Title: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
Volume: 21
Issue: 2
Author(s): Mahila Monajati, Shahram Ala*, Masoud Aliyali, Roya Ghasemian, Fatemeh Heidari, Mohammad Ahanjan, Siavash Moradi, Ali Sharifpour, Mojtaba Mojtahedzadeh and Ebrahim Salehifar
Affiliation:
- Department of Clinical Pharmacy, Faculty of Pharmacy, Pharmaceutical Research Center, Mazandaran University of Medical Sciences, Sari,Iran
Keywords:
Meropenem, critically ill, ventilator-associated pneumonia, gram-negative pathogens, intensive care unit.
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).
