Clostridium Difficile develops resistance to antibiotics, Study Finds

In a recent study published in the PLoS Biology researchers have identified how the hospital superbug Clostridioides difficile (C. diff) can swiftly develop resistance to vancomycin, the primary.

Scientists discovered that within just two months, the bacteria could develop resistance to 32 times the original concentration of the antibiotic.

Clostridioides difficile (C. diff), a bacterium that commonly affects individuals who have been on antibiotics, is recognized by the World Health Organization as a major global public health threat and is responsible for around 2,000 deaths each year.

Currently, antibiotics used to treat C. diff also harm beneficial gut bacteria, resulting in a high rate of reinfection—up to 30 per cent of patients treated with vancomycin experience a second infection within weeks, and the risk of subsequent relapses increases over time.

Scientists have discovered two distinct mechanisms of resistance, both leading to modifications in the terminal D-Ala-D-Ala of muropeptides, the primary vancomycin target. One mechanism involves a novel D, D-carboxypeptidase, whose expression is regulated by a specific two-component signal transduction system. Our research indicates that although C. difficile has the potential to develop high-level vancomycin resistance, this resistance might be clinically limited due to associated effects on essential pathogenic traits. Additionally, these findings highlight potential mutational pathways to resistance that should be monitored in genomic surveillance.

Despite the vital role of vancomycin in healthcare, routine monitoring for resistance is not common in clinical settings, allowing resistance to potentially develop unnoticed in hospitals. If widespread resistance were to occur, it could eliminate this crucial treatment option.

The World Health Organization (WHO) has recognized antimicrobial resistance (AMR) as a leading global public health and development threat. In 2019, it is estimated that bacterial AMR was directly responsible for 1.27 million deaths worldwide and contributed to a total of 4.95 million deaths.

Reference: Buddle JE, Thompson LM, Williams AS, Wright RCT, Durham WM, Turner CE, Chaudhuri RR, Brockhurst MA, Fagan RP. Identification of pathways to high-level vancomycin resistance in Clostridioides difficile that incur high fitness costs in key pathogenicity traits. PLoS Biol. 2024 Aug 15;22(8):e3002741. doi: 10.1371/journal.pbio.3002741. PMID: 39146240