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1.
BMC Health Serv Res ; 23(1): 771, 2023 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-37468855

RESUMO

BACKGROUND AND OBJECTIVE: Currently, the detection rates of methicillin-resistant S. aureus (MRSA) and methicillin-resistant coagulase-negative staphylococci (MRCoNS) in the blood cultures of neonates with sepsis exceed the national average drug resistance level, and vancomycin and linezolid are the primary antibacterial drugs used for these resistant bacteria according to the results of etiological examinations. However, a comprehensive evaluation of their costs and benefits in late-onset neonatal sepsis in a neonatal intensive care unit (NICU) has not been conducted. This study aimed to compare the cost and effectiveness of vancomycin and linezolid in treating neonatal sepsis in the NICU. METHODS: A cost-effectiveness analysis of real-world data was carried out by retrospective study in our hospital, and the cost and effectiveness of vancomycin and linezolid were compared by establishing a decision tree model. The drug doses in the model were 0.6 g for linezolid and 0.5 g for vancomycin. The cost break down included cost of medical ward, NICU stay, intravenous infusion of vancomycin or linezolid, all monitoring tests, culture tests and drugs. The unit costs were sourced from hospital information systems. The effectiveness rates were obtained by cumulative probability analysis. One-way sensitivity analysis was used to analyze uncertain influencing factors. RESULTS: The effectiveness rates of vancomycin and linezolid in treating neonatal sepsis in the NICU were 89.74% and 90.14%, respectively, with no significant difference. The average cost in the vancomycin group was ¥12261.43, and the average cost in the linezolid group was ¥17227.96. The incremental cost effectiveness was ¥12416.33 cost per additional neonate with treatment success in the linezolid group compared to vancomycin group at discharge. Factors that had the greatest influence on the sensitivity of the incremental cost-effectiveness ratio were the price of linezolid and the effectiveness rates. CONCLUSIONS: The cost for treatment success of one neonate in linezolid group was ¥5449.17 more than that in vancomycin group, indicating that vancomycin was more cost-effective. Therefore, these results can provide a reference for a cost effectiveness treatment scheme for neonatal sepsis in the NICU.


Assuntos
Antibacterianos , Custos de Medicamentos , Linezolida , Staphylococcus aureus Resistente à Meticilina , Sepse Neonatal , Vancomicina , Vancomicina/administração & dosagem , Vancomicina/economia , Vancomicina/uso terapêutico , Linezolida/administração & dosagem , Linezolida/economia , Linezolida/uso terapêutico , Antibacterianos/administração & dosagem , Antibacterianos/economia , Antibacterianos/uso terapêutico , Sepse Neonatal/tratamento farmacológico , Análise de Custo-Efetividade , Humanos , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Masculino , Feminino , Lactente , Coagulase/genética , Estudos Retrospectivos , Resultado do Tratamento , China
2.
BMC Pregnancy Childbirth ; 23(1): 485, 2023 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-37391694

RESUMO

BACKGROUND: This study aims to investigate the risk factors for not returning to postpartum blood pressure (BP) follow-up visit at different time points in postpartum discharged hypertensive disorders of pregnancy (HDP) patients. Likewise, females with HDP in China should have a BP evaluation continuously for at least 42 days postpartum and have BP, urine routine, and lipid and glucose screening for 3 months postpartum. METHODS: This study is a prospective cohort study of postpartum discharged HDP patients. Telephone follow-up was conducted at 6 weeks and 12 weeks postpartum, the maternal demographic characteristics, details of labor and delivery, laboratory test results of patients at admission, and adherence to BP follow-up visits postpartum were collected. While logistic regression analysis was used to analyze the factors associated with not returning to postpartum BP follow-up visit at 6 weeks and 12 weeks after delivery, the receiver operating characteristic (ROC) curve was drawn to evaluate the model's predictive value for predicting not returning to postpartum BP visit at each follow-up time point. RESULTS: In this study, 272 females met the inclusion criteria. 66 (24.26%) and 137 (50.37%) patients did not return for postpartum BP visit at 6 and 12 weeks after delivery. A multivariate logistic regression analysis identified education level of high school or below (OR = 3.71; 95% CI = 2.01-6.85; p = 0.000), maximum diastolic BP during pregnancy (OR = 0.97; 95% CI = 0.94-0.99; p = 0.0230)and delivery gestational age (OR = 1.12; 95% CI = 1.005-1.244; p = 0.040)as independent risk factors in predicting not returning to postpartum BP follow-up visit at 6 weeks postpartum, and education level of high school or below (OR = 3.20; 95% CI = 1.805-5.67; p = 0.000), maximum diastolic BP during pregnancy (OR = 0.95; 95% CI = 0.92-0.97; p = 0.000), delivery gestational age (OR = 1.13; 95% CI = 1.04-1.24; p = 0.006) and parity (OR = 1.63; 95% CI = 1.06-2.51; p = 0.026) as risk factors for not returning to postpartum BP follow-up visit at 12 weeks postpartum. The ROC curve analysis indicated that the logistic regression models had a significant predictive value for identify not returning to BP follow-up visit at 6 and 12 weeks postpartum with the area under the curve (AUC) 0.746 and 0.761, respectively. CONCLUSION: Attendance at postpartum BP follow-up visit declined with time for postpartum HDP patients after discharge. Education at or below high school, maximum diastolic BP during pregnancy and gestational age at delivery were the common risk factors for not returning for BP follow-up visit at 6 and 12 weeks postpartum in postpartum HDP patients.


Assuntos
Hipertensão Induzida pela Gravidez , Alta do Paciente , Feminino , Gravidez , Humanos , Pressão Sanguínea , Seguimentos , Hipertensão Induzida pela Gravidez/epidemiologia , Estudos Prospectivos
3.
J Antimicrob Chemother ; 78(8): 1974-1981, 2023 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-37341139

RESUMO

BACKGROUND: Linezolid-induced thrombocytopenia is the main factor restricting the clinical application of linezolid. OBJECTIVES: To investigate the relationship between PNU-14230 concentration and linezolid-induced thrombocytopenia and further develop and validate a risk model for predicting linezolid-induced thrombocytopenia. METHODS: A regression model was constructed to predict the occurrence of linezolid-induced thrombocytopenia, and further externally validated. The predictive performance was evaluated by receiver operating characteristic curve and Hosmer-Lemeshow test. Linezolid Cmin and PNU-142300 concentrations were compared for different kidney function groups. The Kaplan-Meier method was used to estimate the difference in cumulative incidence of linezolid-induced thrombocytopenia among different kidney function patients. RESULTS: In the derivation (n = 221) and validation (n = 158) cohorts, 28.5% and 24.1% of critically ill patients developed linezolid-induced thrombocytopenia. Logistic regression analysis indicated that the independent risk factors were linezolid Cmin, PNU-142300 concentration, baseline platelet count, renal insufficiency (RI) and continuous venovenous haemofiltration (CVVH). The AUC for the risk model was 0.901, and the model was good (P = 0.633). The model also showed good discrimination (AUC 0.870) and calibration (P = 0.282) in the external validation cohort. Compared with normal kidney function patients, patients with RI and CVVH had higher linezolid Cmin and PNU-142300 concentrations (P < 0.001) and higher cumulative incidence of linezolid-induced thrombocytopenia (P < 0.001). CONCLUSIONS: PNU142300 concentration, as well as linezolid Cmin, might identify patients at risk of linezolid-induced thrombocytopenia. The risk prediction model had good predictive performance for linezolid-induced thrombocytopenia development. Concentrations of linezolid and PNU-142300 accumulated in patients with RI and CVVH.


Assuntos
Insuficiência Renal , Trombocitopenia , Humanos , Linezolida/efeitos adversos , Antibacterianos/efeitos adversos , Trombocitopenia/induzido quimicamente , Contagem de Plaquetas
4.
Int J Antimicrob Agents ; 62(2): 106881, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37301313

RESUMO

OBJECTIVES: This study evaluated the intervention effect of clinical pharmacist-mediated optimisation of a linezolid regimen using a population pharmacokinetic (PPK) model. METHODS: Patients treated with linezolid in two medical centres from January 2020 to June 2021 were retrospectively included in the control group; those treated from July 2021 to June 2022 were prospectively enrolled in the intervention group. Clinical pharmacists optimised the dosage regimen according to a published linezolid PPK model in the intervention group. An interrupted times series approach was used to analyse the data. The incidence of linezolid-induced thrombocytopenia (LIT), target attainment of pharmacokinetic/pharmacodynamic parameters and other adverse drug reactions (ADRs) were compared between the two groups. RESULTS: In total, 77 and 103 patients were enrolled in the control and intervention groups, respectively. The intervention group had a lower incidence of LIT and other ADRs than the control group (10.7% vs. 23.4%, P = 0.002; 1.0% vs. 7.8%, P = 0.027). The intervention group exhibited a considerably lower trough concentration (Cmin) and area under the concentration-time curve/MIC ratio (AUC24/MIC) (P = 0.001 and P < 0.001). Cmin and AUC24/MIC rates within the target range were substantially higher in the intervention group (49.6% vs. 20.0%, adjusted P < 0.05; 48.1% vs. 25.6%, adjusted P < 0.05). CONCLUSION: Interventions by clinical pharmacists reduced the incidence of LIT and other ADRs. Implementation of model-informed precision dosing (MIPD) for linezolid markedly increased the Cmin and AUC24/MIC rates within the target range. We recommend MIPD-guided linezolid dose reduction for patients with renal impairment.


Assuntos
Antibacterianos , Trombocitopenia , Humanos , Linezolida/efeitos adversos , Antibacterianos/efeitos adversos , Estado Terminal/terapia , Estudos Prospectivos , Estudos Retrospectivos , Trombocitopenia/induzido quimicamente
5.
BMC Infect Dis ; 22(1): 667, 2022 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-35918657

RESUMO

BACKGROUND: A prospective interventional study comparing outcomes in critically ill patients receiving intermittent infusion (II) or continuous infusion (CI) of vancomycin during continuous venovenous hemofiltration (CVVH) is lacking. The objective of this study was to compare the pharmacokinetic/pharmacodynamics (PK/PD) target attainment, therapeutic efficacy and safety among critically ill patients who received CI or II of vancomycin in a prospective interventional trial and to explore the correlations of effluent flow rate (EFR) with PK/PD indices. METHODS: This prospective interventional study was conducted in two independent intensive care units (ICUs) from February 2021 to January 2022. Patients in one ICU were assigned to receive CI (intervention group) of vancomycin, whereas patients in the other ICU were assigned to receive II regimen (control group). The primary outcome was to compare the PK/PD target attainment, including target concentration and target area under the curve over 24 h to minimum inhibitory concentration (AUC24/MIC). RESULTS: Overall target attainment of PK/PD indices was higher with CI compared with II, irrespective of target concentration (78.7% vs. 40.5%; P < 0.05) or AUC24/MIC (53.2% vs. 28.6%; P < 0.05). There were no significant differences in clinical success (72.2% vs. 50.0%; P = 0.183) and microbiological success (83.3% vs. 75.0%, P = 0.681) between the patients treated with CI or II of vancomycin. Adverse reactions occurred at similar rates (0.0% vs. 4.4%; P = 0.462), and mortality between the two modalities was also not significant different (21.7% vs. 17.9%; P = 0.728). Correlation analysis showed a weak to moderately inverse correlation of EFR with observed concentration (r = - 0.3921, P = 0.01) and AUC24/MIC (r = - 0.3811, P = 0.013) in the II group, whereas the correlation between EFR and observed concentration (r = - 0.5711, P < 0.001) or AUC24/MIC (r = - 0.5458, P < 0.001) in the CI group was stronger. CONCLUSION: As compared to II, CI of vancomycin in critically ill patients undergoing CVVH was associated with improved attainment of PK/PD indices. Furthermore, the inverse correlation of PK/PD indices with EFR was stronger among patients treated with CI of vancomycin. Trial registration The trial was registered in the Chinese clinical trial registration center (21/01/2021-No. ChiCTR2100042393).


Assuntos
Terapia de Substituição Renal Contínua , Hemofiltração , Antibacterianos/uso terapêutico , Estado Terminal/terapia , Humanos , Estudos Prospectivos , Vancomicina/uso terapêutico
6.
J Chemother ; 34(7): 446-458, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35773225

RESUMO

In vancomycin treatment, the rates of correct blood sampling and initial trough concentrations within the target range are very low. Studies of interventions by clinical pharmacists based on population pharmacokinetics (PPK) models are limited. This study aimed to evaluate the intervention effect of clinical pharmacist-mediated optimization of the vancomycin administration regimen based on a PPK model. Retrospectively enrolled patients constituted the control group, and prospectively enrolled patients constituted the intervention group. The vancomycin administration regimen, trough concentration, pharmacokinetic parameters, and clinical outcomes of the two groups were compared. The control and intervention groups comprised 236 and 138 patients, respectively. Compared with those in the control group, the therapeutic drug monitoring (TDM) and correct TDM sampling time rates in the intervention group were significantly higher (76.92% vs. 43.59%; 63.9% vs. 39.0%, both p < 0.001). The rates of an initial trough concentration within 10-20 mg/L and an adjusted regimen were also significantly higher in the intervention group (55.80% vs. 30.51%, 71.95% vs. 39.18%, both p < 0.001). The rate of an area under the curve (AUC) within 400-650 mg·h/L was higher in the intervention group than in the control group (52.7% vs. 36.6%, p < 0.001). The eradication rates of Gram-positive bacteria were 91.4% in the intervention group and 81.3% in the control group (p = 0.049). Eight patients developed acute kidney injury (AKI) in the control group; however, no AKI occurred in the intervention group (p = 0.029). Intervention by clinical pharmacists can increase the rate of correct sampling time. Using the PPK model combined with Bayesian estimation, clinical pharmacists can greatly increase the trough concentration and AUCs within the target range, especially for adjusted regimens. Higher PK/PD target rates resulted in better Gram-positive bacterial eradication and reduced renal toxicity of vancomycin.


Assuntos
Farmacêuticos , Vancomicina , Humanos , Vancomicina/uso terapêutico , Vancomicina/farmacocinética , Estudos Prospectivos , Estudos Retrospectivos , Teorema de Bayes , Antibacterianos/efeitos adversos , Antibacterianos/farmacocinética , Área Sob a Curva , Monitoramento de Medicamentos/métodos
7.
Front Pharmacol ; 13: 817401, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35350761

RESUMO

Background: Due to the lack of updated information on teicoplanin (TEI) for continuous renal replacement therapy (CRRT), no exact dosage regimen has been recommended. The aim of this study was to optimize the dosage regimen of TEI in renal dysfunction patients with or without CRRT, evaluate the influence factors of the eradication of Gram-positive bacteria, and evaluate the effect of CRRT on the clearance of TEI. Methods: Patients with renal dysfunction receiving TEI treatment in the ICU were prospectively recruited and divided into CRRT and non-CRRT groups. Logistic regression analysis was used to screen the factors affecting the eradication of Gram-positive bacteria. The filtrate concentration of the CRRT group was measured at the time of TEI Cmin, and the filtration coefficient of TEI was calculated to evaluate the effect of CRRT on the clearance of TEI. Results: A total of 106 patients were included, 40 cases in the CRRT group and 66 cases in the non-CRRT group. After giving high-loading doses of TEI, 75.8 and 70% of TEI Cmin in the non-CRRT and CRRT groups reached the range of 10-30 mg/L before the 3rd dose, respectively. The risk of G+ bacteria being uneradicated was higher while the APACHEⅡscore was higher than 22.5. The albumin level before the start of TEI administration and before the 6th-8th dose was lower than 32.8 g/L and 29.3 g/L, respectively, and Cmin before the 3rd dose and 6th-8th dose was lower than 13.2 mg/L and 17.1 mg/L, respectively, with the duration of TEI therapy shorter than 10.5 days. The correlation coefficient (r) was 0.6490 between Cmin before the 3rd dose and the albumin level (p < 0.001). The filtration coefficient of TEI was 10.7 ± 2.4% at Cmin and 11.1 ± 2.5% at Cmax. The GFR had no correlation with the filtration coefficient (r = -0.06204; r = -0.08059). The clearance of TEI in CRRT patients was negatively correlated with the albumin level (r = -0.6305, p = 0.0013). Conclusion: The early stage of the albumin level can significantly affect the initial Cmin and clinical efficacy of TEI, and also had effect on the clearance of TEI by CRRT. The filtration coefficient of TEI was stable, even with a higher ultrafiltration rate.

8.
Front Pharmacol ; 13: 832078, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35295325

RESUMO

Objective: The objective of the study was to assess the impact of multifaceted clinical pharmacist-led antimicrobial stewardship (AMS) program on the rational use of antibiotics for patients who receive vascular and interventional radiology therapies. Methods: A quasi-experimental retrospective intervention design with a comparison group was applied to the practice of antibiotic use in the department of vascular and interventional radiology in a Chinese tertiary hospital. We used difference-in-differences (DID) analysis to compare outcomes before and after the AMS intervention between the intervention group and control group, to determine whether intervention would lead to changes in irrationality of antibiotic prescribing, antibiotic utilization, cost of antibiotics, and length of hospital stay. Results: The DID results showed that the intervention group was associated with a reduction in the average consumption of antibiotics (p = 0.017) and cost of antibiotics (p = 0.006) and cost per defined daily dose (DDD) (p = 0.000). There were no significant differences in the mean change of total costs and length of stay between the two groups (p > 0.05). The average inappropriate score of perioperative antimicrobial prophylaxis in the intervention group declined by 0.23, while it decreased by 0.02 in the control group [0.21 (95% CI, -0.271 to -0.143); p = 0.000]. The average inappropriate score of non-surgical antimicrobial prophylaxis in the intervention group declined by 0.14, while it increased by 0.02 in the control group [0.16 (95% CI, -0.288 to -0.035); p = 0.010]. The average inappropriate score of the therapeutic use of antibiotics in the intervention group declined by 0.07, while it decreased by 0.01 in the control group [0.06 (95% CI, -0.115 to -0.022); p = 0.003]. Conclusions: This study provides evidence that implementation of AMS interventions was associated with a marked reduction of antibiotic use, cost of antibiotics, and irrationality of antibiotic prescribing in China.

9.
Front Pharmacol ; 13: 710099, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35185555

RESUMO

Background: Linezolid-induced thrombocytopenia (LIT) is the main factor limiting the clinical application of linezolid (LZD). The incidence and risk factors of LIT in neonatal patients were possibly different from other populations based on pathophysiological characteristics. The purpose of this study was to establish a regression model for predicting LIT in neonatal sepsis patients. Methods: We retrospectively included 518 patients and divided them into the LIT group and the non-LIT group. A logistic regression analysis was used to analyze the factors related to LIT, and a regression model was established. A receiver operating characteristic (ROC) curve was drawn to evaluate the model's predictive value. We prospectively collected 39 patients' data to validate the model and evaluate the effect of LZD pharmacokinetics on LIT. Results: Among the 518 patients, 103 patients (19.9%) developed LIT. The Kaplan-Meier plot revealed that the overall median time from the initiation of LZD treatment to the onset of LIT in preterm infants was much shorter when compared with term infants [10 (6, 12) vs. 13 (9.75, 16.5), p = 0.004]. Multiple logistic regression analysis indicated that the independent risk factors of LIT were lower weight at medication, younger gestational ages, late-onset sepsis, necrotizing enterocolitis, mechanical ventilation, longer durations of LZD treatment, and lower baseline of platelet level. We established the above seven-variable prediction regression model and calculated the predictive probability. The ROC curve showed that the predicted probability of combined body weight, gestational age, duration of LZD treatment, and baseline of platelet had better sensitivity (84.4%), specificity (74.2%), and maximum AUC (AUC = 0.873). LIT occurred in 9 out of 39 patients (23.1%), and the accuracies of positive and negative predictions of LIT were 88.9 and 76.7%, respectively. Compared with the non-LIT patients, the LIT patients had higher trough concentration [11.49 (6.86, 15.13) vs. 5.51 (2.80, 11.61) mg/L; p = 0.028] but lower apparent volume of distribution (Vd) [0.778 (0.687, 1.421) vs. 1.322 (1.099, 1.610) L; p = 0.010]. Conclusion: The incidence of LIT was high in neonatal sepsis patients, especially in preterm infants. LIT occurred earlier in preterm infants than in term infants. The regression model of seven variables had a high predictive value for predicting LIT. LIT was correlated with higher trough concentration and lower Vd.

10.
Eur J Hosp Pharm ; 29(e1): e6-e14, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-33414258

RESUMO

BACKGROUND: There is a significant correlation between augmented renal clearance (ARC) and lower serum trough concentrations of vancomycin (VCM) during therapy. There is a need to evaluate the predictive performance of the population pharmacokinetic (PPK) model used for individual calculation of dosage regimens in ARC patients. OBJECTIVE: Our study aimed to estimate the predictive performance differences of the reported VCM PPK software JPKD-vancomycin and SmartDose in patients with varying renal function status, especially those with ARC. METHODS: Patients receiving VCM treatment from May 2014 to December 2019 were enrolled, and divided into the ARC group, the normal renal function (NRF) group, and the impaired renal function (IRF) group. VCM dosage, trough concentration, area under the curve (AUC) and pharmacokinetic parameters were compared among the three groups. The predictive performance of PPK software was expressed using absolute prediction error (APE), sensitivity, specificity, and regression coefficient (r2) of linear regression analysis between the measured VCM trough concentration and the predicted trough concentration. RESULTS: A total of 388 patients were included: 86 patients in the ARC group, 241 patients in the NRF group, and 61 patients in the IRF group. The daily dose of the adjusted regimen in the ARC group was higher than in the NRF group, but the trough concentration was significantly lower than in the NRF group (2.8±0.6 g vs 1.9±0.6 g, p<0.001; 10.5±5.1 mg/L vs 12.9±6.8 mg/L, p=0.030). The percentage of trough concentrations lower than 10 mg/L was 84.9% in the ARC group. Compared with the APE of the initial dosage regimen, the APE of the adjusted regimen calculated by JPKD was lower in the ARC group (p=0.041) and the NRF group (p<0.001). Specificity of JPKD and SmartDose in the ARC group was higher than in the NRF group (p<0.001; p<0.001). According to the linear regression analysis, the coefficients of determination (r2) were all >0.6 for the initial regimen and adjusted regimen of VCM in the ARC and NRF groups, and the r2 of the adjusted regimen of JPKD was >0.8 in the ARC and NRF groups. In the IRF group, 31.1% of patients had a change in serum creatinine (Scr) level of >50%. The r2 increased from 0.527 to 0.7347 in SmartDose and from 0.55 to 0.7802 in JPKD when using Scr at the sampling time. The ARC group showed a significant decrease in AUC (p<0.001) and an increase in clearance rate (p<0.001) when compared to the NRF group. CONCLUSION: ARC was significantly associated with subtherapeutic serum VCM concentration. The pharmacokinetic parameters of VCM were diverse in patients with different renal function status. The PPK model JPKD and SmartDose had a good predictive performance for predicting VCM trough concentrations of the ARC and NRF patients, especially using JPKD for prediction of the adjusted regimen. The change of Scr is a main factor affecting the accuracy of software prediction.


Assuntos
Antibacterianos , Vancomicina , Creatinina/metabolismo , Humanos , Rim/metabolismo , Taxa de Depuração Metabólica
11.
Eur J Hosp Pharm ; 29(2): 101-108, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-33472817

RESUMO

BACKGROUND: In the neonatal population, individual calculation and adjustment of vancomycin (VCM) doses has been recommended based on population pharmacokinetics (PPK) methods. OBJECTIVE: Our previous study established a Chinese neonatal VCM PPK model. The main goal of this study was to evaluate the predictive performance of this PPK model for VCM trough concentration. METHODS: The data on neonatal severe infection patients treated with VCM were retrospectively collected. The predictive performance of this PPK model was expressed using mean prediction error (MPE), mean absolute prediction error (MAPE), sensitivity and specificity. Linear regression analysis was used to compare predicted and measured VCM concentrations. We drew the receiver operating characteristic (ROC) curve to evaluate the predictive efficacy of the ratio of area under the concentration-time curve over 24 hours to minimum inhibitory concentration (AUC0-24/MIC) and trough concentration for clinical efficacy. RESULTS: A total of 40 neonates with Gram-positive bacterial sepsis were included. After VCM treatment, 32 (80%) neonates were clinically cured. Eight cases were a clinical failure: the trough concentrations and AUC0-24 were lower than that of the clinical cure patients (8.70±4.30 vs 14.30±4.50 mg/L, p=0.003; 404.30±122.80 vs 515.40±131.70, p=0.037). The measured and predicted trough concentration were 11.16 (5.96, 16.53) mg/L and 10.13 (6.61, 15.73) mg/L, respectively. The MPE and MAPE were 4.62% and 13.26% (5.30%, 25.88%), respectively. The proportion of MAPE <30% in the adjusted regimen was higher than the initial regimen (89.66% vs 65.00%, p=0.039). Predictions of sensitivity and specificity by this PPK model were 88.24% and 94.29%, respectively. The coefficients of determination of linear regression analysis were 0.9171 and 0.9009 for the initial and adjusted regimen, respectively. The AUC0-24 was correlated with the trough concentration (r=0.587, p<0.001). The ROC curve indicated that the optimal cut-off points for predicting clinical efficacy were AUC0-24/MIC >425.47 and trough concentration >9.45 mg/L. CONCLUSION: This PPK model has good predictive performance in Chinese neonatal patients. Both AUC0-24/MIC and trough concentration can predict the clinical efficacy of antibacterial treatment.


Assuntos
Sepse Neonatal , Vancomicina , China/epidemiologia , Humanos , Recém-Nascido , Sepse Neonatal/diagnóstico , Sepse Neonatal/tratamento farmacológico , Estudos Retrospectivos , Resultado do Tratamento , Vancomicina/farmacocinética
12.
Front Pharmacol ; 12: 622948, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34177564

RESUMO

Background: Augmented renal clearance (ARC) risk factors and effects on vancomycin (VCM) of obstetric patients were possibly different from other populations based on pathophysiological characteristics. Our study was to establish a regression model for prediction of ARC and analyze the effects of ARC on VCM treatment in critically ill obstetric patients. Methods: We retrospectively included 427 patients, grouped into ARC and non-ARC patients. Logistic regression analysis was used to analyze the factors related to ARC. Receiver operating characteristic (ROC) curve was drawn to evaluate the predictive value of the model for ARC. Patients who received VCM therapy were collected. The published VCM population pharmacokinetic (PPK) model was used to calculate pharmacokinetic parameters. A linear regression analysis was made between the predicted and measured concentrations. Results: Of the 427 patients, ARC was present in 201 patients (47.1%). The independent risk factors of ARC were heavier, greater gestational age, higher albumin level, fewer caesarean section, severe preeclampsia and vasoactive drug; more infection, hypertriglyceridemia and acute pancreatitis. We established the above nine-variable prediction regression model and calculated the predicted probability. ROC curve showed that the predicted probability of combined weight, albumin and gestational age had better sensitivity (70.0%) and specificity (89.8%) as well as the maximal area under the curve (AUC, AUC = 0.863). 41 cases received VCM; 21 cases (51.2%) had ARC. The initial trough concentration in ARC patients was lower than in non-ARC patients (7.9 ± 3.2 mg/L vs 9.5 ± 3.3 mg/L; p = 0.033). Comparing the predicted trough concentration of two published VCM PPK models with the measured trough concentration, correlation coefficients (r) were all more than 0.8 in the ARC group and non-ARC group. AUC was significantly decreased in the ARC group (p = 0.003; p = 0.013), and clearance (CL) increased in the ARC group (p < 0.001; p = 0.008) when compared with the non-ARC group. Conclusion: ARC is a common state in critically ill obstetric patients. The regression model of nine variables had high predictive value for predicting ARC. The published VCM PPK models had good predictive performance for predicting trough concentrations of obstetric patients. Pharmacokinetic parameters of VCM are different in ARC obstetric patients, which results in enhanced VCM clearance and decreased trough concentration.

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