A complete and multifaceted overview of antibiotic use and infection diagnosis in the intensive care unit: results from a prospective four-year registration

Antibiotics are among the most prescribed drugs in the intensive care unit (ICU) [1, 2]. The concept of “antibiotic stewardship” refers to policies and interventions to optimize antibiotic therapy and restrict their unnecessary use [3‐9]. The latter comprises avoiding antibiotic prescription for non-infectious disease, limiting the use of broad-spectrum drugs when a narrower antimicrobial spectrum suffices and shortening duration of therapy when prolonged antibiotic courses do not provide benefit [10‐12].

Surveillance of antibiotic prescription is a first and essential step to measure antibiotic expenditure, to document physicians’ incentives to prescribe antibiotics and to identify areas of potential overuse or misuse which could then be a target for antimicrobial stewardship interventions [5, 13‐15]. In general, surveillance metrics are derived from antibiotic prescription data (pharmacy-based), microbiology results (laboratory-based) or diagnostic codes (administration-based) or a combination thereof. However, surveillance is not the primary purpose of these sources of information and using them often results in poor matching of antibiotic prescription data with the corresponding clinical and microbiological information. As such, their ability to represent the complex nature of the antibiotic treatment decision-making process and thus their practical usefulness is limited [16‐18]. Prospective surveillance is more precise and informative but, since it is demanding in time and resources, is usually only applied for relatively short periods of time or for a limited scope of prescription, e.g. for certain classes of reserved antibiotics [19]. However, the computerization of the patient ICU chart has nowadays offered the potential to record healthcare processes as complete data of high resolution in a way that minimally interferes with the healthcare deliverer’s workflow [20].

In this manuscript, we present a complete and in-depth analysis of global antibiotic prescription and infection diagnosis in a university hospital ICU over a 4-year period. These data were collected with the help of a locally developed software program, which has been designed to link pharmaceutical, clinical and microbiological data together with diagnostic interpretation while performing daily bedside clinical work. As such, we were able to get a bird’s eye view of our local antibiotic prescribing practices, which can then serve as a starting point for the future construction of an antibiotic stewardship program (ASP).

In this manuscript, we demonstrated the versatility of a detailed database in antibiotic use and infection diagnosis, which is prospectively built by linking prescription, clinical and microbiological data on individual ICU patients during clinical workflow. This allowed various analyses that respectively center on patient admissions, prescription indication and infection diagnosis, antibiotic utilization and microbiology and as such may be useful to support various aspects of infection control and antibiotic stewardship. To the best of our knowledge, our study is the largest single-center study providing epidemiological data on antibiotic consumption and infections treated in the ICU in terms of number of ICU beds (36) and timespan covered (4 years).

Our study confirms that the antibiotic burden in the ICU is very high. Respectively, 66% of all admitted patients and 84% of patients with an ICU stay of more than 48 h were exposed to at least one class of antibiotic. These figures are consistent with the results of the one-year prospective surveillance study of Bergmans et al. and with the EPIC II point-prevalence study, which reported antibiotic prescription in 61% and 71% of admitted patients, respectively [1, 2].

The need for detailed antibiotic prescription surveillance and feedback to the clinician was already acknowledged in the very early stages of antimicrobial stewardship, but there is disagreement about which appropriate measures to select [5, 13, 14, 23, 24]. In 2016, the consensus results of an expert panel on metrics assessing the impact of stewardship interventions on a patient level in an acute-care setting were published. Potential metrics were evaluated for four distinct criteria, one of them being the feasibility to monitor the metric in any hospital with an electronic health record. Only six metrics were retained by the expert panel as suitable for ready implementation: incidence of healthcare facility and hospital-onset Clostridium difficile infection, rates of antibiotic-resistant pathogens, days of antibiotic therapy/number of admissions, days of antibiotic therapy/patient days and redundant therapy events. All of these metrics may be derived from separate electronic data sources (clinical, pharmacy, microbiology) and a connection between the different elements is not mandatory; however, these metrics are crude and unable to provide insight into antibiotic prescription. By linking these sources, a deeper understanding of the different factors driving antimicrobial use can be obtained, as illustrated by this study.

For example, the respiratory system accounted for half of identified sources of bacterial infection and more than one third of the total antibacterial DOT. Compared to abdominal infections, which represented the second largest group of bacterial infections and destination for antibiotic consumption, respiratory infections were less frequently categorized as highly probable (76% versus 50%, respectively), which also reflected the amount of DOT that was designated to treat these highly probable infections (85% of the total DOT of abdominal and 56% of the total DOT of respiratory infections). One quarter of the infections that were diagnosed in our ICU were ICU-acquired, which is in contrast with the study of Bergmans et al. where half of the infections were ICU-acquired and almost exclusively occurred in ventilated patients. Whereas the authors of the previous study concluded that stewardship should be focused on the prevention of ventilator-associated respiratory infections, this statement may apply less to our ICU population. In addition, restricting duration of antibiotic therapy in VAP of high probability will offer little gain, as the median treatment duration was only 7 days. In contrast, more restrictive use of antibiotics in suspected respiratory tract infections with cultures remaining negative and/or a swift clinical resolution, could result in a more profound reduction of antibiotic consumption. In addition, we observed that prophylactic treatment accounted for one fourth of the total DOT. Although this figure seems extremely high, more in-depth evaluation showed that two thirds of the antibacterial prophylactic treatment consisted of perioperative prophylaxis and prophylaxis in the immunocompromised patient, which conformed to guidelines with regard to treatment duration in the ICU. Whether aspiration and trauma justify antibiotic prophylaxis, and for what duration, is still a matter of debate; more recent studies promote restrictive use of antibiotics in this setting [25‐29]. We believe that introduction of more restrictive guidelines on prophylaxis in trauma and aspiration, which are currently unavailable in our ICU, could lead to a reduction in antibiotic use, albeit rather limited if we take the total as well as the median DOT for both indications in our ICU into account. This is in contrast with use of the antifungal prophylactic treatment, which is extremely high in our ICU, particularly in the context of intra-abdominal infections. Clear instructions on prophylactic indication and treatment duration, which are also not in place, may restrain our overall use of antifungals [30].

Despite the recognition of the importance of high-quality surveillance data to support antibiotic stewardship, few studies have provided detailed data on ICU global antibiotic consumption and infection diagnosis over an extended period of time [1, 19, 31]. This may reflect the difficulties in continuous prospective collection of infection-related data due to personnel and time restraints. In fact, while the authors of the study of Bergmans et al. felt that their proposed surveillance model in which they categorize antibiotic indications as prophylaxis, bacteriologically proven infections or non-bacteriologically proven (clinical suspicion) infections, would be suitable for more widespread use, there have since been few publications offering a similarly wide scope on antibiotic use in the ICU [1]. In our ICU, the COSARA software platform facilitated the integration of antibiotic, clinical and microbiological information during the workflow of daily bedside clinical rounds and weekly multidisciplinary staff meetings, hereby illustrating that sustained prospective surveillance is an achievable ambition with the help of information technology [20, 21]. The sustainability of this surveillance is probably to a certain extent due to the rather intuitive approach of labeling infections by the physician choosing from a drop-down menu of possible diagnoses and categorization by infection probability. While the result closely reflects physicians’ judgment and attitude in daily practice, it does not formally adhere to criteria such as those provided by the Centers for Disease Control (CDC) or the European Centre for Disease Prevention and Control (ECDC). A previous analysis assessing the validity of the diagnostic information recorded as such in COSARA compared to conventional surveillance data gathered by using checklists based on CDC-NHSN criteria showed good agreement between both surveillance methods [21]. However, a lack of precision may hamper comparisons between centers (as required for benchmarking) and over time (changing perception). This may to a certain extent be remedied by filtering sets of infection labels for the fulfillment of objective criteria as e.g. presence of positive microbiological cultures, biochemical findings exceeding a given threshold and noting of clinical signs in a computerized medical file.

Our study has limitations. First, building the database starting from computerized physician order entry depends on adequate filling in of the “pop-up” questions that are triggered by it, and by the persistent commitment of attending physicians or infection control personnel in linking the various information sources and finalizing infection diagnosis. Second, as stated before, the lack of adherence to strict criteria in labeling infection diagnosis in the current design hampers multicenter application [21]. Probably a trade-off has to be found between practical feasibility of continued registration on the one hand, and precision in diagnosis on the other. In addition, while COSARA software is compatible with various intensive care information systems, the applicability of our surveillance in different ICU settings and staffing structures has not been formally tested. Therefore, further studies are necessary to validate this model in these settings. Third, COSARA does not capture infections for which no antibiotic treatment is prescribed. Fourth, it remains to be tested to what extent high-quality surveillance may translate into effective stewardship intervening in the treatment decisions of the ICU physician.

We were able to obtain a unique bird’s eye view on global antibiotic use and infection diagnosis in our ICU over a 4-year time period by analysis of a multifaceted dataset, which was collected during the daily clinical workflow of ICU physicians with the help of information technology. In doing so, we revealed antibiotic prescription patterns that merit the attention of antibiotic stewardship.