Avaliação dos esquemas terapêuticos antimicrobianos associados à sobrevida em pacientes internados em unidade de terapia intensiva com infecção confirmada em hemocultura por Enterobacterales

Abstract

Introduction: Bloodstream infections (BSIs) are among the most severe infectious complications resulting from hospitalization, and they are associated with high mortality rates. Enterobacterales represent the largest group of clinically significant Gram-negative rods (GNRs). Bacterial resistance has emerged as one of the biggest challenges in intensive care units (ICUs), with GNRs often exhibiting high resistance. Studies have shown that the use of high doses of carbapenems demonstrated superior efficacy compared to conventional doses in treating bloodstream infections caused by Enterobacterales. Objective: The aim of this study was to evaluate the best antimicrobial regimens for treating hospital-acquired infections in patients admitted to an ICU with positive blood cultures for Enterobacterales and to identify protective factors associated with the survival of these patients. Methods: A retrospective, observational, and longitudinal study was conducted with patients admitted to the Adult ICU of an Emergency Hospital Complex between January 2018 and June 2022. The primary outcome was classified as death or discharge from the ICU with resolution of bacteremia. Categorical variables were compared using the Chi-square test, and numerical variables were compared using the Mann-Whitney test. Both adjusted and unadjusted Odds Ratios (OR) were calculated using logistic regression models, with analyses performed in R version 4.0.3 and a 5% significance level. Results: The study assessed 249 patients with positive blood cultures for Enterobacterales, with a mean age of 51.6 years, predominantly male (78.3%). Trauma was the leading cause of admission (75.5%), and hypertension was the most common comorbidity (28.9%). Death occurred in 54.6% of cases and was associated with advanced age, mechanical ventilation time, renal dysfunction, and elevated lactate levels. The most common source of infection was pulmonary (38.2%). Nearly 84% of patients had previous antibiotic use, 24.9% were undergoing hemodialysis, and 59.8% were receiving vasopressors. More than 33% of patients had infections caused by multidrug-resistant microorganisms. The most frequent pathogen in the cultures was Klebsiella sp. (43.4%). Elevated lactate levels were strongly associated with an increased risk of mortality, with an adjusted OR of 2.13 [1.39; 3.48], indicating a 213% increase in the risk of death. Each additional day of mechanical ventilation also increased the likelihood of mortality by 13% (OR 1.13 [1.06; 1.22]). The use of meropenem reduced mortality by 66% (OR 0.34), and prolonged treatment (mean of 10.1 days) was associated with hospital discharge (p < 0.001M). The use of high doses of meropenem also reduced mortality by up to 57% (OR 0.43) in patients with positive blood cultures for Enterobacterales. Creatinine clearance showed an adjusted OR of 0.99 [0.99; 0.99], suggesting that better renal function decreases the risk of mortality. Conclusion: The study pointed out that advanced age, higher lactate levels, and prolonged mechanical ventilation were associated with an increased risk of death, while higher creatinine clearance and the use of meropenem were associated with an increased chance of discharge. Administering higher doses of meropenem helps ensure that its concentrations remain above the minimum inhibitory concentration (MIC) of pathogens for a sufficient duration to maximize the bactericidal effect, especially against multidrug-resistant Enterobacterales. The combination of meropenem + polymyxin was associated with a higher risk of death, which may be related to the severity of cases and the high nephrotoxicity of polymyxin, which increases the risk of renal damage in critically ill patients.