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

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. 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. A sputum culture was taken before 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 reduction of clinical pulmonary infection score (CPIS) compared to high dose with standard group (P=0.038). SOFA score declined significantly in high dose group through the study (P=0.006). A shorter duration of VAP treatment was recorded in 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 high dose of meropenem seems to be safe. However, it did not provide 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 reducing in SOFA and CPIS.

Predictors of Treatment Failure and Mortality among Patients with Septic Shock Treated with Meropenem in the Intensive Care Unit

“…The other factor is that the current dose used in the ICU is not guided by the MIC of bacteria-resistant organisms ( 45 ). The initial 24 h–48 h of high-dose meropenem may be needed to overcome this subtherapeutic concentration in septic shock patients ( 46 , 47 ).…”

Evaluation of Empirical Meropenem Bolus Protocol in Pseudomonas aeruginosa: A Three-Year Analysis in Tertiary Intensive Care Unit

“…The study demonstrated that the clinical success rate was similar between 2-g and 3-g doses over 3 hours infusion, but superiority in sequential organ failure assessment (SOFA) score reduction was found in the latter. 17 …”

“…The study demonstrated that the clinical success rate was similar between 2-g and 3-g doses over 3 hours infusion, but superiority in sequential organ failure assessment (SOFA) score reduction was found in the latter. 17 Various combination of bolus-extended infusion regimens were analyzed and simulated using pharmacokinetics modeling and simulation. Administration of meropenem 1.5-g or 2-g q6-8h preceded by once 0.5-g bolus could achieve and maintain 40% fT > 4 mg/mL until third day of treatment in compartmental analysis and simulation.…”

Differentiation Between Acinetobacter Baumannii Colonization and Infection and the Clinical Outcome Prediction by Infection in Lower Respiratory Tract

“…CRP level and CPIS≥6 ratio are indicators of infection severity. [23][24][25] It is well known that the more severe the infection, the higher the risk of death. Therefore, it is reasonable that these two indicators were associated with the risk of death in the current study.…”