Clinical Effectiveness of a High Dose Versus the Standard Dose of Meropenem in Ventilator-associated Pneumonia Caused by Multidrugresistant Bacteria: A Randomized, Single-blind Clinical Trial

Author(s): Mahila Monajati, Shahram Ala*, Masoud Aliyali, Roya Ghasemian, Fatemeh Heidari, Mohammad Ahanjan, Siavash Moradi, Ali Sharifpour, Mojtaba Mojtahedzadeh, Ebrahim Salehifar

Journal Name: Infectious Disorders - Drug Targets
Formerly Current Drug Targets - Infectious Disorders

Volume 21 , Issue 2 , 2021


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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 outcome 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 provide 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.

The trial protocol was registered with IRCT.ir (registration number IRCT2010010700 3014N19 in April 2018).

Keywords: Meropenem, critically ill, ventilator-associated pneumonia, gram-negative pathogens, intensive care unit.

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Article Details

VOLUME: 21
ISSUE: 2
Year: 2021
Published on: 20 May, 2021
Page: [274 - 283]
Pages: 10
DOI: 10.2174/1871526520666200227102013
Price: $65

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