13th – 15th November 2018 | Sage Gateshead – Newcastle
13th – 15th November 2018 | Sage Gateshead – Newcastle
13th – 15th November 2018 | Sage Gateshead – Newcastle
Day 2: Wednesday 14th November
08:00 – 09:30
Chairs: Dr David Partridge, Consultant Microbiologist, Sheffield Teaching Hospitals & Dr Penny Lewthwaite, Consultant in Infection and Travel Medicine, Leeds Teaching Hospitals
An unusual case of meningitis – thirsty for the diagnosis
Dr Fiona McGill, Academic Clinical Lecturer, Infectious Diseases & MedicalMicrobiology, University of Liverpool
Abstract - An unusual case of meningitis – thirsty for the diagnosis
Introduction: A 64-year-old hotel manager was admitted with an acute severe headache, confusion and fever. He was entirely well 24 hours beforehand. On admission his temperature was 38.7ºC and he was confused with a GCS of 11. He had no photophobia or neck stiffness and no obvious focal neurological abnormality. He was initially treated with IV ceftriaxone, amoxicillin, dexamethasone and aciclovir.
CT of his head showed prominent lateral ventricles. Lumbar puncture could not be performed initially due to agitation. Twelve hours after admission the patient had required multiple doses of lorazepam to control his agitation. He had an acute respiratory deterioration, was intubated and ttransferred to the intensive care unit (ICU).
Methods: Lumbar puncture (LP) in ICU revealed an opening pressure of 24 cm H2O, a leucocyte count of 9650/mm3 ( 90% polymorphs) and a red cell count of 2330/mm3. Cerebrospinal fluid (CSF) protein was 3.02g/L, glucose 2.5mmol/L (serum glucose 6.4 mmol/L).
The following day a blood culture flagged positive and antibiotics were adjusted accordingly. However, the blood culture isolate was later thought to be a probable contaminant. CSF culture had no growth. Meningococcal and pneumococcal PCR were negative in CSF and blood. 16S rRNA gene PCR of the CSF eventually revealed the causative organism.
The patient received 14 days of ceftriaxone and made a good recovery before being discharged in good health.
Discussion: This is an unusual case of bacterial meningitis. We retrospectively looked back through the last ten years of our laboratory records and have not identified any previous cases of meningitis in our hospital with this organism. 16S rRNA gene PCR was crucial in this case to confirm the diagnosis and should be utilised in cases of suspected bacterial meningitis where none of the more common organisms are found.
Death by antibody: a case of Candida glabrata in an extra-corporeal membrane oxygenation (ECMO) patient on secukinumab
Dr Diana Mabayoje, Specialist Registrar, Infectious Diseases & Microbiology, Barts Health NHS Trust, London
Abstract - Death by antibody: a case of Candida glabrata in an extra-corporeal membrane oxygenation (ECMO) patient on secukinumab
Introduction: Candida spp. infections are well recognised in patients on intensive care units. Immunosuppressed patients on ECMO are at even higher risk of acquiring infections.
Case Description: A 42 year old UK born lady was admitted to A&E in septic shock, with one week of fevers. She had a background of psoriatic arthritis, for which she was on an anti-IL 17A drug, Secukinumab. Blood tests of note included Neutrophils 18.6 x109/L, Platelets 81 x109/L, eGFR 19 mls/min, ALT 193 IU/L, CRP 400 mg/L. During the first week of admission she had a cardiac arrest. Echocardiogram revealed an ejection fraction of 25% and she was transferred to the intensive care unit for organ support including VA-ECMO. She remained on ECMO for 10 days. During this period her inflammatory markers continued to rise and she continued to spike fevers on Meropenem and Linezolid.
Post ECMO her heart made a full recovery, but the groin cannulation site was oozing. Her groin was debrided, necrotic tissue grew Pseudomonas aeruginosa. On day 16, Candida glabrata was isolated from blood cultures taken from the central line, vascath, and peripherally. She was started on anidulafungin. The reference lab report confirmed that this was a fully sensitive organism. Subsequent blood cultures remained negative for 12 days before Candida glabrata was isolated again from a peripheral blood culture, the source for which was unclear.
A CT of chest, abdomen, and pelvis revealed a large submucosal gastric collection, measuring 10x13cm. This was drained via CT guidance, and Candida glabrata was isolated. Unfortunately, the patient continued to deteriorate and later died. She has several factors contributing to infection, intensive care stay, ECMO, and the anti- IL17A drug.
Discussion: This case demonstrates an iatrogenic related infection and calls for consideration of early anti-fungal use in this patient group.
Taking the mickey
Dr Helen Casey, Specialty Registrar, Medical Microbiology, North Bristol NHS Trust
Abstract - Taking the mickey
Introduction: A 50-year-old man presented with a swollen right knee and reduced mobility. His GP had diagnosed gout but the patient felt that his symptoms were worsening. He was afebrile on initial assessment but self-discharged soon after presentation. Of note, his C-reactive protein (CRP) was elevated (345mg/L (normal range <6.0)).
Three days later the patient represented with a temperature of 38.5°C, and a hot and erythematous right knee with effusion. Repeat investigations showed a CRP of 375mg/L and total white cell count (WCC) of 12.95×109/L (normal range 4.0-11.0). His past medical history included schizophrenia and personality disorder. He smoked tobacco and cannabis but denied alcohol or current intravenous drug use. His knee was aspirated but no crystals were seen under polarised light microscopy and he was admitted under orthopaedics. He was commenced on intravenous (IV) flucloxacillin for a possible septic arthritis.
Methods: His CRP rose to 472mg/L, and he became progressively more unwell. His knee aspirate had numerous white cells seen but no organisms on Gram stain. The cultures were subsequently negative. On further questioning he reported that two days prior to the onset of his symptoms he caught a field mouse, jarring his knee and elbow in the process. The mouse bit his hand before being released. On examination the bite looked well healed with no sign of infection.
He continued to be febrile with ongoing knee pain and was now developing widespread myalgia and arthralgia. An ultrasound scan of his right thigh showed a large and complex collection along the femur with evidence of myositis. A diagnosis of infective endocarditis was now queried. A trans-thoracic echocardiogram demonstrated a small mobile structure on the aortic valve which could be calcium, a vegetation or artefact and trans-oesophageal echocardiogram was recommended. The CRP remained static at 343mg/L.
Discussion: The patient was then reviewed by the Microbiology/Infectious Diseases team who noted a past history of intravenous drug use, although the patient denied injecting for over 10 years. He reported keeping two snakes, and a lizard that had been previously colonised with a Salmonella spp. He had a long term partner and denied any new sexual contacts. On examination the main findings were multiple swollen painful joints and ongoing pyrexia but no rash or stigmata of endocarditis. At this point an alternative diganosis was proposed and his antibiotics were switched.
Revenge of the reaction
Dr Jill Dixon, ST7, Infectious Diseases/GIM, Royal Victoria Infirmary, Newcastle
Beware, beware, of walking barefoot out there!
Dr Blair Merrick, Specialist Registrar, Infectious Diseases, University College London Hospital
Abstract - Beware, beware, of walking barefoot out there!
Introduction: We describe a series of three patients treated in the Infection and Tropical Medicine department at the Royal Victoria Infirmary, Newcastle upon Tyne, between December 2016 and December 2017. Although their clinical presentations were diverse, each notably had a recent travel history to Thailand, and ultimately the same organism was found to be the cause for their symptoms. We aim to highlight a potentially fatal disease of multifarious presentation, which must be considered in travellers returning from endemic areas such as Southeast Asia.
Methods: The first patient was a 52-year-old female with no significant past medical history. She presented to medical attention in septic shock, which required critical care admission for vasopressor support. Her illness initially began with coryzal symptoms one week prior to admission, whilst still on holiday in Thailand. CT chest revealed a large mediastinal abscess and multiple cavitating nodules within both lung fields. Cultures of pus drained from the abscess grew the implicated organism.
The second patient was a 69-year-old female with a history of type 2 diabetes. She developed malaise and shortness of breath whilst away in Thailand. She presented to medical attention two weeks later with fevers, confusion and a productive cough. CT chest was significant for a right-sided necrotising pneumonia. Blood cultures taken on admission grew the responsible organism.
The third patient was a 38-year-old female with a history of type 1 diabetes. She presented with a complex partial seizure and expressive dysphasia on a background of a several month history of unilateral headache. The headache started shortly after returning from a trip to Thailand. An MRI brain revealed a dural-based lesion in the left temporal area. A craniotomy was performed to remove the mass. Intra-operatively this was found to contain pus, cultures of which grew the offending organism.
Discussion: The responsible organism in all three infections was a gram-negative bacillus, which is found predominantly in the tropical and subtropical regions of Southeast Asia and Northern Australia, although cases have been seen across Central and South America, the Middle East and even Africa. Classically infection occurs due to inoculation through skin abrasions, but may also be acquired through inhalation or ingestion of the bacteria. Clinical disease usually occurs within a few weeks of exposure; however, as the bacteria have the capacity to remain dormant for years, presentation can be decades later. Affected individuals frequently have an underlying immunosuppressive condition such as diabetes mellitus or chronic renal insufficiency. Mortality in untreated infection exceeds 90%.
All three patients were treated with meropenem due to the antimicrobial resistance profile associated with this pathogen. This was followed by a prolonged course of co-trimoxazole or doxycycline (depending on antimicrobial sensitivities) to reduce the risk of relapse (6% in first year and 13% by 10 years). They all went on to make a full recovery and were well at the time of last follow-up. These cases highlight the diversity of presentations seen in this condition. A high index of suspicion is necessary when assessing individuals with a suspected infection and a travel history to an endemic area for the organism, to ensure the diagnosis is considered, and appropriate antimicrobial therapy initiated in a timely fashion.
One of the causes for permanent blindness in HIV patients in resource-limited
Dr Ni Ni Tun, Medical Director, Medical Action Myanmar
Abstract - One of the causes for permanent blindness in HIV patients in resource-limited settings, Myanmar
Introduction: In resoure poor settings, where HIV diagnosis and treatment is limited, many HIV patients usually come with advance presentation. One of the presenting features in advanced AIDS patients is vision impairement. Many cliicians have been struggling in finding out the cause of the blindness in HIV patients. Because of limited diagnosis and treatment facility, it has been a miracle until 2006.
Methods: In 2006, American uveitis specialist came to Myanmar and started training for HIV clinicians to do early diagnosis of CMV retinitis by using indirect ophthalmoscopy and intraocular ganciclovir injection. Regular training and monitoring happened since by that time with Médecins Sans Frontières (MSF-Holland) and Medical Action Myanmar.
Results: A young women aged 24 years was diagnosed as HIV positive on 12thMarch, 2016 with baseline CD4 count of 15cells/ml. Screening for CMV retinitis by indirect ophthalmoscope was done on 25thMarch 2016, and no abnormal finding was detected. On 24th April, 2016, ART was started with Tenofovir, lamivudine and efaverance combination. Follow up screening of CMV eye infection was done on24th May due to low baseline CD4 and CMV was diagnosed (figure 1). Eye vision was 6/6 on both eyes. Intraocular gancyclovir injection to left eye was given (valgancyclovir was unavailable at that time) and ART was continued. After 3 times of weekly intraocular gancyclovir injection, the retinal lesion became inactive and the injection was stopped. Now the patient is more than two years on ART. Her last CD4 count was 332 cells/ml and the retinal lesion remain inactive.
Discussion: Cytomegalovirus (CMV) is a member of the herpes virus family, acquired in childhood and over 90% of adults living in resource-limited settings in middle and low income countries are positive. CMV remains latent for life, but can become active if the immune system becomes significantly impaired.In the setting of HIV infection, cytomegalovirus (CMV) can affect both the central and peripheral nervous systems. It can also cause colitis, esophagitis, adrenalitis, hepatitis and pneumonitis. This usually occurs in patients with severe immunodeficiency: CD4+ lymphocyte counts typically are less than 50/mm3.
CMV retinitis caused over 90% of AIDS-related blindness in developed countries before ART therapy was introduced, and now causes over 90% of AIDS-related blindness in Myanmar, as well as the rest of South East Asia, China, India and Eastern Europe (Russia and the Ukraine). Untreated, CMV retinitis is relentlessly progressive and will destroy the entire retina in 4-6 months. In resource-limited settings, the patient generally does not complain of symptoms until vision loss has occurred, when the damage is already permanent and not reversible. Clinical symptoms may include blurred vision, floaters, scotoma (holes in the vision or blind areas) or flashing lights in the eye. The “gold standard” for diagnosis is indirect ophthalmoscopy through a fully dilated pupil by a trained clinician. Successful treatment of CMV in patients with AIDS requires both, ART and specific medication against CMV. Valganciclovir, an oral version of ganciclovir is the ideal systemic CMV treatment, covering both ocular and extra-ocular disease, but is at the moment unavailable to us. At this time the most cost-effective treatment is intraocular ganciclovir injections. This treatment in combination with ART will effectively stop the progression of CMV, and therefore also limit the occurrence of secondary blinding complications (retinal detachment and IRU) which both increase in frequency in direct proportion to the area of retina that is infected.
The vision loss from CMV is commonly permanent, that is why an early diagnosis is of great importance. To enable early diagnosis, all patients with CD4 < 100 cells/mm3 should be referred for indirect opthalmoscopy without delay and should be screened within the first week of presentation for care.
When is a chest infection not a chest infection?
Patricia Crossey, Critical Care Pharmacist, Royal Liverpool University Hospital
Abstract - When is a chest infection not a chest infection?
Introduction: A 62 year old female was admitted with dysuria, haematuria, fevers and loin pain following a recent cervical smear. She had a recent course of nitrofurantoin from her GP with no improvement in her symptoms. On admission she was tachycardic with bilateral renal angle tenderness. Left sided fine crepitations were also heard on auscultation of her chest and oxygen saturations were 95% on room air. Bloods showed a leucocytosis with a total leukocyte count of 17.6 x 109/L, CRP was 30mg/L. Urinalysis was positive for blood but negative for nitrates and leucocytes. However, in view of her symptoms and a recent mid-stream specimen of urine growing a multi-resistant E.Coli, she was commenced on ciprofloxacin for presumed pyelonephritis.
Methods: Over the next two days she became increasingly short of breath and hypoxic, ultimately requiring 85% inspired oxygen to maintain saturations above 90%. She had type 1 respiratory failure. Initial treatment was broadened with the addition of benzylpenicillin, oseltamivir and furosemide, to cover community acquired pneumonia, influenza and pulmonary oedema – all with no effect. She was transferred to a level two bed for respiratory support on day two of her admission and was commenced on non-invasive ventilation.
The underlying cause of her respiratory failure was unclear. Sequential chest x-rays showed worsening bilateral air space shadowing. Transthoracic echocardiogram revealed no evidence of cardiac failure. Urinary antigen tests were negative for Streptococcus pneumoniae and Legionella pneumophila. Upper respiratory tract swabs were negative for Influenza A and B, RSV, Mycoplasma pneumoniae and Chlamydophila pneumoniae by PCR.
Gradually over the next few days, with supportive treatment and without any new intervention, she slowly improved. Her respiratory symptoms settled, oxygen requirements decreased and she was discharged, on day eight, to a respiratory ward. She underwent a high resolution CT scan which showed ground glass changes in the right upper lobe. This finding was discussed in the lung MDT where the diagnosis of pneumonitis was raised and ultimately led us to identify the true cause of her respiratory failure.
Discussion: This case highlights an unusual cause of pneumonitis. It re-iterates the need for a thorough history taking and to consider all differentials, especially where the initial symptoms do not marry up with the clinical findings. Sometimes, the least likely diagnosis may be the correct one.
An overlooked cause of confusion in a patient with myasthenia gravis
Dr Marco Lee, ST5, Microbiology, Leeds Teaching Hospitals NHS Trust
Abstract - An overlooked cause of confusion in a patient with myasthenia gravis
Introduction: A 58 year old male presented to hospital in December, 2017 with a three-day history confusion, change in behaviour, and vomiting.
No other symptoms were found on systemic enquiry. He has had no recent surgeries, dentalwork, sinusitis, otogenic infections, nor contact with known tuberculosis cases.
His background consists of myasthenia gravis (on mycophenolate for past 3 years), type 2 diabetes mellitus (on metformin and insulin), and a brainstem stroke (on clopidogrel and atorvastatin).
Physical examination showed a normal GCS, normal neurological, cardiovascular, and respiratory systems, no rash, good dentition, and no peripheral stigmata of endocarditis. Blood tests show a raised WBC of 16.7 x109 cells/L (neutrophils 13.7 x 109 cells/L), CRP <5 mg/L, and normal renal and liver function.
Methods: MRI brain showed two frontal ring-enhancing lesions associated with significant oedema.
Two brain biopsies were performed in January, 2018 which showed acute inflammation with necrotic slough, consistent with abscess. Bacterial, fungal, and mycobacterial direct stains and cultures were negative.
[PIC OF H&E stained section (400x magnification)]
Discussion: Further elucidation of social history revealed that he has lived on a farm for the past 14 years. The farm has cattle, sheep, and chickens. He also owns three dogs and three cats.
Feeling sheepish: a rapidly progressing rash in a veterinary worker
Dr Sophie Garrad, Core Medical Trainee, Infectious Diseases, Bradford Teaching Hospitals
Abstract - Feeling sheepish: a rapidly progressing rash in a veterinary worker
Introduction: We present a rare case of severe disseminated rash occurring as a complication of an infection which usually runs a benign course. The report raises the awareness of this potential diagnosis in patients with a similar rash.
Methods: A previously healthy 37 year old women presented to an urban district hospital with a rapid onset prolific blistering and blanching pruritic rash which began on her left arm and spread outward to arms, legs, torso and face over a 48 hour period. She had oedema of her hands restricting finger movements. There were no mucosal lesions and she was afebrile with normal heart rate and blood pressure. Bloods demonstrated elevated eosinophils (1.37 x 109/L), neutrophils (10.5 x 109/L) and C-reactive protein (163mg/L). She had consulted healthcare professionals on several occasions over the preceding days however a diagnosis had not been reached.
Three weeks earlier she had noted a white hard lump on the index finger of her left hand which had blistered, ruptured and released serous fluid. She worked for a veterinary practice and owned a herd of sheep. She was concerned that the rash was due to disseminated infection.
A swab and biopsy of the finger were taken for viral investigations she was treated with intravenous fluids, antihistamines, steroid emollients, flucloxacillin and aciclovir. Potassium permanganate soaks were administered to the arms.
The rash coalesced and exuded large amounts of serous fluid before slowly improving. In total she was hospitalised for seven days and on follow-up two months later, she reported ongoing intermittent lesions. Electron microscopy of the finger tissue later confirmed the diagnosis.
Discussion: This is a rare clinical presentation, with less than 50 published cases. Our patient was distressed by doctors’ unfamiliarity with this condition when she initially sought healthcare advice and we therefore urge clinicians to consider this diagnosis in those who present with rash after contact with sheep.
This zoonotic infection usually presents as a small lesion on the hand which heals without intervention. The rare secondary skin reaction develops two weeks after the initial lesion. The underlying mechanism is unknown but likely due to immunomodulatory virulence factors produced by the virus. Those who are immunosuppressed are more susceptible to such complications3 therefore an HIV test should be considered.
Published case reports describe features comparable to our case. The upper limbs are the commonest site, with potential for spread across the body with mucosal sparing. Management is primarily supportive and there is no evidence for the use of systemic steroids. There have been two case reports of rapid resolution with topical immiquimod.
Within the UK specimens can undergo diagnostic electron microscopy at Colindale laboratories. PCR can also be used in the detection but is not the initial recommend guidance by Public Health England.
Supported by BIA
09:30 – 11:00
Bone and Joint Infection
Dr Bridget Atkins Consultant in Microbiology, Virology & Infectious Diseases, Oxford University Hospitals & Mr Martin McNally, Lead Surgeon, Limb Reconstruction Surgery, Bone Infection
Unit, Oxford University Hospitals
Prevention of infection in orthopaedic surgery
Professor Mike Reed, Consultant Orthopaedic Surgeon, Trauma & Orthopaedics,
The principles of surgery in long bone osteomyelitis
Mr Martin McNally, Lead Surgeon, Limb Reconstruction Surgery, Bone Infection Unit, Oxford University Hospitals
Abstract - The principles of surgery in long bone osteomyelitis
Surgery is an integral part of the management of long bone infection. Workup for surgery in bone infection is directed towards:
- Optimisation of patients with relevant co-morbidities
- confirming the presence and nature of the infection
- understanding the anatomical distribution of the disease
- planning adequate excision and reconstruction
To achieve this, patients must have a planned, specific series of imaging and tissue diagnostic tests. Choice of imaging usually includes plain x-ray and MRI, in the absence of metal implants. CT and 18FDG PET-CT scanning are reserved for special situations.
In theatre, there is no place for an ‘open up and see’ approach. Surgical sampling for microbiology and histology, dead bone excision and reconstruction (bone and soft tissue) should be planned in advance and follow accepted and validated protocols.
There are few occasions when it is necessary to leave wounds open after excision. In a systemically unwell patient, a rapid, life or limb-saving operation may be needed, with minimal reconstruction, followed by a second stage definitive procedure to eradicate infection. However, good workup will usually allow effective treatment in a single operation.
McNally MA, Ferguson JY, Lau ACK, Diefenbeck M, Scarborough M, Ramsden AJ, Atkins BL. Single-stage treatment of chronic osteomyelitis with a new absorbable, gentamicin-loaded, calcium sulphate/hydroxyapatite biocomposite. Bone Joint J 2016; 98-B: 1289-1296.
Morgenstern M, Athanasou NA, Ferguson JY, Metsemakers W-J, Atkins BL, McNally MA. The value of quantitative histology in the diagnosis of fracture-related infection. Bone Joint J 2018; 100-B: 7, 966-972.
McNally M, Ferguson J, Kugan R, Stubbs D. Ilizarov treatment protocols in the management of infected non-union of the tibia. J Orthop Trauma 2017; 31: S47-54.
Metsemakers WJ, Morgenstern M, McNally MA, et al. Fracture-related infection: A consensus on definition from an international expert group. Injury 2018; 49(3):505-510.
Govaert GA, Ijpma FF, McNally MA, et al. Accuracy of diagnostic imaging modalities for peripheral post-traumatic osteomyelitis- a systematic review of the recent literature. Eur J Nucl Med Mol Imaging 2017;44:1393-1407.
Why is management of the soft tissues important?
Mr Alex Ramsden, Consultant Plastic Surgeon, Nuffield Orthopaedic Hospital, Oxford
Abstract - Why is management of the soft tissues important?
Antimicrobial management after resection or debridement-and-retention surgery. What is the evidence for agent, route (oral, intravenous, local) and duration?
Dr Alex Soriano, Head of Infectious Diseases, Hospital Clínic of Barcelona
Abstract - Antimicrobial management after resection or debridement-and-retention surgery. What is the evidence for agent, route (oral, intravenous, local) and duration?
Antimicrobial management after resection or debridement and retention surgery. What is the evidence for agent, route (oral, intravenous, local) and duration?
Orthopaedic implant infections are a challenging problem for orthopaedic surgeons and infectious diseases. The presence of bacterial biofilms over the surface of foreign material makes an important difference with respect to other infections. In general, it is consider that the removal of the implant is necessary to cure the infection, however, depending on the maturity of the biofilm, and the possibility to perform an extensive debridement, it would be possible to retain the implant avoiding a more aggressive surgery. The type and duration of antibiotic treatment will depend on the isolated microorganism, whether the implant has been removed or not, pharmacokinetic parameters, potential interactions, and the safety profile of the different antibiotic options. The main objective of the this lecture will be to cover all these aspects by reviewing the current literature and to discuss potential options for treating orthopaedic implant infections.
Supported by EBJIS
09:30 – 11:00
Lethal clostridial infection: from diarrhoea to septic shock
Professor Sheila Patrick, Professor Emeritus, Centre for Experimental Medicine, Queen’s University Belfast & Dr Harriet Hughes, Consultant in Microbiology & Infectious Diseases, University Hospital of Wales
Clostridial sepsis, blood culture and antimicrobial resistance
Mr Michael Perry, Deputy Lead Scientist, UK Anaerobe Reference Unit, Public Health Wales Microbiology
Abstract - Clostridial sepsis, blood culture and antimicrobial resistance
An interesting and challenging case of infection caused by Clostridium septicum
Dr John Hood, Consultant in Clinical Microbiology, Glasgow Royal Infirmary and Golden Jubilee Hospital
Abstract - An interesting and challenging case of infection caused by Clostridium septicum
On 19 August 2016 a 66yr old male presented to orthopaedic service at the GJNH – 24h history of acute pain and swelling in L knee and feeling generally unwell for 7 days. Rapidly becomes septic – ITU admission for inotropic support.
Left TKR in 2008; episode of pain and raised CRP in this L knee in 2014, but quick resolution. Aortic regurgitation 2007. Type 2 Diabetes 2006.
Hypertension and small CVA 2003. Known asbestos exposure with calcified pleural plaques.
19 Aug: Blood cultures taken, plus x 4 knee aspirates – Gram positive bacilli seen. On call microbiologist advises piperacillin – tazobactam and vancomycin in view of possible clostridium (covering a possible abdominal source).
Clinically stabilising. 2 joint aspirates taken again both show Gram positive bacilli.
Theatre: excision arthroplasty. A total of 7 tissue specimens and a swab of the tibial canal taken.
Progresses well, to ward on 22 Aug. All 15 samples taken so far – grow within 24 – 48h a Clostridium spp. (mast ring – no MALDI)
Plan: CT scan of abdomen and colonoscopy as source of clostridia most likely gut. Continue broad spectrum cover and metronidazole added. Isolate sent to Anaerobic Reference Laboratory, Cardiff for formal ID and sensitivities. Discussion with Dr Hughes as unusual pathogen. Specimen received 25 Aug.
CT scan of Abdo and pelvis: generalised atheromatous disease of the abdominal aorta. Uncomplicated colonic diverticular disease. Mild infrarenal aortitis – without aneurysm or collection.
Continues to progress well. Knee clean and dry. CRP: 485 on 21 Aug to 98 on 2 Sept.
Repeat CT abdo and pelvis
Infrarenal aortic thrombus is becoming slightly more conspicuous, intramural gas resolved but aortic lumen still widely patent.
Very useful discussion with Harriet. The clostridium isolated confirmed as Cl septicum. Sensitive to pen, co-amox, ctr, mero and vanc. Borderline to Metro and rif.
Discussion of literature on C. septicum – esp Seder et al (2009)
Reviewed 26 cases (2 of theirs) – strong association with occult malignancy, especially the gut and haematological; overall 6 month mortality of 64%; 100% mortality for those who do not undergo operative intervention; aortitis – higher risk in elderly and diabetic due to seeding to artherosclerotic lesions; therefore this case is consistent with haematological seeding to the prosthetic knee and aorta.
Plan: continue investigation for malignancy; reconsideration by vascular surgeons of surgery on aorta – literature passed on to both ortho and vascular surgeons; no evidence of polymicrobial infection, therefore rationalise
antimicrobials to IV Ben Pen and oral clindamycin; likely to be prolonged and maybe for life with oral amox post IV course; OPAT ceftriaxone or ertapenem
Orthopaedic surgeons: no need to be hospitalised apart from antibiotics and issue of aortitis. No evidence of haematological malignancy.
Colonoscopy revealed only 3 ‘probably benign’ sigmoid polyps and sigmoid diverticula. Transferred to Vascular Surgery at QUEH
Aortitis with progressive change in his infrarenal aorta leads to excision and reconstruction with deep vein graft. Despite almost 5 weeks of appropriate antimicrobial treatment a tissue sample from the aorta grew quickly the Clostridium septicum!
Vascular FY1 calls duty room at QEUH asking for IVOST!!!!
7 October 2016
Email to Vascular Surgeon explaining that despite 5 weeks appropriate antibiotics C. septicum was still grown from the tissue sample so the therapeutic clock should restart for a further 6 weeks of the IV Ben Pen and oral clindamycin (or perhaps changing to oral rifampicin now) with then review with ?lifelong oral antibiotic cover.
Issues with OPAT and patient threatening to sign himself out!
If a more manageable IV combination was required we suggested IV ceftriaxone and oral rifampicin.
No further discussions with vascular service and microbiology until 28 November 2017.
Patient underwent a 2nd Stage revision (fusion) on 30 October 2017 – 3 tissues and a knee fluid were all negative on both direct and enrichment cultures.
No vascular discharge letter was available from 2016 but a clinic letter from then described IV ceftriaxone stopped on 11 Nov 2016 and discharged home on oral rifampicin only!!! (after a total of 12 weeks IV from admission on 19 Aug 16)
This continued until discussion by Dr Wright in Nov 17 with Dr Hughes on what treatment should be given post his stage 2. Answer: 6 weeks oral amox and oral clindamycin (but not sure if this happened or not!) followed by lifelong oral amox .
From Vascular Clinic notes he was changed from Dec 2017 to oral amox ….but at 1g tds not 500mg tds with an egfr of 10!
Both this gentleman’s orthopaedic and vascular issues seem to be under control.
His main issue now is his CKD Stage 4 with a slow drift down in his egfr from about 50 in Aug 2016 to 10 now. The aetiology of this is believed to be due to the number of contrast CT scans he underwent in 2016.
He will shortly commence routine haemodialysis.
Implementation of the guidelines for faecal transplant treatment of C. difficile infection; benefits versus risks
Dr Jonathan Sutton, Consultant Physician & Clinical Lead for AMR, Gastroenterology, BCUHB Ysbyty Gwynedd, Bangor, Wales
Abstract - Implementation of the guidelines for faecal transplant treatment of C. difficile infection; benefits versus risks
In the last 4 years interest in FMT, as a treatment for recurrent C. difficile, has rapidly increased.
Patient interest in FMT has often eclipsed the acceptance of it by clinicians. FMT is not the novel treatment recent adopters thought it to be having been used for centuries to treat all manner of gastrointestinal diseases. However its recent rediscovery and acceptance as a therapeutic modality has left regulators and the medical profession struggling to keep up.
In this session we will explore the FMT journey to accepted medical practice, and the challenges this has caused. Why regulation is important and why the development of guidelines has been greatly needed.
Recent national and international guidelines offer a standard by which to deliver FMT. This adds legitimacy to a treatment which despite the trial data has been adopted slowly in some areas. They offer a firm foundation for those developing a service.
The guidelines also suggest potential future developments for FMT to improve governance. We look at why these are especially important as FMT goes beyond recurrent C. difficile.
Supported by Microbiology Society and Society for Anaerobic Microbiology
09:30 – 11:00
The Year in Antimicrobial Stewardship
Mrs Tejal Vaghela, Antimicrobials and Acute Admissions Pharmacy Team Leader, West Hertfordshire Hospitals & UKCPA PIN Chair
Recent advances in antimicrobial stewardship
Professor Martin Llewelyn, Professor in Infectious Diseases, Brighton and Sussex Medical School
Abstract - Recent advances in antimicrobial stewardship
Examples of antimicrobial steward ship initiatives in community practice
Dr Diane Ashiru-Oredope, Lead Pharmacist, HCAI & AMR Division, Public Health England
Abstract - Examples of antimicrobial steward ship initiatives in community practice
This session will highlight examples antimicrobial stewardship activities in community practice including community pharmacy, care homes and community healthcare trusts. Recent findings from a randomised controlled trial in community pharmacy will also be presented.
Examples for novel antimicrobial stewardship implemented in secondary care
Mr Adel Sheikh, Lead Antibiotic/Respiratory Pharmacist, Portsmouth Hospital
Abstract - Examples for novel antimicrobial stewardship implemented in secondary care
Antibiotic resistance is for ever becoming not only a national problem, but a worldwide issue. As the current rate of resistance occurring if nothing is done it is estimated that by 2050 their could be 10 million deaths that are accountable to antibiotic resistance which could cost around 66 trillion pounds.
In Europe an average of 25,000 people die each year due to antibiotic resistance.
Hospitals account for about 20% of the antibiotic prescribing in the UK, and therefore improvements need to be made to help control the unnecessary use of antibiotics.
The UK government vial PHE have issued several national CQUINS to try and get hospitals engaged into antimicrobial resistance, by setting targets to improve treatment for patients with sepsis, engaging doctors in more thorough antibiotic reviews within 72 hours of initiation and to try and reduce the need for broad spectrum antibiotics.
Many hospitals throughout the uK have come up with Novel ways to improve antibiotic stewardship within their trust and this session will highlight some of the good work done by them.
Supported by UKCPA
11:00 – 11:30
COFFEE, Exhibition & Poster Viewing
Dr Katie Jeffery, Oxford and Dr David Partridge, Sheffield
11:30 – 12:15
Professor David Dockrell, Professor of Infection Medicine, University of Edinburgh
Management of Staphylococcus aureus bacteremia (SAB)
Professor Richard Proctor, Professor Emeritus of Medicine, Medical Microbiology & Immunology, University of Wisconsin-Madison, USA
Abstract - Management of Staphylococcus aureus bacteremia (SAB)
S. aureus infections are a leading cause of morbidity and mortality in children and adults. Worldwide, S. aureus is number one cause of pyogenic infections. In the developed world, it is the leading cause for children needing hospitalization and surgery, the #1 cause of bacteremia in people >65 years old, the #1 cause of deep skin infections, the most frequent cause of endocarditis, the #1 cause of surgical site infections, and the #2 cause hospital infections. Thus, the burden of disease is huge. Many of these infections result in S. aureus bacteremia (SAB) with rates/100,000/yr ranging from 20 – 38 overall and 100 in patients >70 years old and almost 2,000 in HIV positive patients. SAB is a feared disease because the mortality rate has stubbornly remained ~20% (range 16-31%) despite medical progress over the past 2 decades. Of course, the most feared complication of SAB is endocarditis because this often doubles the mortality rate in many series. Therefore, the updated strategies for the diagnosis and management of endocarditis will be reviewed.
New information on the immune dysfunction seen with SAB will be discussed as this predicts mortality. Updates on antibiotic management will be covered, including data on the value of combination antibiotic therapy for methicillin-resistant S. aureus (MRSA). Finally, the impact of care bundles and decolonization will be discussed as ways to reduce mortality and prevent infections.
12:15 – 13:15
Platinum Sponsored Satellite Symposium
Respiratory infections and the NHS winter bed crisis: challenges and potential solutions
Dr Duncan Wyncoll, Consultant in Intensive Care Medicine, Guy’s and St Thomas’ NHS Foundation Trust, London, UK
Welcome and introduction: respiratory infections and the NHS winter bed crisis
Dr Duncan Wyncoll
Understanding the epidemiology of pneumonia and the vital role of susceptibility testing
Dr Andrew Dodgson, Consultant Microbiologist, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK
Challenges in the treatment of HAP*/VAP† and CAP‡
Professor Antoni Torres, Professor of Medicine at the Faculty of Medicine, University of Barcelona and Chief of the Respiratory Intensive Care Unit of the Hospital Clínic of Barcelona, Barcelona, Spain
Panel discussion and Q&A
(*Hospital-acquired pneumonia, †Ventilator-associated pneumonia, ‡Community-acquired pneumonia)
Supported by Pfizer
13:45 – 14:15
LUNCH, Exhibition & Poster Viewing
13:15 – 14:15
TB and other mycobacteria
Dr Patrick Lillie, Hull and Dr Nikhil Premchand, Northumbria
Antibiotics and resistance
Mr Adel Sheikh, Portsmouth and Dr Gavin Barlow, Hull
13:15 – 14:05
Challenging patients with skin infections; effective management in the face of winter pressures
Re-engineering the complex infection patient pathway for the good of all
Sam Lippett, Lead Anti-Microbial Pharmacist, Brighton & Sussex University Hospitals NHS Trust
SSTI – not so simple
Dr Wael Elamin, Consultant Microbiologist, Mid Essex Hospital Trust
Supported by Correvio
14:15 – 15:30
Plenary Session: Resistance surveillance: trends and benefits of a sentinel surveillance programme
Professor David Livermore, Professor in Medical Microbiology, Norwich Medical School, University of East Anglia
Professor Alasdair MacGowan, Consultant Microbiologist, North Bristol NHS Trust
BSAC surveillance of Gram-positive bacteria: a review of non-susceptibility
Dr Carolyne Horner, Senior Clinical Affairs Officer, British Society for Antimicrobial Chemotherapy
Abstract - BSAC surveillance of Gram-positive bacteria: a review of non-susceptibility
Collection of surveillance data is crucial for our understanding of antibiotic resistance trends.
The British Society for Antimicrobial Chemotherapy (BSAC) Bacteraemia Resistance Surveillance Programme has monitored the antimicrobial susceptibility in the major organisms causing clinically significant bacteraemia in the UK and Ireland since 2001.
Consecutive isolates causing bacteraemia are collected, and the Gram-positive pathogens comprise Staphylococcus aureus, coagulase-negative staphylococci, Streptococcus pneumoniae, Enterococcus spp., β-haemolytic streptococci, α-/non-haemolytic streptococci. The number of laboratories participating in the surveillance has varied ranging from 24 to 40, each collecting 7-20 isolates/species per year. Minimum inhibitory concentrations are determined centrally by BSAC agar dilution and interpreted using EUCAST breakpoints.
Susceptibility trends for each of the pathogens (2013-2017) will be presented and discussed.
BSAC surveillance of Gram-negative bacteria: a review of non-susceptibility
Professor David Livermore, Professor in Medical Microbiology, Norwich Medical School, University of East Anglia
Abstract - BSAC surveillance of Gram-negative bacteria: a review of non-susceptibility
Resistance in Gram-negative bacteria is a global concern, with rising rates in many countries and with cephalosporins, fluoroquinolones and carbapenems all undermined in turn. Nevertheless, for many key resistances – including to cephalosporins, fluoroquinolones and aminoglycosides for Enterobacteriaceae and P. aeruginosa – the BSAC Bacteraemia Surveillance shows that percentage resistance rates in the UK and Ireland are no higher than a decade earlier. Carbapenemase-producing Enterobacteriaceae remain on the borders of the surveillance’s detection, with just 0-4 examples per annum among c. 1250 Enterobacteriaceae collected.
Scratch beneath the surface however, and there are few reasons for complacency First, as shown a decade ago with the rise of CTX-M ESBLs, such periods of stability can end with sudden, dramatic rises in resistance rates as a new gene proliferates. Second, whilst percentage rates are stable, the annual tally of bacteraemias due to Gram-negative pathogens continues to rise, increasing the burden of resistance. Third, resistance to penicillin-inhibitor combinations is rising, with that for co-amoxiclav in E. coli – the commonest agent in bacteraemia –now standing at 51%! Fourth, declines in cephalosporin, fluoroquinolone and aminoglycoside resistance, which were apparent for E. coli, Klebsiella and Enterobacter around the end of the last decade, when the UK greatly reduced cephalosporin and fluoroquinolone use, have now ceased or, for E. coli and Klebsiella, reversed. Lastly, resistance rates among Gram-negative opportunists may be higher outside bacteraemia – those for P. aeruginosa from acute lower respiratory infections are around double the bacteraemia rates.
Non-susceptibility of bacterial pathogens causing hospital-onset pneumonia in the UK and Ireland, 2008-2016
Miss Alicia Russell, PhD Student in Molecular Microbiology, John Innes Centre, Norwich
Abstract - Non-susceptibility of bacterial pathogens causing hospital-onset pneumonia in the UK and Ireland, 2008-2016
The British Society for Antimicrobial Chemotherapy (BSAC) Respiratory Resistance Surveillance Programme has monitored the antimicrobial susceptibility of isolates causing hospital-onset (HO-) lower respiratory tract infections (LRTI) since 2008/2009. Antimicrobial susceptibilities of Enterobacterales, Acinetobacter species, Pseudomonas species and Staphylococcus aureus collected from centres across the UK and Ireland have been determined by the agar dilution method and using EUCAST breakpoints, the proportion of all isolates susceptible, intermediate and resistant to different antimicrobial agents have been determined for the collection period between 2008 and 2016. Susceptibility trends for each bacterial group over this time, along with associated resistance mechanisms, will be presented and discussed in this talk.
Surveillance data are an important resource to inform treatment guidelines. A review of available NHS Trust and international guidelines for antimicrobial treatment of hospital-associated pneumonia (HAP) was completed. A summary of the results will be presented, including the finding that doxycycline is one of the most commonly prescribed antibiotics for treatment of HAP amongst the NHS guidelines studied, despite its coverage being inappropriate for the largely Gram-negative aetiology of HAP.
The impact of antibiotic use on antimicrobial resistant infections
Dr Susan Hopkins, Healthcare-Associated Infection & Antimicrobial Resistance, Deputy Director, National Infection Service, Public Health England
Abstract - The impact of antibiotic use on antimicrobial resistant infections
The spread of antimicrobial resistance (AMR) is an important health threat, as it means that antibiotics may no longer work when needed to treat infections. Antibiotics are unlike other drugs used in medicine, as the more we use them the less effective they become. Equally unlike other challenges, such as climate change, tobacco use and obesity, elimination of the problem is not possible, as we require effective antibiotics to treat serious infections.
Antibiotic resistance is not a new challenge, but has been around for many decades. In the past, AMR was not regarded as a major problem as new antibiotics were regularly developed and could be used to treat infections caused by bacteria resistant to drugs already widely in use. However, we have reached the situation where patients with gram-negative urinary tract infections are frequently hospitalised as no effective oral antibiotics exist to treat their infections. Therefore efforts must be made to ensure we understand the impact of antibiotic use on bacteria and develop and deliver interventions to improve appropriate and necessary antibiotic use.
This presentation will highlight the impact of antibiotic use on AMR and changes to the incidence of infection when the impact of selective pressure of certain antibiotics is altered.
Q & A
Chair + Speakers
Supported by BSAC
15:30 – 16:15
J.D. Williams Lecture
Dr Albert Mifsud, BIA President
Fungi and human health: The good, the bad, and the unknown
Professor Tom Rogers, Professor of Clinical Microbiology, Trinity College Dublin & St James’s Hospital
Abstract - Fungi and human health: The good, the bad, and the unknown
Evidence for the existence of fungi on the Earth dates back more than 500 million years, long pre-dating humans. They have evolved from motile aquatic eukaryotes to being land-based with filamentous growth which facilitates propagation through aerial dispersal of spores.
In the past century the most notable contribution of fungi to human health has been through Fleming’s discovery of penicillin produced by Penicillium sp. They also play a critical role in our biosphere, recycling nutrients through digestion of dead and decaying matter, having symbiotic interactions with other living organisms, and are important in production of foodstuffs, domestic and medicinal products, as well as in cancer research.
As many as 5 million fungal species may exist in nature yet only a small number are known to be human pathogens. Fifty years ago medical practice would have viewed fungal infections – predominantly due to Candida or Aspergillus spp. – as rare events but their profile has changed in modern medicine through increasing populations of at-risk immunocompromised and critical care patients, and with international travel. The overall incidence of fungal infections is likely underestimated and there have been dramatic reports of Cryptococcus gattii infections originating in British Columbia, and newly identified Candida auris causing outbreaks in critical care, all giving recognition to fungi as emerging human pathogens.
With only three main antifungal drug classes for systemic therapy, and a limited number of new drugs on the horizon, a major concern is antifungal drug resistance. In the case of Aspergillus fumigatus multi-triazole drug resistance appears to have been an unintended consequence of widespread agricultural use of triazole fungicides.
Ribosomal gene and next generation sequencing have facilitated changes in fungal taxonomy as well as enhancing the investigation of fungal outbreaks that have occurred across continents. Now, ‘deep’ sequencing techniques are revealing new evidence for the importance of fungi in microbiomes both in health and disease. Examples come from recent intestinal mycobiome analysis in Crohn’s disease patients suggesting complex interactions between Candida tropicalis, bacterial species and biofilm production, and evidence for a pathogenic role in bronchiectasis. These new technologies may provide greater insights into the interplay between microbial communities and fungus-host interactions.
A final thought is: what impact might climate change have on fungal pathogenesis? Already, amphibian populations around the World are being decimated by the fungal disease chytridiomycosis which may link to this. Should we humans be fearful?
16:15 – 16:45
COFFEE, Exhibition & Poster Viewing
16:15 – 16:45
Public health and epidemiology, ICP + OPAT
Dr Albert Mifsud, London and Dr Mark Melzer, London
16:45 – 17:15
Scientific Free Papers – Room A
Dr Ray Fox, Consultant in Infectious Diseases, Queen Elizabeth University Hospital &
Dr Mark Melzer, Consultant in Microbiology & Infectious Diseases, Barts Health NHS
Evaluation of antifungal treatment effectiveness in C. auris candidemia
Dr Nuria Tormo, Clinical Microbiologist, Consorcio Hospital General Universitario, Valencia, Spain
Abstract - Evaluation of antifungal treatment effectiveness in C. auris candidemia
Introduction: Multi-drug resistant C. auris has emerged as a cause of insidious hospital outbreaks and complicated infections. Clinical severity and antifungal resistance lead to high mortality rates and presence of frequent complications. The aim of this study is to evaluate the effectiveness of the antifungal treatment of C. auris candidemia.
Methods: A descriptive study was conducted with patients microbiologically diagnosed by C. auris candidemia during 10-months period (14/10/2017-07/08/2018) in a 508-bed tertiary institution belonging to the Spanish National Public health Service.
Demographic information, patient type (critical, medical or surgical), persistence of candidemia after initiation of antifungal treatment, antifungal treatment administered and duration, hospital stay and Critical Care Unit (CCU) stay, complementary diagnostic tests, consultations to Infectious Diseases (ID) and mortality were collected.
Data were analyzed with SPSS 24.0 software.
Results: Fifteen patients (13 men and 2 women) with a median age of 57 (34-80) years. At the end of the study, five (33%) were still admitted to the hospital and two (13%) were still in the CCU. All patients had been admitted to the CCU before or during candidemia. Ten (67%) were critical patients (surgical), four (27%) had medical pathology and one (7%) was non-critical surgical patient. The median hospital stay was 64 (29-275) days and the median CCU stay 29 (1-58) days. Seven (47%) were colonized prior to candidemia.
All were treated with echinocandins since the diagnosis. Two were still in treatment at the end of the study. Eleven (73%) were treated with anidulafungin, three (20%) with caspofungin and one with caspofungin followed by anidulafungin. One patient changed from anidulafungin to liposomal amphotericin B (LAB) and seven (47%) were concomitantly treated with echinocandins and LAB, with a delay of onset with respect to the echinocandin of 4 (1-30) days. The median duration of treatment was 15 (4-43) days with echinocandins and 7 (2-39) days with LAB.
Candidemia persisted in seven (47%) patients. Four of them received combined treatment with echinocandins and LAB, another patient changed to LAB and two continued with the same equinocandin. All evaluable patients achieved clinical and microbiological response.
Transthoracic echocardiography was performed in ten (67%) patients and none had endocarditis. Examination of the fundus was negative for chorioretinitis in nine (60%) who performed the test. Three (20%) patients developed a peripheral vascular thrombosis, all with favorable evolution. ID were consulted in 9 (60%) of the episodes.
Three patients died. Two were previously colonized, but none had persisted candidemia or received combination treatment. All patients who received combination treatment survived although 4/7 (57%) had persistent candidemia.
Fischer’s exact test could not established a statistically significant relationship between mortality and previous colonization. The relationship with combined treatment and persistent candidemia was not evaluated because none of deads had these conditions.
Discussion: The CDC recommends treatment with echinocandins and change to LAB in those patients without clinical response or with persistent funguemia more than 5 days. Many clinicians use combination treatment in severe patients or in refractory cases, since the combination may be synergistic.
In our study, one patient with persistence candidemia changed from anidulafungin to LAB and four added concomitant treatment with LAB. The sample is short and the mortality may be due to many causes not analyzed in this study, so no statistically significant relationships have been found.
The absence of ocular complications, which are more frequent in candidemias due to C. albicans, is notorious.
Despite the resistance of C.auris to antifungals, the early use of echinocandins in patients with candidemia and its association with LAB in refractory cases is effective in critically ill patients.
Secrets of the hospital underbelly: metagenomics of AMR in hospital sewage
Dr Meghan Perry, Clinical Lecturer in Infectious Diseases, University of Edinburgh and NHS Lothian
Abstract - Secrets of the hospital underbelly: metagenomics of AMR in hospital sewage
Introduction: An important aspect of research into antimicrobial resistance is understanding its ecosystem. It is well established that hospital wastewater can contain multidrug resistant organisms but no previous attempt has been made to correlate the resistance in sewage with antimicrobial usage within the hospital. This work aims to study whether resistance gene abundance levels in sewage can reflect clinical activity within the hospital.
Methods: Using composite samplers sewage was collected over a 24 hour period from 8 collection points at the Western General Hospital, Edinburgh and simultaneously from community sewage works. High throughput shotgun sequencing was performed using Illumina HiSeq4000 and reads analysed using the online pipeline MGmapper and Resfinder. The results were analysed with databases of hospital antimicrobial usage and clinical isolates using R.
Results: Each collection point, as a representation of a range of medical and surgical specialties, had different patterns of antimicrobial use. There was variance in resistance gene abundance and diversity in sewage between each collection point and between hospital and community sewage samples. Using a generalised liner mixed effects model accounting for random effects of observation, collection point and antimicrobial class, we saw a clear relationship between both length of stay and antimicrobial usage at the class level on resistance gene abundance in hospital sewage. No relationship between resistance in clinical isolates and resistance gene abundance in sewage was found.
Discussion: This is the first representation of how resistance gene abundance in hospital sewage reflects hospital antimicrobial usage and demonstrates that antimicrobial usage is a major driver of antimicrobial resistance gene outflow from the hospital into the sewage environment. It further emphasises the importance of minimising antimicrobial use to minimise faecal carriage of AMR and may have implications for infection control.
Risk factors for resistant bacteraemia in patients with suspected sepsis: cohort study using linkage of routinely collected national data
Mr William Malcolm, Pharmaceutical Advisor, HAI and Infection Control Group, Health Protection Scotland
Abstract - Risk factors for resistant bacteraemia in patients with suspected sepsis: cohort study using linkage of routinely collected national data
Introduction: Essential to initial treatment of suspected sepsis is early administration of appropriate antibiotics. Initial antibiotic treatment is usually empirical and choice based on local prescribing guidelines. These guidelines generally do not take account of patient characteristics and the likelihood of antibiotic resistance in individual patients. The empiric regimen for initial treatment of sepsis on admission to hospital varies amongst NHS boards in Scotland but the most commonly recommended combination is amoxicillin plus gentamicin plus metronidazole. We aimed to characterise risk factors for having a bacteraemia non-susceptible to this regimen among patients who have a blood culture taken on admission to hospital.
Methods: Blood culture and susceptibility data were obtained from the Health Protection Scotland Electronic Communication of Surveillance in Scotland (ECOSS) dataset. Patient-level hospitalisation data were obtained from National Services Scotland (NSS) General/Acute Inpatient dataset (SMR01) and community NHS prescriptions from NSS Prescribing Information System (PIS). In Scotland all individuals have a patient identifier, the Community Health Index (CHI) number, which enables record linkage across multiple datasets. Public Benefit and Privacy Panel approval to link data was obtained.
We identified patients aged ≥16 years with a blood culture result in ECOSS from 01/01/2016 to 30/09/2017. We defined suspected sepsis as having had a blood culture taken, irrespective of result. Using culture and susceptibility results, positive cultures were defined as non-susceptible if the isolate was resistant to both amoxicillin and gentamicin, or resistant to metronidazole. Susceptible organisms and negative blood cultures were combined to form the comparator group.
Where more than one sample was taken during a hospital admission, de-duplication based on the European Centre for Disease Control protocol for the submission of data to the European Antimicrobial Resistance Surveillance Network was conducted. Only one sample per admission, the ‘most resistant’ sample, was included in the analysis.
Blood culture data were linked using CHI to SMR01 and PIS to determine demographics, co-morbidity and previous antibiotic exposure. Samples taken from day three onwards were excluded. Multivariable logistic regression was undertaken to determine risk factors for non-susceptibility.
Results: A total of 102,760 samples were analysed: 1,064 (1.0%) were non-susceptible to the empiric regimen. Of those, 839 (79%) were non-susceptible to amoxicillin and gentamicin and 225 (21%) to metronidazole.
Multivariable logistic regression found increasing age associated with non-susceptibility. Those aged ≥85 years were 3.57 (95%CI 2.15-6.39) times more likely to be non-susceptible compared to those aged 16-24, as were males (OR 1.24; 95%CI 1.10-1.40) and those residing in a care home (OR 2.01; 95%CI 1.66-2.43). Increasing comorbidity was associated with increased likelihood of non-susceptibility – those with a Charlson score of ≥5 were 1.44 (95%CI 1.15-1.79) times more likely to be non-susceptible than those with a score of zero and those with ≥4 previous hospitalisations were 2.61 (95%CI 2.11-3.22) times more likely than those with no previous hospitalisations.
Exposure to any antibiotic in the community in the previous three months was found to be associated with non-susceptibility and those previously prescribed an antibiotic were 1.20 times (95%CI: 1.06-1.37) more likely to be non-susceptible.
Discussion: Risk factors for non-susceptibility to the commonly used antibiotic regimen for sepsis have been characterised. Exposure to any antibiotic in the three months prior to admission is a risk factor for non-susceptibility; next we will examine cumulative exposure to all antibiotics and to specific antibiotics in the three, six and 12 months prior to blood culture. Following this, we aim to develop risk prediction models as the next step towards developing a clinical decision support tool to help clinicians identify patients at risk of being non-susceptible to the commonly recommended empirical treatment for sepsis in NHS Scotland.
Supported by BIA
16:45 – 17:15
Scientific Free Papers – Room B
Dr Anne Tunbridge, Consultant in Infectious Diseases, Sheffield Teaching Hospitals & Dr Mike Kelsey, Consultant Microbiologist, Whittington Health, London
Cross-reactive CD8 T cell responses to Japanese encephalitis virus and dengue virus recognise Zika virus sequences and have anti-viral function
Dr Lance Turtle, Senior Clinical Lecturer in Infectious Diseases, University of Liverpool
Abstract - Cross-reactive CD8 T cell responses to Japanese encephalitis virus and dengue virus recognise Zika virus sequences and have anti-viral function
Introduction: The genus Flavivirus contains the most important arboviral pathogens of man, including dengue virus (DENV), yellow fever virus (YFV), Zika virus (ZIKV) and Japanese encephalitis virus (JEV). Flaviviruses are closely related and exhibit significant immunological cross-reactivity. This cross-reactivity has the potential to enhance disease, as with heterotypic DENV infection, or to ameliorate disease, such as JEV infection following DENV infection. Previous studies suggest a role for CD8 T cells in both protection and pathology in dengue, whereas in Zika and JE the available data suggest a protective role. CD8 T cell responses are readily generated by live flavivirus vaccines; T cell responses against flaviviruses are also cross-reactive and therefore vaccines that stimulate CD8 T cell responses may have more broadly protective effects.
The ZIKV outbreak in South America of 2015/16 therefore prompted us to examine whether CD8 T cell responses against DENV and JEV could recognise ZIKV, and whether they had anti-viral function. Including previous work on JEV conducted in South India as well in the UK, we have now mapped 30 peptide T cell epitopes or antigenic regions of JEV. Twenty-three (76.7%) of these peptides have > 70% identity with ZIKV (strain P243, isolated from a case of neurological disease in Recife, Brazil), and three epitopes have 100% sequence identity.
Methods: We studied three individuals with known responses against DENV and JEV that we had recruited previously, and 26 newly recruited subjects. We separated PBMC and screened for T cell responses against JEV and DENV peptide libraries by IFNγ-ELISpot assay, and measured neutralising antibody against DENV1-4, JEV and ZIKV by viral plaque reduction assay. A flow cytometric T cell killing assay was used to compare the cytotoxic potential of DENV, JEV and ZIKV responses.
Results: Seventeen of 29 subjects (59%) had dengue exposure, either diagnosed clinical illness or residence in a dengue endemic area and detectable neutralising antibody. Two subjects had recovered from JE, seven had received flavivirus vaccines (JE and/or yellow fever) and two were negative controls without known flavivirus exposure. Of the 26 newly recruited subjects, 12 had positive IFNγ-ELISpot assays. In total to date, 9 minimal CD8 T cell epitopes either have been shown to cross-react with ZIKV variants in ex-vivo IFNγ assays (5 epitopes, every case tested), or were identical in sequence with ZIKV (4 epitopes). Only one subject had ZIKV neutralising antibody, indicating that the majority of subjects were not ZIKV exposed. Short-term T cell cultures expanded to DENV/JEV peptides could recognise ZIKV variant peptides equally well, further demonstrating that these responses are part of a single cross-reactive pool of CD8 T cells, and do not represent a distinct population of responding cells. Short-term T cell cultures expanded to DENV/JEV peptides lysed autologous target cells labelled with ZIKV peptides, indicating that CD8 T cells primed to DENV or JEV could recognise and kill ZIKV infected cells, mediating anti-viral function.
Discussion: In flavivirus endemic areas, antibody responses can be sub-optimal due to interference from circulating flaviviruses, antigenic sin, and unknown factors. Recent experience with the dengue vaccine Dengvaxia also lend weight to the notion that flavivirus vaccines aimed at generating antibody responses alone may be insufficient. Our findings imply that inclusion of CD8 T cell antigenic determinants into novel flavivirus vaccines may be beneficial and is worthy of consideration in vaccine design.
Spatial dynamics of ground-level malaria prevention; tackling severe paediatric malaria in Sierra Leone through motorcycle mapping and community empowerment
Dr Edward Monk, Clinical Fellow in Infectious Diseases, Manchester University NHS Foundation Trust
Abstract - Spatial dynamics of ground-level malaria prevention; tackling severe paediatric malaria in Sierra Leone through motorcycle mapping and community empowerment
Introduction: Malaria is a leading cause of paediatric death in Sierra Leone. Rurally, bed net distribution is advertised through vehicle-mounted announcements with ticket distribution at village level. These tickets are subsequently exchanged in person for bed nets at Primary Health Units (PHUs) during ‘Wel Bodi’ week: the final destination of bed net distribution is unrecorded. Records at Nixon Memorial Methodist Hospital in Segbwema, Njaluahun chiefdom, Kailahun district, Sierra Leone, were hand-searched in May 2017 and rarely resulted in reliable inpatient origin or primary diagnosis documentation. We report the implementation of an innovative public health tool from July 2017, designed to serve the staff of Nixon Memorial Methodist Hospital and the students of its affiliated nursing school, and example its utilisation through the design of a malaria primary prevention project throughout Njaluahun chiefdom that is currently in progress.
Methods: Local community members were recruited and trained to survey the 1,950 villages in the 11 chiefdoms served by Nixon Memorial Methodist Hospital, using OpenDataKit and OsmAnd. Surveyors were paired with local motorcycle drivers to reach all villages identified by satellite imaging and ascertain each community’s definition of their village’s name/names (including alternative spellings), district, chiefdom and section. The main outcomes were a comprehensive map (OpenStreetMap) and ‘Gazetteer’ production to ascertain patient origin on hospital arrival through a step-wise record of patient origin, linked to true GPS coordinates. Improved coding was addressed by implementing a specially designed ‘stamp’, added to clinical notes on patient arrival by the hospital registrar in order to 1) focus the clinician’s attention to identify a primary diagnosis in relation to the patient’s presentation, 2) provide a standardised area to record the primary diagnosis and 3) allow a platform for the hospital registrar to question illegible or ambiguous entries.
Ongoing: Bed net distribution will be mapped comprehensively from points of distribution in June 2019, using a Gazetteer (identical to that currently used in the hospital) at each of the 14 PHUs within Njaluahun chiefdom. This will allow village-level comparisons between severe malaria incidence in under-fives (currently being audited at Nixon Memorial Methodist Hospital) and the proportion of the under-five population receiving nets in the 134 villages of Njaluahun chiefdom, calculated from local surveying and satellite counts of dwellings/population-projections.
Results: Twelve months after initial implementation, patient origin is continuing to be recorded reliably and sustainably with ongoing stamp record of primary diagnosis and minimal external influence. Villages with multiple names, or the same name are being successfully coded to GPS coordinates. A ‘dashboard’ has been designed and implemented to visualise diagnoses both spatially and temporally in a manner accessible to end-users (hospital staff and nursing school students). The initial mapping effort has also provided a proof of concept, allowing the development of a methodology ´playbook´ of workflows and product-modelling. This has been utilised in further humanitarian efforts in both Tanzania and Uganda.
Discussion: The hospital´s nursing school (with a student-body of 300) continues to provide community outreach services, including drives combating malaria, across Njaluahun chiefdom. Recording village-level bed net distribution and paediatric severe malaria caseload offers this organisation, participating in community outreach, a tailored dataset to ask “why is this village having paediatric cases of severe malaria”. We intend for this dataset to not only direct community outreach project planning but also stimulate public health and primary prevention discussion within the nursing school student body, strengthening understanding that can be taken with community nurse graduates as they relocate within the country for their future roles. In addition to this, multiple sub-Saharan communities are benefiting from our proof of concept, utilising Android technology now widely available across the continent.
Hospital-associated influenza transmission and its management in a UK teaching hospital
Dr Ben Warne, Specialty Registrar in Infectious Diseases, Cambridge University Hospitals
Abstract - Hospital-associated influenza transmission and its management in a UK teaching hospital
Introduction: Seasonal influenza is a major cause of morbidity. However, its impact and potential for transmission in secondary care are poorly understood. In this study we combine clinical, epidemiological and genomic data to investigate the burden of influenza-associated morbidity and the extent of transmission within a UK teaching hospital. We also describe changes in clinical practice implemented in response to suspected nosocomial outbreaks.
Methods: All patients attending Cambridge University Hospitals with influenza A detected by PCR between August 2016-April 2017 were included. An epidemiological investigation was conducted in parallel with genetic analysis of samples to develop independent evidence of transmission pathways. Algorithms were developed to interrogate ward movement data to detect co-location of a potentially infectious patient with a susceptible one. A ward-time cluster was defined as a sequence of two or more patients on the same ward where there was an overlap of the intervals of infectiousness and of susceptibility. Genome sequencing was attempted using RNA extracted directly from samples. Whole and partial genome sequences were included in phylogenetic analyses to infer transmission networks. Ward movement, prescribing and laboratory data were derived from electronic records for all confirmed influenza cases for 2016-17 and compared to a second cohort from August 2017-May 2018. Further clinical data were manually abstracted, including judgement of whether infection was community- or hospital-acquired based on symptom duration and length of stay at time of swabbing.
Results: In 2016-17 influenza A was diagnosed in 326 patients, median age 76 years. Of these, 313 (96.0%) were admitted to hospital; 98/313 (31.3%) infections were acquired during the admission. All-cause mortality during the admission was 10.2%; 11/32 deaths were associated with hospital-acquired influenza.
The majority of inpatients (58.8%) were linked in 33 ward-time clusters. Whole genome sequences were available for 180/313 samples and partial genomes for a further 29 samples. Using whole genomes, 64.4% of isolates were phylogenetically linked within 22 putative clusters; this rose to 73.8% within 31 clusters using partial genomes. Combining epidemiologic and genomic data demonstrated that 43/61 (70.5%) hospital-acquired cases fell within 7 transmission networks (range 2-22 patients) across 10 wards. Additionally, we identified clusters imported into hospital, including transmission in 3 outpatient units and 3 care homes.
In response to influenza transmission, programmes of staff education and reviews of influenza management were undertaken prior to the 2017-18 winter, when 763 further influenza cases were identified (48.9% influenza A, 51.1% influenza B). Isolation of patients on admission rose from 50% of influenza cases in 2016-17 to 79% in 2017-18. Median time from admission to sample collection for community-acquired cases fell from 9.7 to 5.2 hours. Median time from admission to first antiviral dose fell from 45.2 to 10.1 hours.
Discussion: We have demonstrated that influenza is an important but poorly recognised cause of morbidity and mortality in secondary care. A substantial proportion of influenza cases were acquired during the patient admission and are therefore likely to be amenable to changes in infection control measures. We have demonstrated that better use of existing resources can lead to considerable improvement in patient management.
Combining genomic and epidemiologic approaches provides a powerful and tractable tool for assessing influenza transmission, a critical step in guiding infection control practices. However, these approaches also highlight the complexity of transmission: their individual use can over-estimate patient clustering, while combined they reveal gaps in networks, which may represent asymptomatic or untested patients, healthcare workers and hospital visitors.
Although we have studied a single centre, similar transmission is likely to occur throughout secondary care. Responding to this problem requires the engagement of many disciplines, utilising a range of approaches to better understand, manage and prevent transmission.
Supported by BIA
17:15 – 18:15
Symposium on NICE Guidelines on Sore Throat, Otitis Media and Sinusitis
Dr Mitul Patel, Consultant Microbiologist, Birmingham Women’s and Children’s NHS Foundation Trust
Dr Tessa Lewis
GP & Medical Advisor, NICE Management of Common Infections Committee Chair, Blaenavon Medical Practice, Wales
Dr Kieran Hand
Consultant Pharmacist Anti-Infectives, University Hospital Southampton
Dr Susan Hopkins
Deputy Director, National Infection Service Public Health England
Supported by NICE Managing Common Infections Committee
Abstract - Symposium on NICE Guidelines on Sore Throat, Otitis Media and Sinusitis
In 2016, NICE was commissioned by the Department of Health and Social Care to produce clinical syndrome specific guidelines for managing common infections, with the aim of guiding appropriate use of antimicrobials and minimising antimicrobial resistance. A standing committee of experts is producing the guidelines and is working closely with Public Health England. The members of the committee will present and discuss the first set of published guidelines on upper respiratory tract infections. https://www.nice.org.uk/about/what-we-do/our-programmes/nice-guidance/antimicrobial-prescribing-guidelines
17:15 – 18:15
Paediatric Clinical Cases and Stewardship
Dr Sanjay Patel, Consultant in Paediatric Infectious Diseases and Immunology, Southampton Children’s Hospital &
Dr Stephane Paulus, Consultant in Paediatric Infectious Diseases, John Radcliffe Hospital, Oxford
Children are not just small adults (!) – interactive cases
Dr Sanjay Patel & Dr Stephane Paulus
Supported by BPAIIG
Abstract - Children are not just small adults (!) - interactive cases
17:15 – 18:15
Haematological Infections – BMT High Risk Patients
Dr Erin Hurst, Consultant Haematologist, Northern Centre for Cancer Care, Newcastle
Immunotherapy for viral infections
Dr Mary Slatter, Consultant in & Clinical Programme Director Paediatric HSCT, Great North Children’s Hospital
Modern management of CMV with new agents
Professor Per Ljungman, Professor of Heamatology, Karolinska Institutet, Sweden
Supported by BIA
Abstract - Modern management of CMV with new agents
CMV remains an important pathogen especially in transplant patients. The therapy options have until now been limited to drugs although being effective having significant toxicity issues. These drugs include ganciclovir, valganciclovir, foscarnet, and cidofovir. Over the last decade there have been several agents in clinical trials both antiviral drugs and vaccines. Most studies have been performed in allogeneic hematopoietic stem cell transplant (HSCT) recipients since this population is at high risk for CMV associated complications.
Letermovir is an inhibitor of the CMV terminase complex and is specific for human CMV with no effect on other human or animal herpesviruses. It is available both as an oral and an iv formulation and was studied as prophylaxis in allogeneic HSCT recipients both in phase II and phase III. The primary endpoint of the phase III randomized, placebo-controlled study was clinically significant CMV infection (CS-CMVi) defined as CMV disease and need for preemptive therapy. Letermovir given until 14 weeks after HSCT were able to significantly reduce CS-CMVi at 24 weeks after HSCT. The toxicity was limited without significant bone marrow or renal toxicity. Furthermore, all-cause mortality was decreased in the letermovir arm at week 24 after HSCT. Today letermovir is licensed for prophylaxis against CMV in HSCT patients in Europe. There is currently no data on the use of letermovir for preemptive therapy or treatment of CMV disease. There is also very limited data regarding the risk for development of resistance.
Maribavir is an oral inhibitor of the UL97 kinase and has effects against CMV also against ganciclovir resistant strains. It has in vitro effect also against EBV but not against other human herpesviruses. It was studied in a dose of 100 mg BID as prophylaxis both in HSCT and solid organ transplant patients and failed to meet the primary endpoint of preventing CMV disease. More recently it has been used for therapy of resistant and refractory CMV infections in a phase II study including three different dose levels; 400 mg BID, 800 mg BID, and 1200 mg BID. Viral clearance at 6 weeks were with all groups combined 66.7% and similar between the dose levels. Phase III studies are ongoing and it is currently not licensed in Europe.
Brincidofovir is a lipid conjugate of cidofovir that is orally bioavailable having broad-spectrum antiviral effects. It was successful in preventing CMV in phase II but failed to reach the primary endpoint of CS-CMVi in phase III.
Additional studies are needed to establish the place of the new antiviral agents for management of CMV in other patient populations that allogeneic HSCT recipients.
18:15 – 19:00
Hospital and Ventilator Associated Pneumonia: AGAR, PCR,
Dr Anne Tunbridge, Consultant in Infectious Diseases, Sheffield Teaching Hospitals
Metagenomics – Which is Right?
Dr Vanya Gant, Divisional Clinical Director for Infection, University College London Hospital
GALA Festival Evening
Marquee at SAGE
Admission by pre-booked ticket only