ABSTRACT
Pediatric sepsis syndrome is one of the most common reasons for pediatric intensive care unit hospitalization (PICU). Cefoperazone/sulbactam is a time-dependent beta-lactamase inhibitor combination which has been widely used in the treatment of sepsis. But the pharmacokinetic (PK) and pharmacodynamic (PD) data of cefoperazone/sulbactam are unknown in children with sepsis. The present work aimed to determine whether the usual dosing regimens of cefoperazone/sulbactam (1 hour infusion, 50 mg kg-1, every 12 hours) were suitable for these patients in PICU. A total of fourteen patients were enrolled and the PK parameters were estimated by non-compartmental analysis using WinNonlin software. The t1/2 and AUC0-12 of cefoperazone and sulbactam were 3.60 and 1.77 h, and 900.97 and 67.68 h µg mL-1, respectively. The Vd and CL of cefoperazone and sulbactam were 1.65 L and 5.16 L, and 17.41 mL min-1 and 122.62 mL min-1, respectively. The probability of target attainments (PTAs) of cefoperazone at different minimum inhibitory concentrations (MICs) based on the percentage time that concentrations exceed the minimum inhibitory concentration (% T > MIC) value were performed by Monte Carlo simulation and PTA was >90% at MICs ≤16 µg mL-1. The PK/PD profile of dosing regimens tested will assist in selecting the appropriate cefoperazone/sulbactam regimens for these patients. At a target of 80% T > MIC, the usual dosing regimens can provide good coverage for pathogens with MICs of ≤32 µg mL-1. The ratio between cefoperazone and sulbactam at 1 : 1 may be more suitable in pediatric sepsis. Individual dose and therapeutic drug monitoring in clinical practice will help achieve the best therapeutic effect while minimizing toxicity.
Subject(s)
Sepsis , Sulbactam , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Cefoperazone/pharmacology , Cefoperazone/therapeutic use , Child , Humans , Monte Carlo Method , Sepsis/drug therapy , Sulbactam/pharmacology , Sulbactam/therapeutic useABSTRACT
Acute lung injury (ALI) is a serious clinical syndrome that can cause respiratory failure and threaten the life of the patients. A biomarker that can predict the syndrome can contribute to a better clinical management of the patients. In adults, genetic polymorphisms in inflammatory-response genes have been shown to be a promising biomarker. However, the pathogenesis of ALI in adult is known to be different from that in children and no previous study has investigated the association between inflammatory gene polymorphisms and pediatric ALI (PALI) risk. In this work, we examined the association between 12 polymorphisms in six inflammatory-response genes (TNF, IL6, IL10, IL18, NFKB1 and NFKBIA) and risk of PALI. A total of 1075 children with ALI and 1382 non-ALI controls were recruited. The polymorphisms were genotyped employing RFLP method. The risk association was estimated via logistic regression analysis, with Pâ¯<â¯0.004 being statistically significant after Bonferroni correction. A statistically significant association was observed for IL10 rs1800896 (heterozygous, Pâ¯<â¯0.0001; homozygous variant, Pâ¯<â¯0.0001; allele, Pâ¯<â¯0.0001) and TNF rs1800629 (heterozygous, Pâ¯<â¯0.0001; homozygous variant, Pâ¯=â¯0.0012; allele, Pâ¯<â¯0.0001) polymorphisms. On the other hand, no significant association was found for IL6 rs1800795, rs1800796 and rs1800797 polymorphisms, IL10 rs3021097 polymorphism, NFKB1 rs28362491 polymorphism, NFKBIA rs2233406 and rs696 polymorphisms, IL18 rs1946518 and rs187238 polymorphisms, and TNF rs1799964 polymorphism. In conclusion, IL10 rs1800896 and TNF rs1800629 may serve as a risk biomarker for pediatric ALI among Chinese.
Subject(s)
Acute Lung Injury/genetics , Asian People/genetics , Biomarkers/analysis , Cytokines/genetics , Genetic Predisposition to Disease , Inflammation/genetics , Polymorphism, Single Nucleotide , Acute Lung Injury/epidemiology , Acute Lung Injury/pathology , Adolescent , Case-Control Studies , Child , Child, Preschool , China/epidemiology , Female , Follow-Up Studies , Genotype , Humans , Infant , Inflammation/epidemiology , Inflammation/pathology , Interleukin-10/genetics , Interleukin-18/genetics , Male , NF-KappaB Inhibitor alpha/genetics , Prognosis , Tumor Necrosis Factor-alpha/geneticsABSTRACT
In the present study, we investigated the association of 12 polymorphisms in six inflammatory-response genes (TNF, IL6, IL10, IL18, NFKB1 and NFKBIA) with risk of acute kidney injury (AKI) in children. The polymorphisms were genotyped in 1138 children with AKI and 1382 non-AKI controls. Logistic regression analysis was performed to calculate the odds ratio for estimating the risk association. After accounting for Bonferroni correction and adjustment for potential confounders, significant association was observed for NFKB1 rs28362491, NFKBIA rs2233406 and NFKBIA rs696 polymorphisms (P < 0.004). All three polymorphisms were associated with a reduced risk of AKI. For rs28362491 polymorphism, the OR for ID vs. II comparison was 0.75 (95% CI = 0.58-0.83) while that for DD vs. II was 0.44 (95% CI = 0.30-0.67). For rs2233406 polymorphism, the CT vs. CC comparison showed an OR of 0.90 (95% CI = 0.39-0.99), while the TT vs. CC comparison showed an OR of 0.43 (95% CI = 0.33-0.80). For rs696 polymorphism, the OR for AG vs. AA comparison was 0.71 (95% CI = 0.43-0.89), while the GG vs. AA comparison showed an OR of 0.39 (95% CI = 0.21-0.71). In conclusion, NFKB1 rs28362491, NFKBIA rs2233406 and NFKBIA rs696 polymorphisms may serve as biomarkers for predicting risk of AKI in children.
