The data exposed in this study demonstrate that, globally, during the ICU stay, in the pre-intervention period, 91.4% of the patients received at least one antimicrobial agent and, although not significant, there was a slight reduction in the post-intervention period to 90.0%, reflecting the individual declines of each ICU. High percentages in the use of antimicrobials within intensive care units are recurrent in the literature. De Bus L et al. [3], when conducting a study for four years in an ICU at the University Hospital in Ghent, observed that 84% of patients, with a stay > 48 h, were exposed to at least one class of antibiotics. Álvarez-Lerma F et al. [11], when evaluating this data in an ICU of a general hospital in Barcelona, reports that in the year before the intervention 77.8% of the patients received one or more antimicrobials, and in the following year, after the intervention, there was a reduction to 71.4%. At a London University Hospital, Candeloro CL et al. [1], over a study period of 30 days, found that 73% of patients, with a stay > 24 h, were exposed to some antimicrobial. In contrast, lower percentages were reported in ICUs in hospitals in the United States and Europe that had 57% of patients using antimicrobials [4].
One of the main factors that lead to the extensive use of antimicrobials in intensive care units is associated with the severity of patients, a condition that, in most cases, requires the early start of antibiotics, due to the greater probability of contracting infections, representing about 20% of total hospital infections. These infected patients have an even higher risk of mortality [2, 5, 4].
The parenteral route was, in general, the main choice for the administration of antimicrobials, corroborating with the data found in the literature [6, 1]. Candeloro CL et al. [1] reports that among 90% of prescriptions directed to the parenteral route, only 5.8% were transferred to the enteral route. After the intervention, reductions in the indication of these pathways, although not significant, were observed globally linked to reductions in the ICU 1. One of the factors that may have contributed to this de-escalation, especially in this unit, was the participation in a project to improve patient safety, with a round-trip and multidisciplinary visit, requiring from this unit more active monitoring of the rational use of antimicrobials. The predilection of the parenteral route may be related, among others, to the necessary immediacy of the results, also, the options for the oral route are limited. The switch from parenteral to enteral in ICUs is a very controversial subject. Changing the route may bring some important results, such as early discharge, less risk of bacteremia, less use of venous access, and incidence of thrombophlebitis, and lower cost of treatment [12].
The most prescribed antimicrobial classes, individually in units with global reflex, were related to carbapenems, followed by glycopeptides. In addition to those described, studies also show significant values for cephalosporin and beta-lactam prescriptions (piperacillin + tazobactam) in intensive care units [2, 1, 8, 12]. The data reveal that the most recurrent antimicrobial therapy involves agents of a broad spectrum and that it is often performed empirically, during the uncertainty of the diagnosis, not always representing the appropriate therapy [2, 4]. That is why it is important to send cultures before starting antimicrobials, making it possible to verify the response to treatment more quickly. Empirical therapy should be guided by accurate and recent antibiograms, in addition to having standardized approaches that take into account the susceptibility pattern of bacteria commonly isolated in the units [4].
The mean duration of antimicrobial therapy was 703 LOT / 1000pd, with a significant reduction globally. The literature is scarce regarding the use of this indicator in ICUs. In Brazil, Marcelino FAB [2], found a rate slightly above the finding (median = 844 LOT / 1000pd). These high rates reflect the complexity of infections acquired by patients in intensive care units. Also, the age group of the population observed, in this study requires a longer time for recovery, enabling the acquisition of secondary infections. Each patient received an average of 1.8 ± 0.2 antimicrobials during their stay in the units, indicating that the combination of antimicrobial therapy is common in hospital ICUs. There was a significant reduction in this data when observed globally, linked to a reduction in the number of antimicrobials prescribed in the ICU2.
Similar to the number of prescriptions, the highest rates related to the time of use of antimicrobials have been described for carbapenems followed by glycopeptides. These findings reflect the main diagnostic indications observed in this study, which referred to respiratory infections and septic shock. This data corroborates with several studies that point out the respiratory system as the most affected in ICUs [3, 2, 12, 4]. When comparing the data from this study with others, it was found that the rate regarding the time spent using carbapenems was higher than the findings by De Bus L et al. [3] (236 DOT / 1000pd) and Candeloro CL et al. [1] (196 DOT / 1000pd), a higher rate about glycopeptides (187 DOT / 1000pd); and lower when compared to the study by Rupali P et al. [7] (426 DOT / 1000pd). Studies still demonstrate a relevance to the time of use of beta-lactams in ICUs, in which the rates ranged from 116 DOT / 1000pd to 296 DOT / 1000pd [3, 7, 6, 1].
Overall, significant increases in the exposure time of penicillins and tigecycline have been observed. However, there were marked reductions in the time of use of glycopeptides and polymyxin B. When comparing the pre- and post-intervention periods, individually in the units, it was found that, in ICU 1, there was a significant increase in the number of azithromycin and tigecycline prescriptions with longer exposure time for penicillins and tigecycline. While, in ICU 2, a notable increase was found in the number of prescriptions and time of exposure to penicillin, with a reduction in the time of use of carbapenems, glycopeptides, and polymyxin B. The results of this study are consistent with the findings by Hwang H [9] when assessing the impact of interventions led by infectious disease specialists on antibiotic use in a large Korean hospital.
The median length of stay, overall, in the units, was 14 days. The literature describes, for intensive care units, one remained ranging from 6 to 18 days [2, 7, 11, 12]. These observed variations can be explained due to the characteristics of the patients seen at each institution.
As for the percentage of general mortality, this study found an average of 25.0% ± 3%. Similar data were observed by Rupali P et al. [7] in which in the pre-intervention phase mortality was 22.4% and in the intervention phase 27.6%. Higher percentages were found by Marcelino FAB [2] (33.0%) and lower ones as described by De Bus L et al. [3] (10.7%), Gasparetto J et al. [12] (12.6%), and Álvarez-Lerma F et al. [11], this reports that in the previous year the intervention the mortality percentage was 13.7% and in the following year after the intervention is reduced to 11.1%.
Although intervention in the present study slightly decreased the use of antimicrobials, there were no changes in the length of stay and survival of patients.
The strengths of this study include the prospective design with comparison before and after interventions of a team of infectologists in the rationalization of the use of antimicrobials in intensive care units, the direct investigation of the prescriptions enabling a greater precision of the analysis regarding the use of antimicrobials and the use of the DOT and LOT indicators according to the new recommendations for monitoring the use of antimicrobials. However, some limitations were noted: First, the study was conducted at a single center. Second, comorbidities have not been evaluated. Third, the adequacy of the prescriptions was not addressed. Fourth, no data were obtained on the prevalence of bacterial pathogens and their susceptibility patterns.