International Journal of Antimicrobial Agents 44 (2014) 520–527

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International Journal of Antimicrobial Agents journal homepage: http://www.elsevier.com/locate/ijantimicag

Blood culture-guided de-escalation of empirical antimicrobial regimen for critical patients in an online antimicrobial stewardship programme Hsiu-Yin Wang a,1 , Cheng-Hsun Chiu b,∗,1 , Ching-Tai Huang c,1 , Chun-Wen Cheng c , Yu-Jr Lin d , Ying-Jen Hsu e , Chi-Hua Chen a , Shin-Tarng Deng a , Hsieh-Shong Leu c a

Department of Pharmacy, Chang Gung Memorial Hospital, Taoyuan, Taiwan Molecular Infectious Disease Research Centre, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan c Division of Infectious Diseases, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan d Biostatistical Centre for Clinical Research, Chang Gung Memorial Hospital, Taoyuan, Taiwan e Department of Management Information System, Chang Gung Memorial Hospital, Taoyuan, Taiwan b

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Article history: Received 13 May 2014 Received in revised form 23 July 2014 Accepted 28 July 2014 Keywords: Blood culture De-escalation Hospital-wide computerised antimicrobial approval system Antimicrobial stewardship

a b s t r a c t A blood culture-guided review strategy was applied to a hospital-wide computerised antimicrobial approval system (HCAAS) at a medical centre in Taiwan. The study aimed to evaluate the impact of this deployment on prescribers’ behaviours, antimicrobial consumption, antimicrobial expenditure and healthcare quality in adult intensive care units (ICUs). The HCAAS automatically identifies patients with positive blood cultures and notifies the pre-assigned infectious diseases (ID) physicians for an online second review of the current antimicrobial regimen. Patients from 16 adult ICUs were selected as a focus group. Descriptive analysis, McNemar’s test, interrupted time-series analysis and univariate regression analysis were applied. The number of prescriptions assigned for second review increased from 304 in 2010 to 682 in 2012. The approval rate for the antimicrobial regimen in the second review exceeded 70%. In disapproved cases, prescribers accepted the recommendation from ID physicians in 66.1% of cases in the first year; the acceptance rate increased to 80.6% in 2012. Among the restricted antimicrobial agents, consumption gradients decreased for all eight drug classes. The overall antimicrobial expenditure gradient declined significantly following deployment of the second review strategy. The healthcareassociated infection rate continued to decrease over time, and the mortality and ICU re-admission rates remained stable after deployment. A blood culture-guided review of antimicrobial use based on clinical and microbiological evidence improves accuracy in choosing appropriate antimicrobial agents and encourages de-escalation. Consumption and expenditure gradients of antimicrobial agents decreased after the intervention, and healthcare quality was not compromised. © 2014 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

1. Introduction Initial prescription of broad-spectrum antimicrobial agents to critically ill patients is supported by many studies as well as the latest Surviving Sepsis Campaign guidelines [1]. On the other hand, evidence has clearly shown that antimicrobial use is strongly related to the development and spread of antimicrobial-resistant pathogens [2–4]. Reckless de-escalation may cause unpredicted

∗ Corresponding author. Tel.: +886 3 328 1200x8896; fax: +886 3 328 8957. E-mail address: [email protected] (C.-H. Chiu). 1 These three authors contributed equally to this work.

disease progression, especially for critically ill patients, and therefore hinder a reduction in antimicrobial use. De-escalation should be considered, however, when the clinical condition of a patient is stable or the causative pathogens and their antimicrobial susceptibilities are identified to prevent the development of antimicrobial resistance and adverse drug reactions and to reduce expenditure [1]. Several studies and an individual patient data meta-analysis have reported that procalcitonin-guided treatment can reduce antimicrobial exposure with no impact on the mortality rate and treatment failure in patients with acute respiratory infection [5–8]. A hospital-wide computerised antimicrobial approval system (HCAAS) was developed in 2004 at Chang Gung Memorial Hospital (CGMH), a 3700-bed medical centre in northern Taiwan [9]. This

http://dx.doi.org/10.1016/j.ijantimicag.2014.07.025 0924-8579/© 2014 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

H.-Y. Wang et al. / International Journal of Antimicrobial Agents 44 (2014) 520–527

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Fig. 1. Schematic of the flow of the blood culture-guided second review strategy deployed on the hospital-wide computerised antimicrobial approval system (HCAAS). The HCAAS automatically identifies patients with positive blood culture results and simultaneously notifies infectious diseases (ID) physicians for a second review. This process was incorporated into the original HCAAS in 2010. CPOE, computerised physician order entry.

antimicrobial stewardship programme (ASP) system built under the Health Information System (HIS) is an intranet-based interface. Infectious diseases (ID) physicians can access relevant information via the HCAAS and HIS, including the clinical course of patients, laboratory results and images, for real-time, on-line prescription vetting and then communicate with prescribers. De-escalation should be patient-specific and evidence-based, providing sufficient clinical credibility and timeliness. In April 2010, implementation of the HCAAS was extended with a blood culture-guided review strategy to provide clinical and microbiological evidence that can encourage and guide de-escalation. The system automatically identifies patients with positive blood culture results and notifies the assigned ID physicians for a second review of the previously approved prescription. This study aimed to evaluate the impact of the deployment of second review on prescribers’ responses, antimicrobial consumption, antimicrobial expenditure and healthcare quality in adult intensive care units (ICUs). 2. Materials and methods 2.1. Intervention The blood culture-guided second review strategy was implemented under the existing HCAAS (Fig. 1). Patients in 16 adult ICUs (223 beds) were selected as a focus group for this study. Antimicrobial agents were classified as ‘restricted’ or ‘non-restricted’ as described in previous studies [10–12].

Restricted antimicrobial agents in CGMH are: third- and fourth-generation cephalosporins (ceftriaxone, ceftazidime and cefepime); fluoroquinolones (ciprofloxacin, levofloxacin and moxifloxacin); glycopeptides (vancomycin and teicoplanin); antivancomycin-resistant enterococci agents (anti-VREs) (linezolid and daptomycin); carbapenems (imipenem/cilastatin, ertapenem, meropenem and doripenem); piperacillin/tazobactam; amikacin; and antifungal agents (fluconazole, voriconazole, amphotericin B, liposomal amphotericin B, anidulafungin, micafungin and caspofungin). For all non-ICU patients, prescription of non-restricted agents did not require approval from ID physicians, whilst all prescriptions for ICU patients required approval from ID physicians to prevent suboptimal regimens. For the second review, the HCAAS sends an alert of positive blood culture results to the pre-assigned ID physician by mobile phone. The ID physician must re-evaluate all antimicrobial agents, relevant medical information, updated blood culture results and antimicrobial susceptibilities within a 48h buffer period, the same buffer period as the initial review. During the 48-h period, antimicrobial agents were dispensed via the unitdose department to ensure the safety of the patients. For disapproved cases, ID physicians provide alternative recommendations through the bidirectional communication platform of the HCAAS. 2.2. Data collection The case number for blood culture-guided second review, mortality rate in the hospital’s ICUs, 3-day re-admission rate,

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H.-Y. Wang et al. / International Journal of Antimicrobial Agents 44 (2014) 520–527

healthcare-associated infection (HAI) rate and patient-days were collected via the HIS. The Acute Physiology and Chronic Health Evaluation (APACHE) II score of individual adult ICU patients, consumption of antimicrobial agents and medication expenditures were retrieved from the Statistical Analysis System Enterprise Guide 4.2. Data were collected at monthly intervals between 2008 and 2012. 2.3. Measurement The Antimicrobial Stewardship Subcommittee is a subcommittee under the Infection Control Committee at CGMH and is responsible for: (i) analysing the approval rate, recommendation acceptance rate and feedback to prescribers in HCAAS; (ii) surveillance of antimicrobial consumption and expenditures; and (iii) monitoring healthcare quality indicators such as ICU mortality rate, 3-day re-admission rate in ICUs, and HAI rate. In this study, both the process and outcome measurements of antimicrobial stewardship were analysed [13,14]. 2.4. Process measurement The number of cases identified by the HCAAS was collected at monthly intervals and was analysed for approval rate, recommendation acceptance rate in disapproved cases, and reasons for disapproval. Consumption of antimicrobial agents was converted into defined daily doses (DDDs) [Anatomical Therapeutic Chemical (ATC)/DDD 2013] according to World Health Organization (WHO) guidelines and was expressed as DDDs per 1000 patient-days [15]. Expenditure for antifungal agents was incorporated into the calculation of overall antimicrobial agent expenditure. The change in antimicrobial expenditure relative to overall drug expenditure was measured to assess the impact on the hospital’s global budget system. The change in antimicrobial expenditure relative to 1000 patient-days was also analysed to evaluate the patient-level impact. Approval or disapproval for the initial antimicrobial regimen in the blood culture-based second review was analysed to evaluate the effectiveness of the strategy on guiding de-escalation. 2.5. Outcome measurement The ultimate goal of the ASP is to improve patient outcomes and safety by promoting appropriate use of antimicrobial agents [16]. Compared with studies merely measuring the reduction in antimicrobial consumption, efforts focused on optimising treatment demonstrated improvements in the clinical outcome of patients [17]. Patient mortality, HAI and ICU re-admission rates were therefore chosen as outcome indicators. The mortality rate was calculated as the number of deaths divided by the number of patients discharged from ICUs. The denominator of the HAI rate was the number of episodes per 1000 patient-days. The ICU readmission rate was calculated as the number of patients who were re-admitted to ICUs within 3 days of discharge divided by the number of patients who were discharged from ICUs. 2.6. Statistical analysis Descriptive analysis was used to present the second review approval rate, recommendation acceptance rate and reasons for disapproval. McNemar’s test was applied to analyse the concordance of the recommendation before and after the intervention. Interrupted time-series analysis and univariate regression analysis were applied to compare the level and trends before and after the intervention in terms of outcome measurements. A P-value

Fig. 2. (A) Disapproval rate (—•—) from the blood culture-guided second review by infectious diseases (ID) physicians and (B) acceptance rate (—•—) for the recommendations from the ID physicians by prescribers over time.

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Blood culture-guided de-escalation of empirical antimicrobial regimen for critical patients in an online antimicrobial stewardship programme.

A blood culture-guided review strategy was applied to a hospital-wide computerised antimicrobial approval system (HCAAS) at a medical centre in Taiwan...
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