Comparison of two empirical prolonged infusion dosing regimens for meropenem in patients with septic shock: A two-center pilot study

Eisert, Albrecht; Lanckohr, Christian; Frey, Janina; Frey, Otto; Wicha, Sebastian G.; Horn, Dagmar; Ellger, Bjoern; Schuerholz, Tobias; Marx, Gernot; Simon, Tim-Philipp

doi:10.1016/j.ijantimicag.2021.106289

Cited by 7 publications

(4 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Regarding poor clinical outcomes associated with elevated meropenem MIC [18][19][20], the development of guidance for appropriate meropenem dosage optimization for empirical treatment should be considered to overcome antimicrobial resistance in the ICU [21]. High-dosage regimens of meropenem using prolonged infusion over 3 h could be considered for the empirical treatment in critically ill patients [22][23][24][25], which is supported by our simulation results revealing the low PTA of empirical therapy using the current dosing regimen. Previous studies have reported the positive impact of prolonged meropenem infusion on clinical outcomes such as hospital mortality in critically ill patients [26,27].…”

Section: Discussionsupporting

confidence: 58%

Population Pharmacokinetics of Meropenem in Critically Ill Korean Patients and Effects of Extracorporeal Membrane Oxygenation

et al. 2021

View full text Add to dashboard Cite

Limited studies have investigated population pharmacokinetic (PK) models and optimal dosage regimens of meropenem for critically ill adult patients using the probability of target attainment, including patients receiving extracorporeal membrane oxygenation (ECMO). A population PK analysis was conducted using non-linear mixed-effect modeling. Monte Carlo simulation was used to determine for how long the free drug concentration was above the minimum inhibitory concentration (MIC) at steady state conditions in patients with various degrees of renal function. Meropenem PK in critically ill patients was described using a two-compartment model, in which glomerular filtration rate was identified as a covariate for clearance. ECMO did not affect meropenem PK. The simulation results showed that the current meropenem dosing regimen would be sufficient for attaining 40%fT>MIC for Pseudomonas aeruginosa at MIC ≤ 4 mg/L. Prolonged infusion over 3 h or a high-dosage regimen of 2 g/8 h was needed for MIC > 2 mg/L or in patients with augmented renal clearance, for a target of 100%fT>MIC or 100%fT>4XMIC. Our study suggests that clinicians should consider prolonged infusion or a high-dosage regimen of meropenem, particularly when treating critically ill patients with augmented renal clearance or those infected with pathogens with decreased in vitro susceptibility, regardless of ECMO support.

show abstract

Section: Discussionsupporting

confidence: 58%

Population Pharmacokinetics of Meropenem in Critically Ill Korean Patients and Effects of Extracorporeal Membrane Oxygenation

et al. 2021

View full text Add to dashboard Cite

show abstract

“…The concentration-time profile of meropenem was predicted for each patient based on a previously published meropenem population PK model in conjunction with the patient's dosing history and specific covariates, because meropenem concentrations were not available from the patients. In total, five two-compartment population PK models of meropenem in patients in the ICU were identified in literature, [26][27][28][29][30] and the PK model developed by Ehmann et al was selected as the model most representative of the study population due to its inclusion of multiple covariate relationships based on a wide distribution of covariate values, as well as similar population characteristics as the study patients. 29 Briefly, the population PK model had been built upon densely sampled meropenem serum concentrations (1376 observations) in 41 non-CRRT critically ill patients (mostly patients with sepsis) receiving standard dosing of meropenem (1000 mg as 30-min i.v.…”

Section: Pharmacokinetic Model Derived Pk/pd Indexmentioning

confidence: 99%

Multistate modeling for survival analysis in critically ill patients treated with meropenem

Peng,

Minichmayr,

Liu

et al. 2023

CPT Pharmacom & Syst Pharma

View full text Add to dashboard Cite

Appropriate antibiotic dosing to ensure early and sufficient target attainment is crucial for improving clinical outcome in critically ill patients. Parametric survival analysis is a preferred modeling method to quantify time‐varying antibiotic exposure ‐ response effects, whereas bias may be introduced in hazard functions and survival functions when competing events occur. This study investigated predictors of in‐hospital mortality in critically ill patients treated with meropenem by pharmacometric multistate modeling. A multistate model comprising five states (ongoing meropenem treatment, other antibiotic treatment, antibiotic treatment termination, discharge, and death) was developed to capture the transitions in a cohort of 577 critically ill patients treated with meropenem. Various factors were investigated as potential predictors of the transitions, including patient demographics, CLCRCG (creatinine clearance calculated by Cockcroft–Gault equation), fT>MIC (time that unbound concentrations exceed the minimum inhibitory concentration), and microbiology‐related measures. The probabilities to transit to other states from ongoing meropenem treatment increased over time. A 10 mL/min decrease in CLCRCG was found to elevate the hazard of transitioning from states of ongoing meropenem treatment and antibiotic treatment termination to the death state by 18%. The attainment of 100% fT>MIC significantly increased the transition rate from ongoing meropenem treatment to antibiotic treatment termination (by 9.7%), and was associated with improved survival outcome. The multistate model prospectively assessed predictors of death and can serve as a useful tool for survival analysis in different infection scenarios, particularly when competing risks are present.

show abstract

“…Adherent villi, capsules, lipopolysaccharides (LPS) and glycosylated lipids or iron carriers constitute the main virulence factors leading to CRKP pathogenicity, and multiple mechanisms of drug resistance exist, of which carbapenemase (KPC) and metallo-β-lactamase (MBL) production are the most common. 5 Previous studies [6][7][8] showed that when the MIC of CRKP to carbapenems is less than 16 mg/L, infection treatment can be achieved through appropriate dose increases of carbapenems, longer infusion times, and shorter dosing intervals. However, for high-level CRKP strains (MIC ≥ 16 mg/L), carbapenems are no longer available for the treatment of this type of infection.…”

Section: Introductionmentioning

confidence: 99%

The Efficacy and Influencing Factors of Polymyxin B in High-Level Carbapenem-Resistant Klebsiella pneumoniae Infections

Jia¹,

Zhao²,

Zhang³

et al. 2023

IDR

View full text Add to dashboard Cite

Background Polymyxin B (PMB) is a remedial treatment for carbapenem-resistant Klebsiella pneumoniae (CRKP) infection; however, there is a paucity of reports on the treatment of high-level CRKP infections with polymyxin B. Studies are needed to explore its treatment efficacy and associated influencing factors. Methods Patients with high-level CRKP infections treated with PMB during hospitalization from June 2019 to June 2021 in a hospital were retrospectively studied, and risk factors affecting the efficacy were explored by subgroup analysis. Results A total of 92 patients were enrolled, and the results showed that the PMB-based regimen had a bacterial clearance rate of 45.7%, an all-cause discharge mortality rate of 22.8%, and an incidence of acute kidney injury (AKI) of 27.2% for high-level CRKP treatment. The combination of β-lactams other than carbapenems facilitated bacterial clearance, and the combination of electrolyte disturbances and higher APACHE II scores was detrimental to microbial clearance. Risk factors for all-cause discharge mortality were advanced age, concomitant antifungal drugs, concomitant tigecycline and incidence of AKI. Conclusion PMB-based regimens are an effective option for the treatment of high-level CRKP infections. However, the optimal dose of treatment and the choice of combination regimens need to be explored in further studies.

show abstract

Comparison of two empirical prolonged infusion dosing regimens for meropenem in patients with septic shock: A two-center pilot study

Cited by 7 publications

References 37 publications

Population Pharmacokinetics of Meropenem in Critically Ill Korean Patients and Effects of Extracorporeal Membrane Oxygenation

Population Pharmacokinetics of Meropenem in Critically Ill Korean Patients and Effects of Extracorporeal Membrane Oxygenation

Multistate modeling for survival analysis in critically ill patients treated with meropenem

The Efficacy and Influencing Factors of Polymyxin B in High-Level Carbapenem-Resistant Klebsiella pneumoniae Infections

Contact Info

Product

Resources

About