Clinical outcomes of empirical high-dose meropenem in critically ill patients with sepsis and septic shock: a randomized controlled trial

Abstract

Background: Appropriate antimicrobial dosing is challenging because of changes in pharmacokinetics (PK) parameters and an increase in multidrug-resistant (MDR) organisms in critically ill patients. This study aimed to evaluate the effects of an empirical therapy of high-dose versus standard-dose meropenem in sepsis and septic shock patients. Methods: We performed a prospective randomized open-label study to compare the changes of modified sequential organ failure assessment (mSOFA) score and other clinical outcomes of the high-dose meropenem (2-g infusion over 3 h every 8 h) versus the standard-dose meropenem (1-g infusion over 3 h every 8 h) in sepsis and septic shock patients. Patients' characteristics, clinical and microbiological outcomes, 14 and 28-day mortality, vasopressor-and ventilator-free days, intensive care unit (ICU) and hospital-free days, percent of the time of antibiotic concentrations above the minimum inhibitory concentration (%T>MIC), and safety were assessed. Results: Seventy-eight patients were enrolled. Median delta mSOFA was comparable between two groups (-1 in the high-dose group vs. -1 in the standard-dose group; P value = 0.75). There was no difference between the two groups regarding clinical and microbiological cure, 14-and 28-day mortality, vasopressor-and ventilator-free days, and ICU-and hospital-free days. In patients admitted from the emergency department (ED) with a mSOFA score ≥ 7, the high-dose group demonstrated significantly better microbiological cure compared with the standard-dose group (75% (9/12 patients) vs. 20% (2/10 patients); P value = 0.03). Likewise, the high-dose group presented higher microbiological cure rate in patients admitted from ED who had either APACHE II score > 20 (83.3% (10/12) vs. 28.6% (2/7); P value = 0.045) or on mechanical ventilator (87.5% (7/8) vs. 23.1% (3/13); P value = 0.008) than the standard-dose group. Adverse events were comparable between the two groups.(Continued on next page)

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

“…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].…”

Urosepsis among Sudanese Patients: A Paradigm from Limited Resources Country

“…Increased the incidence of MDR organisms in the last few decades that causing UTI, makes the treatment process more complicated [7], this is due to empirical broad spectrum antibiotics prescription among hospitalization patients [36], it's observed that in GHRDS, the selection of antibiotics base on culture and sensitivity (C/S) wasn't usually followed. Meropenem was the most effective antibiotics against all bacterial isolates, except P. aeruginosa showed fully resistant to all classes of antimicrobial used in this study, this event was consistent with Tospon and might be show the effectiveness if used in large dose [38]. Unlike cefepime was fully resistant to all isolates compare with Yarlagadda study showed susceptible to cefepime [39], it's may due to excessive used.…”

A New Method for Optimizing Sepsis Therapy by Nivolumab and Meropenem Combination: Importance of Early Intervention and CTL Reinvigoration Rate as a Response Marker

“…In this work, we modeled the carbapenem antimicrobial agent, meropenem, as the representative antibiotics (7). For simulating realistic administration regimens of this drug, we chose to model a continuous i.v.…”

“…Despite the global trend of decreasing sepsis burden, progress in the treatment of sepsis has been modest (2)(3)(4). An immediate administration of broad-spectrum antibiotics is the first-line treatment for the improvement of patient outcomes and reduction of mortality and morbidity due to sepsis (5)(6)(7)(8). Efforts were also made to avoid hyper-inflammation, which characterizes the early stage of this disorder, by administering anti-inflammatory agents, including toll-like receptor (TLR) antagonists, anti-cytokine therapies, and corticosteroids (3).…”