Background
Antimicrobial exposure increases the selection for various drug-resistant organisms [
1]. Numerous studies have demonstrated the association between antimicrobial use and MDRO detection [
2‐
4]. However, to our knowledge, there are few data to support the concept that reducing antibiotic use actually leads to improvements in antibiotic susceptibilities [
1]. Moreover, antimicrobial stewardship was demonstrated to reduce MDRO and was strongly recommended in clinics [
5]. The World Health Organization (WHO) strongly recommends that governments implement antimicrobial stewardship programs directed at containing antimicrobial resistance [
6]. However, a considerable gap exists between theory and clinical practice [
7]. Antibiotic use is increasing even in some countries such as Norwegian with a low antibiotic resistance rate [
8,
9].
In China, the overuse of antibiotics is common [
10], and the prevalence of antimicrobial resistance isolates is higher than that in North America and Europe [
11]. Data reported by the Chinese Ministry of Health (MOH) National Antimicrobial Resistance Investigation Net (Mohnarin) indicates that antimicrobial resistance is rising steadily [
12]. In 2011, Chinese MOH established policies concerning the antimicrobial stewardship to improve the intelligent use of antibiotics. Most hospitals in China gradually implemented the policies. These policies included restricting the kinds of antibiotics, setting the targets for antibiotic prescription in hospitalized patient and prophylactic use of antibiotics in clean operations (Please see the detail of polices in methods of
Antimicrobial stewardship). However, to the best of our knowledge, no studies have shown whether the antimicrobial stewardship can reduce infection or colonization with MDRO in critically ill patients. Therefore, in the present study, we aimed to elucidate the role of the antimicrobial stewardship on the antimicrobial consumption and infection or colonization with MDRO in critically ill patients.
Discussion
Infection with MDRO is frequently observed during clinical treatment [
15‐
17], especially in critically ill patients [
18]. Preventing infection with MDRO is very important to our clinic workers. To the best of our knowledge, this is the first study concerning the effect of the antimicrobial stewardship program of Chinese MOH on colonized or infected with MDRO in critically ill patients. In the present study, we found that DDD in the hospital and in most departments decreased significantly after the implementation of the antimicrobial stewardship.
Consequently, the MDRO isolation in critically ill patients correspondingly decreased when they admitted into ICU. However, we found a low relationship between DDD in the ICU and increased MDRO rate from ICU admission to discharge. Moreover, we did not find a positive relationship between DDD in the ICU and MRDO at ICU or between the DDD of carbapenem and carbapenem-resistant A. baumannii.
Antimicrobial stewardship can reduce the DDD in the entire hospital and in the majority of the departments. After the intervention, we found that the rational use of antibiotics had improved. In the preventative use of antibiotics in clean operation, for example, the percentage decreased from nearly 100 to 35%, which was in line with previous data [
19]. Consequently, the DDD was decreased significantly from 96 to 65 in our hospital and was decreased in most departments (Table
2). Our results confirmed the previous results in China [
20]. However, our DDD is still higher than the standard claimed by the policy. Therefore, we should conscientiously execute this policy to improve antibiotic use.
Antimicrobial stewardship can help to decrease the MDRO isolation in critically ill patients. Along with the decrease in antimicrobial consumption in our study, the proportion of colonization or infection with MDRO in critically ill patients decreased significantly to 13%. Furthermore, we found a good positive correlation between antibiotic consumption and MDRO in our hospital (Fig.
3). Previous studies demonstrated the association between antimicrobial use and MDRO detection [
2‐
4,
21]. Bassetti et al. found a significant correlation between antibiotic consumption and increased resistance for
K. pneumonia [
21]. A recent study in China demonstrated that increased consumption of carbapenem may contribute to the development of resistance in
A. baumannii to imipenem, meropenem, and other antimicrobials [
4]. However, Most previous studies were demonstrated that with the increased consumption of antimicrobials, the MDRO increased correspondingly [
2‐
4,
21‐
23]. There was only the some correlation between MDRO and antimicrobial consumption. Whether the decrease antimicrobial consumption could reduce the MDRO was not very clear. Interestingly, we found that the proportion of patients colonized or infected with MDRO decreased along with reduced consumption of antibiotics.
In some departments, such as the thoracic surgery department, the DDD did not decrease; however, the MDRO isolation rates in this department decreased significantly in critically ill patients. Several reasons may explain this decrease. First, DDD did not equal to rational application of antimicrobials. Moreover, the sample from such departments was small and could not achieve significance. Finally, MDRO are easily transmitted from patient to patient through hand contact with doctors, nurses and hospital workers [
22,
23]. Additionally, critically ill patients were transferred several times to different departments before being initially admitted into the ICU. Therefore, the incidence of MDRO isolates in patients from different departments and throughout the hospital decreased, although DDD did not decrease.
Carbapenem-resistant
A. baumannii is a serious problem in the clinic, especially in the ICU [
24,
25]. Although the DDD of carbapenem did not decrease in the entire hospital and in the ICU, the carbapenem-resistant
A. baumannii isolates decreased both at the time of ICU admission and at ICU discharge. Moreover, we did not find a good relationship between carbapenem consumption and carbapenem-resistant
A. baumannii. Because previous studies have examined whether carbapenem restriction can reduce the rates of carbapenem-resistant
A. baumannii and have had inconsistent findings [
4,
26], further explorations are warranted to confirm these results.
Our study has several limitations. First, this study was performed in a single center. Because drug resistance rates vary among hospitals and units, the results may not be representative and reproducible in other institutions. However, in one hand, antibiotic overuse is common in China [
10], and antimicrobial stewardship can improve the use of antibiotics. In another hand, the results of antimicrobial consumption in our study was in line with previous report [
20]. Additionally, studies have demonstrated that the rational use of antibiotics could prevent antimicrobial resistance [
27]. Therefore, we believe that our study can benefit other hospitals.
Second, we did not analyze the individual risk factors for colonization or infection with resistant microorganisms. Factors that would affect the MDRO isolation, such as hand hygiene, isolating the high-risk patients, and taking precautions, were not analyzed. However, during this pre-post study period in our hospital, we had taken executive infection control measures. We found that the compliance of hand hygiene did not significantly change in our department. Therefore, we believe that the decrease of DDD is an important factor for reducing the rate of MDRO. We also plan to investigate and analyze the risk factors concerning infection and MDRO.
Third, we did not screen the MDRO since rectal swabs, and the proportion of undetected MDRO colonizations could consequently be high. However, the policy of screen was the same during the two periods, therefore, it will not be influence our results hugely.
Finally, our study did not address the issue of antibiotic use and resistance in the community. The consumption of antimicrobials in agricultural industry may also promote antibiotic resistance [
28,
29]. However, the MDRO isolation of patients who arrived from emergency department also decreased from 40 to 18% and may not affect our results.
Acknowledgements
We thank all patients and clinicians from the Zhongda Hospital in Nanjing, China, for their cooperation and participation in the study; Yaxiang Shi (Computer Information Center, Zhongda hospital, School of Medicine, Southeast University) for getting the consumption of antibiotics of our hospital. This work was supported by major special projects of Ministry of Health of China (grant number: 201202011), and fund of the key discipline of Jiangsu province (grant number KJXW11.3.).