Abstract
High variability of linezolid blood concentrations with partial subtherapeutic levels was observed in critically ill patients who received a standard intravenous dose of linezolid, contributing to drug resistance and toxicity. Continuous infusions of linezolid have been suggested as an alternative and provide good serum and alveolar levels without fluctuations in trough concentration. This study aimed to assess the effectiveness and safety of continuous linezolid infusion versus the standard regimen in critically ill patients. A prospective randomized controlled study was conducted on 179 patients with nosocomial pneumonia. Patients were randomized into two groups. The first group received IV linezolid 600 mg twice daily, while the second group received 600 mg IV as a loading dose, followed by a continuous infusion of 1200 mg/day (50 mg/h) for at least 8–10 days. The continuous infusion group showed a higher clinical cure rate than the intermittent infusion group (p = 0.046). Furthermore, efficacy was proven by greater improvement of P/F ratio (p = 0.030) on day 7 of treatment, a lower incidence of developing sepsis after beginning treatment (p = 0.009), and a shorter time to reach clinical cure (p < 0.001). Hematological parameters were also assessed during the treatment to evaluate the safety between the two groups. The incidence of thrombocytopenia was significantly lower in the continuous infusion group than in the intermittent infusion group. In addition, a stepwise logistic regression model revealed that the intermittent infusion of linezolid was significantly associated with thrombocytopenia (OR =4.128; 95% CI = 1.681–10.139; p =0.001). The current study is the first to assess the clinical aspects of continuous infusion of linezolid beyond pharmacokinetic studies. Continuous infusion of linezolid outperforms intermittent delivery in safety and improves clinical effectiveness in critically ill patients with Gram-positive nosocomial pneumonia.
Highlights
Nosocomial pneumonia is the most common cause of mortality among intensive care unit (ICU) patients [1,2]
It is well established that linezolid has time-dependent activity, and the most critical pharmacokinetic parameters to predict its antibacterial effect include the time that the free drug concentrations remain above the minimum inhibitory concentration (T > MIC), as well as the area under the curve (AUC) over 24 h/minimum inhibitory concentration (MIC) (AUC/MIC) [9–12]
Linezolid has been frequently utilized over glycopeptides for the treatment of Grampositive nosocomial pneumonia in critically ill patients following the increase in multidrugresistant Gram-positive bacteria in the last decade, and glycopeptides have been associated with frequent episodes of nephrotoxicity [9,30,31]
Summary
Nosocomial pneumonia is the most common cause of mortality among intensive care unit (ICU) patients [1,2]. Staphylococcus aureus is one of the most causative Grampositive bacteria in hospital-acquired and ventilator-acquired pneumonia, with mortality rates up to 40% [5,6]. Linezolid is effective against Gram-positive bacteria, including methicillin-resistant. It is well established that linezolid has time-dependent activity, and the most critical pharmacokinetic parameters to predict its antibacterial effect include the time that the free drug concentrations remain above the minimum inhibitory concentration (T > MIC), as well as the area under the curve (AUC) over 24 h/minimum inhibitory concentration (MIC) (AUC/MIC) [9–12]. Increased variability in linezolid blood concentrations associated with partial subtherapeutic serum drug levels has been reported in critically ill patients receiving linezolid’s usual dose (600 mg twice/day), which could lead to drug resistance and toxicity [13–16]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
