area under the concentration-time curve and minimally inhibitory concentration\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ePK/PD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ePharmacokinetics/pharmacodynamics\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eTDM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eTherapeutic drug monitoring\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eCL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eClearance\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eScr\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eSerum creatinine\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eAKI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eAcute kidney injury\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eICU\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eIntensive care unit\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eMSSA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eMethicillin-susceptible Staphylococcus aureus\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;The authors would like to acknowledge Zhenyu Pan, Yuan Li, Ziyun Duan and Jie Mi for their attribution in samples collecting and useful insights to the results.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConceived and designed the protocol: Yalin Dong, Tao Zhang. Determination of samples: Xinyan Han, Yan Wang, Jiao Xie, Qianting Yang, Sasa Hu. Statistical analyses: Hua Cheng, Tao Zhang. Drafting manuscript: Yalin Dong, Jingjing Yi, Tao Zhang. All authors contributed to the interpretation of data and critical revisions of the manuscript for important intellectual content. Tao Zhang had final responsibility for the decision to submit for publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work is supported by the National Science Fund for Distinguished Young Scholars (82404762).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical Approval Statement and Consent to Participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe ethics has been approved by the Ethic Committee of Stomatology College Affiliated to Xi\u0026apos;an Jiaotong University (2024-XJKQIEC-KY-QT-0050-001). Informed consent for the use of routinely collected data has been waived according to local requirements. All associated procedures were conducted in accordance with the approved guidelines.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003e Schouwenburg S, Preijers T, Flint RB, et al. lPrediction of Vancomycin Area-under-the-curve using Trough Concentrations Only: Performance Evaluation of Pediatric Population Pharmacokinetic Models. The Journal of infectious diseases. 2025.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e Rybak MJ, Le J, Lodise TP, et al. Therapeutic monitoring of vancomycin for serious methicillin-resistant Staphylococcus aureus infections: A revised consensus guideline and review by the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists. 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Journal of the Pediatric Infectious Diseases Society. 2014;3(2):127\u0026thinsp;\u0026minus;\u0026thinsp;31.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e Resztak M, Sobiak J, Czyrski A. Recent Advances in Therapeutic Drug Monitoring of Voriconazole, Mycophenolic Acid, and Vancomycin: A Literature Review of Pediatric Studies. Pharmaceutics. 2021;13(12).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-pharmacology-and-toxicology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"phat","sideBox":"Learn more about [BMC Pharmacology and Toxicology](http://bmcpharmacoltoxicol.biomedcentral.com)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/phat/Default.aspx","title":"BMC Pharmacology and Toxicology","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"vancomycin, pediatrics, therapeutic drug monitoring, therapeutic window, pharmacodynamics","lastPublishedDoi":"10.21203/rs.3.rs-7050678/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7050678/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective\u003c/strong\u003e Methicillin-resistant \u003cem\u003eStaphylococcus aureus\u003c/em\u003e (MRSA) infections among children are escalating annually. Vancomycin stands as the frontline therapeutic agent against MRSA infections. However, determining the therapeutic window for vancomycin in pediatric patients remains a challenge.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e This retrospective study collected data from hospitalized children aged 1 month to 18 years, who underwent routine therapeutic drug monitoring for vancomycin. We analyzed the distribution patterns of vancomycin concentrations in these patients. Factors influencing clinical outcomes and adverse reaction (nephrotoxicity) were investigated. ROC analysis was used to establish the therapeutic window for vancomycin in pediatric patients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e A comprehensive dataset encompassing 183 pediatric patients with 330 samples was analyzed. The mean trough concentration (\u003cem\u003eC\u003c/em\u003e\u003csub\u003e\u003cem\u003emin\u003c/em\u003e\u003c/sub\u003e) of vancomycin was 7.6 ± 5.5 mg/L. 74.3% of patients exhibited concentrations below the conventionally recommended therapeutic window of 10-20 mg/L. Patients responding positively to treatment exhibited significantly higher \u003cem\u003eC\u003c/em\u003e\u003csub\u003e\u003cem\u003emin\u003c/em\u003e\u003c/sub\u003e values (8.4 ± 5.7 mg/L) compared to those with treatment failure (5.9 ± 4.4 mg/L, \u003cem\u003eP\u003c/em\u003e = 0.006). Similarly, patients who developed nephrotoxicity had significantly elevated \u003cem\u003eC\u003c/em\u003e\u003csub\u003e\u003cem\u003emin\u003c/em\u003e\u003c/sub\u003e levels (17.8 ± 5.3 mg/L) compared to those without nephrotoxicity (6.4 ± 3.9 mg/L, \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.001). Both univariate and multivariate logistic regressions revealed that the \u003cem\u003eC\u003c/em\u003e\u003csub\u003e\u003cem\u003emin\u003c/em\u003e\u003c/sub\u003e of vancomycin was the predictor of both clinical outcomes and adverse reaction. Furthermore, receiver operating characteristic curve analysis pinpointed that \u003cem\u003eC\u003c/em\u003e\u003csub\u003e\u003cem\u003emin\u003c/em\u003e\u003c/sub\u003e of vancomycin with 5.9 mg/L and 14.8 mg/L associated with clinical effectiveness and safety, respectively. Referring to the therapeutic window of adults, vancomycin underexposure in pediatrics is serious extremely.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e Based on our findings, we propose a revised therapeutic window of 5.9-14.8 mg/L for vancomycin in pediatric patients, which could aid in optimizing treatment outcomes and minimizing adverse effects.\u003c/p\u003e","manuscriptTitle":"Therapeutic Drug Monitoring of Vancomycin in Pediatric Patients: A Retrospective Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-30 04:28:24","doi":"10.21203/rs.3.rs-7050678/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-08-27T10:00:10+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-08-25T12:34:26+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-08-20T19:17:00+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"186588095142479632154419633922675116282","date":"2025-08-17T01:19:11+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"123967078511297800272021820327742755228","date":"2025-08-16T21:31:49+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"282127950163808204457635203675800663937","date":"2025-08-15T08:36:36+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-08-07T21:24:14+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"182188818754146010108523422023580824719","date":"2025-07-29T02:25:39+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"139954484479142265649787733103998032611","date":"2025-07-28T00:01:41+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-07-25T09:21:16+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-07-23T08:52:33+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-07-15T12:21:30+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-07-15T12:21:11+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pharmacology and Toxicology","date":"2025-07-05T05:29:35+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pharmacology-and-toxicology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"phat","sideBox":"Learn more about [BMC Pharmacology and Toxicology](http://bmcpharmacoltoxicol.biomedcentral.com)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/phat/Default.aspx","title":"BMC Pharmacology and Toxicology","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"429e3f22-2796-4ff9-9303-db3d14a5b480","owner":[],"postedDate":"July 30th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-11-24T16:06:14+00:00","versionOfRecord":{"articleIdentity":"rs-7050678","link":"https://doi.org/10.1186/s40360-025-01035-6","journal":{"identity":"bmc-pharmacology-and-toxicology","isVorOnly":false,"title":"BMC Pharmacology and Toxicology"},"publishedOn":"2025-11-18 15:58:06","publishedOnDateReadable":"November 18th, 2025"},"versionCreatedAt":"2025-07-30 04:28:24","video":"","vorDoi":"10.1186/s40360-025-01035-6","vorDoiUrl":"https://doi.org/10.1186/s40360-025-01035-6","workflowStages":[]},"version":"v1","identity":"rs-7050678","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7050678","identity":"rs-7050678","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}