Outcomes

The primary outcome measure of this study was the change in CAR-DOT, expressed as DOT per 100 patient-days per month.

The secondary outcome measure of this study was the total DOT per month per 100 patient-days of 3 antipseudomonal agents: CAR, piperacillin/tazobactam (PIPC/TAZ), and cefepime (CFPM), because these antibiotics are regarded as broad-spectrum, similar to CAR. This parameter was calculated to check whether CAR was simply being replaced with other broad-spectrum antipseudomonal agents. The total DOT per month per 100 patient-days of other antipseudomonal agents, such as piperacillin, ceftazidime, aztreonam, aminoglycosides, and fluoroquinolones, also were calculated.

We measured the incidence of antibiotic-resistant bacteria detections and Clostridioides difficile infection (CDI) per 1000 patient-days between April 2012 and May 2018, the period for which data were available, as an indicator of the outcome of the ASP. Carbapenemase-producing Enterobacteriaceae was defined as a gram-negative Enterobacteriaceae-producing carbapenemase regardless of genotype. Carbapenem-resistant Pseudomonas aeruginosa was defined as Pseudomonas aeruginosa that was resistant to CAR and either aminoglycoside or fluoroquinolone in Clinical and Laboratory Standards Institute's standard antimicrobial susceptibility tests, regardless of whether carbapenemase was produced. Clostridioides difficile infection was defined as the number of patients with positivity of CD toxin. We also included the incidence of candidaemia, which was previously reported to be associated with CAR use in low-birthweight neonates [11]. Samples collected within 48 hours of admission were excluded. In order to exclude duplicates, only the first sample was considered if the same strain was detected from the same patient more than once. There were no major changes in infection control policy in the hospital during this period.

We evaluated the cost of purchasing CAR each year from 2012 to 2017 in order to assess the economic impact of the ASP. As the costs were calculated annually according to the Japanese fiscal year (from April to March), we compared the costs in units of a fiscal year (ie, 2012 for Phase 1, 2015 for Phase 2, and 2017 for Phase 3). We calculated the actual cost of purchasing CAR (taking into consideration the cost of switching from branded to generics and fluctuations in drug prices) and the adjusted cost of purchasing CAR on the basis of the price of branded CAR in April 2012.