- Volume 2, Issue 2, 2020

Introduction: Faecal microbiota transplantation (FMT) is an effective and licensed treatment for recurrent and refractory Clostridium difficile infection (CDI) and has shown encouraging signals for treatment of ulcerative colitis (UC). Access to FMT has been limited by the introduction of new regulations in the UK. Centres producing FMT are now required to hold a manufacturing licence from the Medicines and Healthcare products Regulatory Agency (MHRA).

Methods:The first licenced FMT service in UK - University of Birmingham Microbiome Treatment Centre (UoBMTC) was launched in 2017. Policies and procedures were developed in accordance with MHRA ‘Good Manufacturing Practice’ guide.

Results: Since August 2018, 132 FMT aliquots have been supplied for recurrent and refractory CDI to 39 NHS Trusts across UK. Twenty-nine of these Trusts did not have access / perform FMT prior to this service. In all cases, FMT was delivered within 48 hours (unless delayed delivery was requested). The service is the sole supplier of FMT since 2018 via an NHS Innovation and Technology Tariff. UoBMTC has also to date supplied 360 FMT aliquots for a multi-centre trial of FMT in UC (STOP-Colitis). Furthermore, the service has provided FMT to other refractory conditions within clinical settings.

Conclusions: Development of a licenced FMT facility has greatly enhanced equality of access for this treatment across the NHS. FMT is provided at a zero-cost model for CDI and is available within 48 hours of request. UoBMTC continues to facilitate research in this field by providing FMT for clinical trials exploring its use for other indications.

Ticks are able to transmit zoonotic pathogens to humans including the most frequently reported Borrelia burgdorferi, and the lesser known Anaplasma phagocytophilum, Borrelia miyamotoi, Babesia spp., and Rickettsia spp. Ticks also play an important role in the spread and maintenance of disease lifecycles. Lyme disease is currently the only tick-borne disease monitored by health professionals in Scotland, however, it is still underreported and misdiagnosed. In this study adult female ticks from 32 hedgehogs from various locations in Scotland were tested for the presence of tick-borne infections using PCR and confirmed by sequencing. PCR results showed there was an 18.75% incidence of B. burgdorferi, 34.38% of B. miyamotoi, 12.5% of Rickettsia spp., 3.13% of A. phagocytophilum, and 3.13% of Babesia spp. 100% of the ticks were confirmed as Ixodes ricinusand from hedgehog hosts. A co-infection of B. burgdorferi and B. miyamotoi was found by PCR and has not been previously reported in the UK. B. burgdorferi was confirmed by sequencing as B. afzelii, however, B. miyamotoi has not been confirmed by sequencing. Another co-infection of B. miyamotoi, Babesia spp., and Rickettsia spp. was found by PCR, however, not confirmed by sequencing. Detection of co-infections in human cases is difficult due to the similar nature of the infections, making it difficult to differentiate between pathogens. This study aims to develop a methodology capable of distinguishing between pathogens, identify the tick and host species, and determine the prevalence of tick-borne disease in Scotland by PCR.

Aim: There are no reliable estimates of the half-lives of maternal antibodies to the antigens found in the primary series vaccines. We aimed to calculate the half-lives of passively acquired antibodies in infants born to mothers participating in studies of tetanus, diphtheria and acellular pertussis (Tdap) vaccination during pregnancy. We aimed to determine whether decay rates varied according to maternal age, birthweight, sex, socioeconomic status, country, or vaccine received.

Methods: De-identified individual participant data from infants born to women taking part in 9 studies of maternal immunization, in 8 countries (UK, Belgium, Thailand, Vietnam, Canada, Pakistan, USA and the Netherlands) were combined. Blood samples were taken at two timepoints before any Tdap containing vaccines were received by the infant: at birth and at 2-months of age. Decay rates for each antigen were log2-transformed and meta-analysis performed. Half-lives were calculated by taking the reciprocal of the absolute value of the mean decay rates.

Results: A total of 4,091 samples were included in the analysis and there was significant variation between studies. There was significant variation in the half-lives of the 6 antigens of interest (p<0.001), with estimates ranging from 28.1 days for diphtheria to 35.6 days for filamentous haemagglutinin. The decay of maternal antibodies did not significantly differ by country-level socioeconomic status, maternal age, sex, birthweight or maternal vaccination.

Conclusion: Maternal antibodies decay at different rates for the different antigens, however the magnitude of the differences are small. Differences in laboratory techniques may account for some of the variability between studies.

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) <0.001

E coli (%)199 (70.8)811 (69.4)0.665

Demographics Age (mean, SD)64.1, 19 58.7, 22 <0.001

Male 137 (48.8)328 (28) <0.001

Associations Gram negative bacteraemia 35 (12.4) 37 (3.1) 0.001

Colonisation with CPE 21 (7.5) 31 (2.7) <0.001

Speciality Renal 84 (30.0) 196 (16.8)<0.001

Urology 47 (16.7) 104 (8.9) <0.001

Resistance Trimethoprim 219 (77.9)354 (30.3)<0.001

Ciprofloxacin 214 (76.2)160 (13.7)<0.001

Gentamicin135 (48). 64 (5.5) <0.001

ESBL infection is associated with worse outcomes and significant premorbid conditions. The oral crossover resistance prevented long term prophylaxis.

Options are needed to reduce colonisation burden of resistant organisms such as faecal microbiota transplantation.

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.

The difficulty in treating life-threatening infections caused by MRSA is a global problem and conventional antibiotics are failing to provide effective therapy due to resistance development thus the need for innovative strategies to combat the problem... Nanoplexes are drug nanoparticles which form complex with oppositely charged polyelectrolyte and have shown to be effective drug delivery of antibiotics. The aim of this study is toexplore the in vitromolecular pattern of vancomycin (VCM) and dextran (VCM-DXT)nanoplexes in fluorescence emission enhancement, maximized membrane disruption, decrease protein concentration and DNA concentration inMRSA for a mechanistic understanding of VCM-DXT elimination of the bacteria. The nanoplexes were characterized for their in vitro electrical conductivity, membrane disruption, protein concentration determination and DNA quantification.The in vitroelectrical conductivity of the VCM-DXT-nanoplexes demonstrated an increase in the electrical conductivity from 0.321 ± 0.01 to 0.39 ± 0.11 mS cm-1. These indicatean increase in membrane permeability of bacteria by destroying the cell membrane leading to the leakage of cellular substance in combating infectious diseases. Furthermore, the VCM-DXT-nanoplexes revealed a maximum MRSA membrane destruction and high emission enhancement intensity of the biofilm obtained from high-resolution transmission microscopy and fluorescence microscopy respectively. The VCM-DXT-nanoplexes demonstrated 3-fold and 1.98-fold decreased in protein concentration and DNA quantification respectively compared to the control. The novel VCM-DXTnanoplexes could be a promising delivery system of VCM by effectively eliminating MRSA infections and prevention of emergence of resistance. This could go a long way in preserving the potency of VCM and extending the time-lapse before the development of resistance.

BACKGROUND: UK’s 5y (2019-24) national action plan on antimicrobial resistance(AMR) projects 1 death/3 seconds(global) by 2050, if AMR rise not tackled. Accurate diagnosis of infectious condition and prompt optimal antibiotic/s are corner stones of any antimicrobial stewardship(AMS), sepsis programme and reducing mortality. We present our experience of developing a novel paperless E-referral pathway for all infection consultations from hospital and primary care to spearhead the hospital AMS and sepsis programmes.

MATERIAL/METHODS: Hospital webdesigners customized existing software application (www.nervecentresoft [http://www.nervecentresoft/]ware.com) & developed user friendly E-referral system (includes basic clinical details, referral urgency/coloured flag and grade/contact of submitter); it auto populates patient demographics and ward location from patient information system. Reports can be generated to query agreed parameters (&KPI). E-referrals accessible both on hospital computers or iPhone/iPAD.

RESULTS: AMS (Apr18-Mar19): >13K ward/phone AMS interventions; total referrals:13,312; 9438(70.1%) responded in 60-min;11923(90%)120min; E-referrals/d: 30-80; Referral Peaks: 3pm & 11am; Referrals from hospital [10,709(80.2%)], GP/prim care [2654 (19.8%)]; Clinical areas: [eg. male cardiac:491(3.6%); HDU:793(5.9%), etc]; E-referrals addressed/consultant [eg. Consultant A(4590(34.3%), etc]. Details & graphs to be presented.

CONCLUSION: E-referral pathway has spearheaded trust AMS & sepsis programmes. Urgent referrals are picked without delay; KPI of referral response within 60mins; significant reduction in calls for consultant Infection via switch board or medical secretaries; auditable workload figures for team to inform UKAS inspection, new consultant business cases or quality matrix; improved accountability and informs annual appraisal / job plan.

Aerococcus urinae is a gram positive, alpha haemolytic cocci that rarely is associated with urinary tract infections, bacteraemia and infective endocarditis. We describe a case of recurrent aerococcus urinae endocarditis with associated cerebral embolic phenomena.

A 76 year old man presented with sudden onset right sided weakness and dysphasia. CT and MRI head imaging showed infarcts in the left pons and cerebellum suspicious of embolic aetiology.

He had a background of a prosthetic mitral valve replacement following an episode of culture negative infective endocarditis associated with discitis and a psoas abscess 3 years previously. A 16S rRNA PCR on valve tissue had yielded an aerococcus urinae.

The anaerobic bottle of a blood culture taken on his present admission flagged positive at 48 hours but no organisms were seen on gram stain. However, Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI – TOF MS) identified an aerococcus urinae 4 hours later. The same organism was also identified in the aerobic bottle which had flagged positive later the same day with gram positive cocci in clusters. Susceptibility testing revealed a MIC (Minimum Inhibitory Concentration) of 0.032, 1 and 8mg/L for penicillin, vancomycin and gentamicin respectively.

A transthoracic echocardiogram confirmed reoccurrence of endocarditis with a 1.5cm lesion on the mitral valve. There was no evidence of other embolic phenomena. The patient was managed medically with initial treatment with intravenous vancomycin and gentamicin followed by benzylpenicillin and gentamicin for 6 weeks. The patient made slow rehabilitative progress and remained debilitated by his right sided hemiparesis.

The present report describes a case of infective endocarditis complicated with aortic root abscess caused by Cardiobacterium hominis (C. hominis) in a 56 year old man. C. hominis is amicroaerophilic, pleomorphic Gram-negative bacillusand member of the HACEK group (Haemophilusspecies, Aggregatibacter actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens and Kingella kingae) a group of bacteria known to be a rare cause of endocarditis. With prompt diagnosis and initiation of antimicrobial and surgical management, a successful outcome was achieved.

Microbial Invasion of the Amniotic Cavity (MIAC) is a term used to describe positive amniotic fluid culture for bacteria or genital mycoplasmas. MIAC can affect both mother and fetus. It is a common cause of preterm labour with intact membranes and prelabour rupture of membranes. It is also associated with cervical insufficiency, an asymptomatic short cervix, idiopathic vaginal bleeding, placenta previa, and clinical chorioamnionitis at term. It is also related to neonatal sepsis, pneumonia and respiratory distress syndrome (RDS) and cerebral palsy. the objective of this study is to determine the etiology of Intraamniotic Infections among women delivered in Soba University Hospital, Khartoum Sudan in February- March 2016. In this cross sectional study, 246 deliveries were included samples of the amniotic fluid were taken after delivery. MIAC is detected 31.3% of the women under study. Staphylococcus aureus constitutes the major isolates (62.1%) followed by E. coli and Klebsiella spp. None of the isolates were Streptococcus agalactiae. There is a statistically significant association between MIAC and maternal infection during the third trimester, mode of delivery and birth asphyxia but not neonatal sepsis.

Introduction

Increased education may improve awareness of antimicrobial resistance (AMR), however 43% of people aged 16-65 in England lack skills to understand health information1.This study aimed to improve patient knowledge on short course antibiotics using a patient information leaflet (PIL) incorporating Health Literacy (HL) techniques supporting the Governments’ 5 year 2019 AMR strategy.

Introduction

Increased education may improve awareness of antimicrobial resistance (AMR)1 however 43% of people aged 16-65 in England lack skills to understand health information2. This study aimed to improve patient knowledge on short course antibiotics using a patient information leaflet (PIL) incorporating Health Literacy (HL) techniques supporting the governments’ 5 year 2019 AMR strategy.

Interest in searching and developing new antimicrobial agents to combat microbial resistance has been growing recently. Therefore, a greater attention has been paid to both screening and evaluation methods of antibiotics activity. The present study aimed to evaluate the potency of some antibiotics containing pharmaceutical products of some Egyptian market companies using microbiological assay based on agar diffusion method and using standard strains in order to determine their therapeutic efficacy.

These antibiotics such as gentamicin, ciprofloxacin, doxycycline, amoxicillin and ceftriaxone were purchased from local pharmacies and evaluated in the current study.

The results of this study showed the relative potency of gentamicin was 41.4%-120% and 28%-41% for ciprofloxacin. While for doxycycline relative potency was 26%-72.6% and 16%-88% for Amoxicillin. As well as ceftriaxone potency was ranged between 48%-97.4%. One product of ceftriaxone, two products from gentamicin and two from amoxicillin were estimated to be within the acceptable range of bioequivalence (80%-120%), while the other products showed unacceptable relative potency. A complaint reporting system about quality and effectiveness problems needs to be considered as a priority source of such information to inform decision-makers.

Key words: antimicrobial resistance, antibiotices, evaluation, microbiological assay, agar diffusion method, potency

Little data exists on the clinical impact on adults who swab positive for more than one respiratory virus at once. Should this be associated with higher morbidity/mortality, there would be implications for patient care and potentially infection prevention measures. We reviewed 190 throat/nasopharyngeal swabs positive for respiratory viruses in York Teaching Hospitals NHS Foundation trust between October 2017 and February 2018. Data, collected from the hospital inpatient computer records, included: age, admission/discharge dates, presenting complaint, past medical history, time to swab (from admission), use of oseltamivir, flucloxacillin and other antibiotics, positive microbiology, highest recorded MEWS (excluding ITU), length of ITU stay and discharge status. The modal length of stay was 2-10 days. 69% of patients were aged over 40. There was no difference between admission to ITU and single/multiple respiratory viruses. The presence of influenza virus was higher in patients with a pre-existing cardiac comorbidity compared with pre-existing respiratory or other comorbidities. There did not appear to be a correlation between the number of patients with any comorbidity having multiple respiratory viruses. Interestingly, 18% of patients with multiple respiratory viruses died, compared with 10% of patients with singular viruses. Given the small numbers of patients included, further work is needed. A repeat review is planned across two hospital trusts in the near future.

Background—

Focal brain lesions associated with HIV infection can be due to cerebrovascular diseases, primary CNS lymphoma, toxoplasmosis, progressive multifocal leukoencephalopathy or other opportunistic infections. We report a challenging case of an adult HIV infected male with focal brain lesions.

Case Description--

A 62 years old male, presented with history of cough with mucoid expectoration for 3 months and abnormal behaviour for 2 weeks.

Clinical examination revealed delayed obeying of commands and no other sensorimotor deficits. MRI brain revealed ill-defined space occupying lesions involving bilateral frontal lobes. HIV antibodies and HBsAg tests were positive. CT chest revealed multiple cavitatory lesions in left upper lobe. Pharyngeal candidiasis was seen during bronchoscopy. Bronchoscopic alveolar lavage revealed Nocardia species. Tests for MTB were negative.

Lung biopsy showed Cytomegalovirus pneumonitis with Aspergillosis. PET scan revealed non FDG avid gliotic changes in brain. CSF and bone-marrow examinations were normal. Brain lesion was considered to be a manifestation of Nocardiosis and biopsy was planned. CD4 count was 103/mm3. Intravenous ceftriaxone, ganciclovir, caspofungin, fluconazole and oral septran were started. Patient was started on HAART(Tenofovir, lamivudine, efavirenz) 1 week later, after explaining the risk of Immune reconstitution inflammatory syndrome. CNS lesion biopsy revealed High grade B-cell Non- Hodgkin’s lymphoma. Palliative external Radiotherapy to whole brain was given. The patient has improved clinically and is on regular follow up from 1 year.

Conclusion—

Extensive evaluation and work up is required in cases of focal brain lesions in patients with HIV. Brain biopsy often provides the definitive diagnosis.