Human and Porcine Transmission of Clostridioides difficile Ribotype 078, Europe.

Genomic analysis of a diverse collection of Clostridioides difficile ribotype 078 isolates from Ireland and 9 countries in Europe provided evidence for complex regional and international patterns of dissemination that are not restricted to humans. These isolates are associated with C. difficile colonization and clinical illness in humans and pigs.

Typhlocolitis associated with Clostridium difficile ribotypes 078 and 110 in neonatal piglets from a commercial Irish pig herd.

BACKGROUND: Clostridium difficile is a recognised cause of typhlocolitis and diarrhoea in neonatal pigs but has never been confirmed in association with pathology and disease in Irish pigs. CASE PRESENTATION: Four neonatal piglets, with a history of diarrhoea were referred to the Central Veterinary Research Laboratory, Backweston for necropsy. They were from a fully integrated, commercial pig farm with approximately 1000 sows. Three piglets had acute, superficial, erosive and suppurative typhlocolitis and the other had mild suppurative mesocolitis. Clostridium difficile (C. difficile) toxins A/B were detected using ELISA in the colonic contents from each piglet. C. difficile isolates from two of the piglets were PCR-ribotyped as 078 and an isolate from a third pig was ribotyped as 110. CONCLUSIONS: This is the first report confirming C. difficile in association with typhlocolitis in Irish pigs.

Suspected IgG4-related disease of the submandibular salivary gland and periorbital soft tissue in a man with latent tuberculosis.

A 77-year-old Lithuanian man presented to our institution with recurrent episodes of periorbital cellulitis, submandibular swelling and sialadenitis. Investigations revealed a positive QuantiFERON, raised inflammatory markers and normal autoimmune screen. Cross-sectional imaging showed no signs of occult malignancy, and work-up for mycobacterial infection including imaging and bronchoalveolar lavage did not show active tuberculosis. During hospitalisation, the patient developed fevers of unknown origin, which were investigated with a positron emission tomography (PET) scan and a bone marrow aspiration, without evidence of occult infection or malignancy. Serum IgG4 level was three times the upper limit of normal. The patient responded well to oral steroids but relapsed after completing a slow taper. Serum IgG4 level was three times the upper limit of normal. He had an American College of Rheumatology/European League Against Rheumatism score of 20, in conjunction with involvement of orbital and salivary tissue. Therefore, IgG4-related disease was considered the most likely diagnosis, despite prominent fevers, which are among the exclusion criteria for this diagnosis. After a multidisciplinary review including rheumatology and ophthalmology, the patient was commenced on maintenance methotrexate with remission of symptoms.

Identification of a novel sequence type of Escherichia coli as the causative agent of pyelonephritis and bloodstream infection.

INTRODUCTION: Globally, extra-intestinal pathogenic Escherichia coli are one of the predominant causative agents of bacteraemia. CASE PRESENTATION: This case report outlines a presentation of community-acquired pyelonephritis and secondary bloodstream infection in an 81-year-old man. Laboratory investigations revealed that the causative isolate was a multi-drug-resistant E. coli of a novel multi-locus sequence type. This sequence type (ST) was designated ST-458 and was most closely related to the globally prevalent ST-131 lineage. CONCLUSION: This is the first report of a novel E. coli ST, ST-458, which caused pyelonephritis and bacteraemia.

Possible Interplay Between Hospital and Community Transmission of a Novel Clostridium Difficile Sequence Type 295 Recognized by Next-Generation Sequencing.

OBJECTIVE To use next-generation sequencing (NGS) analysis to enhance epidemiological information to identify and resolve a Clostridium difficile outbreak and to evaluate its effectiveness beyond the capacity of current standard PCR ribotyping. METHODS NGS analysis was performed as part of prospective surveillance of all detected C. difficile isolates at a university hospital. An outbreak of a novel C. difficile sequence type (ST)-295 was identified in a hospital and a community hostel for homeless adults. Phylogenetic analysis was performed of all ST-295 and closest ST-2 isolates. Epidemiological details were obtained from hospital records and the public health review of the community hostel. RESULTS We identified 7 patients with C. difficile ST-295 infections between June 2013 and April 2015. Of these patients, 3 had nosocomial exposure to this infection and 3 had possible hostel exposure. Current Society for Healthcare Epidemiology of America (SHEA)- Infectious Diseases Society of America (IDSA) surveillance definitions (2010) were considered in light of our NGS findings. The initial transmission was not detectable using current criteria, because of 16 weeks between ST-295 exposure and symptoms. We included 3 patients with hostel exposure who met surveillance criteria of hospital-acquired infection due to their hospital admissions. CONCLUSION NGS analysis enhanced epidemiological information and helped identify and resolve an outbreak beyond the capacity of standard PCR ribotyping. In this cluster of cases, NGS was used to identify a hostel as the likely source of community-based C. difficile transmission. Infect Control Hosp Epidemiol 2016;37:680-684.

Identification of a novel mutation at the primary dimer interface of GyrA conferring fluoroquinolone resistance in Clostridium difficile.

The aim of this study was to determine whether alternative resistance mechanisms, other than mutation in the quinolone resistance-determining region (QRDR) of DNA gyrase, could confer fluoroquinolone resistance in Clostridium difficile. An in vitro-generated C. difficile mutant exhibiting increased fluoroquinolone resistance was isolated through antibiotic selection on ciprofloxacin. The QRDR of this mutant was investigated by chain-termination sequencing and was found to be devoid of mutation. To determine the nature of the non-QRDR resistance mechanism in this strain, the genomes of the mutant and wild-type strains were sequenced. The gyrBA region from a collection of clinical isolates exhibiting variable fluoroquinolone resistance levels was also sequenced and was compared with that present in 918 publicly available C. difficile genomic data sets. Whole-genome sequence analysis of the fluoroquinolone-resistant mutant revealed a single non-synonymous substitution (Ala384Asp) at the predicted primary dimer interface of GyrA, far beyond the classically defined QRDR. This novel mutation caused increased resistance to ciprofloxacin, ofloxacin, levofloxacin and moxifloxacin while conferring hypersusceptibility to novobiocin. Several novel extra-QRDR polymorphisms in C. difficile DNA gyrase were identified among clinical isolates, whilst observed fluoroquinolone resistance in strains devoid of gyrBA mutations confirmed the existence of DNA gyrase-independent resistance mechanisms in this species. In conclusion, we report the first non-QRDR mutation to confer fluoroquinolone resistance in C. difficile. Although the Ala384Asp substitution was not detected in clinical isolates, this study revealed a diversity of alternative extra-QRDR polymorphisms in DNA gyrase whose association with fluoroquinolone resistance warrants further investigation.

Extramedullary relapse of IgA-lambda myeloma after recent bortezomib therapy: a case report.

Intracranial plasmacytomas are an uncommon presentation of extramedullary relapse of multiple myeloma. The optimal management of extramedullary plasmacytomas remains unclear, with initial reports of bortezomib showing promising clinical results. We describe a case of multiple extracellular, including intracranial, plasmacytoma, with no evidence of marrow involvement, in a patient with relapsed IgA multiple myeloma. To our knowledge, this is the first reported case of a patient with rapid extramedullary relapse of disease despite recent exposure to bortezomib and dexamethasone.