Discussion

In this study, we used a 2-phased approach to assess whether IV amoxicillin-clavulanate might present a narrower spectrum alternative to IV piperacillin-tazobactam for general surgery inpatients. Our rate of inappropriate piperacillin-tazobactam prescribing was similar to other studies. ^{Reference Beahm and Fryters3,Reference Mekdad and AlSayed5} To our knowledge, this study is the first to evaluate recommending the use of IV amoxicillin-clavulanate as part of a PAF strategy to decrease piperacillin-tazobactam use.

We present several considerations for recommending IV amoxicillin-clavulanate as a narrower-spectrum alternative to piperacillin-tazobactam. Pseudomonas aeruginosa is a pathogen responsible for many hospital-acquired infections and has high rates of resistance to antibiotics. ^{Reference Mehrad, Clark and Zhanel10} As expected, piperacillin-tazobactam use is associated with piperacillin-tazobactam–resistant strains of P. aeruginosa. ^{Reference Harris, Perencevich and Roghmann2} Because P. aeruginosa coverage is not indicated in many community-acquired infections, including community-acquired intra-abdominal infections, ^{Reference Mazuski, Tessier and May1} using IV amoxicillin-clavulanate (which does not cover P. aeruginosa) is a strategy implemented to “preserve” piperacillin-tazobactam antipseudomonal activity. At our institution, Enterobacterales susceptibility to amoxicillin-clavulanate is very similar to piperacillin-tazobactam and ceftriaxone. ⁹ Also, IV amoxicillin-clavulanate maintains coverage of Enterococcus spp (whereas a cephalosporin and metronidazole combination does not), which may be warranted in specific circumstances.

We primarily evaluated the use of the IV (vs oral) amoxicillin-clavulanate for several reasons. First, the use of oral amoxicillin-clavulanate as step-down therapy for intra-abdominal infections is a well-established practice both at our institution and elsewhere. ^{Reference Mazuski, Tessier and May1} We specifically evaluated the AMS niche for a new product. In addition, we anticipated that much of the IV piperacillin-tazobactam use captured during this study would occur shortly after initiation, given the high turnover of this patient population.

Several reasons may explain why uptake of IV amoxicillin-clavulanate suggestions was low. Primarily, IV amoxicillin-clavulanate is new to both the Canadian market and is a recent addition (January 2021) to our formulary. Prescribers may not have been aware of its availability and place in practice. Also, IV administration is different than oral dosing for amoxicillin-clavulanate, so practitioner unfamiliarity may have played a role. In several cases, the surgical team chose to switch patients to oral amoxicillin-clavulanate instead of IV administration. A delay between the patient assessment by the AMS team and the surgical team reviewing the recommendation may have contributed to this finding.

This study had several limitations. The PAF portion of the study took place over 16 weeks, which may not have been an adequate amount of time to observe the uptake of suggestions. Second, we only completed PAF of patients on piperacillin-tazobactam once per week, and the median days of antibiotic therapy was 4.5 for the patients reviewed during phase 1. More frequent PAF would have allowed earlier intervention and would potentially have increased the uptake of IV amoxicillin-clavulanate. Third, although the general surgery department was informed about the PAF phase of the project, no targeted education was given to prescribers, which may have been another way to target piperacillin-tazobactam use. In addition, we did not collect information on whether infections were community or hospital acquired, which may have affected suggestion uptake, although this information was factored into AMS recommendations. Finally, this was a pilot quality-improvement study, and we did not assess clinical outcomes of interest, such as antimicrobial resistance or complications of broad-spectrum antibiotics.

Although we intended to evaluate the use of IV amoxicillin-clavulanate, it is clear that AMS interventions to optimize piperacillin-tazobactam use on general surgery units are needed and that IV amoxicillin-clavulanate is unlikely to have a substantial role as an alternative antimicrobial choice. Future studies evaluating strategies to address piperacillin-tazobactam prescribing on general surgery units are warranted.