In this study, 83 % of the gram-positive spectrum antibiotics used in ICUs were found to be inappropriate. Compliance with the evaluation of de-escalation was very low in our ICUs. Renal failure was caused inappropriate use and increased the frequency of inappropriate use of antibiotics by about 2-fold.
In Turkey, 71.3% of patients in the ICU are treated with antibiotics . This widespread using leads to unnecessary and inappropriate use. It is recommended to use different quality parameters to evaluate inappropriate antibiotics used. Dresser et al. recommend that presence of uncertainty of indication, the continuation of empirical treatment without evidence of infection, the unnecessary prophylaxis and drug contraindications as quality criteria for the evaluation of inappropriate antibiotic use. . For the same evaluation, Kallen et al. recommended that appropriate microbiological sampling, therapeutic drug monitoring for vancomycin and aminoglycoside, taking surveillance cultures and periodically sharing local resistance data. . The incidence of inappropriate empirical antibiotic use in ICUs varies between 14.1-78.9 % due to differences in evaluation criteria [4, 12]. In Turkey, this incidence ranges from 30 % to % 50 %. [13-15]. Our frequency of inappropriate antibiotic use was found higher than the literature, since the incompatibility with any of the criteria was considered sufficient to determine inappropriateness definition.
Since 2003, a national antibiotic restriction program has been implemented in Turkey. Previous studies have been shown that these programs reduce nosocomial infection, length of hospital stay, mortality and microbial resistance rates. They have a positive effect on health expenditures [3, 16, 17]. However, several studies were shown that increased prescriptions of non-restricted antibiotics may be eliminated these positive effects [2, 3]. In our study, it was shown that antibiotics, all of which are under a restricted antibiotic program, are used inappropriately with high frequency. This indicates that inappropriate antibiotic use in ICUs can not be prevented by restriction programs alone and that the system should be supported by prospective audit and feedback mechanisms . The results of an intervention study conducted by Güçlü et al. was shown that antibiotic restriction programs can be activated by supporting prospective control and feedback mechanisms .
In our study, the most common reason for inappropriateness was the continuation of antibiotics without microbiological evidence, In ICU, the de-escalation algorithm reduces the duration of treatment and the frequency of microbial resistance without increasing mortality [3, 18-20]. In studies conducted in Turkey, it is stated that the necessity of de-escalation was 10 % . On the other hand, the necessity of de-escalation in ICUs was shown to be higher. Mutters et al study was shown that compliance with the evaluation of therapy discontinuation or de–escalation was 2.4-8% . In our study, the compliance of the early period (3 days) de-escalation was found to be quite low. The frequency of de-escalation was found to be slightly higher in the late period (5 days). Considering that the frequency of appropriate microbiological sampling is high, it is thought that this may have been due to late results (blood culture) or late recognition. Despite the increase compared to the early period, the frequency of late de-escalation was found to be low. The most important reason for this is thought to be the unwillingness of clinicians to discontinue treatment despite the culture results. It appears that the restricted antibacterial program alone does not seem to be sufficient for proper de-escalation in ICUs. There is a need to develop an effective de-escalation strategy supported by local treatment guidelines.
Another important reason for inappropriateness in our study was the lack of proper antibiotic dose adjustment according to the eGFR. Renal failure and renal replacement therapies cause plasma concentration changes and affect drug concentrations . Renal replacement therapies (RRT), especially continuous RRT, have also been shown to cause significant pharmacokinetic changes on the antibiotic groups we which evaluated [22-24]. Therefore, antibiotic doses may remain suboptimal in ICU patients when compared to the normal population. [5, 25, 26]. In our study, the frequency of RRT was 21.7%. And also, 6.7% of all patients received continuous RRT during the study. Also, elevation in creatinine serum level was found to be the determining major risk factor for the inappropriate use of antibiotics. Therefore, creatinine clearance changes need to be periodically evaluated to determine appropriate doses of antibiotics in collaboration with clinical pharmacists, infectious diseases specialists and clinical staff in ICUs . There are several limitations to this study. First, our data was collected from a single center and appropriateness of antibiotics was evaluated for only antibiotics effective against Gram positive microorganism. This prevents general assessments on the effectiveness of the national antibiotic restriction programe. Second, there is no global consensus on the criteria for evaluation of inappropriate use of antibiotics in ICUs. Using different criteria may limit the applicability of the our study results. Third, observing outcome measures related with inappropriate use of antibiotics such as mortality, duration of hospital or ICU stay, changing antimicrobial resistance pattern and secondary infection such as C.difficille infections could not be evaluated. Despite all these limitations, the goal of the study to was to provide data about appropriateness use of antibiotics in order to improve an effective antimicrobial stewardship program. Therefore, these results should be supported by an interventional( before-after ) study.