Retrospective Evaluation of Vancomycin Monitoring in Chinese Adults with Gram-Positive Coccal Infections

Retrospective Evaluation of Vancomycin Monitoring in Chinese Adults with Gram-Positive Coccal Infections | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 3 February 2026 V1 Latest version Share on Retrospective Evaluation of Vancomycin Monitoring in Chinese Adults with Gram-Positive Coccal Infections Authors : Fengping Xu 0009-0006-1021-4741 , Yue Yin , Xiaohui Wang , Qiu Li , and Dongna Zou [email protected] Authors Info & Affiliations https://doi.org/10.22541/au.177010035.58048200/v1 106 views 41 downloads Contents Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Objective:This study conducted therapeutic drug monitoring (TDM) to compare the clinical value of two pharmacokinetic/pharmacodynamic (PK/PD) parameters for vancomycin therapy, namely trough concentration (10-20 mg/L) and AUC 0-24h /MIC (400-650 mg·h·L -1 ), in Chinese patients. Methods: A total of 103 adult patients were enrolled in this study. All patients underwent trough concentration monitoring, and 87 of them completed the AUC 0-24h /MIC assessment. The target attainment rates of the two parameters were compared, and their correlations with clinical outcomes and safety were analyzed. Results: The results showed that 40.78% (42/103) of patients attained the target trough concentration range, while 39.08% (34/87) reached the target AUC 0-24h /MIC threshold, with no statistically significant difference between these attainment rates ( χ 2 = 0.008, P = 0.929). The overall clinical efficacy rate of vancomycin treatment for Gram-positive coccal infections was 88.35%, with a microbiological eradication rate of 93.20% and an incidence of acute kidney injury (AKI) of 5.83%. Further analysis showed that neither of the two PK/PD parameters was significantly associated with clinical outcomes ( P > 0.05). Conclusion: This study found no significant association between vancomycin PK/PD parameters (trough concentration and AUC 0-24h /MIC) and clinical efficacy or microbiological eradication in Chinese patients. Notably, pharmacokinetic parameters showed potential clinical value in predicting vancomycin-associated nephrotoxicity. Given the weak correlation between current therapeutic targets and clinical outcomes, it is recommended to further validate this through large-scale, multicenter prospective cohort studies. Original Article Retrospective Evaluation of Vancomycin Monitoring in Chinese Adults with Gram-Positive Coccal Infections Fengping Xu 1 , Yue Yin 2 , Xiaohui Wang 2 , Qiu Li 3* , Dongna Zou 1* 1.Department of Pharmacy, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China,250022. 2.Shandong First Medical University,Jinan,China,250000. 3.Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan,China,250021. Abstract: Objective:This study conducted therapeutic drug monitoring (TDM) to compare the clinical value of two pharmacokinetic/pharmacodynamic (PK/PD) parameters for vancomycin therapy, namely trough concentration (10-20 mg/L) and AUC 0-24h /MIC (400-650 mg·h·L -1 ), in Chinese patients. Methods: A total of 103 adult patients were enrolled in this study. All patients underwent trough concentration monitoring, and 87 of them completed the AUC 0-24h /MIC assessment. The target attainment rates of the two parameters were compared, and their correlations with clinical outcomes and safety were analyzed. Results: The results showed that 40.78% (42/103) of patients attained the target trough concentration range, while 39.08% (34/87) reached the target AUC 0-24h /MIC threshold, with no statistically significant difference between these attainment rates ( χ² = 0.008, P = 0.929). The overall clinical efficacy rate of vancomycin treatment for Gram-positive coccal infections was 88.35%, with a microbiological eradication rate of 93.20% and an incidence of acute kidney injury (AKI) of 5.83%. Further analysis showed that neither of the two PK/PD parameters was significantly associated with clinical outcomes ( P > 0.05). Conclusion: This study found no significant association between vancomycin PK/PD parameters (trough concentration and AUC 0-24h /MIC) and clinical efficacy or microbiological eradication in Chinese patients. Notably, pharmacokinetic parameters showed potential clinical value in predicting vancomycin-associated nephrotoxicity. Given the weak correlation between current therapeutic targets and clinical outcomes, it is recommended to further validate this through large-scale, multicenter prospective cohort studies. Keywords: vancomycin; therapeutic drug monitoring; blood drug concentrations; AUC 0-24h /MIC; Clinical outcomes. Introduction As a key antibiotic for the treatment of gram-positive bacterial infections, vancomycin has a narrow therapeutic window and significant interindividual variability, making therapeutic drug monitoring (TDM) an essential strategy for optimizing efficacy and minimizing toxicity [1-4] . The China Vancomycin Therapeutic Drug Monitoring Guidelines (2020 Update) [1] recommend monitoring trough concentration (C min ) or the 24-hour area under the concentration-time curve (AUC 0-24h ),with target trough levels of 10-15 mg/L for adults, or 10-20 mg/L in cases of severe Methicillin-Resistant Staphylococcus aureus (MRSA). The recommended AUC 0-24h target range is 400-650 mg·h·L -1 . However, due to insufficient evidence regarding efficacy and safety, the recommended target values for AUC 0-24h and trough concentration have been a subject of ongoing debate [1-2,5-8] Although higher trough concentrations (15-20 mg/L) have traditionally been recommended, studies have shown that even achieving these higher trough concentrations does not significantly improve clinical efficacy and may actually increase the risk of nephrotoxicity [9] . In addition, higher AUC 0-24h /minimum inhibitory concentration (MIC) values have been significantly associated with treatment failure, persistent bacteremia, and mortality, which further calls into question the current recommended dosing and monitoring methods [10] . Especially, there are few pharmacokinetic/pharmacodynamic (PK/PD) studies on vancomycin specifically for Chinese patients, and these studies often lack a comprehensive evaluation that integrates clinical outcomes or microbiological efficacy. The lack of such evidence has led to confusion in actual clinical practice, especially when determining the optimal treatment dosage. The current trend is gradually shifting towards dose adjustment guided by AUC 0-24h [11-12] , but more clinical studies are needed to confirm the efficacy and safety of this approach in different patient populations. 1.Materials and methods 1.1 Objects of study This retrospective study enrolled patients with Gram-positive cocci infections treated with vancomycin at Shandong Provincial Hospital Affiliated to Shandong First Medical University from July 2020 to August 2022. Inclusion criteria were: (1) ≥1 vancomycin therapeutic drug monitoring, (2) vancomycin-sensitive isolates confirmed by antimicrobial susceptibility testing, and (3) complete clinical/microbiological data. Exclusion criteria included: concomitant anti-cocci agents, colonization, missing key laboratory data, minors, pregnant/lactating women, or inadequate specimens. Data collected included demographics, laboratory parameters (serum creatinine, inflammatory markers, liver enzymes), vancomycin regimens (dose, concentrations), and clinical/microbiological outcomes. 1.2 Determination of blood drug concentration Blood concentration monitoring was performed according to guidelines [1] : (1) Starting trough concentration: For those with normal renal function, venous blood (2-4 mL) was collected 48 hours after drug administration and 30 minutes before the next dose; for renal insufficiency, blood was collected 72 hours after drug administration and 30 minutes before the next dose. (2) Subsequent trough concentration: After adjusting the dosing regimen, re-measure at the same timing as the starting trough concentration. Vancomycin blood concentrations were measured using a homogeneous enzyme-amplified immunoassay (HEA) with the Abbott ARCHITECT i1000SR system. 1.3 Medication regimen Empirical vancomycin therapy was initiated based on clinical presentation, imaging findings, and inflammatory markers, prior to obtaining culture results. Subsequent adjustments to the regimen were made based on susceptibility testing and adverse effects: the current dose was maintained with weekly trough monitoring if clinical efficacy was satisfactory, even with subtherapeutic concentrations. The study population included specific subgroups such as adults, elderly patients, obese individuals, and those with renal impairment. 1.4 Criteria for evaluation of efficacy and safety Based on the Guidelines for Clinical Trials of Antimicrobial Agents [13-15] , therapeutic outcomes are categorized as: Clinically Effective: Resolution or stabilization of symptoms/signs with normalized non-microbiological parameters. Residual abnormalities may be considered effective if attributable to physiological phenomena, post-infection status, or underlying diseases (without active infection). Clinically Ineffective: Persistent/worsening symptoms or switch to alternative antibiotics (e.g., linezolid or tigecycline) [16] . Microbiological Efficacy Assessment [17] : Based on etiological examination: Eradication: Negative follow-up culture. Presumed eradication: Symptom resolution without available culture. Replacement: New pathogen isolated without infection signs. Persistence/Reinfection: Original or new pathogen isolated with ongoing infection. Microbiological clearance included cases of eradication, presumed eradication, and replacement. Adverse Reaction Assessment Criteria: Vancomycin-associated acute kidney injury (VA-AKI) criteria [18] : Fulfillment of any of the following conditions: (1) An increase in serum creatinine (Scr) ≥0.3 mg/dL (26.5 μmol/L) within 48 hours; (2) An increase in Scr ≥44.2 μmol/L or ≥1.5 times the baseline within 7 days. In addition, the concomitant use of nephrotoxic agents should be avoided [19] . 1.5 AUC 0-24h /MIC calculation \begin{equation} AUC=\frac{Total\ vancomycin\ dose\ (mg)\ over\ 24\ h}{[CrCL\ \times\ 0.79\ +\ 15.4]}\nonumber \\ \end{equation} Where CrCL represents creatinine clearance calculated using the Cockcroft–Gault equation [24] . The MIC was determined using the broth microdilution (BMD) method recommended by the Clinical and Laboratory Standards Institute (CLSI) [25] . The AUC 0-24h /MIC was calculated as the daily mean AUC divided by the corresponding MIC. 1.6 Statistical treatment Statistical analyses were performed using R software (version 4.3.0). For continuous variables following a normal distribution, data were expressed as mean ± standard deviation ( x±s ); for non-normally distributed data, they were presented as median and interquartile range (IQR). Differences between groups were assessed using the t-test or Welch’s t -test ( t′ -test). Categorical variables were compared using the χ² test. Logistic regression was employed to evaluate the association between vancomycin PK/PD parameters and clinical or microbiological efficacy. Before applying the logistic regression model, a goodness-of-fit test was conducted to verify the model’s suitability for the data. Multiple linear regression was performed to identify factors influencing the AUC 0-24h /MIC. A P -value of < 0.05 was considered statistically significant. 2. Results 2.1 General information and pathogenetic findings A total of 103 patients treated with vancomycin for Gram-positive bacterial infections were included in the study based on the inclusion and exclusion criteria. Among them, 14 patients had missing weight data and 2 patients had missing creatinine values. Blood drug concentrations were remeasured in 39 patients following adjustments to the dosing regimen. The baseline information of the patients—including gender, weight, age, vancomycin blood concentrations, AUC 0-24h values, MIC values, dosing regimen, infection site, microbiological findings, and creatinine clearance—is presented in Table 1. Tab.1 103 Basic information of the patient Parameters Mean±SD or Percentage (%) ( n = 103) Man (%) 73 (70.87) Weight (kg) 70.12 ± 14.01 Age (year) 58.02 ± 14.53 Treatment Duration (Days) 8.65 ± 5.72 Body Temperature (℃) 37.67 ± 0.93 Procalcitonin (PCT, ng/mL) 7.13 ± 14.79 C-Reactive Protein (CRP, mg/L) 79.23 ± 70.34 White Blood Cells (WBC, 10 ^9 /L) 9.95 ± 5.73 Creatinine Clearance (CrCl, ml/min) 110.36 ± 55.31 MIC = 0.5 (mg/L) 50 (48.54) MIC = 1 (mg/L) 47 (45.63) Infection Sites( n = 103) － Abdominal infection 20 (19.42) Bloodstream infection 18 (19.42) Surgical site infection 13 (12.62) Pulmonary infection 12 (11.65) Skin and soft tissue infection 10 (9.71) Multisystem infection 7 (6.80) Osteoarticular infection 7 (6.80) Other infections 16 (15.53) Pathogen profile ( n = 103) － Staphylococcus Aureus (SA) Methicillin-sensitive Staphylococcus aureus 13 (12.62) Methicillin-resistant Staphylococcus aureus 20 (19.42) Enterococcus Enterococcus faecium 32 (31.07) Enterococcus faecalis 12 (11.65) Enterococcus spp. 4 (3.88) Coagulase-Negative Staphylococci (CoNs) Methicillin-resistant Staphylococcus epidermidis 8 (7.77) Methicillin-sensitive Staphylococcus epidermidis 1 (0.97) Staphylococcus haemolyticus 5 (4.85) Staphylococcus hominis 4 (3.88) Other CoNS 3 (2.91) Other Lactococcus 1 (0.97) 2.2 Vancomycin trough concentration and AUC 0-24h /MIC compliance Among the 103 patients, the initial and adjusted vancomycin trough concentrations were measured, and the results are summarized in Table 2. After adjusting the dosing regimen, the average trough concentration was 17.31 ± 11.74 mg/L, with 31 patients having levels below 10 mg/L, 42 patients between 10-20 mg/L, and 30 patients above 20 mg/L. A total of 40.78% of patients had trough concentrations within the target range (10-20 mg/L), while 59.22% were outside the target range. The differences among the three groups were statistically significant ( P < 0.001). A total of 87 patients were included in the evaluation based on the AUC 0–24h /MIC calculation formula. After adjusting the treatment regimen, the average AUC 0–24h /MIC for vancomycin therapy was 476.60 ± 234.16 mg·h·L -1 . Among the patients, 35 had AUC 0–24h /MIC levels below 400 mg·h·L -1 , 34 patients between 400 and 650 mg·h·L -1 , and 18 patients above 650 mg·h·L -1 . The proportion of patients within the recommended target range was 39.08%, while those outside the target concentration range accounted for 60.92%. The differences between the three groups were statistically significant ( P < 0.001), as shown in Table 3. Tab.2 Statistics on Trough Concentration Target Attainment Trough Concentration Group (mg/L) Number of Cases at Initial Dosing (%) Number of Cases After Adjustment (%) ＜10 40(38.84%) 31(30.10%) 10-20 35(33.98%) 42(40.78%) ＞20 28(27.18%) 30(29.12%) Tab.3 Statistics on AUC 0-24h /MIC Target Attainment AUC 0-24h /MIC Group (mg·h·L -1 ) Number of Cases at Initial Dosing (%) Number of Cases After Adjustment (%) ＜400 34(39.08%) 35(40.23%) 400-650 31(35.63%) 34(39.08%) ＞650 22(25.29%) 18(20.69%) 2.3 Analysis of Vancomycin Therapeutic Drug Monitoring Results Among the 103 patients treated with vancomycin, the overall clinical efficacy rate was 88.3%, and the microbiological eradication rate was 93.2%. Subgroup analysis stratified by trough concentration showed that in the 10-20 mg/L group ( n = 42), the clinical efficacy and microbiological eradication rates were 90.5% and 92.9%, respectively. No statistically significant differences in efficacy were observed among the subgroups ( P > 0.05). The overall incidence of acute kidney injury (AKI) was 5.8% (6/103). Notably, the incidence of AKI was significantly higher in the group with trough concentrations 0.05), as shown in Table 4. Among the 87 patients monitored using AUC 0–24h /MIC, the overall clinical efficacy rate and microbiological eradication rate were 89.7% and 92.0%, respectively. In patients with AUC 0–24h /MIC values within the 400-650 range ( n = 34), both the efficacy rate and eradication rate were 91.2%. The overall incidence of acute kidney injury (AKI) was 5.7% (5/87), with a significantly higher AKI incidence observed in the group with AUC 0–24h /MIC >650 compared to the other groups ( P < 0.05), as shown in Table 5. Tab.4 Comparison of Efficacy and Adverse Effects at Different Vancomycin Trough Concentrations Ct 0 （mg/L） Clinically effective（%） Microbial clearance（%） AKI（%） ＜10mg/L 31(77.50) 34(85.00) 0(0.00) 10-20mg/L 30(85.71) 31(88.57) 1(2.86) ＞20mg/L 21(75.00) 27(96.43) 7(25.00) Total 82(79.61) 92(89.32) 8(7.77) Statistical Analysis χ 2 =1.280 P= 0.527 χ2=2.187 P= 0.335 χ2=16.154 P ＜0.001 Ct（mg/L） Clinically effective（%） Microbial clearance（%） AKI（%） ＜10mg/L 28(90.32) 28(90.32) 0(0.00) 10-20mg/L 38(90.48) 39(92.86) 1(2.38) ＞20mg/L 25(83.33) 29(96.67) 5(16.67) Total 91(88.35) 96(93.20) 6(5.83) Statistical Analysis χ 2 =1.035 P =0.596 χ 2 =0.982 P =0.612 χ 2 =9.253 P =0.010 Note: Ct 0 =initial trough concentration; Ct = trough concentration after adjustment. Tab.5 Comparison of Efficacy and Adverse Effects at Different Vancomycin AUC 0-24h /MIC Pre-AUC 0-24h /MIC Clinically effective（%） Microbial clearance（%） AKI（%） ＜400 26(76.47) 27(79.41) 0(0.00) 400-650 27(87.10) 28(90.32) 4(12.90) ＞650 18(81.82) 22(100.00) 3(13.64) Total 71(81.61) 77(88.51) 7(8.05) Statistical Analysis χ2 =1.221 P =0.543 χ2 =5.772 P =0.570 χ2 =4.893 P =0.087 Post-AUC 0-24h /MIC Clinically effective（%） Microbial clearance（%） AKI（%） ＜400 32(91.43) 32(91.43) 0(0.00) 400-650 31(91.18) 31(91.18) 2(5.88) ＞650 15(93.33) 17(94.44) 3(16.67) Total 78(89.66) 80(91.95) 5(5.75) Statistical Analysis χ2 =0.979 P =0.613 χ2 =0.192 P =0.909 χ2 =6.097 P =0.047 Note: Pre-AUC 0-24h /MIC = initial AUC 0-24h /MIC before adjustment; Post-AUC 0-24h /MIC = AUC 0-24h /MIC after adjustment. 2.4 Clinical/microbiologic efficacy correlation analysis of vancomycin therapy The number of cases with assessable clinical and microbiological efficacy among the enrolled patients was 103. The correlations between vancomycin PK/PD indices [trough concentration (C min ), area under the curve from 0 to 24 h (AUC 0-24h ), and the ratio of AUC 0-24h to minimum inhibitory concentration (AUC 0-24h /MIC)], different sites of infection, different bacterial types, and overall clinical outcomes (clinical and microbiological efficacy) in Chinese adult patients were assessed after adjusting the administration regimen, as shown in Tables 6-8 and Supplementary Tables1-4. No significant correlation was found between PK/PD indices and either clinical or microbiological outcomes ( P > 0.05). Tab.6 Multivariate logistic regression analysis of clinical/microbiological efficacy of vancomycin treatment Factor Clinical efficacy Microbial efficacy Wilder χ 2 p value Wilder χ 2 p value Cmin (n=103) 0.006 0.938 1.002 0.317 AUC 0-24h (n=87) 0.205 0.651 0.545 0.460 AUC 0-24h /MIC (n=87) 0.114 0.736 0.416 0.519 Site of infection (n=103) 3.460 0.943 0.218 1.000 Type of pathogenic organism (n=103) 1.833 0.608 0.203 0.997 Tab.7 Correlation analysis of vancomycin trough concentrations and efficacy at common sites of infection Site of infection Trough concentration Ct(mg/L) Clinical efficacy ( n =103) p value Microbial efficacy ( n =103) p value Clinically effective Clinically ineffective Eradication Non-Eradication Overall N (%) 91 (88.35%) 12 (11.60%) 0.938 96 (93.20%) 7 (6.80%) 0.317 average value ± SD 17.34 ± 11.92 17.06 ± 14.45 17.63 ± 12.01 13.00 ± 5.79 Intra-abdominal infection N (%) 17 (85.00%) 3 (15.00%) 0.416 17 (85.00%) 3 (15.00%) 0.384 average value ± SD 16.01 ± 8.00 17.00±8.41 16.64 ± 7.87 13.47 ± 8.68 Bloodstream infections N (%) 15 (83.33%) 3 (16.67%) 0.983 16 (88.89%) 2 (11.11%) 0.635 average value ± SD 20.31 ± 15.61 20.12 ± 7.70 20.84 ± 15.23 15.77 Lung infections N (%) 11 (91.67%) 1 (8.33%) 0.993 12 (100.00%) 0 (0.00%) average value ± SD 18.50 ± 12.13 4.36 17.32 ± 12.26 Surgical site N (%) 13 (100.00%) 0 (0.00%) 13 (100.00%) 0 (0.00%) Median (IQR) 11.59 (8.05, 17.03) 11.59 (8.05, 17.03) Tab.8 Correlation analysis of vancomycin AUC 0-24h /MIC and efficacy at common sites of infection Site of infectio AUC 0-24h /MIC Clinical efficacy ( n =87) p value Microbial efficacy ( n =87) p value Clinically effective Clinically ineffective Eradication Non-Eradication Overall N (%) 78 (89.66%) 9 (10.34%) 80 (91.95%) 7 (8.05%) average value ± SD/(IQR) 428.34 (314.06, 606.90) 526.46 ± 270.75 505.87 ± 302.12 428.35 ± 136.34 Intra-abdominal infection N (%) 16 (88.89%) 2 (11.11%) 0.757 15 (83.33%) 3 (16.67%) 0.669 average value ± SD 532.88 ± 274.53 474.11 537.77±283.44 469.25 ± 64.04 Bloodstream infections N(%) 12 (80.00%) 3 (20.00%) 0.428 13 (86.67%) 2 (13.33%) 0.688 average value ± SD 212.96 ± 94.92 639.40 ± 397.29 532.60 ± 309.93 443.71 Lung infections N (%) 7 (100.00%) 0 (0.00%) 7 (100.00%) 0 (0.00%) average value ± SD 605.70 ± 267.38 605.70 ± 267.38 Surgical site N (%) 12 (100.00%) 0 (0.00%) 12 (100.00%) 0 (0.00%) average value ± SD 471.18 ± 202.14 471.18 ± 202.14 2.5 Correlation analysis between Ct and AUC 0-24h/ MIC After dose adjustment, the target attainment rates for trough concentration (10-20 mg/L) and AUC 0-24h /MIC (400-650 mg·h·L -1 ) were 40.78% and 39.08%, respectively, with no significant difference between the two according to chi-square test ( χ² = 0.057, P = 0.812). Multiple linear regression analysis revealed that daily vancomycin dose (D 24h ), MIC value, creatinine clearance (CL), and trough concentration (Ct) were all significant predictors of AUC 0-24h /MIC ( R² = 0.635, P < 0.05). Variance inflation factor (VIF) assessment confirmed the absence of significant multicollinearity among independent variables (all VIF < 2). The derived regression equation was: AUC 0-24h /MIC = 613 + 13.84(D 24h ) − 390.8(MIC) − 1.64(CL) + 8.025(Ct). Scatter plots indicated a good linear correlation between these variables and AUC 0-24h /MIC, as shown in Fig.1. Fig.1 Regression standardized residual scatter plot Discussion This study systematically evaluated the monitoring indicators for vancomycin therapy and highlighted the complex performance of traditional PK/PD parameters (trough concentration and AUC 0-24h /MIC) in clinical application among Chinese patients. While previous guidelines [1-2,5-7] have recommended these parameters as standard efficacy metrics, a growing body of evidence has raised concerns regarding their correlation with clinical outcomes [26-28] . In the present study, no significant association ( P > 0.05) was observed between these PK/PD parameters and either clinical efficacy or microbiological clearance in the Chinese patient cohort. These findings are consistent with the conclusions drawn from prospective multicenter studies conducted by Shen K and colleagues [29-30] . The study found that favorable therapeutic outcomes could still be achieved when the trough concentration was <10 mg/L or the AUC 0-24h /MIC was <400 mg·h·L -1 . For example, in Wan M’s study, the clinical efficacy rate in the <10 mg/L trough concentration group reached 88%, with no significant difference compared to the high-concentration group ( P = 0.973) [31] . Although early studies [32-33] suggested that trough concentrations <10 mg/L may induce Vancomycin-Intermediate Staphylococcus aureus (VISA) and Heterogeneous Vancomycin-Intermediate Staphylococcus aureus (hVISA), and treatment guidelines [34] recommend maintaining levels above 10 mg/L, this recommendation diverges significantly from clinical outcomes observed in China. This discrepancy may be attributed to the negligible vancomycin resistance rate among MRSA strains (0% from 2018 to 2022) [35-37] and the low prevalence of Vancomycin-Resistant Staphylococcus aureus (VRSA) in Asia (1.2%) [38] . Previous studies have proposed reduced AUC 0-24h /MIC target thresholds, with Mogle BT et al. [39] recommending ≥297 and Brown et al. [40] suggesting ≥211. While trough concentration monitoring remains widely used due to its operational simplicity [41] , its effectiveness has increasingly been questioned. Recent evidence supports adopting AUC 0-24h /MIC as the preferred monitoring target [8,12] , as it better balances therapeutic efficacy and nephrotoxicity risk. However, these PK/PD parameters hold significant value in predicting nephrotoxicity. Studies have demonstrated a significant positive correlation between vancomycin trough concentrations and the risk of AKI [42,43] . When trough concentrations reach ≥20 mg/L, the risk of AKI increases to 37% [9] , while an AUC 0-24h >600 is associated with a significantly elevated risk of VA-AKI ( P < 0.05) [44-45] . Notably, although high trough concentrations (≥15 mg/L) increase nephrotoxicity risk [46] , they do not reduce treatment failure rates, highlighting an efficacy-toxicity dissociation. Based on these findings, the 2020 Chinese guidelines revised the target trough concentration for pediatric patients to 5-15 mg/L [47] . Our results further support reevaluating traditional targets in adults. Although no significant difference in AKI incidence was observed between monitoring methods ( χ² = 0.057, P = 0.812) [48] , AUC 0-24h -guided monitoring may better balance efficacy and safety [1,44-45,49] . Although the 2009 IDSA guidelines [3] recommended vancomycin trough concentrations as a surrogate marker for AUC/MIC, subsequent clinical practice has revealed that its accuracy is influenced by factors such as the MIC. Studies have demonstrated [50] that when the MIC is 1 mg/L, a daily dose of 3-4 g is required to achieve a 90% probability of target attainment (PTA), underscoring the critical role of MIC in dose optimization. In this study, for isolates with MIC ≤1 mg/L, both trough concentrations of 10-20 mg/L and AUC 0-24h /MIC ratios of 400-650 were associated with clinical efficacy rates exceeding 90%. However, the PTA remained approximately 40%, with no significant difference observed between the two monitoring approaches ( χ² = 0.057, P = 0.812). A multicenter retrospective study by Yu et al. [51] further confirmed a strong correlation between trough concentrations and AUC 0-24h within the 15-20 mg/L range, supporting their complementary roles in therapeutic drug monitoring. It is important to note that, as a retrospective analysis, this study has limitations, including a modest sample size ( n = 103) and population heterogeneity. Large-scale prospective studies are needed to validate these findings. Future research should focus on: (1) establishing therapeutic targets specific to the Chinese population; (2) evaluating the cost-effectiveness of optimized monitoring strategies; and (3) developing predictive models that integrate host immune biomarkers with PK/PD parameters. Such efforts will advance vancomycin therapy from concentration-based monitoring toward precision dosing, thereby optimizing efficacy while minimizing the risk of nephrotoxicity. Conclusion This study found no significant correlation between vancomycin PK/PD parameters (trough concentration and AUC 0-24h /MIC) and clinical efficacy or microbiological clearance in Chinese patients ( P > 0.05). However, these pharmacokinetic indicators demonstrated potential value in predicting vancomycin-associated nephrotoxicity. Given the relatively small sample size ( n = 103), high heterogeneity among patients, and potential selection bias due to the retrospective design, future studies should aim to validate the current guideline-recommended efficacy targets through large-scale, multicenter, prospective cohort studies, with an emphasis on improving patient population homogeneity and standardizing efficacy evaluation criteria. Ethical approval This is a single-center retrospective study, approved by the Ethics Committee of Shandong First Medical University Affiliated Provincial Hospital (Approval No. SWYX: NO.2024-1011). Due to the retrospective nature of the study, the requirement for obtaining informed consent from patients was waived. Funding This study was supported by the Shandong Pharmaceutical Association’s Project (Kjyw2024-1), Wu Jieping Medical Foundation (320.6750.2023-26-16), the Natural Science Foundation of Shandong Province (ZR2023ZD28) and the National Natural Science Foundation of China (82070861). Conflict of interest statement The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Acknowledgments The authors would like to thank Professor Dongna Zou and Professor Qiu Li for their valuable guidance in microbiology analysis and their support of the research funding for the project, who also served as the co-corresponding authors of this study. 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Should the trough concentration of vancomycin be abandoned in therapeutic drug monitoring? A multicentre, retrospective study of critically ill patients without any form of dialysis [J]. International Journal of Antimicrobial Agents, 2023, 61(6): 106812. https://doi.org/10.1016/j.ijantimicag.2023.106812 Supplementary Material File (image1.tiff) Download 453.12 KB Information & Authors Information Version history V1 Version 1 03 February 2026 Copyright This work is licensed under a Non Exclusive No Reuse License. Authors Affiliations Fengping Xu 0009-0006-1021-4741 Shandong Provincial Hospital View all articles by this author Yue Yin Shandong First Medical University School of Pharmacy View all articles by this author Xiaohui Wang Shandong First Medical University School of Pharmacy View all articles by this author Qiu Li Shandong Provincial Hospital View all articles by this author Dongna Zou [email protected] Shandong Provincial Hospital View all articles by this author Metrics & Citations Metrics Article Usage 106 views 41 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Fengping Xu, Yue Yin, Xiaohui Wang, et al. Retrospective Evaluation of Vancomycin Monitoring in Chinese Adults with Gram-Positive Coccal Infections. Authorea . 03 February 2026. DOI: https://doi.org/10.22541/au.177010035.58048200/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. 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