Trends in the epidemiology of Clostridioides difficile infection in Germany

Vehreschild, Maria J. G. T.; Schreiber, Stefan; Müller, Lutz von; Epple, Hans–Jörg; Weinke, Thomas; Manthey, Carolin; Oh, Jun; Wahler, S; Stallmach, Andreas

doi:10.1007/s15010-023-02044-5

Cited by 5 publications

(1 citation statement)

References 49 publications

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“…While the European Center for Disease Prevention and Control (ECDC) estimates the overall CDI mortality rate at 4.1% (Annual Epidemiological Report for 2016-2017), hospitalized patients with CDI face mortality rates of up to 28% [5]. In Germany, although CDI incidence has been decreasing since 2015, the severity of individual cases has remained unaltered [6].…”

Section: Introductionmentioning

confidence: 99%

Microbiota-Based Therapeutics as New Standard-of-Care Treatment for Recurrent Clostridioides difficile Infection

Stallhofer,

Steube,

Katzer

et al. 2024

Visc Med

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Background: Clostridioides difficile (C. difficile) is a spore-forming bacterial species that ubiquitously exists in the environment. Colonization by C. difficile is highly prevalent in infants, while fewer than 5% of adults are asymptomatic carriers. Disruption of the microbiome, such as through antibiotic treatment, triggers the germination of bacterial spores into numerous vegetative cells. These cells then produce enterotoxins that result in watery diarrhea and colonic inflammation. If left untreated, C. difficile infection (CDI) can lead to pseudomembranous colitis with the potentially life-threatening complication of toxic megacolon. Summary: Over the past few decades, the incidence, morbidity, and mortality associated with CDIs have increased. They have emerged as the primary cause of nosocomial gastrointestinal infections in industrialized countries, posing a significant burden on healthcare systems. Despite antibiotics often being the cause of CDIs, they remain the standard treatment. However, a considerable number of patients treated with antibiotics will experience recurrent CDI (rCDI). Microbiota-based therapies targeting the core issue of CDI – antibiotic-induced dysbiosis – hold promise for rCDI treatment. While data for probiotics are insufficient, numerous studies have highlighted the effectiveness of fecal microbiota transplantation (FMT) as a safe and viable therapeutic option for rCDI. This approach is now endorsed by multiple guidelines. Nonetheless, regulatory prerequisites, such as comprehensive stool donor screening, restrict the widespread adoption of FMT beyond specialized centers. Recently, the US Food and Drug Administration has approved two commercial microbiota-based therapeutics to prevent CDI recurrence. These therapeutics are available by prescription in the USA. RBX2660 (REBYOTA™) comprises a diverse consortium of live microbes derived from human stool and is administered via enema. On the other hand, SER-109 (VOWST™) is an orally administered spore-based medication. In this review, we discuss the potential of microbiota-based treatments for rCDI against the background of medico-legal challenges associated with classical FMT. Key Messages: FMT has emerged as a highly effective cure for rCDI. Nonetheless, regulatory prerequisites and laborious preparation procedures impede its widespread use. The establishment of ready-to-use microbiota-based therapeutics in clinical practice is necessary. In the USA, the recent approval of the first two commercial medications, including a spore-based oral preparation, marks a significant step forward.

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Section: Introductionmentioning

confidence: 99%

Microbiota-Based Therapeutics as New Standard-of-Care Treatment for Recurrent Clostridioides difficile Infection

Stallhofer,

Steube,

Katzer

et al. 2024

Visc Med

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Association of ward-level antibiotic consumption with healthcare-associated Clostridioides difficile infections: an ecological study in five German university hospitals, 2017–2019

Rohde,

Mischnik,

Behnke

et al. 2023

Journal of Antimicrobial Chemotherapy

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Objectives To analyse the influence of antibiotic consumption on healthcare-associated healthcare onset (HAHO) Clostridioides difficile infection (CDI) in a German university hospital setting. Methods Monthly ward-level antibiotic consumption measured in DDD/100 patient days (pd) and CDI surveillance data from five university hospitals in the period 2017 through 2019 were analysed. Uni- and multivariable analyses were performed with generalized estimating equation models. Results A total of 225 wards with 7347 surveillance months and 4 036 602 pd participated. With 1184 HAHO-CDI cases, there was a median incidence density of 0.17/1000 pd (IQR 0.03–0.43) across all specialties, with substantial differences among specialties. Haematology-oncology wards showed the highest median incidence density (0.67/1000 pd, IQR 0.44–1.01), followed by medical ICUs (0.45/1000 pd, IQR 0.27–0.73) and medical general wards (0.32/1000 pd, IQR 0.18–0.53). Multivariable analysis revealed carbapenem (mostly meropenem) consumption to be the only antibiotic class associated with increased HAHO-CDI incidence density. Each carbapenem DDD/100 pd administered increased the HAHO-CDI incidence density by 1.3% [incidence rate ratio (IRR) 1.013; 95% CI 1.006–1.019]. Specialty-specific analyses showed this influence only to be valid for haematological-oncological wards. Overall, factors like ward specialty (e.g. haematology-oncology ward IRR 2.961, 95% CI 2.203–3.980) or other CDI cases on ward had a stronger influence on HAHO-CDI incidence density (e.g. community-associated CDI or unknown association case in same month IRR 1.476, 95% CI 1.242–1.755) than antibiotic consumption. Conclusions In the German university hospital setting, monthly ward-level carbapenem consumption seems to increase the HAHO-CDI incidence density predominantly on haematological-oncological wards. Furthermore, other patient-specific factors seem to be equally important to control HAHO-CDI.

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Epidemiological and clinical burden of Clostridioides difficile infections and recurrences between 2015 − 2019: the RECUR Germany study

Tricotel,

Antunes,

Wilk

et al. 2024

BMC Infect Dis

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Background This real-world study assessed the epidemiology and clinical complications of Clostridioides difficile infections (CDIs) and recurrences (rCDIs) in hospital and community settings in Germany from 2015 − 2019. Methods An observational retrospective cohort study was conducted among adult patients diagnosed with CDI in hospital and community settings using statutory health insurance claims data from the BKK database. A cross-sectional approach was used to estimate the annual incidence rate of CDI and rCDI episodes per 100,000 insurants. Patients’ demographic and clinical characteristics were described at the time of first CDI episode. Kaplan-Meier method was used to estimate the time to rCDIs and time to complications (colonic perforation, colectomy, loop ileostomy, toxic megacolon, ulcerative colitis, peritonitis, and sepsis). A Cox model was used to assess the risk of developing complications, with the number of rCDIs as a time-dependent covariate. Results A total of 15,402 CDI episodes were recorded among 11,884 patients. The overall incidence of CDI episodes declined by 38% from 2015 to 2019. Most patients (77%) were aged ≥ 65 years. Around 19% of CDI patients experienced at least one rCDI. The median time between index CDI episode to a rCDI was 20 days. The most frequent complication within 12-months of follow-up after the index CDI episode was sepsis (7.57%), followed by colectomy (3.20%). The rate of complications increased with the number of rCDIs. The risk of any complication increased by 31% with each subsequent rCDI (adjusted hazard ratio [HR]: 1.31, 95% confidence interval: 1.17;1.46). Conclusions CDI remains a public health concern in Germany despite a decline in the incidence over recent years. A substantial proportion of CDI patients experience rCDIs, which increase the risk of severe clinical complications. The results highlight an increasing need of improved therapeutic management of CDI, particularly efforts to prevent rCDI.

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Trends in the epidemiology of Clostridioides difficile infection in Germany

Cited by 5 publications

References 49 publications

Microbiota-Based Therapeutics as New Standard-of-Care Treatment for Recurrent <i>Clostridioides difficile</i> Infection

Microbiota-Based Therapeutics as New Standard-of-Care Treatment for Recurrent <i>Clostridioides difficile</i> Infection

Association of ward-level antibiotic consumption with healthcare-associated Clostridioides difficile infections: an ecological study in five German university hospitals, 2017–2019

Epidemiological and clinical burden of Clostridioides difficile infections and recurrences between 2015 − 2019: the RECUR Germany study

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