Infection Control & Hospital Epidemiology
treatment outcomes of IDs treated by the targeted antibiotics, antibiotic consumption, and antibiotic expenditure.
Material and Methods Study settings and design
From February 1 to September 30, 2013, we conducted a cluster- randomized controlled study at 6 general medical wards in Siriraj Hospital, a 2,200-bed tertiary-care university hospital in Bangkok, Thailand. The Siriraj Institutional Review Board approved this study with a waiver of informed consent.
Antimicrobial stewardship at Siriraj Hospital
The Siriraj ASP was officially established in 2007 by a multi- disciplinary team composed of ID physicians, ID clinical fellows, general pharmacists, and microbiologists. The hospital antibiotic formulary includes 3 classes of antibiotics: general, restricted, and controlled antibiotics. General antibiotics can be prescribed by any physician without restriction, and restricted antibiotics require approval from ID physicians before dispensing (preprescription authorization). Controlled antibiotics can be prescribed by any physician for use within the first 72 hours of the index prescription; thereafter, application of such antibiotics requires approval from an ID physician: postprescription review and authorization (PPRA). The list of controlled antibiotics at Siriraj Hospital includes piperacillin/tazobactam, imipenem/cilastatin, and meropenem. These were the targeted antibiotics in the present study.
Study subjects
The study subjects were hospitalized patients aged >15 years who received at least 1 dose of the targeted antibiotics. The need for informed consent was waived; thus, all eligible patients were automatically enrolled in the study. The study subjects could be enrolled more than once if they underwent multiple hospitalizations during the study period. However, only the first prescription during a given hospitalization was included in the study.
Randomization
The unit of randomization was the medical ward. Three medical wards were randomly assigned to the intervention group; an additional 3 wards were assigned to the standard-of-care or control group. Owing to the cluster-randomization design and the nature of antibiotic approval processes, blinding was impossible. However, the research team did not reveal the research hypothesis to patients or related personnel.
Standard of care and study intervention
Standard of care: PPRA of targeted antibiotics by ID clinical fellows (fellow PPRA). Prior to the study period, the PPRA was conducted by an ID clinical fellow under an ID physician’
ssupervision.To prescribe the targeted antibiotic, the responsible physician was required to complete the drug-use evaluation form for targeted antibiotics. The form included data about the infection site, the causative pathogen if culture results were available, and an indi- cation of targeted antibiotics. A prescription for targeted antibiotics could be made by any physician for use within the first 72 hours of
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the index prescription. Continuation of targeted antibiotics beyond 72 hours required approval from an ID clinical fellow under an ID physician’s supervision. The decision to continue the targeted antibiotics was classified as approved, temporarily approved, or not approved. If the targeted antibiotic was appropriately prescribed, it could be continued for up to 14 days. Additional approval was required if a longer duration of the targeted antibiotic became necessary. The approval processes began within the 72 hours after initiation of the targeted antibiotics. In the case of waiting for further information, the targeted antibiotic could be temporarily approved for an additional 72 hours. If the targeted antibiotic was inappropriately prescribed, it had to be discontinued. Alternative antibiotic regimens could be suggested if necessary. The ID clinical fellow could independently approve the prescription of targeted antibiotics; however, final agreement from an ID physician was required before discontinuing any prescription of targeted anti- biotics. The responsible physician could directly consult the ID service consultation team for a second opinion. The recommen- dation from the ID service consultation team was considered final.
Intervention: PPRA of targeted antibiotics by trained general phar- macist (pharmacist PPRA). The intervention processes were iden- tical to those for fellow PPRA except that a trained general pharmacist, rather than a clinical ID fellow, was responsible for approval of the targeted antibiotics. The trained general pharmacist could independently approve the prescription of targeted anti- biotics; however, final agreement froman IDphysician was required before discontinuing any prescription of targeted antibiotics. The pharmacists had received 3-month intensive training in
ASP. The ASP training course included attending an 8-hour lecture course, a monthly interactive case discussion, and daily ward rounds with an ID physician. The 8-hour lecture course focused on all important aspects for ASP implementation: ASP concept, basic laboratory interpretation, rational antibiotic use for common infections, pharmacokinetic/pharmacodynamic approach to antibiotic therapy, and basic concept of antibiotic allergy. Only trained pharmacists who passed a qualification exam (10 clinical scenarios) could participate in this study.
Data collection
Patient characteristics and clinical outcomes were obtained by reviewing medical records; data on antibiotic use and expenditure were retrieved directly fromthe Siriraj Hospital electronic database. The primary outcome was a favorable clinical response of patients receiving the targeted antibiotics; the secondary outcome was the defined daily dose (DDD) of targeted antibiotics. We also collected data about other outcomes of IDs treated with the targeted anti- biotics, the DDDs of all antibiotics, and antibiotic expenditure. An independent ID physician determined the appropriateness of
the antibiotic recommendation, and that physician retrospectively reviewed all patients’ medical records and drug-use evaluation forms. The initial recommendation was any recommendation made within the first 72 hours of the index prescription or any recommendation with a temporarily approved decision. The final recommendation was any recommendation made after the first 72 hours of index prescription together with the decision to approve or not.
Sample size calculation
Based on a previous study conducted at our hospital,12 the favorable clinical response was ~60%, with an intracluster
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