Population pharmacokinetics and target attainment of ciprofloxacin in critically ill patients

The impact of ceftriaxone pharmacokinetic alterations on protein binding and PK/PD target attainment still remains unclear. We evaluated pharmacokinetic/pharmacodynamic (PK/PD) target attainment of unbound ceftriaxone in critically ill patients with severe community-acquired pneumonia (CAP). Besides, we evaluated the accuracy of predicted vs. measured unbound ceftriaxone concentrations, and its impact on PK/PD target attainment. A prospective observational cohort study was carried out in adult patients admitted to the intensive care unit with severe CAP. Ceftriaxone 2 g q24h intermittent infusion was administered to all patients. Successful PK/PD target attainment was defined as unbound trough concentrations above 1 or 4 mg/L throughout the whole dosing interval. Acceptable overall PK/PD target attainment was defined as successful target attainment in ≥90% of all dosing intervals. Measured unbound ceftriaxone concentrations (CEFu) were compared to unbound concentrations predicted from various protein binding models. Thirty-one patients were included. The 1 mg/L and 4 mg/L targets were reached in 26/32 (81%) and 15/32 (47%) trough samples, respectively. Increased renal function was associated with the failure to attain both PK/PD targets. Unbound ceftriaxone concentrations predicted by the protein binding model developed in the present study showed acceptable bias and precision and had no major impact on PK/PD target attainment. We showed suboptimal (i.e., <90%) unbound ceftriaxone PK/PD target attainment when using a standard 2 g q24h dosing regimen in critically ill patients with severe CAP. Renal function was the major driver for the failure to attain the predefined targets, in accordance with results found in general and septic ICU patients. Interestingly, CEFu was reliably predicted from CEFt without major impact on clinical decisions regarding PK/PD target attainment. This suggests that, when carefully selecting a protein binding model, CEFu does not need to be measured. As a result, the turn-around time and cost for ceftriaxone quantification can be substantially reduced.

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Population Pharmacokinetics and Probability of Target Attainment of Different Dosing Regimens of Ceftazidime in Critically Ill Patients with a Proven or Suspected Pseudomonas aeruginosa Infection

Antibiotics ◽

10.3390/antibiotics10060612 ◽

2021 ◽

Vol 10 (6) ◽

pp. 612

Author(s):

Annabel Werumeus Buning ◽

Caspar J. Hodiamont ◽

Natalia M. Lechner ◽

Margriet Schokkin ◽

Paul W. G. Elbers ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Critically Ill ◽

Critically Ill Patients ◽

Hematologic Malignancy ◽

Compartment Model ◽

Target Attainment ◽

Worst Case ◽

Optimal Dosing ◽

Population Pk ◽

Pseudomonas Aeruginosa Infection

Altered pharmacokinetics (PK) of hydrophilic antibiotics in critically ill patients is common, with possible consequences for efficacy and resistance. We aimed to describe ceftazidime population PK in critically ill patients with a proven or suspected Pseudomonas aeruginosa infection and to establish optimal dosing. Blood samples were collected for ceftazidime concentration measurement. A population PK model was constructed, and probability of target attainment (PTA) was assessed for targets 100% T > MIC and 100% T > 4 × MIC in the first 24 h. Ninety-six patients yielded 368 ceftazidime concentrations. In a one-compartment model, variability in ceftazidime clearance (CL) showed association with CVVH. For patients not receiving CVVH, variability in ceftazidime CL was 103.4% and showed positive associations with creatinine clearance and with the comorbidities hematologic malignancy, trauma or head injury, explaining 65.2% of variability. For patients treated for at least 24 h and assuming a worst-case MIC of 8 mg/L, PTA was 77% for 100% T > MIC and 14% for 100% T > 4 × MIC. Patients receiving loading doses before continuous infusion demonstrated higher PTA than patients who did not (100% T > MIC: 95% (n = 65) vs. 13% (n = 15); p < 0.001 and 100% T > 4 × MIC: 20% vs. 0%; p = 0.058). The considerable IIV in ceftazidime PK in ICU patients could largely be explained by renal function, CVVH use and several comorbidities. Critically ill patients are at risk for underexposure to ceftazidime when empirically aiming for the breakpoint MIC for P. aeruginosa. A loading dose is recommended.

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Pharmacokinetics of linezolid in critically ill patients on continuous renal replacement therapy: Influence of residual renal function on PK/PD target attainment

Journal of Critical Care ◽

10.1016/j.jcrc.2018.11.016 ◽

2019 ◽

Vol 50 ◽

pp. 69-76 ◽

Cited By ~ 2

Author(s):

Helena Barrasa ◽

Amaia Soraluce ◽

Arantxazu Isla ◽

Alejandro Martín ◽

Javier Maynar ◽

...

Keyword(s):

Renal Function ◽

Renal Replacement Therapy ◽

Continuous Renal Replacement Therapy ◽

Replacement Therapy ◽

Critically Ill ◽

Critically Ill Patients ◽

Residual Renal Function ◽

Target Attainment

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Population pharmacokinetics and simulations of imipenem in critically ill patients undergoing continuous renal replacement therapy

International Journal of Antimicrobial Agents ◽

10.1016/j.ijantimicag.2018.10.006 ◽

2019 ◽

Vol 53 (1) ◽

pp. 98-105 ◽

Cited By ~ 3

Author(s):

Sanwang Li ◽

Feifan Xie

Keyword(s):

Renal Replacement Therapy ◽

Continuous Renal Replacement Therapy ◽

Replacement Therapy ◽

Population Pharmacokinetics ◽

Critically Ill ◽

Critically Ill Patients

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Effectiveness and Safety of Potassium Replacement in Critically Ill Patients: A Retrospective Cohort Study

Critical Care Nurse ◽

10.4037/ccn2019705 ◽

2019 ◽

Vol 39 (1) ◽

pp. e13-e18

Author(s):

Drayton A. Hammond ◽

Jarrod King ◽

Niranjan Kathe ◽

Kristina Erbach ◽

Jelena Stojakovic ◽

...

Keyword(s):

Intensive Care ◽

Critically Ill ◽

Serum Potassium ◽

Critically Ill Patients ◽

Odds Ratio ◽

Target Range ◽

Target Attainment ◽

Serum Potassium Concentration ◽

Rule Of Thumb ◽

Potassium Replacement

Background Rules of thumb for potassium replacement are used in intensive care units despite minimal empirical validation. Objective To evaluate the effectiveness and safety of rule-of-thumb potassium replacement in critically ill patients with mild and moderate hypokalemia. Methods A retrospective, observational study was done of patients with mild (potassium, 3-3.9 mEq/L) and moderate (potassium, 2-2.9 mEq/L) hypokalemia admitted to a medical intensive care unit who received potassium replacement. Expected and actual frequencies of replacement that achieved target potassium concentrations (≥ 4 mEq/L) were compared by using a χ2 test. Logistic regression analysis was used to assess whether rule-of-thumb administration affected the probability of target attainment within 24 hours of replacement. Results Serum potassium concentrations were checked within 24 hours after potassium replacement on 354 of 577 days (61.4%) when replacement was provided. Concentrations were within target range in 82 instances (23.2%). Of 62 episodes of replacement expected to achieve the target according to the rule-of-thumb estimation, 22 did (35%). Rule-of-thumb administration was associated with greater likelihood of target attainment (odds ratio, 2.12; 95% CI, 1.18-3.85; P = .01). This difference in likelihood remained significant after adjustment for covariates (odds ratio, 2.18; 95% CI, 1.04-4.56; P = .04). Conclusion In critically ill patients given potassium replacement without regard to a formal protocol, the target serum potassium concentration was achieved more often than expected according to the rule-of-thumb estimation but less than one-third of the time.

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