The data exposed in this study demonstrate that, in the combined ICUs, 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 %. 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 > 48h, 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 > 24h, 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, 4, 5]. These differences found in the literature may be related to the type of care provided in the intensive care units of each hospital. In the present study, the high percentage of the use of antimicrobials portrays the predominant admission of highly complex and polytrauma patients.
The parenteral route was, in general, the main choice for the administration of antimicrobials, corroborating with the data found in the literature [1, 6]. 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 in the combined ICUs linked to reductions in the ICU 1. 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 with the longest exposure time were related to carbapenems, followed by glycopeptides, reflecting the main diagnostic indications observed in this study, which refer to respiratory infections and septic shock. In addition to the antimicrobials described, studies still show expressive values of cephalosporin prescriptions in intensive care units [1–3, 6–8, 12]. These findings corroborate with several studies that point out respiratory infections, followed by urinary infections, which explains the emphasis on cephalosporins, as the main predictors for the use of antimicrobials in ICUs [2–4, 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 in the combined 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 in the combined ICUs, linked to a reduction in the number of antimicrobials prescribed in the ICU2.
In the combined ICUs, significant increases were observed in the exposure time of penicillins and tigecycline, with 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 exposure time for penicillins and tigecycline. While in ICU 2, a notable increase was found for the exposure time of 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 evaluating the impact of interventions led by specialists in infectious diseases in the use of antibiotics in a large Korean hospital.
It appears that the use of antimicrobials against multi-resistant microorganisms was significantly affected by the intervention of specialists. Vancomycin continues to be used as a first-line treatment for serious infections caused by multidrug-resistant staphylococci. However, a reduction in multiple-resistant Staphylococcus aureus (MRSA) susceptibility, as well as resistance to vancomycin has been reported recently in many countries. On the other hand, tigecycline provides an alternative treatment for infections complicated by MRSA, vancomycin-resistant enterococci, in addition to other multiple drug resistance microorganism isolates [13, 14]. When increasing the use of penicillins, mainly represented by piperacillin-tazobactam, it can be explained as an effective strategy as an alternative to the use of carbapenems in the treatment of infections of low to moderate severity, originated from urinary or biliary sources, caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae [15].
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. 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 infectious diseases specialist 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.