Penetration of Cefotaxime into Cerebrospinal Fluid in Neonates and Young Infants

Chen, Xing-Kai; Shi, Haiyan; Leroux, Stéphanie; Xu, Huilin; Zhou, Yue; Zheng, Yi; Huang, Xin; Li, Yan; Jacqz-Aigrain, Évelyne; Zhao, Wei

doi:10.1128/aac.02448-17

Cited by 11 publications

(8 citation statements)

References 21 publications

(16 reference statements)

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“…Platelets are produced in the bone marrow; therefore, we speculated that antibiotics with high cerebrospinal fluid transferability may show high expression rates of DITP before data mining. However, signals were not detected for antibiotics with high cerebrospinal fluid transferability, such as ceftriaxone 17 and cefotaxime, 18 whereas TEIC, 19 an antibiotic with poor cerebrospinal fluid transferability, was detected. Therefore, it may be difficult to explain the risk of developing DITP based on cerebrospinal fluid transferability.…”

Section: Discussionmentioning

confidence: 94%

Evaluation of the Expression Profile of Antibiotic-Induced Thrombocytopenia Using the Japanese Adverse Drug Event Report Database

2021

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Drug-induced thrombocytopenia (DITP) can be triggered by antibiotics; however, the details remain unclear. Here, we evaluated the expression profiles of DITP using the Japanese Adverse Drug Event Report (JADER) database. We analyzed reports of DITP between April 2004 and January 2021 from the JADER database. The reporting odds ratio (ROR) and 95% confidence interval (CI) were used to detect DITP signals. Factors thought to affect DITP, such as male sex and an age of at least 60 years, were added as covariates. We evaluated the time-to-onset profile and hazard type using the Weibull shape parameter. The JADER database contained 1,048,576 reports. Twelve of 60 antibiotics showed signals for DITP; the RORs (95% CIs) for ampicillin/sulbactam, ceftazidime, cefozopran, ciprofloxacin, fluconazole, fos-fluconazole, linezolid, pazufloxacin, piperacillin/tazobactam, teicoplanin, trimethoprim/sulfamethoxazole, and voriconazole were 1.75 (1.41-2.16), 1.77 (1.42-2.18), 1.35 (1.06-1.72), 2.56 (2.19-2.98), 1.93 (1.67-2.23), 2.08 (1.76-2.46), 5.29 (2.73-9.60), 1.92 (1.51-2.41), 1.54 (1.05-2.19), 1.47 (1.16-1.84), 1.92 (1.73-2.14), and 2.32 (1.59-3.30), respectively. In multiple logistic regression analysis, 7 and 6 antibiotics were detected for the factors age and male sex, respectively. The median times-to-onset of DITP for ciprofloxacin (oral treatment), fluconazole, linezolid, piperacillin/tazobactam, and trimethoprim/sulfamethoxazole were 91, 91, 11.5, 10, and 9 days, respectively. Furthermore, the 95% CI of the Weibull shape parameter β for these antibiotics was above and excluded 1, indicating that the antibiotics were the wear out failure type. We revealed the expression profiles of DITP following treatment with 12 antibiotics.

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Section: Discussionmentioning

confidence: 94%

Evaluation of the Expression Profile of Antibiotic-Induced Thrombocytopenia Using the Japanese Adverse Drug Event Report Database

2021

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“…An opportunistic sampling design was chosen to collect PK samples. Blood samples were obtained from the blood remaining after blood-gas or biochemical analyses (23,24). Infusion and sample times were recorded precisely.…”

Section: Methodsmentioning

confidence: 99%

Reappraisal of the Optimal Dose of Meropenem in Critically Ill Infants and Children: a Developmental Pharmacokinetic-Pharmacodynamic Analysis

Wang

Chen

et al. 2020

Antimicrob Agents Chemother

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Data of developmental pharmacokinetics (PK) of meropenem in critically ill infants and children with severe infections are limited. We assessed the population PK and defined the appropriate regimen to optimize treatment in this population based on developmental PK-pharmacodynamic (PD) analysis. Blood samples were collected from pediatric intensive care unit patients with severe infection treated with standard dosage regimens for meropenem. Population PK data were analyzed using NONMEM software. Fifty-seven patients (mean age, 2.96 years [range, 0.101 to 14.4]; mean body weight, 15.8 kg [range, 5.0 to 65.0]) were included. A total of 135 meropenem concentrations were obtainable for population PK modeling. The median number of samples per patients was 2 (range, 1 to 4). A two-compartment model with first-order elimination was optimal for PK modeling. Weight and creatinine clearance (estimated by the Schwartz formula) were significantly correlated with the PK parameters of meropenem. The probabilities of target attainment for pathogens with low MICs of 1 and 2 μg/ml were 87.5% and 68.6% following administration of 40 mg/kg/dose (every 8 h [q8h]) as a 4-h infusion and 98.0% and 73.3% with high MICs of 4 and 8 μg/ml following administration of 110 mg/kg/day as a continuous infusion in critically ill infants and children under 70% fT>MIC (the free time during which the plasma concentration of meropenem exceeds the MIC), respectively. The standard dosage regimens for meropenem did not meet an appropriate PD target, and an optimal dosing regimen was established in critically ill infants and children. (This study has been registered at ClinicalTrials.gov under identifier NCT03643497.)

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“…As shown Table 1 Because neutrophils are produced in bone marrow, we speculated that antibiotics with high migration to bone marrow may have a high risk of inducing agranulocytosis before data mining. However, signals were not detected for antibiotics with high cerebrospinal fluid transferability, such as ceftriaxone [10] and cefotaxime [11], whereas teicoplanin [12], an antibiotic with poor cerebrospinal fluid transferability, was detected. Therefore, these findings suggested that the risk of agranulocytosis could not be clarified by analysis of migration to the bone marrow only.…”

Section: Resultsmentioning

confidence: 96%

Comprehensive Analysis of Antibiotic-induced Agranulocytosis Using the Japanese Adverse Drug Event Report Database

Asai¹,

Yamamoto²,

Y³

2021

Preprint

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Although infrequent, drug-induced agranulocytosis can be stimulated by antibiotics. Here, we analyzed the Japanese Adverse Drug Event Report database to identify profiles of antibiotic-induced agranulocytosis. Ten of 60 antibiotics showed signals for agranulocytosis; the reporting odds ratios (95% confidence intervals) for ampicillin/sulbactam, amikacin, cefmetazole, cefozopran, clindamycin, ciprofloxacin, imipenem/cilastatin, kanamycin, teicoplanin, and vancomycin were 2.65 (1.79–3.80), 2.49 (1.91–4.34), 4.48 (2.27–6.92), 2.77 (1.88–3.95), 1.64 (1.04–2.47), 2.01 (1.40–2.82), 2.78 (2.11–3.60), 6.05 (2.16–13.7), 2.05 (1.31–3.07), and 3.54 (2.73–4.54), respectively. The median times-to-onset of agranulocytosis for ampicillin/sulbactam, cefmetazole, cefozopran, clindamycin, imipenem/cilastatin, kanamycin, teicoplanin, and vancomycin were 20, 6, 10, 16, 12, 3, 18, and 13 days, respectively. The 95% confidence intervals of the Weibull shape parameter β for these antibiotics were over and excluded 1, indicating that the antibiotics were the wear out failure type. These findings provided insights into the characteristics of antibiotic-induced agranulocytosis.

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Penetration of Cefotaxime into Cerebrospinal Fluid in Neonates and Young Infants

Cited by 11 publications

References 21 publications

Evaluation of the Expression Profile of Antibiotic-Induced Thrombocytopenia Using the Japanese Adverse Drug Event Report Database

Evaluation of the Expression Profile of Antibiotic-Induced Thrombocytopenia Using the Japanese Adverse Drug Event Report Database

Reappraisal of the Optimal Dose of Meropenem in Critically Ill Infants and Children: a Developmental Pharmacokinetic-Pharmacodynamic Analysis

Comprehensive Analysis of Antibiotic-induced Agranulocytosis Using the Japanese Adverse Drug Event Report Database

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