As per the results of this study, inappropriate gram-positive spectrum antibiotics usage in ICUs was as high as 83%. Compliance with the evaluation of de-escalation was very low in the ICUs selected for this study. Renal failure increased the frequency of inappropriate antibiotic use by approximately 2-fold.
In Turkey, 71.3% of patients in ICUs are treated with antibiotics . This widespread use is unnecessary and inappropriate. It is recommended that different quality parameters be used to evaluate inappropriate antibiotic usage. Dresser et al. advise considering uncertain indications, continuation of empirical treatment without evidence of infection, unnecessary prophylaxis, and drug contraindications as quality criteria for the evaluation of inappropriate antibiotic use. . For similar evaluations, Kallen et al. recommend considering appropriate microbiological sampling, therapeutic drug monitoring for vancomycin and aminoglycoside, surveillance cultures and periodic sharing of local resistance data. . The incidence of inappropriate empirical antibiotic use in ICUs reportedly varies between 14.1-and 78.9% due to differences in evaluation criteria [4, 12]. In Turkey, this incidence ranges from 30-50%. [13-15]. The frequency of inappropriate antibiotic use as per our study is higher than that in the literature, since non-compliance with any of the criteria used in the study was considered sufficient to fulfil the definition of inappropriateness .
Since 2003, a national antibiotics restriction programme has been implemented in Turkey. Previous studies have shown that these programmes reduce the number of nosocomial infections, length of hospital stay, mortality and microbial resistance rates. The programme has had a positive effect on health expenditures [3, 16, 17]. However, several studies also showed that increased prescriptions of non-restricted antibiotics may eliminate these positive effects [2, 3]. The results of our study, show that the studied antibiotics, all of which are part of a restricted antibiotics programme, are used inappropriately and with high frequency. This indicates that inappropriate antibiotic use in ICUs cannot be prevented by restriction programmes alone and that the system should be supported by prospective audit and feedback mechanisms . In fact the results of an intervention study conducted by Güçlü et al. was shown that antibiotic restriction programmes can be strengthened by supporting prospective control and feedback mechanisms .
The results of our study, revealed the continuation of antibiotics without microbiological evidence, as the most common factor adding to their inappropriate use. In ICUs, the de-escalation algorithm reduces the duration of treatment and frequency of microbial resistance without increasing mortality [3, 18-20]. Other studies conducted in Turkey, indicate such de-escalation is necessary in 10 % of the cases . On the other hand, the necessity of de-escalation in ICUs was shown to be higher. Mutters et al reported that compliance with the evaluation of therapy discontinuation or de–escalation ranged from 2.4-8% . In our study, the compliance in the early period of de-escalation (3 days) was found to be quite low. The frequency of de-escalation was slightly higher in the late period (5 days). Considering that the frequency of appropriate microbiological sampling is high, the above results may be attributed to late results (blood cultures) or late recognition. Despite the increased frequency compared to that in the early period, the frequency of late de-escalation was found to be low. The unwillingness of clinicians to discontinue treatment despite the results of the cultures is likely the important reason for this result. It appears that the restricted antibacterial programme alone does not seem to be sufficient for proper de-escalation in ICUs. Therefore it is crucial to develop an effective de-escalation strategy supported by local treatment guidelines.
Another important reason for inappropriate antibiotic usage in our study was the lack of proper antibiotic dose adjustment according to the eGFR. Renal failure and renal replacement therapies (RRTs), cause plasma concentration changes and affect drug concentrations . RRTs, especially the continuous type, have also been shown to cause significant pharmacokinetic changes on the antibiotic groups that were evaluated in this work [22-24]. Therefore, antibiotic doses may remain suboptimal in ICU patients when compared to the normal population. [5, 25, 26]. The frequency of RRTs in our study was 21.7%. Moreover, 6.7% of all patients received continuous RRT during the study. Also, elevated creatinine serum levels were found to be the 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 is study suffers from several limitations First, our data were collected from a single centre and the appropriateness of antibiotics was evaluated only for antibiotics effective against gram-positive microorganisms. These limitations prevent general assessments of the effectiveness of the national antibiotic restriction programme. Second, no global consensus currently exists on the criteria for evaluatng the inappropriate use of antibiotics in ICUs. Using different criteria may limit the applicability of the our study results. Third, this work did not evaluate the outcome measures related with the inappropriate use of antibiotics, such as mortality, duration of hospital or ICU stay, changing antimicrobial resistance patterns, and secondary infections (e.g. C. difficile infections). Despite all these limitations, this study successfully provided important insights into the appropriateness of antibiotic use towards improving the ASP. These results should be validated in the future via an interventional (before-after) study.