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Molecular typing is an essential tool to monitor Clostridium difficile infections and outbreaks within healthcare facilities. Molecular typing also plays a key role in defining the regional and global changes in circulating C. difficile types. The patterns of C. difficile types circulating within Europe (and globally) remain poorly understood, although international efforts are under way to understand the spatial and temporal patterns of C. difficile types. A complete picture is essential to properly investigate type-specific risk factors for C. difficile infections (CDI) and track longrange transmission. Currently, conventional agarose gel-based polymerase chain reaction (PCR) ribotyping is the most common typing method used in Europe to type C. difficile. Although this method has proved to be useful to study epidemiology on local, national and European level, efforts are made to replace it with capillary electrophoresis PCR ribotyping to increase pattern recognition, reproducibility and interpretation. However, this method lacks sufficient discriminatory power to study outbreaks and therefore multilocus variable-number tandem repeat analysis (MLVA) has been developed to study transmission between humans, animals and food. Sequence-based methods are increasingly being used for C. difficile fingerprinting/ typing because of their ability to discriminate between highly related strains, the ease of data interpretation and transferability of data. The first studies using whole-genome single nucleotide polymorphism typing of healthcare-associated C. difficile within a clinically relevant timeframe are very promising and, although limited to select facilities because of complex data interpretation and high costs, these approaches will likely become commonly used over the coming years.

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With advances in the identification and molecular taxonomy of Aeromonas spp., these organisms, which are widely distributed in the environment, are increasingly being recognised as human pathogens. Clinical infections include gastroenteritis, skin and soft tissue infections and bacteraemia. Antibiotic resistance poses a potential problem in the antimicrobial therapy of infections cased by Aeromonas spp. While most strains are susceptible to chloramphenicol, ciprofloxacin, co-trimoxazole and the aminoglycosides, the activity of amoxycillin/clavulanate and the acylureidopenicillins is inconsistent. Addition of a beta-lactamase inhibitor does not significantly enhance the activity of the acylureidopenicillins. Aztreonam and the carbapenems, imipenem and meropenem remain highly active. Although resistance to the first and second generation cephalosporins is variable, more than 90% of Aeromonas spp. are susceptible to the third generation agents. Of potential significance is the identification of chromosomally-encoded inducible beta-lactamases, associated with resistance to extended spectrum penicillins, cephalosporins, monobactams and carbapenems, in clinical isolates of Aeromonas spp. Two distinct enzymes are produced: the A1 enzyme, a serine beta-lactamase behaving as a group 1 cephalosporinase, and the A2 enzyme, a metallo beta-lactamase which hydrolyses a wide range of beta-lactam agents including the carbapenems. The clinical relevance of these enzymes in Aeromonas spp. is unclear.

Background Experimental evidence (Fisher et al, 1989) & a small clinical trial (IMPACT) respectively suggested peri-operative endocrine therapy (ET) may improve long-term disease-related outcome in patients undergoing primary surgery for ER positive (ER+) breast cancer (BC) & that tumor Ki67 levels after 2 weeks of peri-operative aromatase inhibitor (POAI) therapy might offer an effective way of predicting outcome & the need for additional adjuvant treatment. POETIC (*Peri-Operative Endocrine Therapy - Individualising Care) is a phase III randomized controlled trial designed to test these hypotheses & provide data to determine whether 2 week Ki67 improves prediction beyond that by baseline Ki67 of the group who have a higher risk of relapse in the first years after diagnosis in spite of best current standard of care. Patients & methods Postmenopausal patients with ER+ BC were randomised 2:1 to either, POAI (centre choice: letrozole 2.5mg or anastrozole 1mg daily) for 14 days prior to & 14 days following surgery or no POAI (Control). Randomization was stratified by treating center; adjuvant treatment was per UK routine practice. Tissue samples were collected at baseline & surgery (FFPE) for blinded Ki67 testing. Primary endpoint was Time to Recurrence (TTR: time from randomization to loco-regional or distant recurrence or BC death). A secondary endpoint was Ki67 at baseline & after 2 weeks of AI. Results Between 2008 & 2014, 4480 patients (2976 AI, 1504 Control) were randomized from 130 UK centers. Median age was 67 (IQR 62-75), 18% had grade 3 tumors, 39% were node positive and 61% had tumor size>2cm. For adjuvant ET 314 patients (7.2%) received tamoxifen (Tam), 3695 (84.6%) an AI, 251 (5.7%) Tam changing to AI and 109 (2.5%) changing from AI to Tam. On 8 August 2017, median follow-up was 60.7 months (IQR 49.5 to 72.2). 408/4480 (9.1%) patients have had a TTR event; 263 (8.8%) allocated to POAI compared to 145 (9.6%) controls: HR=0.91 (95%CI: 0.74, 1.12) Log-rank p=0.37. Adjusted HR=0.91 (95%CI: 0.74, 1.11). The relationship of Ki67 (baseline & after 2 weeks) with TTR in both the POAI & control groups will be presented for the overall ER+ population & HER2 defined sub-groups. Discussion There was no significant evidence that four weeks of POAI improved TTR compared with no POAI. POETIC will provide definitive evidence on the role of 2 week POAI-treated Ki67 to inform future practice & trials in terms of the potential to identify a group of patients for whom current standard of care appears insufficient in the few years post diagnosis. Citation Format: Robertson JFR, Dowsett M, Bliss JM, Morden JP, Wilcox M, Evans A, Holcombe C, Horgan K, Kirwan C, Mallon E, Sibbering M, Skene A, Vidya R, Cheang M, Banerji J, Kilburn L, Dodson A, Smith I. Peri-operative aromatase inhibitor treatment in determining or predicting longterm outcome in early breast cancer – The POETIC* Trial (CRUK/07/015) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr GS1-03.