Extraintestinal Clostridioides difficile Infections: Epidemiology in a University Hospital in Hungary and Review of the Literature

Extraintestinal manifestations of Clostridioides difficile infections (CDIs) are very uncommon, and according to the literature, poor outcomes and a high mortality have been observed among affected individuals. The objective of this study was to investigate the incidence rate of extraintestinal infections caused by C. difficile (ECD) in a tertiary-care university hospital in Hungary. During a 10-year study period, the microbiology laboratory isolated 4129 individual strains of C. difficile; among these, the majority were either from diarrheal fecal samples or from colonic material and only n = 24 (0.58%) were from extraintestinal sources. The 24 extraintestinal C. difficile isolates were recovered from 22 patients (female-to-male ratio: 1, average age: 55.4 years). The isolates in n = 8 patients were obtained from abdominal infections, e.g., appendicitis, rectal abscess or Crohn’s disease. These extraintestinal cases occurred without concomitant diarrhea. In all, but two cases C. difficile was obtained as a part of a polymicrobial flora. Our isolates were frequently toxigenic and mostly belonged to PCR ribotype 027. Resistance to metronidazole, vancomycin, clindamycin and rifampin were 0%, 0%, 20.5% and 9.7%, respectively. The increasing amount of reports of C. difficile extraintestinal infections should be noted, as these infections are characterized by a poor outcome and high mortality rate.

Omadacycline Gut Microbiome Exposure Does Not InduceClostridium difficileProliferation or Toxin Production in a Model That Simulates the Proximal, Medial, and Distal Human Colon

ABSTRACTA clinically reflective model of the human colon was used to investigate the effects of the broad-spectrum antibiotic omadacycline on the gut microbiome and the subsequent potential to induce simulatedClostridium difficileinfection (CDI). Triple-stage chemostat gut models were inoculated with pooled human fecal slurry from healthy volunteers (age, ≥60 years). Models were challenged twice with 107CFUC. difficilespores (PCR ribotype 027). Omadacycline effects were assessed in a single gut model. Observations were confirmed in a parallel study with omadacycline and moxifloxacin. Antibiotic instillation was performed once daily for 7 days. The models were observed for 3 weeks postantibiotic challenge. Gut microbiota populations andC. difficiletotal viable and spore counts were enumerated daily by culture. Cytotoxin titers and antibiotic concentrations were also measured. Gut microbiota populations were stable before antibiotic challenge. Moxifloxacin instillation caused an ∼4 log10CFU/ml decline in enterococci andBacteroides fragilisgroup populations and an ∼3 log10CFU/ml decline in bifidobacteria and lactobacilli, followed by simulated CDI (vegetative cell proliferation and detectable toxin). In both models, omadacycline instillation decreased populations of bifidobacteria (∼8 log10CFU/ml),B. fragilisgroup populations (7 to 8 log10CFU/ml), lactobacilli (2 to 6 log10CFU/ml), and enterococci (4 to 6 log10CFU/ml). Despite these microbial shifts, there was no evidence ofC. difficilebacteria germination or toxin production. In contrast to moxifloxacin, omadacycline exposure did not facilitate simulated CDI, suggesting this antibiotic may have a low propensity to induce CDI in the clinical setting.

Hospital-based Clostridium difficile infection surveillance reveals high proportions of PCR ribotypes 027 and 176 in different areas of Poland, 2011 to 2013

As part of the European Clostridium difficile infections (CDI) surveillance Network (ECDIS-Net), which aims to build capacity for CDI surveillance in Europe, we constructed a new network of hospital-based laboratories in Poland. We performed a survey in 13 randomly selected hospital-laboratories in different sites of the country to determine their annual CDI incidence rates from 2011 to 2013. Information on C. difficile laboratory diagnostic testing and indications for testing was also collected. Moreover, for 2012 and 2013 respectively, participating hospital-laboratories sent all consecutive isolates from CDI patients between February and March to the Anaerobe Laboratory in Warsaw for further molecular characterisation, including the detection of toxin-encoding genes and polymerase chain reaction (PCR)-ribotyping. Within the network, the mean annual hospital CDI incidence rates were 6.1, 8.6 and 9.6 CDI per 10,000 patient-days in 2011, 2012, and 2013 respectively. Six of the 13 laboratories tested specimens only on the request of a physician, five tested samples of antibiotic-associated diarrhoea or samples from patients who developed diarrhoea more than two days after admission (nosocomial diarrhoea), while two tested all submitted diarrhoeal faecal samples. Most laboratories (9/13) used tests to detect glutamate dehydrogenase and toxin A/B either separately or in combination. In the two periods of molecular surveillance, a total of 166 strains were characterised. Of these, 159 were toxigenic and the majority belonged to two PCR-ribotypes: 027 (n = 99; 62%) and the closely related ribotype 176 (n = 22; 14%). The annual frequency of PCR-ribotype 027 was not significantly different during the surveillance periods (62.9% in 2012; 61.8% in 2013). Our results indicate that CDIs caused by PCR-ribotype 027 predominate in Polish hospitals participating in the surveillance, with the closely related 176 ribotype being the second most common agent of infection.