Clinical Effectiveness of a High Dose Versus the Standard Dose of Meropenem in Ventilator-Associated Pneumonia Caused by Multidrug-Resistant Bacteria: A Randomized, Single-Blind Clinical Trial Publisher Pubmed



Monajati M¹ ; Ala S¹ ; Aliyali M² ; Ghasemian R³ ; Heidari F⁴ ; Ahanjan M⁵ ; Moradi S⁶ ; Sharifpour A^{7, 8} ; Mojtahedzadeh M⁹ ; Salehifar E¹
Source: Infectious Disorders - Drug Targets Published:2021

Abstract

Background: Meropenem standard doses are based on the minimum inhibitory concentration of sensitive pathogens and the pharmacokinetic parameter of not critically ill patients. We compared the efficacy of high versus standard dose of meropenem in ventilator-associated pneumonia (VAP). Methods: 24 out of 34 eligible patients were randomized to receive meropenem 3 g q8h (high dose group, 11 patients) or 2 g q8h (standard-dose group, 13 patients) as a 3h infusion. The primary out-come was considered as clinical success that was defined as stable hemodynamic, improved sequential organ failure assessment (SOFA) score, stable or improved PaO2/FiO2 after 7 days. Sputum culture was taken before the intervention. Results: Clinical success rate was not significantly different between the high and standard-dose group (54.5% vs. 38.5%, P= 0.431). There was a significant difference in the reduction of clinical pulmonary infection score (CPIS) compared to a high dose to the standard group (P=0.038). SOFA score declined significantly in the high dose group throughout the study (P=0.006). A shorter duration of VAP treatment was recorded in the high dose group (P=0.061). We did not observe any significant adverse event related to meropenem. Acinetobacter spp. (34.8%), Klebsiella spp. (32.6%) and Pseudomonas aeruginosa (19.5%) isolated more frequently from sputum cultures. Conclusion: Treatment with the high dose of meropenem seems to be safe. However, it did not pro-vide a significantly higher clinical success rate in comparison with the standard dose, but could be considered as an appropriate empirical treatment in patients with severe infection due to reduction in SOFA and CPIS. © 2021 Bentham Science Publishers.