3 Years of COMBACTE-CDI

COMBACTE-CDI: A timeline

In June 2018 the very first sample arrived at the University of Leeds – the COMBACTE-CDI academic lead. By the beginning of July 2018, 849 samples had been received by Leeds. The second sample collection began in October 2018, and midway through the month reached 974 samples, counting up to a total of 2142 samples from both sampling periods.

In December 2018 the sample period was concluded with 3167 samples received by the University of Leeds from 12 countries across Europe.

The sample processing at Leeds was only the first step in the pipeline, that involved further sample testing with EFPIA partner, bioMerièux, followed by testing of the C. difficile isolates by the team at the National Laboratory for Health, Environment and Food in Slovenia, and whole genome sequencing carried out by another EFPIA partner, GSK.

The sample testing results were used to determine eligibility for inclusion in the case/control study, which launched in December 2018. The case/control study examined patient’s outcomes and risk-factors for CDI within different ‘diagnostic’ subsets of patients.

The large number of different diagnostic methodologies used in the sample testing period, uniquely enables COMBACTE-CDI to stratify the data in this way. Published clinical trials have often needed to add sensitivity analyses to compensate for different diagnostic methodologies. The different subsets analysed for the COMBACTE-CDI case/control study will enable accurate future clinical trial design.

By August 2019 the database lock has been finalized, achieving a 95% return rate for requested case report forms. The cases/controls were identified during the sample collection study in 2018 and comprise several case definitions based on different diagnostic criteria:

• Case defined as difficile toxin positive (gold standard method – CCNA) positive
• Case defined as difficile toxin positive (new novel method –SIMOA)
• Case defined as free toxin negative but positive for a cytotoxigenic strain (by culture or detection of toxin gene)
• Control defined as negative by all assays

Scientific Results

In 2018, three COMBACTE-CDI abstracts were submitted and accepted at ECCMID 2019. During the cinference, one of the three COMBACTE-CDI posters (‘Detection of Clostridium difficile infection across whole healthcare economies in Europe: results from COMBACTE-CDI’; Davies et al.) was top-rated poster at ECCMID 2019. Only six such ratings are awarded during the congress.

“Everyone was excited by the results, we’ve had a lot of questions about when the case control study was going to be done, in order to see the results. People were shocked by the proportion of undiagnosed cases of CDI in the community  – which is 50%. One of the most important conclusions was the need for education as there is a big chance for educating community doctors and educating the community in general about CDI, and not just hospital-acquired infections“ said Dr. Kerrie Davies.

In 2019, nine COMBACTE-CDI abstracts were accepted at ECCMID 2020. Due to the conference’s cancellation due to the COVID-19 pandemic, the abstracts were published online.