Reduction strategies for inpatient oral third-generation cephalosporins at a cancer center: An interrupted time-series analysis

Abstract

Oral third-generation cephalosporins (3GCs) are not recommended for use owing to their low bioavailability and the risk of emergence of resistant microorganisms with overuse. A standardized and effective method for reducing their use is lacking. Here, in a 60-month, single-institution, interrupted time-series analysis, which was retrospectively conducted between April 1, 2017, and March 31, 2022, we evaluated the effectiveness of a four-phase intervention to reduce the use of 3GCs in patients at a cancer center: Phase 1 (pre-intervention), Phase 2 (review of clinical pathways), Phase 3 (establishment of infectious disease consultation service and implementation of antimicrobial stewardship program), and Phase 4 (educational lecture and pop-up displays for oral antimicrobials at the time of ordering). Although no significant changes were observed in Phases 3 and 4, the first intervention resulted in a significant decrease in the trend and level of days of therapy (DOT) for 3GCs. The level for cephalexin DOT and the trend for sulfamethoxazole-trimethoprim DOT increased in Phase 4, and the trend for amoxicillin and amoxicillin-clavulanate DOT increased in Phase 3. Macrolide DOT showed a decreasing trend in Phases 2 and 4 and decreasing and increased levels in Phases 3 and 4, respectively; no change was observed for quinolones. Actual and adjusted purchase costs of 3GCs decreased significantly during all study periods, while those for oral antimicrobials decreased in Phase 2, and actual purchase costs increased in Phases 3 and 4. No significant reduction in resistant organisms, length of hospital stay, or mortality was observed. This is the first study on the effects of oral 3GC reduction strategies in patients with cancer. We conclude that even facilities that substantially use antimicrobials can efficiently reduce the use of 3GCs.

Fig 1. Trends in the days of third-generation cephalosporin therapy per 100 patients, by month, during Phases 1 to 4.

Each dot refers to the third-generation cephalosporins (3GCs) per 100 patients each month, and the slope is based on the linear regression in the four phases: Phase 1 (pre-intervention period from April 1, 2017, to May 31, 2019); Phase 2 (review of clinical pathways from June 1, 2019, to March 31, 2020); Phase 3 (establishing an infectious disease (ID) consultation service and implementing the antimicrobial stewardship program (ASP) from April 1, 2020, to June 30, 2021); Phase 4 (educational lecture and pop-up displays for oral antimicrobials from July 1, 2021, to March 31, 2022).

Fig 2. Trends in the days of cefalexin therapy per 100 patients, by month, during Phases 1 to 4.

Each dot refers to cefalexin per 100 patients in each month, and the slope is based on the linear regression in the four phases: Phase 1 (pre-intervention period from April 1, 2017, to May 31, 2019); Phase 2 (review of clinical pathways from June 1, 2019, to March 31, 2020); Phase 3 (establishing an ID consultation service and implementing the ASP from April 1, 2020, to June 30, 2021); and Phase 4 (educational lecture and pop-up displays for oral antimicrobials from July 1, 2021, to March 31, 2022).

Fig 3. Trends in the days of amoxicillin and amoxicillin-clavulanate therapy per 100 patients, by month, during Phases 1 to 4.

Each dot refers to the amoxicillin and amoxicillin-clavulanate per 100 patients each month, and the slope is based on the linear regression in the four phases: Phase 1 (pre-intervention period from April 1, 2017, to May 31, 2019); Phase 2 (review of clinical pathways from June 1, 2019, to March 31, 2020); Phase 3 (establishing an ID consultation service and implementing the ASP from April 1, 2020, to June 30, 2021); and Phase 4 (educational lecture and pop-up displays for oral antimicrobials from July 1, 2021, to March 31, 2022).

Fig 4. Trends in the days of sulfamethoxazole-trimethoprim therapy per 100 patients, by month, during Phases 1 to 4.

Each dot refers to the sulfamethoxazole-trimethoprim per 100 patients each month, and the slope is based on the linear regression in the four phases: Phase 1 (pre-intervention period from April 1, 2017, to May 31, 2019); Phase 2 (review of clinical pathways from June 1, 2019, to March 31, 2020); Phase 3 (establishing an ID consultation service and implementing the ASP from April 1, 2020, to June 30, 2021); and Phase 4 (educational lecture and pop-up displays for oral antimicrobials from July 1, 2021, to March 31, 2022).

Fig 5. Trends in the days of quinolone therapy per 100 patients, by month, during Phases 1 to 4.

Each dot refers to the quinolones per 100 patients in each month, and the slope is based on the linear regression in the four phases: Phase 1 (pre-intervention period from April 1, 2017, to May 31, 2019); Phase 2 (review of clinical pathways from June 1, 2019, to March 31, 2020); Phase 3 (establishing an ID consultation service and implementing the ASP from April 1, 2020, to June 30, 2021); and Phase 4 (educational lecture and pop-up displays for oral antimicrobials from July 1, 2021, to March 31, 2022).

Fig 6. Trends in the days of macrolides therapy per 100 patients, by month, during Phases 1 to 4.

Each dot refers to the macrolides per 100 patients each month, and the slope is based on the linear regression in the four phases: Phase 1 (pre-intervention period from April 1, 2017, to May 31, 2019); Phase 2 (review of clinical pathways from June 1, 2019, to March 31, 2020); Phase 3 (establishing an ID consultation service and implementing the ASP from April 1, 2020, to June 30, 2021); and Phase 4 (educational lecture and pop-up displays for oral antimicrobials from July 1, 2021, to March 31, 2022).

Fig 7. Trends in the incidence of extended-spectrum β-lactamase (ESBL)- producing Enterobacteriaceae per 1000 patients, by month, during the pre-intervention period (Phase 1) and interventional period (Phases 2–4).

Each dot refers to ESBL-producing Enterobacteriaceae per 1000 patients in each month; the slope is based on linear regression in the four phases: Phase 1 (pre-intervention period from April 1, 2017, to May 31, 2019); Phase 2 (review of clinical pathways from June 1, 2019, to March 31, 2020); Phase 3 (establishing an infectious disease (ID) consultation service and implementing the antimicrobial stewardship program from April 1, 2020, to June 30, 2021); and Phase 4 (educational lecture and pop-up displays for oral antimicrobials from July 1, 2021, to March 31, 2022).

Fig 8. Trends in the incidence of penicillin-resistant Streptococcus pneumoniae (PRSP) per 1000 patients, by month, during the pre-intervention period (Phase 1) and interventional period (Phases 2–4).

Each dot refers to the PRSP per 1000 patients in each month; the slope is based on linear regression in the four phases: Phase 1 (pre-intervention period from April 1, 2017, to May 31, 2019); Phase 2 (review of clinical pathways from June 1, 2019, to March 31, 2020); Phase 3 (establishing an infectious disease (ID) consultation service and implementing the antimicrobial stewardship program from April 1, 2020, to June 30, 2021); and Phase 4 (educational lecture and pop-up displays for oral antimicrobials from July 1, 2021, to March 31, 2022).

Fig 9. Trends in the incidence of resistant Haemophilus influenzae per 1000 patients, by month, during the pre-intervention period (Phase 1) and interventional period (Phases 2–4).

Each dot refers to resistant H. influenzae per 1000 patients each month; the slope is based on linear regression in the four phases: Phase 1 (pre-intervention period from April 1, 2017, to May 31, 2019); Phase 2 (review of clinical pathways from June 1, 2019, to March 31, 2020); Phase 3 (establishing an infectious disease consultation service and implementing the antimicrobial stewardship program from April 1, 2020, to June 30, 2021); and Phase 4 (educational lecture and pop-up displays for oral antimicrobials from July 1, 2021, to March 31, 2022).

Fig 10. Trends in the incidence of Clostridioides difficile infection (CDI) per 1000 patients, by month, during the pre-intervention period (Phase 1) and interventional period (Phases 2–4).

Each dot refers to the CDI per 1000 patients each month, and the slope is based on linear regression in the four phases: Phase 1 (pre-intervention period from April 1, 2017, to May 31, 2019); Phase 2 (review of clinical pathways from June 1, 2019, to March 31, 2020); Phase 3 (establishing an infectious disease (ID) consultation service and implementing the antimicrobial stewardship program from April 1, 2020, to June 30, 2021); and Phase 4 (educational lecture and pop-up displays for oral antimicrobials from July 1, 2021, to March 31, 2022).

Fig 11. Trends in the incidence of methicillin-resistant Staphylococcus aureus (MRSA) per 1000 patients, by month, during the pre-intervention period (Phase 1) and interventional period (Phases 2–4).

Each dot refers to MRSA per 1000 patients each month, and the slope is based on linear regression in the four phases: Phase 1 (pre-intervention period from April 1, 2017, to May 31, 2019); Phase 2 (review of clinical pathways from June 1, 2019, to March 31, 2020); Phase 3 (establishing an infectious disease (ID) consultation service and implementing the antimicrobial stewardship program from April 1, 2020, to June 30, 2021); and Phase 4 (educational lecture and pop-up displays for oral antimicrobials from July 1, 2021, to March 31, 2022).

Fig 12. Trends in in-hospital mortality by month during the pre-intervention period (Phase 1) and interventional period (Phases 2–4).

Each dot refers to the in-hospital mortality each month, and the slope is based on the linear regression in the four phases: Phase 1 (pre-intervention period from April 1, 2017, to May 31, 2019); Phase 2 (review of clinical pathways from June 1, 2019, to March 31, 2020); Phase 3 (establishing an infectious disease (ID) consultation service and implementing the antimicrobial stewardship program from April 1, 2020, to June 30, 2021); and Phase 4 (educational lecture and pop-up displays for oral antimicrobials from July 1, 2021, to March 31, 2022).

Fig 13. Trends in the length of hospital stay by month during the pre-intervention period (Phase 1) and interventional period (Phases 2–4).

Each dot refers to the length of hospital stay each month, and the slope is based on linear regression in the four phases: Phase 1 (pre-intervention period from April 1, 2017, to May 31, 2019); Phase 2 (review of clinical pathways from June 1, 2019, to March 31, 2020); Phase 3 (establishing an infectious disease (ID) consultation service and implementing the antimicrobial stewardship program from April 1, 2020, to June 30, 2021); and Phase 4 (educational lecture and pop-up displays for oral antimicrobials from July 1, 2021, to March 31, 2022).