# Incidence of hospital-acquired toxin-producing clostridioides difficile infection between the pre-pandemic (2017–2019) and pandemic (2020–2022): a retrospective cohort study

## TL;DR

Hospital-acquired C. difficile infections increased by 79.8% during the pandemic compared to the pre-pandemic period, with proton pump inhibitors and immunosuppression as key risk factors.

## Contribution

This study is the first to show a significant rise in C. difficile infections during the pandemic, despite enhanced infection control measures.

## Key findings

- The incidence of C. difficile infections increased by 79.8% during the pandemic period.
- Proton pump inhibitor use significantly increased during the pandemic and was linked to higher infection rates.
- Patients during the pandemic had a 92% higher risk of acquiring C. difficile infections compared to pre-pandemic.

## Abstract

In 2020, the World Health Organization declared SARS-CoV-2 a global public health emergency. Healthcare systems were forced to reorganize care delivery and implement wide-ranging infection control strategies. Among hospital-acquired infections, toxin-producing Clostridioides difficile infection remains a major concern due to its transmission via contact and its association with high morbidity and mortality. Although primarily aimed at preventing viral transmission, the measures introduced during the COVID-19 pandemic may have influenced the incidence of other nosocomial infections, including toxin-producing Clostridioides difficile infection.

This study aimed to evaluate and compare the incidence of nosocomial toxin-producing Clostridioides difficile infection during the pandemic and pre-pandemic periods, and to confirm associated risk factors across both periods.

We conducted a retrospective observational cohort study at A Coruña University Hospital, including data from 2017 to 2022. Patients meeting criteria for nosocomial Clostridioides difficile infection were categorized into pre-pandemic (2017-2019) or pandemic (2020-2022) cohorts. Variables analyzed included demographics (age, sex), prior antibiotic use, antiulcer therapy, immunosuppression and surgical history. Incidence rates were calculated and compared between periods, and associations between risk factors and toxin-producing Clostridioides difficile infection were analyzed using odds ratios (OR).

A total of 249 nosocomial toxin-producing Clostridioides difficile infection cases were identified: 89 pre-pandemic and 160 during the pandemic, reflecting a 79.8% increase. Patients hospitalized during the pandemic faced a 92% greater risk of toxin-producing Clostridioides difficile infection (RR=1.92; CI95%: 1.48-2.49; P=0.001). Established risk factors such as prior antibiotic exposure (80% during the pandemic vs 86.5% pre-pandemic; P=0.20) and immunosuppression was frequent (39.3% pre-pandemic; 46.9% pandemic; P=0.25).

Notably, the use of proton pump inhibitors significantly increased during the pandemic (P=0.02; 95%CI: 0.02–0.36). Surgical history, particularly gastrointestinal surgery, was significantly associated with complications (OR=6.6, 95%CI: 2.18-20.18). The incidence density of toxin-producing Clostridioides difficile infection (TCDI) during the pandemic years was 1.44 TCDI/10,000 patient-days. Predisposing factors included solid organ neoplasms (pre-pandemic 33.7%; pandemic 33.1%; P=0.36), secondary immunosuppression (pre-pandemic 31.5%; pandemic 40.6%; P= 0.41).

Patients admitted experienced a significantly higher risk of acquiring toxin-producing Clostridioides difficile infection during the pandemic. The data also indicate an increase in mortality associated with this infection and highlight proton pump inhibitor use as a contributing factor to the higher incidence.