Common Hospital-Administered Antibiotics Linked to C Difficile, Adverse Drug Reactions

This article was originally published by HCPLive®. It has been lightly edited.

Several antibiotics commonly administered to ICU patients may be associated with a greater risk of Clostridioides difficile infection and related adverse drug reactions, according to a study published in Pharmaceuticals.¹

Of more than 100,000 suspected adverse drug reaction reports registered in EudraVigilance, most related to C difficile were associated with ciprofloxacin, ceftriaxone, and piperacillin/tazobactam, highlighting the importance of antibiotic surveillance and monitoring programs to reduce the risk of adverse events.

“There is a heterogeneous relationship between antibiotic use in the intensive care unit (ICU) and C difficile," the authors wrote. "The most used antibiotics in the ICU are non-selective in their action, disrupting gut microbiota and creating an environment in which C difficile thrives.”

The CDC estimated C difficile to cause almost half a million infections in the US each year, noting patients are 7 to 10 times more likely to develop it when taking antibiotics or during the month thereafter. Understanding which antibiotics are associated with a greater risk of C difficile is essential for developing safe and effective treatment regimens not likely to cause adverse drug reactions.²

To assess the risk of C difficile associated with the use of commonly administered antibiotics, investigators retrospectively reviewed C difficile Individual Case Safety Reports submitted to EudraVigilance spontaneously reported as adverse drug reactions associated with the use of ceftriaxone, colistimethate, ciprofloxacin, gentamicin, linezolid, meropenem, and piperacillin/tazobactam.¹ Total adverse drug reactions and total C difficile cases for these 7 drugs were centralized and used to calculate the proportion of adverse drug reactions related to C difficile.

Antibiotics

Image credit: neirfy - stock.adobe.com

Between January 1, 2003, and August 7, 2023, a total of 119,123 adverse drug reactions were reported in EudraVigilance. The greatest proportions of adverse drug reactions related to C difficile were observed for ciprofloxacin (31%), ceftriaxone (29%), piperacillin/tazobactam (14%), and linezolid (12%). Although the number of reports for C difficile was greatest for ciprofloxacin, both meropenem and piperacillin/tazobactam had the greatest proportion of adverse drug reactions related to C difficile from the total Individual Case Safety Reports (3%).

A retrospective analysis of Individual Case Safety Reports in EudraVigilance between January 1, 2003, and December 31, 2022, showed the greatest average reports per year for ciprofloxacin (40.5; 95% CI, 27.6–53.4) and piperacillin/tazobactam (25.3; 95% CI, 13.6–36.9), and the lowest for linezolid (2.8; 95% CI, 1.8–3.8) and colistimethate (1.5; 95% CI, 0.7–2.3). For meropenem and gentamicin, the average number of reports per year was 13.6 (95% CI, 7.6–19.5) and 4.9 (95% CI, 3.3–6.5), respectively.

Further analysis of reports with unfavorable outcomes showed the greatest frequency of an unfavorable outcome was observed for ciprofloxacin (21.8%) and meropenem (20.5%). Conversely, the lowest frequency of an unfavorable outcome was calculated for gentamicin (11.8%) and ceftriaxone (13.2%). Also, the greatest frequency of fatal adverse drug reactions was seen in colistimethate (15%), meropenem (14%), and ciprofloxacin (13.6%).

Investigators performed a disproportionality analysis to evaluate the probability of reporting C difficle related to these 7 antibiotics compared to amikacin, ceftazidime, clindamycin, imipenem/cilastatin, and levofloxacin; results showed all studied antibiotics had a lower reporting probability when compared to clindamycin.

“There is a pressing need to promote responsible antibiotic usage to prevent adverse events and preserve the efficacy of these valuable medications," the investigators concluded. "An increasing rate of severe forms of C difficile imposes the necessity to carry out surveillance and monitoring programs for the consumption of antibiotics. Implementing standardized laboratory tests to characterize C difficile's nature accurately is also essential.”

References:

1. Vintila BI, Arseniu AM, Morgovan C, et al. A Pharmacovigilance Study Regarding the Risk of Antibiotic-Associated Clostridioides difficile Infection Based on Reports from the EudraVigilance Database: Analysis of Some of the Most Used Antibiotics in Intensive Care Units. Pharmaceuticals. 2023; 16(11):1585. doi:10.3390/ph16111585
2. Centers for Disease Control and Prevention. What is C. diff? C. diff (Clostridioides difficile). September 7, 2022. Accessed November 27, 2023. https://www.cdc.gov/cdiff/what-is.html