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The intestine is the primary colonisation site for carbapenem-resistantEnterobacteriaceae(CRE) and serves as a reservoir of CRE that cause invasive infections (e.g. bloodstream infections). Antibiotics disrupt colonisation resistance mediated by the gut microbiota, promoting the expansion of CRE within the intestine. We usedex vivofaecal cultures to measure the impact of antibiotics (that promote CRE intestinal colonisation) on the faecal microbiota from healthy human donors. We demonstrated that antibiotics decreased the abundance of gut commensals (includingBifidobacteriaceaeandBacteroidales) in human faecal microbiota, resulting in an enrichment of nutrients and a depletion of microbial metabolites. We measured the nutrient utilisation abilities, nutrient preferences, and metabolite inhibition susceptibilities of several carbapenem-resistantEnterobacteriaceaestrains, includingEscherichia coli,Klebsiella pneumoniae, andEnterobacter hormaechei. Nutrients (which were elevated with antibiotics) acted as carbon and nitrogen sources to support CRE growth, where CRE strains showed an ordered preference for specific nutrients. These nutrients were also increased in faeces from antibiotic-treated mice but decreased following intestinal colonisation with carbapenem-resistantE. coli. Microbial metabolites (which decreased with antibiotics) were inhibitory towards CRE growthin vitro. Carbapenem-resistantE. coligrowth was decreased in faecal samples from mice treated with a mixture of inhibitory metabolites compared with PBS-treated mice. These findings demonstrated that killing gut commensals with antibiotics disrupts colonisation resistance by enriching nutrients that support CRE growth and depleting metabolites that inhibit CRE growth. These results support the development of new microbiome therapeutics to prevent CRE intestinal colonisation, which would also prevent the subsequent development of invasive CRE infections.

Background Vulnerable patients with intestinal colonisation of multidrug-resistant organisms (MDROs) are recognised to be at increased risk of invasive MDRO driven infection. Intestinal Microbiota Transplantation (IMT aka FMT) is the transfer of healthy screened donor stool to an affected recipient, and recent interest has focused on its impact on the reduction of invasive MDRO infection. Objectives To describe ‘How to’ establish a clinical IMT pathway for patients at risk of MDRO invasive infection, with special considerations for optimising administration and assessment of endpoints. Sources Expert guidelines and peer-reviewed clinical studies are encompassed and discussed. Content IMT is offered to patients with MDROs detected on rectal or stool screening and either at risk of MDRO invasive infection due to altered immune status or those with recurrent MDRO-mediated invasive disease and considered at risk of further disease. Donor screening should include pathogens with theoretical or demonstrated risk of transmission (including MDROs themselves and SARS-CoV-2) to take into consideration the relative immunosuppressed state of potential recipients. Delivery of IMT occurs when the patient is free from active infection, but no additional antibiotics are indicated. If administered when future immunosuppression is to take place, IMT is aligned at least two weeks beforehand to ensure sufficient time for engraftment. Patients are followed up in terms of adverse effects from IMT and clinicians are advised to discuss with the IMT multidisciplinary team on choice of antibiotics if needed to take into consideration the impact upon the intestinal microbiome. Prevention of invasive disease is the primary measure of success, rather than using intestinal decolonisation as a binary outcome. Repeat IMT is considered case-by-case. Implications Future research areas should include randomised studies that consider clinical outcomes and cost-effectiveness, and better understanding of mechanisms to identify markers of treatment success and functional components that could be used therapeutically.

The gut microbiome can be adversely affected by chemotherapy and antibiotics prior to hematopoietic cell transplantation (HCT). This affects graft success and increases susceptibility to multidrug-resistant organism (MDRO) colonization and infection. We performed an initial retrospective analysis of our use of fecal microbiota transplantation (FMT) from healthy donors as therapy for MDRO-colonized patients with hematological malignancy. FMT was performed on eight MDRO-colonized patients pre-HCT (FMT-MDRO group), and outcomes compared with 11 MDRO colonized HCT patients from the same period. At 12 months, survival was significantly higher in the FMT-MDRO group (70% versus 36% p = 0.044). Post-HCT, fewer FMT-MDRO patients required intensive care (0% versus 46%, P = 0.045) or experienced fever (0.29 versus 0.11 days, P = 0.027). Intestinal MDRO decolonization occurred in 25% of FMT-MDRO patients versus 11% non-FMT MDRO patients. Despite the significant differences and statistically comparable patient/transplant characteristics, as the sample size was small, a matched-pair analysis between both groups to non-MDRO colonized control cohorts (2:1 matching) was performed. At 12 months, the MDRO group who did not have an FMT had significantly lower survival (36.4% versus 61.9% respectively, p=0.012), and higher non relapse mortality (NRM; 60.2% versus 16.7% respectively, p=0.009) than their paired non-MDRO-colonized cohort. Conversely, there was no difference in survival (70% versus 43.4%, p=0.14) or NRM (12.5% versus 31.2% respectively, p=0.24) between the FMT-MDRO group and their paired non-MDRO cohort. Collectively, these data suggest that negative clinical outcomes, including mortality associated with MDRO colonization, may be ameliorated by pre-HCT FMT, even in the absence of intestinal MDRO decolonization. Further work is needed to explore this observed benefit.

Immune checkpoint inhibitors (ICPIs) are efficacious treatments for several cancers. However, most patients fail to demonstrate durable complete responses. The gut microbiome composition influences the ICPI response. Two recent proof-of-concept studies have demonstrated the utility of fecal microbiota transplantation to transform ICPI responsiveness in refractory patients, providing intriguing evidence for the future of microbiota modulation within oncology.

Faecal Microbiota Transplantation (FMT) is widely utilised for recurrent Clostridioides difficile infection. Use of FMT for the intestinal eradication of multidrug-resistant organisms (MDROs) has been described in the literature with decolonisation rates from 37.5% to 87.5%. We perform FMT via naso-gastric tube using donor stool prepared anaerobically, using prevention of invasive disease as an endpoint. FMT was considered for either; 1) Patients who were colonised with >1 MDRO (carbapenem-resistant Enterobacteriaceae, vancomycin resistant Enterococci or extended-spectrum beta lactamase (ESBL) and at risk of invasive MDRO disease or 2) patients who had recurrent MDRO-mediated invasive disease. Sixteen MDRO colonised/infected patients underwent FMT. Nine patients had a haematological disorder. Eight of these patients had had prolonged admissions (range 6-20 weeks) complicated by septic episodes (5/9 had a MDR bacteraemia) pre-FMT. Post FMT all patients had shorter admissions including five who received higher intensity immunosuppression. Only 1/9 developed MDRO-mediated invasive disease. Seven FMT patients had recurrent ESBL urinary tract infections (UTIs). 4/7 were renal transplant patients. Following FMT the 3 non-transplant patients had no further UTIs up to six month period. Four transplant patients had reduced number of infections, admissions and use of antibiotics. 5/13 (39%) patients were not MDRO colonised on rectal screens post-FMT (follow up range 12 weeks – 24 months). Although decolonisation rates were low, patient outcomes post-FMT were apparently improved. Mechanisms of FMT have not fully been established, improvement of colonisation resistance by restoration of microbiota composition or functionality in at risk groups could be more important than intestinal eradication.

Recurrent UTIs are associated with increased hospitalisation and antibiotic use. We investigated patients with recurrent ESBL versus non-ESBL UTIs to identify risk factors and potential treatments. A30 month retrospective case-control study was performed in patients with recurrent EBSL versus non-ESBL UTI. Definition :1) > three in a year (>two weeks apart) or 2) > two in six months (>one week apart) with the same profile. 3) ESBL UTIs were Enterobacteriaceae resistant to cefalexin AND ceftazadime/ceftriaxone. 281/1449 “recurrent UTI” patients were ESBLs. Patients were more likely to be older, male, with associated bacteraemia, colonisation with carbapenemase-producing Enterobacteriaceae (CPE) and higher resistance rates to non beta-lactam antibiotics. 75% of renal patients were transplant cases, 81% of urology patients had a tube insertion. Recurrent ESBL UTIRecurrent non-ESBL UTIp value Number (%)Number (%)(Chi-squared test) Patients 281 1168 Organism Klebsiella spp (%)42 (14.9) 10 (0.8)

Fecal microbiota transplantation (FMT) yields variable intestinal decolonization results for multidrug-resistant organisms (MDROs). This study showed significant reductions in antibiotic duration, bacteremia, and length of stay in 20 patients colonized/infected with MDRO receiving FMT (compared with pre-FMT history, and a matched group not receiving FMT), despite modest decolonization rates.

Adult-onset measles is rare in the UK, particularly in patients with a complete vaccination history.We present a case of a UK-born patient who received all childhood vaccinations, had no history of recent travel or unwell contacts who was diagnosed with measles complicated by pneumomediastinum. This case highlights the need to consider measles in any patient presenting with a constellation of a macular rash, fever and conjunctivitis, regardless of vaccination status. The nature of the rash can provide an important clue to the diagnosis. Liaison with infection specialists facilitates early diagnosis, allowing for appropriate initial investigations, improving clinical management and early infection control precautions being instituted.

Skin and soft tissue infections (SSTIs) can be sub-divided based on the anatomical structure(s) affected from superficial to deep. Impetigo affects children more commonly than adults, starting as a macule of erythema and evolving into vesicles that rupture, leaving a golden crusted appearance. Fever and systemic signs are absent. It is highly transmissible and children should be excluded from school until exposed lesions have resolved. Folliculitis is a superficial infection presenting with small papules or pustules on an erythematous base around a hair. Fever and systemic signs are absent. If extension into deeper tissues occurs a dermal abscess (‘boil’ or ‘furuncle’) may occur, and several lesions may coalesce into a ‘carbuncle’. Deeper infection may cause discomfort, fever, and systemic upset. Any hair-bearing area may be affected, but sites most commonly affected include the face, scalp, axilla, inguinal area, thighs, or eyelid (‘stye’), and may be associated with shaved or occluded skin. Cellulitis is rapidly spreading erythema of the skin associated with pain, swelling, fever, and systemic features such as nausea and malaise. It may be seen as a complication of tinea pedis, superficial abrasions, or insect bites, venous insufficiency, lymphoedema, chronic ulcers, and diabetes. It is almost always unilateral and bilateral cellulitis is extremely rare and should prompt consideration of an alternative diagnosis. The Eron grading system can help guide treatment and admission decisions: ● Class I: the patient has no signs of systemic toxicity and no uncontrolled comorbidities. ● Class II: the patient is either systemically unwell or systemically well but with a comorbidity such as peripheral vascular disease, chronic venous insufficiency, diabetes, or obesity, which may complicate or delay resolution of infection. ● Class III: the patient has significant systemic upset such as acute confusion, tachycardia, tachypnoea, hypotension, or unstable comorbidities that may interfere with a response to treatment, or a limb-threatening infection due to vascular compromise. ● Class IV: the patient is septic or has life-threatening infection such as necrotizing fasciitis.

Patients with bone and joint infections can present with native joint septic arthritis, osteomyelitis, or implant-associated bone and joint infections. Patients often present with an acute onset of hot, swollen, painful joint with restricted function in one or more joints over a couple of weeks. On examination the affected joint is painful with a limited range of movement, and fever is present. Risk factors for septic arthritis include an abnormal joint architecture due to pre-existing joint disease, e.g. patients with rheumatoid arthritis, or patients on haemodialysis, with diabetes mellitus, or older than 80 years of age. The differential diagnosis includes reactive arthritis, pre-patellar bursitis, gout, Lyme disease, brucellosis, and Whipples disease. Staphylococcus aureus is the most common cause of septic arthritis, followed by Group A streptococcus and other haemolytic streptococci including B, C and G. Gram-negative rods such as Escherichia coli are implicated in the elderly, immunosuppressed, or patients with comorbidities. Pseudomonas aeruginosa is implicated in intravenous (IV) drug users and patients post-surgery or intra-articular injections. Kingella kingae causes septic arthritis in children younger than four years of age. Neisseria gonorrhoeae, Neisseria meningitidis, and Salmonella species can also cause septic arthritis as part of a disseminated infection. Septic monoarthritis commonly occurs in patients with disseminated gonococcal infection. Blood cultures, white blood cell count, C reactive protein (CRP), electrolytes, and liver function tests are indicated. Serial CRP is useful in monitoring response to treatment. If there is a history of unprotected sexual intercourse, gonococcal testing is recommended. Brucella serology and Tropheryma whippei serology may be considered based on the clinical history. Joint fluid aspiration should be performed by a specialist within the hospital. Joint fluid aspirate is processed in the laboratory for microscopy, culture, and sensitivity. Gram stain can show an increase in neutrophils and presence of bacteria. The guidelines provided by the British Society for Rheumatology on the management of hot swollen joints in adults has provided advice for empirical treatment for suspected septic arthritis, but the local antibiotic policy should also be considered. Initial treatment is with intravenous flucloxacillin 2g four times daily, or 450– 600mg four times daily of intravenous clindamycin to cover S. aureus.

INTRODUCTION AND OBJECTIVES:Patients with an underlying urological diagnosis colonised with multidrug-resistant organisms (MDRO) such as ESBL are predisposed to recurrent UTIs. Treatment can be pro...

Background We describe drug-induced liver injury (DILI) secondary to antituberculous treatment (ATT) in a large tuberculosis (TB) centre in London; we identify the proportion who had risk factors for DILI and the timing and outcome of DILI. Methods We identified consecutive patients who developed DILI whilst on treatment for active TB; patients with active TB without DILI were selected as controls. Comprehensive demographic and clinical data, management and outcome were recorded. Results There were 105 (6.9%) cases of ATT-associated DILI amongst 1529 patients diagnosed with active TB between April 2010 and May 2014. Risk factors for DILI were: low patient weight, HIV-1 co-infection, higher baseline ALP, and alcohol intake. Only 25.7% of patients had British or American Thoracic Society defined criteria for liver test (LT) monitoring. Half (53%) of the cases occurred within 2 weeks of starting ATT and 87.6% occurred within 8 weeks. Five (4.8%) of seven deaths were attributable to DILI. Conclusions Only a quarter of patients who developed DILI had British or American Thoracic Society defined criteria for pre-emptive LT monitoring, suggesting that all patients on ATT should be considered for universal liver monitoring particularly during the first 8 weeks of treatment. Electronic supplementary material The online version of this article (doi:10.1186/s12879-017-2330-z) contains supplementary material, which is available to authorized users.

Characteristics of pDILI. This table contains details of the 105 patients including the kinetics of pDILI, symptoms at presentation, initial regimen, management and overall outcome. (DOCX 20Â kb)

Background Carbapenemase producing Enterobacteriaceae (CPE) are increasingly impacting on patient management and hospital infection control practice. Stem cell transplant patients are among the most susceptible to invasive infections. Here we explored how this cohort are affected by CPE colonization. Methods All patients who underwent an autologous or allograft stem cell transplant (SCT) between September 15 and December 17 at a large tertiary hospital who were CPE positive on routine rectal screening were reviewed. Length of stay (LoS) post SCT, including readmissions for sepsis and number of days of antibiotics therapy, was assessed. Controls were matched for time and type of SCT in a three controls to one case ratio. T-test was performed to analyze differences between groups (statistical significance attributed when P < 0.05). Results The case sample had 20 SCT CPE-positive patients, of which allograft (n = 9) and autograft (n = 11). The control sample was made up of 59 SCT CPE-negative patients, allograft (n = 27), and autograft (n = 32). All patients had antibiotic therapy post SCT. Average LoS for the case sample was significantly longer in the autograft group (41.7 vs. 23.6 days, case vs. control, P = 0.01), but not significant in the allograft group (75.1 vs. 58 days, P = 0.12). Both autograft and allograft case samples had significantly longer duration of meropenem therapy, 24.8 vs. 14.4 days for allograft (P = 0.03) and 9.4 vs. 5.5 days for autograft (P = 0.03), cases vs. control. Colistin therapy was longer in both case samples (P = 0.03 in autograft and P = 0.006 in allograft). Tigecycline therapy was significantly longer in the autograft case vs. control sample (P = 0.006), with teicoplanin and piperacillin–tazobactam therapy significantly longer in the autograft case vs. control sample, P = 0.015 and P = 0.03, respectively. Conclusion The LoS post SCT and duration of antibiotic therapy were found to be key proxy measures of worsening outcomes for CPE-positive patients vs. CPE-negative patients who had undergone SCT. Although reasons for CPE colonization vary, there appears to be an overall negative impact on patient outcomes and increased use of more toxic agents, demonstrating the need for early directed CPE decontamination therapy of these at-risk patients, such as use of Faecal Microbiota Transplant (FMT). Disclosures All authors: No reported disclosures.

In the UK, national guidelines recommend that all HIV-positive women should refrain from breastfeeding for prevention of mother to child transmission (PMTCT). However, the World Health Organisation recommends that HIV positive mothers from low income countries should exclusively breastfeed until six months and continue until twelve months with anti-retroviral therapy (ART) for mother and/or child. In our clinic, a high proportion of HIV positive women are from Africa and mixed messages regarding breast feeding may occur. The decision to not breast feed is sensitive and difficult, particularly where bottle feeding may be associated with HIV. A 2010 BHIVA position statement suggests that in exceptional circumstances breastfeeding may be supported with intense monitoring if the mother has an undetectable viral load. However, there is currently not sufficient evidence regarding transmission or ART toxicity. After a clinic disclosure of breastfeeding at four months post-delivery, we examined our current practice to investigate how monitoring may need to change if breastfeeding were supported in certain circumstances. A review of notes was undertaken to consider ART and viral load in the post natal-period to assess potential risks of breastfeeding in our cohort. All HIV-positive pregnant women who delivered during 2009-10 were eligible. 41 women were identified as having a live delivery of which 30 (73.2%) identified as Black African. 18 (44.0%) were new diagnoses in pregnancy. In total, 28 (68.2%) were on ART, or ART was indicated for the mother, and 13 for PMTCT only (table 1). A viral load greater than 100 was found in 4 (9.8%) at delivery. All of the babies delivered were HIV negative. The mean time to post-delivery viral load was 65.4 days (range 24-584). Of those who were meant to be undetectable on ART, 6/28 (21.4%) had a viral load > 100 copies/ml. 12(92.3%) of those who took ART for PMTCT were detectable at post-delivery viral load. Our clinic review suggests that if breast feeding is to be supported in certain circumstances: i) increased frequency of monitoring will be necessary for those on ART; ii) those on ART for PMTCT only would need to continue ART in the post natal period with such monitoring. (Published: 11 November 2012) Citation: Abstracts of the Eleventh International Congress on Drug Therapy in HIV Infection Patel K et al. Journal of the International AIDS Society 2012, 15 (Suppl 4):18228 http://www.jiasociety.org/index.php/jias/article/view/18228 | http://dx.doi.org/10.7448/IAS.15.6.18228

Objective To describe tuberculosis (TB) relapse/recurrence in patients treated at the UK’s largest TB centre and identify characteristic which predicted recurrence. Design Retrospective observational cohort study. Methods All patients treated at our centre between 1st Jan 2002–31st Dec 2013 were identified from the local TB register. We excluded patients who died due to TB or whose outcome was unknown. Details of patients with more than one notification episode of TB were obtained from patient records. Results In total, 3534 patients were treated for TB during the 12-yr period. After exclusions, 3515 patients were included in the study. Of these, 42 patients had two notifications of TB; none were treated more than twice. Of these 42, we considered 14 to be true relapses/recurrences. 28 patients were considered on review not to have had a true relapse/recurrence: of these, 11 had their first treatment episode at a different centre; 9 were re-starts of treatment because of non-adherence during the first TB episode; 2 had intracranial tuberculomas diagnosed within 12 months of initial episode; 6 were errors in notification. Of 14 patients considered to be true relapses/recurrence, 6 were microbiologically confirmed on relapse/recurrence and a further 8 were re-treated on clinical grounds. None exhibited drug resistance and 2 were HIV positive. The 14 true relapse/recurrence patients had mean age = 42 yrs (range 18–83 yrs) and 6 were males. The sites of relapse were: pulmonary in 6 cases, 3 patients had intracranial tuberculomas, 2 patients had bony TB, 3 patients had TB lymphadenitis. The mean time to relapse/recurrence was 41 months (range 2–96 mo). All 14 patients responded favourably to re-treatment. The true relapse rate of TB treated at the centre was 0.4%. The age, gender and ethnicity of the relapse cases were similar to the overall TB case-mix. Conclusions Our true relapse/recurrence rate of TB is very low, and had no obvious risk factors. We cannot determine retrospectively whether these were recurrence or reinfection, but strain typing (DNA fingerprinting) could differentiate these.

Introduction and objectives NICE guidance advises neuroradiology to investigate CNS signs in patients with miliary tuberculosis (TB). The aims of our study were to describe our population of patients with tuberculomas in the presence of miliary disease and identify any clues to the best radiological modality. Methods The radiology and clinical history was retrospectively reviewed for all patients treated for miliary tuberculosis at one centre between 01/01/2009 and 31/12/2013. Results 53/1650 (3.2%) of patients during this period were diagnosed with miliary (disseminated) tuberculosis. 27/53 (50.9%) underwent further neuroimaging. 10/53 (18.9%) miliary TB patients had evidence of tuberculomas on neuroimaging (M:F 6:4, age range 22:81). 2/10 had evidence of tuberculomas on both CT (2/2 with contrast) and MRI, 5/10 had a negative CT (2/5 with contrast) but an MRI result which revealed tuberculomas. 3 patients did not have a CT scan (MRI only). All 10 patients were HIV negative and had fully sensitive TB, 9/10 had neurological signs which warranted the subsequent neuroimaging. Conclusion Tuberculomas are seen in a fifth of patients with miliary tuberculosis. Based on our findings, guidelines should be adapted to suggest that both use of contrast and MRI should be utilised preferentially.

Introduction We describe the incidence and management of drug induced liver injury (DILI) in active TB at the largest UK centre, using a nurse-led local protocol derived from 1998 BTS guidelines. Methods All active TB cases were identified from April 2010 to May 2014. Patients were identified with DILI by following criteria: Type 1 DILI(ALT >3x upper limit normal (ULN-55iu/l), Type 2 DILI (ALP >2x ULN(150 iu/l) and Bilirubin >21 iu/l) or Type 3 DILI (Bilirubin >40 iu/l). Patient demographics, TB treatment (ATT), timing, management and outcomes of DILI were described. Baseline characteristics and ATT doses were matched with controls. Results 105 individuals with DILI were identified out of 1529 patients with active TB (6.9%). 81% were on standard first line therapy (Rifampicin (R), Isoniazid (H), Pyrazinamide (Z) and Ethambutol (E)). 7.8% were on Moxifloxacin (M) instead of E and 1.9% were on RHME. Type 1 DILI was most frequent (81%) with median peak ALT 296 iu/l (IQR 227–505). Median time from treatment start to onset of DILI was 12.5 days (7–30). Symptoms at presentation included nausea/vomiting (54%), abdominal pain (18%) and jaundice (12.4%). 45.7% patients had all medication stopped, 7.6% continued ethambutol with amikacin (A), 26.7% continued all medication, 6.7% stopped Z only, 3.8% substituted Z for a quinolone. Median time from stopping to reintroduction was 10 days (6–17). Of 66 reintroduction patients, regimens included H >R >E(45%), H>R>E>M (31%) and R>E>M (15%). Median time from reintroduction to full treatment restart was 14 days (12–18). 81% of patients were uneventfully reintroduced, 5% suffered a 2nd DILI. 32% patients required hospital admission and 4(3.8%) died. DILI cases were matched to 200 controls. Cases more likely (P Conclusion DILI remains the most important toxicity of ATT and usually occurs during the first month. The BTS guideline provides a useful template for the diagnosis and management of DILI which may be largely nurse led and ambulatory. Most patients are successfully reintroduced without pyrazinamide. HIV status, body weight and quinolone use are risk factors.