Antimicrobial consumption in five adult intensive care units: a 33-month surveillance study

Antimicrobials are the most frequently misused therapeutic drugs worldwide [1]. Antimicrobial- associated adverse effects are frequently mild, but sometimes can be life-threatening and require emergency care [2, 3]. The widespread consumption of antimicrobial agents especially broad-spectrum ones may reflect the physician’s concern and the need for effective therapy for severely ill patients. Additionally, it cannot be dissociated from the worldwide problem of antimicrobial resistance (AMR) [4–6]. Ecological data have confirmed higher AMR in countries with higher antimicrobial consumption [7]. The global emergence of AMR has increased patient morbidity, mortality, and health care costs. [8]. With the global concern of rising AMR, the World Health Organization (WHO) has established a five-pillar global action plan to be adopted by member states to address the AMR challenge at the national level [9]. Increasing knowledge of antimicrobial consumption and resistance through surveillance is one of those five pillars. Similarly, the strategic plan for combating AMR in Gulf Cooperation Council (GCC) States called for monitoring the trends of the antimicrobial consumption using different metrics [10].

As stewardship programs can be cost-effective in reducing unnecessary consumption of restricted and non-restricted antimicrobials [11, 12], King Abdulaziz Medical City-Riyadh (KAMC-R) established a stepwise stewardship program and created guidelines for antimicrobial consumption. However, data on the amount of antimicrobial consumption at a tertiary care setting is largely lacking, both locally and nationally [14, 15]. Estimating the baseline antimicrobial consumption may serve multiple stewardship purposes; to identify hospital units/wards of highest consumption, to monitor the impact for future interventions, and to feedback prescribing physicians with the prescription patterns. The latter by itself has been proven very beneficial in reducing antimicrobial consumption [13]. Therefore, the objective of this study was to quantify service-specific antimicrobial consumption using different metrics in intensive care settings.

ICU-specific antimicrobial consumptions at a major tertiary care hospital were presented in this report using multiple metrics; including DDD, DOT, and the frequency of daily consumption. The calculation of different metrics was essential to improve the clinical and benchmarking usability of this data. For example, it has been shown that the choice of indicator for the surveillance of antimicrobial consumption is critical to evaluate the impact of any stewardship program [15, 18] and to enhance the ability to predict future AMR [19]. Additionally, complementary and sometimes conflicting findings of the impact of antimicrobial stewardship have been reported based on whether DDDs versus DOTs are calculated [15, 18, 20]. This is further complicated by the main stewardship target; the length of stay, number of patients receiving treatment, or duration of treatment [15, 18, 20]. Moreover, DDDs and DOTs are theoretically reflecting different aspects of antimicrobial consumption [21].

The main finding of this study was the high consumption of broad-spectrum antimicrobial agents, specifically carbapenems and piperacillin/tazobactam irrespective of the metrics used. Unfortunately, this study cannot determine the magnitude of inappropriate consumption in the above broad-spectrum antimicrobials. Nevertheless, it has been reported that between 14 and 79% of international antibiotic consumption to treat severe infections in hospitals are inappropriate [22]. Similarly, a recent local study reported that 66% of the consumption of carbapenems and piperacillin/tazobactam in a surgical ward at a tertiary care hospital was either unjustified by culture-test result or done without culture [23]. These rates highlight clinician’s inclination to prescribe broad-spectrum agents. Consistent with current findings, several reports from this hospital [24, 25] and other hospitals in GCC states [26, 27] identified the emergence and/or high burden of carbapenem-resistant Enterobacteriaceae and carbapenem-resistant Acinetobacter. Infections caused by these resistant pathogens are highly fatal and need poly-antimicrobial therapy including carbapenems [28].

Comparison of the consumption rates from this study with local data is impossible or at least difficult. Previous data quantifying antimicrobial consumption at healthcare settings in Saudi Arabia are very limited [14, 15]. For example, none of the published reports have used a prospective design, stratified the consumption by service/location, or used a comprehensive list of antimicrobial groups as shown in this report. On the other hand, the consumption of carbapenems in this study was considerably higher than the rates reported by several reports around the world. For example, it was 255.9 DDDs per 1000 patient-days in current ICUs compared with 36.9 in French ICUs [29], 37.8 in the US National Nosocomial Infections Surveillance (NNIS) medical-surgical ICUs [30], 81.4 in German ICUs [31], 90.0 in the International Nosocomial Infection Control Consortium (INICC) ICUs [32], 58–143 in Swedish ICUs [33], 196.5 in Italian ICUs [34], and 257.1 in Australian & New Zealand ICUs [35].

Unlike carbapenems, the consumption of piperacillin/tazobactam and vancomycin in this study was more comparable to rates reported by above international reports. For example, the consumption of piperacillin/tazobactam in this study was 134.3 DDDs per 1000 patient-days which was similar to Australian & New Zealand ICUs (124.7) [35], higher than NNIS, INICC, and France ICUs (47.2–75.5) [29, 30, 32], and lower than Italian and German ICUs (277.2–412.9) [31, 34]. Similarly, the consumption of vancomycin in this study was 98.2 DDDs per 1000 patient-days which was higher than NNIS, INICC, and German ICUs (36.7–91.9) [30–32] but lower than Italian and Australian & New Zealand ICUs (146.9–191.8) [34, 35].

As most of the DOT-based international reports of antimicrobial consumption were derived from whole hospital data [21, 36] or pediatric/neonatal populations [37, 38], comparing the current ICU-specific DOT rates is challenging. Nevertheless, this study had slightly higher carbapenems (235.7 versus 196.3) but lower piperacillin/tazobactam (145.9 versus 296.3) and vancomycin (129.5 versus 187.2) compared with a study done in an adult ICU in Canada [39]. Fairly similar to this study, piperacillin/tazobactam and/or carbapenems were among the most frequently consumed broad-spectrum antimicrobial agents in Canadian, Australian, and New Zealand ICUs [35, 39]. On the other hand, the majority of international studies show that penicillins [29–31, 34] or cephalosporins [32, 33, 39] are the most frequently consumed antimicrobials in adult ICUs. They represented 30–50% and 26–37% of all antimicrobial consumption in these studies compared with only 16.8 and 5.2% in the current ICUs, respectively.

A major limitation of this study was the inability to address the concurrent appropriateness of antimicrobial consumption. Additionally, the study only targeted antimicrobials frequently consumed in the selected ICU settings, the study does not include less frequently consumed antimicrobials nor those initiated before transfer to the ICU. The target population was National Guard soldiers, employees, and their families at a tertiary care setting. Therefore, interpretation and comparisons of the current findings should be done accordingly. Finally, the study was not designed to take in consideration variations among ICUs in patient mix or predominant bacterial pathogens and their susceptibility patterns. Nevertheless, using the current data to monitor the long-term impacts of different interventions of an antimicrobial stewardship program can potentially help to improve the current prescription practices, reduce cost, and avoid side effects.

Despite the presence of local written guidelines for antibiotic consumption and the availability of accessible microbiology services, the current finding showed high consumption of broad-spectrum antimicrobial agents such as meropenem and piperacillin/tazobactam in multiple ICUs in a tertiary care hospital. Meropenem consumption was higher than similar ICUs internationally. The findings highlight the urgent need for an effective antimicrobial stewardship program. The GCC Center for infection control has identified AMR as a major threat, and this study represents one of many proposed efforts assisting in mitigating the emergence of AMR in the region [10]. Surveillance and benchmarking of antimicrobial consumption and providing feedback to stakeholders, specifically prescribing physicians can reduce the amount of antimicrobial consumption and probably resistance [13, 40]. Future studies focusing on concurrent monitoring of antimicrobial resistance and identifying patient and physician characteristics associated with specific prescription patterns may help in improving judicious antimicrobial consumption.