Discussion

In this pilot study, we were able to quantify the CDI risk of antibiotics used in our facility by dividing the number of CDI cases associated with each antibiotic by a measure of antibiotic consumption (DOT for inpatient and number of pills dispensed for outpatient medications). The denominator data were readily available from our pharmacy and through our ASP. These calculations provided an institution-specific risk profile that reflected our antibiotic use pattern and guided our stewardship efforts. Although the risk estimates may not be generalizable to other institutions, the approach provides a simple way to describe institution-specific antibiotic CDI risk. Future studies should validate this approach to measuring CDI risk of antibiotics and should evaluate whether changes in ASP recommendations can shift CDI risk and/or decrease CDI events.

Overall, PTZ was the most common IV antibiotic given prior to CDI (n = 9 cases). We will leverage this finding to encourage more rational PTZ use, especially when anaerobic or antipseudomonal coverage is not indicated. Ceftriaxone (CTX) was associated with 5 CDIs. CTX is one of the most common antibiotics used in the hospital, and the CDI rate with this antibiotic was relatively low (0.72 CDI per 1 KDOT). In diseases for which ampicillin-sulbactam is an alternative to CTX (eg, community-acquired pneumonia), favoring the former may increase CDIs; ampicillin-sulbactam had a higher CDI rate (1.58 CDI per 1 KDOT).

Meropenem was associated with 2 CDI cases but had the highest CDI rate among the IV antibiotics for inpatients (3.56 CDI per 1 KDOT). Although the CDI rate is likely affected by low consumption and use in high-risk (ie, critically ill) patients, our finding was consistent with the prevailing literature. ^{Reference Brown, Khanafer, Daneman and Fisman4,Reference Slimings and Riley6} We have limited the use of meropenem to those at risk for extended-spectrum β-lacatmase–producing Enterobacterales, and we are considering opportunities to further reduce inappropriate use. Cefepime had a lower CDI risk than PTZ. Although some data suggest that PTZ is protective of CDI, ^{Reference Slimings and Riley6} our findings suggest that cefepime may be preferentially recommended over PTZ in infections when either is appropriate.

In common diseases like inpatient urinary tract infections, we may recommend de-escalation to oral regimens like AMC or cefuroxime. Cefuroxime had higher CDI risk (3.17 CDI per 1 KDOT) than AMC (1.16 CDI per 1 KDOT). However, it is doubtful that AMC was safer, given that it was associated with 5 outpatient CDI cases. We were unable to combine inpatient and outpatient AMC data because the measures differ. Also, we were unable to determine whether all dispensed antibiotics were consumed. Finally, being an inpatient increases CDI risk. ^{Reference Freedberg, Salmasian, Cohen, Abrams and Larson7}

High-risk antibiotics (cephalosporins, ciprofloxacin, and clindamycin) ^{Reference Brown, Khanafer, Daneman and Fisman4–Reference Slimings and Riley6} were also identified as high risk in our study. Some narrow-spectrum and lower-risk antibiotics were also associated with CDI in our study (ie, vancomycin, metronidazole, azithromycin, trimethoprim-sulfamethoxazole), perhaps due to high utilization or their use in combination with higher-risk antibiotics. We did not assess the effects of multiple antibiotic exposures on CDI risk.

Most CDI cases were not severe. Increased age has been associated with increased severity, ^{Reference Czepiel, Dróżdż and Pituch8} consistent with our results. Only 10.26% of cases had chemotherapy prior to CDI, consistent with studies in which no specific chemotherapy has been shown to be an independent risk factor for CDI. ^{Reference Neemann and Freifeld9} PPIs were commonly used prior to CDI, similar to prior studies. ^{Reference Ofori, Ramai, Dhawan, Mustafa, Gasperino and Reddy10}

Our study had several limitations. We considered every antibiotic exposure as an independent exposure, and we did not analyze the effects of combined antibiotics or multiple antibiotics given prior to CDI. We also limited our chart review to our institution’s records; thus, antibiotics prescribed and CDI diagnosed elsewhere were not included. The single-center nature of the study limited generalizability and did not supplant the established antibiotic risk based on larger studies. Although we examined the association between antibiotics and the development of CDI, causality cannot be inferred. The relatively small sample size limited comparisons of CDI risk across antibiotics. We intend to conduct a future study when we have additional years of data and can examine how modified antimicrobial policies may have changed CDI risk for individual antibiotics.

In this single-institution evaluation, simple calculations using readily available data to stratify CDI risk to help guide antibiotic stewardship policies to reduce CDI.