No Time Dependence of Ciprofloxacin Pharmacokinetics in Critically Ill Adults: Comparison of Individual and Population Analyses

The aim of this prospective PK study was to evaluate the pharmacokinetics of ciprofloxacin dosed within the first 36 h (early phase) and after 3 days of treatment (delayed phase) using individual and population PK analysis. The secondary aim of the study was to evaluate possible dosing implications of the observed PK differences between early and delayed phases to achieve a PK/PD target for ciprofloxacin of AUC24/MIC ≥ 125. Blood concentrations of ciprofloxacin (1 and 4 h after dose and trough) were monitored in critically ill adults in the early and delayed phases of the treatment. Individual and population PK analyses were performed. Complete concentration-time profiles in the early phase, delayed phase, and both phases were obtained from 29, 15, and 14 patients, respectively. No systematic changes in ciprofloxacin PK parameters between the early and delayed phases were observed, although variability was higher at the early phase. Both individual and population analyses provided similar results. Simulations showed that after standard dosing, it is practically impossible to reach the recommended ciprofloxacin PK/PD target (AUC/MIC ≥ 125) for pathogens with MIC ≥ 0.5 mg/L. A dosing nomogram utilizing patients’ creatinine clearance and MIC values was constructed. Both individual and population analyses provided similar results. Therapeutic drug monitoring should be implemented to safeguard the optimal ciprofloxacin exposure.

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P43 Pharmacokinetics and target attainment of antibiotics in critically ill children – a systematic review of current literature

Archives of Disease in Childhood ◽

10.1136/archdischild-2019-esdppp.81 ◽

2019 ◽

Vol 104 (6) ◽

pp. e35.1-e35

Author(s):

S Hartman ◽

R Brüggemann ◽

L Orriëns ◽

N Dia ◽

M Schreuder ◽

...

Keyword(s):

Critically Ill ◽

Patient Population ◽

Current Knowledge ◽

Volume Of Distribution ◽

Critically Ill Children ◽

Therapeutic Drug ◽

Healthy Children ◽

Target Attainment ◽

Critically Ill Adults ◽

Ill Adults

BackgroundPharmacokinetics (PK) are severely altered in critically ill patients due to changes in volume of distribution (Vd) and/or drug clearance (Cl). To what extent this affects the PK of antibiotics in critically children is largely unknown. We aimed to identify gaps in current knowledge and to compare published PK parameters and target attainment of antibiotics in critically ill children to healthy children and critically ill adults.MethodsSystematic literature search in PubMed, EMBASE and Web of Science. Articles were labelled as relevant when they included information on PK of antibiotics in critically ill, non-neonatal, pediatric patients. Extracted PK-parameters included Vd, Cl, trough concentrations, AUC, probability of target attainment, and elimination half-life.Results45 relevant articles were identified. Studies focusing on vancomycin were most prevalent (15/45). Other studies included data on penicillins, cephalosporins, carbapenems and aminoglycosides, but data on ceftriaxone, ceftazidime, penicillin and metronidazole could not be found. Critically ill children generally show a larger Vd and higher Cl than healthy children and critically ill adults. Reduced target attainment was described in critically ill children for multiple antibiotics, including amoxicillin, piperacillin, cefotaxime, vancomycin, gentamicin, teicoplanin, amikacin and daptomycin. 32/45 articles included information on both Vd and Cl, but a dosing advice was given in only 18 articles.ConclusionThe majority of studies focus on agents where therapeutic drug monitoring is applied, while other antibiotics lack data altogether. The larger Vd and higher Cl that is observed in critically ill children might warrant a higher dose or extended infusions of antibiotics in this patient population to increase target attainment. Studies frequently fail to provide a dosing advice for this patient population, even if the necessary information is available. Our study shows gaps in current knowledge and encourages future researchers to provide dosing advice for special populations whenever possible.Disclosure(s)Nothing to disclose

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Imipenem Population Pharmacokinetics: Therapeutic Drug Monitoring Data Collected in Critically Ill Patients with or without Extracorporeal Membrane Oxygenation

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00385-20 ◽

2020 ◽

Vol 64 (6) ◽

Author(s):

Wenqian Chen ◽

Dan Zhang ◽

Wenwen Lian ◽

Xiaoxue Wang ◽

Wenwen Du ◽

...

Keyword(s):

Therapeutic Drug Monitoring ◽

Extracorporeal Membrane Oxygenation ◽

Critically Ill ◽

Drug Monitoring ◽

Critically Ill Patients ◽

Small Sample ◽

Therapeutic Drug ◽

Blood Concentrations ◽

Membrane Oxygenation ◽

Population Pk

ABSTRACT Carbapenem pharmacokinetic (PK) profiles are significantly different in critically ill patients because of the drastic variability of the patients’ physiological parameters. Published population PK studies have mainly focused on specific diseases, and the majority of these studies had small sample sizes. The aim of this study was to develop a population PK model of imipenem in critically ill patients that estimated the influence of various clinical and biological covariates and the use of extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT). A two-compartment population PK model with creatinine clearance (CLCR), body weight (WT), and ECMO as fixed effects was developed using the nonlinear mixed-effects model (NONMEM). A Monte Carlo simulation was performed to evaluate various dosing schemes and different levels of covariates based on the pharmacokinetic/pharmacodynamic index (ƒ%T>MIC) for the range of clinically relevant MICs. The results showed that there may be insufficient drug use in the clinical routine drug dose regimen, and 750 mg every 6 h (q6h) could achieve a higher treatment success rate. The blood concentrations of imipenem in ECMO patients were lower than those in non-ECMO patients; therefore, dosages may need to be increased. The dosage may need adjustment for patients with a CLCR of ≤70 ml/min, but the dose should be lowered carefully to avoid the insufficient drug exposure. Dose adjustment is not necessary for patients with WT ranging from 50 to 80 kg. Due to the large variation in PK profile of imipenem in critically ill patients, therapeutic drug monitoring (TDM) should be carried out to optimize drug regimens.

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