Antimicrobial resistance is currently one of the greatest public health threats and an emerging crisis for humans [1]. Once a pathogen acquires resistance, it erodes the effectiveness of antibiotics, leading to increased mortality, length of hospital stay, and medical costs [2]. Unfortunately, the introduction of new licensed antibiotics has dwindled since the 1990s due to technical difficulties, regulatory hurdles, and the fact that antibiotics are less-lucrative than other pharmaceuticals [3].

The emergence of antimicrobial-resistant organisms is mainly caused by excessive and inappropriate antibiotic usage [4]. The proportion of inappropriate antibiotic prescription, which induces selective pressure, is approximately 20% to 50% worldwide [5]. Therefore, the importance of the antimicrobial stewardship programs (ASPs) has been emphasized [5]. Accordingly, the Korean Ministry of Health and Welfare established the Korean National Action Plan on Antimicrobial Resistance in 2016 [6].

The first step to implement proper antimicrobial stewardship policy is identifying the current situation. According to the ‘seven core elements’ of successful ASPs proposed by the Centers for Disease Control and Prevention, monitoring antibiotic use and resistance patterns is indispensable [7]. In Korea, available data on antibiotic consumption at hospital level are still limited.

This study was performed to evaluate the amount of antibiotic consumption and trends in antibiotic usage at hospital level in Korea. To this end, we obtained and analyzed antibiotic prescription data for inpatients at a tertiary care hospital between 2004 and 2013.

The results from the present study reflect the recent status of antibiotic usage at hospital level in Korea and can be used for implementation of antimicrobial stewardship policies. Few studies analyzing antibiotic usage trend at hospital level have been performed in Korea. Jun et al. [10] reported that average antibiotic consumption among patients at a tertiary care hospital over 18 years of age was 644.6 DDD/1,000 patient-days between 2001 and 2012. Song et al. [11] reported that annual antibiotic consumption among all patients ranged from approximately 750 to 850 DDD/1,000 patient-days at a tertiary hospital between 2000 and 2006.

There was a significant decreasing trend in consumption of nonbroad-spectrum antibiotic throughout the study period. Conversely, the consumption of broad-spectrum antibiotics and antibiotics against MDR pathogens increased. This trend was observed both at hospital-level [9,10] and national-level [12,13] analysis in Korea. A comparable trend of antibiotic usage has been observed in other countries. A study conducted in an Italian tertiary care hospital, with a comparable number of beds (840 beds), found significant increasing trends in consumption of BL/BLIs, carbapenems and vancomycin [14]. In acute care hospitals in the UK, use of carbapenems and piperacillin/tazobactam increased by 60.4% and 94.8%, respectively [15]. Similarly, data from European Surveillance of Antibiotic Consumption (ESAC) projects, which represents European countries, show that consumption of broad-spectrum penicillins, BL/BLI, carbapenems, and polymyxin usage increased significantly in 2013 compared with usage in 2009 [16].

We suggest that these trends reflect the current problem of increasing antimicrobial-resistant pathogens. While we did not analyze pathogens isolated from other sites, we identified a significant increase in the antimicrobial resistance rate to broad-spectrum antibiotics of bloodstream pathogens isolated at the study hospital. Consistent with our findings, the Korean Antimicrobial Resistance Monitoring System (KARMS), comprising a total of 35 secondary and tertiary care participating hospitals, reported that the antimicrobial resistance rate of E. coli and K. pneumoniae to broad-spectrum antibiotics has been increasing [17]. According to the KARMS, the E. coli and K. pneumoniae resistance rates to FQs were 30% in 2004, increasing to 42% and 34%, respectively, in 2013 [17]. Similarly, the E. coli and K. pneumoniae resistance rate to cefotaxime were 10% and 30%, respectively, in 2004, increasing to 29% and 40%, respectively, in 2013 [17]. The issue of increasing antimicrobial resistance of gram-negative Enterobacteriaceae is not limited to Korea. A multi-national study in Asian-Pacific countries found that the rate of community-acquired ESBL-producing E. coli and K. pneumonia increased from 6.3% and 9.4%, respectively, in 2002 to 14.6% and 26.2%, respectively, in 2013 [18]. This trend resulted in increasing consumption of antibiotics against MDR pathogens, including carbapenems. KARMS reported that the carbapenem susceptibility rates of E. coli and K. pneumoniae decreased from 100% and 99.3% in 2011 to 99% and 97% in 2015, respectively [17]. Considering that carbapenems are one of the most reliable last-resort treatment for gram-negative pathogens, this finding is troubling. The high prevalence of resistant gram-positive pathogen is also noticeable. In 2013, we found that half of S. aureus isolates from blood were methicillin-resistant S. aureus (MRSA). This finding was consistent with results of the KARMS study: the proportion of MRSA between 2013 and 2015 was 66% to 72% [17]. Regarding MRSA, the proportion of community-acquired isolates increased from 5.9% in 2005 to 13.3% in 2014 [19].

Guidelines for community-based infection may have affected the antibiotic prescription trends of the present study. The Infectious Disease Society of America and the American Thoracic Society introduced the concept of healthcare-associated pneumonia in 2005 and empirical coverage of MDR pathogens, such as MRSA and Pseudomonas aeruginosa, has been promoted since then [20]. Accordingly, the 2007 updated guidelines for community-acquired pneumonia recommended double anti-pseudomonal antibiotic coverage for cases in which Pseudomonas is a consideration; an example is piperacillin/tazobactam plus respiratory FQ combination therapy [21]. The Korean guidelines for community-acquired pneumonia treatment released in 2009 recommend that Pseudomonas infection should be suspected in patients with structural lung diseases such as bronchiectasis, exacerbation of recurrent chronic obstructive lung disease, systemic antibiotic use within the preceding 3 months, and alcoholism [22]. Consequently, there has been increased concern among physicians regarding MDR pathogens, driving excessive broad-spectrum antibiotic consumption [23].

We found that patients in ICUs consumed substantially more antibiotics, particularly antibiotics against MDR pathogens, compared with patients in GWs. For patients in ICUs, higher rates of MDR pathogens justify the use of regimens combining different broad-spectrum antibiotics, even when the presumed infection probability is low, because inappropriate empirical therapy may lead to poor prognosis [24]. Furthermore, there has been a significant increase in antimicrobial resistance for major pathogens isolated from ICUs in Korean hospitals [25]. However, study results indicate that 30% to 60% of antibiotics used in ICUs are inappropriate and therefore appropriate intervention measures are necessary to prevent further emergence of MDR pathogens, which are highly correlated with selective pressure [24].

ASPs are one of the most demanding strategies to reduce unnecessary and improper antibiotic usage [26]. In the current study, the antibiotic consumption trend may have been affected by ASPs as well. The preauthorization-of-antibiotic-use program was newly implemented in the study hospital in 2008, and other ASPs, such as education for proper antibiotic use and feedback to prescribers after drug use evaluation, were reinforced at the same time. As a result, overall antibiotic consumption began to decrease from this point. However, a rebound in the total antibiotic consumption occurred from 2011. The phenomenon can be explained by lack of manpower. At the beginning of 2011, one infectious diseases specialist resigned from the study hospital and ASPs were operated by one person. As indicated above, the most important requirements for appropriate operation of ASPs in Korea are reinforcement of manpower capable of performing ASPs.

There are potential limitations to the present study. First, the data of our study were derived from records at a tertiary care hospital and many of the patients potentially had underlying illnesses. Furthermore, we did not analyze outpatient data, which account for approximately 80.9% of total antibiotic consumption [13]. Therefore, the results of the present study may not be applicable to the general population. Secondly, antibiotic consumption was measured by DDD instead of days of therapy (DOT). According to a recent guideline for antibiotic stewardship programs, DOT is preferred to DDD as a measure of antibiotic consumption [27]. However, we could not use DOT because only the total amount of antibiotic consumption per patient was available. As one of the known shortcomings of DDD, antibiotic consumption may be underestimated among pediatric patients or patients with decreased renal function. Thirdly, analysis of the antimicrobial resistance rate was limited to three major pathogens isolated from blood. There are other pathogens that reflect the overall status of antimicrobial resistance in a hospital, such as P. aeruginosa, A. baumannii, and Enterococcus faecium. As there were insufficient isolates to analyze trends of antimicrobial resistance rate over time, we were only able to include E. coli, K. pneumoniae, and S. aureus.

Despite these limitations, the data derived from this study are likely to be a reasonable indicator of trends of systemic antibiotic usage at hospital-level. In conclusion, over the 10-year study period, a stepwise increase in the consumption of broad-spectrum antibiotics and antibiotics against MDR pathogens was observed at a tertiary care hospital in Korea. Conversely, over the same period, a significant decreasing trend in the consumption of nonbroad-spectrum antibiotics was observed.