High-Risk Antibiotic Use Linked to Hospital-Associated C Diff Infections

Use of high-risk antibiotics is linked to C diff infections, but the class of antibiotics with the strongest link has changed over time underscoring the need for ongoing assessment.

Hospital-level use of high-risk antibiotics correlates with higher occurrences of hospital-associated Clostridioides difficile (C diff) infections, according to a retrospective analysis of data from 171 United States hospitals collected from 2016-2017.

The study, published in Infection Control & Hospital Epidemiology, looked at 4 classes of antibiotics considered high risk — cephalosporins, carbapenems, fluoroquinolones, and clindamycin — which accounted for about half of all antibiotics used. Investigators analyzed microbiological and pharmacy data included in the BD Insights Research Database and found a 12% increase in hospital-associated C diff infections for every 100-day increase in use of these antibiotics throughout the hospital.

A closer look at individual antibiotic classes, compared with reports that looked at data from earlier years, revealed a changing landscape.

“(W)e found fluoroquinolones have decreased in relative amount while cephalosporins and carbapenems have increased,” study author L. Clifford McDonald, MD, medical epidemiologist with the US Centers for Disease Control and Prevention, told Contagion®. “Meanwhile, we no longer found fluoroquinolones associated, as an individual class, with higher hospital rates of C diff infections while, instead, the cephalosporins appear to be the primary driver of C diff infections in hospitals. This highlights the importance of continually reassessing associations between antibiotic use and outcomes, in this case C diff infections, to guide local, regional, and national stewardship efforts.”

The findings support antimicrobial stewardship programs taking a targeted approach to reduce C diff infections, which are the most common health care-associated infection, affecting more than 500,000 Americans each year and resulting in about 30,000 deaths.

“While C diff is not an antibiotic-resistant organism in the sense of it developing important resistance to the drugs used in C diff infection treatment, it is intrinsically resistant to many antibiotics and commonly acquires new resistance to antibiotics used to treat other common infections,” McDonald told Contagion®.

“Use of antibiotics can select for specific strains of C diff, some of which may be more virulent and likely to spread, causing serious infections and deaths. This is what happened with the fluoroquinolone-resistant 027 strain of C diff that emerged in the year 2000 and spread worldwide. This strain continues to be found in US hospitals but is waning, and this decline in the 027 strain may be 1 reason we no longer see as strong an association between fluoroquinolone use and C diff infection rates. Because C diff in this way is acting like an antibiotic-resistant pathogen, our findings highlight why it will be important to continually relook over time at the associations of antibiotic use and resistance to advise local stewardship efforts in where to focus,” McDonald continued.

Overall, the correlation of high-risk antibiotic use with C diff infections was 0.22, with teaching hospitals showing a higher correlation of 0.38 compared with 0.19 for nonteaching hospitals. Other factors associated with a higher incidence of C diff infections included a larger proportion of patients older than 65; a higher rate of community-onset, non-hospital associated C diff infections; longer average length of stay; and higher proton pump inhibitor use.

“Next steps would be to validate these findings in other contemporary datasets and, if it is confirmed that antibiotic drivers of C diff infections in hospitals are changing over time, there should be a process developed for ongoing reassessments of the association of antibiotics and outcomes in national surveillance systems such as the NHSN [National Healthcare Safety Network] antibiotic use and resistance module—so as to constantly inform local stewardship efforts,” McDonald said.

A study released earlier this year found that fluoroquinolone use decreased by 50% across the VA health care system from 2006 to 2016. That study also found a 50% decrease in hospital-onset or health care-acquired C diff over the same period. An uptick in cephalosporin use also was noted.

The prevalence of C diff has been a growing focus of infection prevention efforts in health care settings. Efforts to address the issue have included research into the effectiveness of treatments such as fecal microbiota transplantation (FMT) and prevention measures such as uses of disinfectants along with efforts to better understand the role of fungi in C diff infections.