FEDERATION OF
infection societies
CONFERENCE 2018

13th – 15th November 2018 | Sage Gateshead – Newcastle

FEDERATION OF
infection societies
CONFERENCE 2018

13th – 15th November 2018 | Sage Gateshead – Newcastle

FEDERATION OF
infection societies
CONFERENCE 2018

13th – 15th November 2018 | Sage Gateshead – Newcastle

Posters

TB AND OTHER MYCOBACTERIA – Poster Nos. 189-197

189
It’s all in the name (species)

Abstract - 189

Poster 189

It’s all in the name (species)

Julie Samuel
Newcastle upon Tyne Hospitals NHS Foundation Trust

Introduction: 66 year old man presented to the haematology department in March 2012 with pancytopenia. A diagnosis of myelodysplasia /chronic myelomonocytic leukaemia was made and he initially did not require any specific treatment for this. He was monitored in the clinic for several years and had few problems with his blood condition but by August 2016 the situation began to change. A repeat bone marrow examination at that time showed an increase in the number of leukaemia cells indicating progression of his disease. He was commenced on azacytidine treatment and referred for consideration of a stem cell transplant.

He proceeded with MUD transplant in February 2017 . He developed graft versus host disease requiring steroids fairly early on post – transplant as well as an episode of neutropenic sepsis. He recovered from these complications and was discharged a month later.Subsequently a number of problems developed: there was reactivation of CMV infection and worsening abnormalities of kidney and liver function.  By mid April however he began to deteriorate with increasing concern about the level of CMV in his blood and worsening diarrhoea due to GvHD. He was admitted again in April 2017 to have these complications treated and discharged within 2 weeks. Admitted again as an emergency in May 2017, increasingly short of breath and weak for the preceding few days and had experienced high fevers and rigors. He was started on broad spectrum antibiotics. He began to develop worsening liver failure and pneumonia.

He initially improved on the ITU but then gradually became more oxygen dependent with worsening lung function. He remained deeply jaundiced and his liver function did not improve. Renal function also deteriorated . Due to ongoing concerns with multi organ failure, a decision was made not to institute further invasive support measures and patient unfortunately passed away within a month of this final admission.

Methods: Mid April Hickman line blood culture – flagged positive but no organism seen on gram stain. Day 4: faint growth on FAA and chocolate agar, gram positive beaded bacilli. Day 5 : MALDI ID available, Auramine stain positive. Isolate referred to Reference lab for formal identification and sensitivities. 2 weeks later final ID received. Blood cultures continued to remain positive with the same organism till a week before patients death.

Discussion: When blood culture first flagged up positive in April , no treatment was initiated other than line removal as patient remained clinically well.

The final admission in May was attributed to systemic M abscessus infection and quadruple therapy was commenced.

Proposed cause of death 1a. Systemic infection with mycobacterium abscessus 1b. Immunosuppression following haemopoietic stem cell transplant 1c. Progressive myelodysplasia/chronic myelomonocytic leukaemia.

Key lessons learnt:

  • Delay in getting a formal identification  significantly impacted patient’s management.
  • Significance of collecting peripheral and line blood cultures in parallel
  • Line associated infection with M. abscessus led to serious and life threatening complications in the bone marrow transplant recipient.
  • Was Hickman line truly the source of M abscessus?

190
Skin infection with Mycobacterium szulgai: a successful but complicated treatment

Abstract - 190

Poster 190

Skin infection with Mycobacterium szulgai: a successful but complicated treatment

Jemima Horsley Downie1, Han Davidson2, Ali Robb1, Suren Kanagasundaram1, Ewan Hunter1
1Newcastle upon Tyne Hospitals NHS Foundation Trust. 2Newcastle upon Tyne Hospitals Pharmacy Department

Introduction: This abstract highlights lessons learned in the management of Mycobacterium szulgai infection.

Methods: A 56 year old gentleman presented with a nodular, pustular eruption affecting the dorsum of both hands. This was first noticed during a prolonged ITU admission with sepsis. Past medical history included haemodialysis-dependent end-stage renal failure secondary to reflux nephropathy and metallic aortic and mitral valve replacements necessitating warfarin therapy, and peripheral vascular disease. Two previous renal transplants had failed, and he had been iatrogenically immunosuppressed for many years. At presentation he was on tacrolimus and prednisolone 10mg daily. Two months after his ITU admission he continued developing new subdermal nodules which subsequently ulcerated. At this point tacrolimus therapy was stopped and after review by dermatology a skin biopsy from the left arm was sent for histopathology and microbiology investigations.

Results: This demonstrated necrotising granulomatous inflammation with occasional elongated, slightly beaded acid fast bacilli, morphologically suggestive of an atypical mycobacterial infection. A mycobacterium species was isolated which was identified by the National Mycobacterial Reference Service in Birmingham using whole genome sequencing as Mycobacterium szulgai.

Discussion: Due to the slow-growing nature of M. szulgai, full antimicrobial sensitivities were not available until 4 months after the biopsy was taken. During this time the patient’s existing skin lesions became drier, very few new lesions developed, and he remained systemically well with no fevers or evidence of deep-seated or visceral infection. It was therefore decided not to start treatment until a definitive antimicrobial regimen could be chosen, based on full sensitivities. Various factors favoured avoiding rifampicin: concurrent warfarin therapy with labile INRs, glucocorticoid steroid dependence, and haemodialysis three times weekly affecting pharmacokinetics. Macrolide antibiotics are often considered the mainstay of non-tuberculous mycobacterial treatment and treatment with a clarithromycin-based regimen was planned. After close collaboration with the nephrologists and renal pharmacists, a schedule of clarithromycin 500mg BD, moxifloxacin 400mg OD and ethambutol 1.2g 4 to 6 hours pre-dialysis three times weekly was chosen.

Due to the risk of QTc prolongation with prolonged clarithromycin therapy, weekly ECGs were performed initially. The patient’s QTc increased from a baseline of 410 to 470milliseconds on treatment, and then plateaued. ECG monitoring was performed monthly thereafter.

After 1 month of treatment the existing skin lesions had dried up completely and no new lesions had formed. At 3 months the lesions had almost entirely disappeared, leaving only mild scarring. Five months into treatment the patient was admitted to accident and emergency after collapsing and was found to have a ventricular arrhythmia with a QTc of 543 milliseconds. His potassium on admission was raised at 6.4 mEq/L but not felt to have been the sole cause of the arrhythmia. His antibiotics were stopped by the admitting team and repeat ECGs 1-2 months later showed a normal QTc of <430 milliseconds.

Due to this gentleman’s good response to treatment, and clinical ambiguity regarding the cardiac arrhythmia and its cause, antimicrobial treatment was not re-started. Instead, clinical vigilance for new skin lesions or other signs of disseminated infection was maintained, and eight months after stopping antimicrobial therapy he remains well.

This case highlights the importance of ECG monitoring in patients taking drugs causing QTc prolongation. It also demonstrates success in treating M. szulgai localised to the skin using a short course of treatment (5½ months) with a non-rifampicin-based regimen, although may also highlight the difficulty in judging when systemic treatment is required, as opposed to natural control of infection by the patient’s immune system on recovering from sepsis and reduction in iatrogenic immunosuppression.

191
Using the UK multi-drug resistant tuberculosis (MDR-TB) monitoring guideline to improve the monitoring of patients in the community

Abstract - 191

Poster 191

Using the UK multi-drug resistant tuberculosis (MDR-TB) monitoring guideline to improve the monitoring of patients in the community

Phoebe Cross1, Toby Capstick1, Amy Robinson2, Hugh McGann1
1Leeds Teaching Hospitals. 2Bradford Teaching Hospitals

Introduction: The complex treatment regimens used to treat multi-drug resistant tuberculosis (MDR-TB) frequently result in significant drug toxicity, which may impact on adherence and adversely affect treatment outcomes. Despite this, monitoring for drug toxicity is often poorly executed.

An internal audit in our tertiary centre demonstrated frequent unintentional omissions of monitoring in the later stages of treatment. Therefore in 2015 we implemented the following interventions:

  • Personalised monitoring plans for each patient documented at the point of hospital discharge and updated in each subsequent clinic letter
  • Improved integration with ECG and audiometry departments, allowing testing to occur immediately prior to TB clinic follow-up appointments

Re-audit was performed after implementation of the changes and the results are presented here.

Methods: Data was collected for 19 patients diagnosed and treated for MDR-TB from 2011 to 2017. Adherence to monitoring standards, defined by the UK TB Drug Monographs (www.tbdrugmonographs.co.uk), were compared pre and post-intervention.

Results: Overall, performance was generally superior following the intervention. Improvements were seen in monthly audiometry (84% vs 19%), renal function monitoring (94% vs 69%) and three-monthly ECGs (80% vs 10%) . There was a decline in the monitoring of amikacin levels and no change in monthly thyroid function tests. Visual acuity was not indicated in the first cohort but was performed in 64% of the second cohort.

Discussion: Since 2015, the outpatient toxicity monitoring of MDR-TB patients at our centre has improved significantly in completing audiometry assessments, ECGs and renal monitoring which we attribute to the interventions described above as well as increased awareness of the UK TB Drug Monograph website. Six patients in the second cohort required a switch in medication due to toxicity concerns which highlights the importance of this project. On-going work to continuously improve monitoring include exploring the feasibility of in-house testing of amikacin levels, reviewing visual acuity practices and uploading ECGs and audiometry reports to our electronic records system to aid assessment of toxicity trends.

192
A vole lot of problems

Abstract - 192

Poster 192

A vole lot of problems

Anna Wild, Louise Berry, Pradhib Venkatesan
Infectious Diseases, Nottingham City Hospital

Introduction: A 40 year old lady with a background of sarcoidosis was referred following an MRI scan of her back. Her sarcoidosis had been diagnosed whilst having cardiac investigations for a SVT. Biopsies had shown well-formed granulomas, which were AFB smear negative. She was on prednisolone treatment. She had fairly good health prior to referral and lives in a rural area surrounded by fields and lakes. She had no unusual travel history or any known exposure to tuberculosis. 

Methods: She had been experiencing leg and back pains for 6 months before an MRI scan was performed and showed destruction of the L4 vertebra, with an adjacent right psoas abscess. A radiological biopsy of the psoas abscess yielded no positive microbiology, including after prolonged cultures and was 16s RNA PCR negative.

Previously sputum specimens had grown Staphylococcus aureus. She was empirically placed on a course of Flucloxacillin and Clindamycin for 6 weeks, but her inflammatory markers remained elevated with a CRP 44 and ESR 79. Her serum ACE was 44. Subsequently spinal surgeons agreed to perform an open biopsy of vertebral bone and the psoas abscess. However this did also not yield any pathogens or have specific histological features. 

In the meantime her chest deteriorated and became productive of green sputum. Her chest Xray showed new bilateral, upper lobe cavitation. Three sputum samples were AFB smear positive, M. tuberculosis complex PCR positive, with no rifampicin resistance gene mutations. She was commenced on anti-mycobacterial treatment. 

Discussion: Further results revealed an unusual causative organism. It transpired that the patient lived close to fields and lakes; her cat was catching house mice and outdoor rodents and bringing them into the house. This included dead voles. The patient was left to then clear up their entrails.

The organism, as per the literature, has been difficult to process for sensitivities in the laboratory. On treatment her sputum is now AFB smear and culture negative. Clinical experience of this organism is limited. 

Not all that is M. tuberculosis complex PCR positive is conventional M. tuberculosis.

193
TB outbreaks and contact tracing in congregate settings – a retrospective analysis in a large ethnically diverse urban environment – Birmingham UK

Abstract - 193

Poster 193

TB outbreaks and contact tracing in congregate settings – a retrospective analysis in a large ethnically diverse urban environment – Birmingham UK

Darryl Braganza Menezes1, Hanna Kaur2, Tom Marshall1, Emmanouil Tranos1, Gemma Hawthorne3, Pretin Davda3, Martin Dedicoat3
1University of Birmingham. 2Birmingham Chest Clinic. 3Heartlands Hospital, Birmingham

Introduction: We report the results of a 7-year retrospective study undertaken in a large, ethnically diverse UK city looking at TB outbreak events (defined as an active case of TB requiring a tracing episode involving multiple contacts) occurring in congregate settings (non-household locations with social/ occupational congregation of individuals).

Methods: A contemporaneously recorded, comprehensive patient database containing demographic data on patients (index and contacts), as per public health legislation was used to derive the data for this analysis. 

Results: Over a 7-year period of time (2010-2017) 183 different incidents were recorded occurring in 114 congregate settings. Locations for outbreak events varied with 98 (53%) index cases in educational establishments (including primary, secondary, college and university settings), 31 (17%) in health care settings (including hospital and community services as well as nursing homes) and 54 (30%) in business and social settings. There were 7612 contacts screened at 114 congregate settings out of which there were 50 active cases (0.67%) and 546 (7.17%) latent cases. Of note, there were 1735 (23%) of identified contacts who did not engage in screening.

Discussion: Our data demonstrate a large number of outbreak events occurring in an urban environment in the UK with multiple events occurring in the same location following contact tracing episodes. In addition to this, there remains a large number of contacts who do not engage in screening who possibly remain at risk of developing active TB. This raises the possibility of missed opportunities in contact tracing using current methodology and provides a basis to assess alternative approaches such as social network analysis, with a view to increasing up take of screening amongst exposed individuals.

194
To treat or not to treat

Abstract - 194

Poster 194

To treat or not to treat

Eve Hamilton1, Simon Howard2, Edmund Ong1
1RVI, Newcastle upon Tyne, 2Public Health, North East

Introduction: Tuberculosis is a significant public health risk with high morbidity and mortality if left untreated. Treatment is with multiple drugs for a minimum of 6 months with the potential for significant toxicity. It is imperative that patients comply fully with treatment to ensure successful treatment and to reduce the development of resistant organisms. 

Methods: This is a case of 82-year-old female, originally from India who moved to the UK 15 years ago. She had a background of Alzheimer-type dementia, recent fractured neck of femur, hypertension and type 2 diabetes. Currently nursing home resident in contact with other residents. Presented with general deterioration, poor appetite and new behaviour of spitting out food and medication. New cough which was unresponsive to amoxicillin. Sputum sample sent by GP was positive for AFB. She was admitted on the local infectious diseases ward and quadruple therapy was commenced. It quickly became evident that the patient was not able to reliably take medication. . This case explores the ethical difficulties in decisions to treat smear positive tuberculosis in patients with progressive terminal illness and a risk for development of mycobacterial resistance with non-compliance and /or unreliable drug delivery This is was opposed to the public health perspective in terms of communicable risk to the public with non-treatment and ability to discharge the patient back to the community. In this case a multidisciplinary case conference was organised to balance this requirement against individual patient needs: chaired by CCDC, involving medical and nursing teams, GP, social care, local authority public health team and family. It explores the complexities of discharging a patient with untreated TB back into the community.

Discussion: The case highlights decisions to treat / not to treat and capacity to deliver treatment practically versus the prognosis of other end stage processes. These situations are only likely to become more common in future with aging populations, complex co-morbidities and movement of people. It highlights the need to identify better options for long-term care which can also be made available much more quickly. This patient was eventually discharged to a nursing home after 5 months as an inpatient. She died within 2 weeks of discharge.

195
Experience of screening for latent TB infection (LTBI) in high risk community populations using extended testing eligibility criteria

Abstract - 195

Poster 195

Experience of screening for latent TB infection (LTBI) in high risk community populations using extended testing eligibility criteria

Natasha Ratnaraja1, Pavanjit Jheeta2, Tracy Morrod2
1University Hospitals Coventry and Warwickshire. 2Sandwell and West Birmingham Hospitals

Introduction: Sandwell & West Birmingham Clinical Commissioning Group (CCG) serves an ethnically diverse population with high rates of Tuberculosis (TB) infection (34.9 per 100,000 population) (PHE, 2018). In 2011, migrants accounted for 7% and 22% of the population in Sandwell and Birmingham respectively (NOMIS 2011 Census data).

In 2015, the Collaborative Strategy for England (2015-2020) recommended new entrant screening for latent TB infection (LTBI).

In 2016, the CCG implemented Interferon Gamma Release Assay (IGRA) screening of new entrants aged 16 to 35 years from high incidence countries (TB incidence of ≥ 150/100,000 population) in accordance with NHS England screening recommendations. However, retrospectively identifying and inviting patients for testing in General Practice was found to be resource intensive. Only 776 samples were received from General Practices for IGRA testing between 2nd June 2016 and 24th August 2017, with a positivity rate of 21.88%. We share our experiences of increasing possibilities for community testing using extended criteria.

Methods: In order to increase eligibility, NHS England agreed to pilot extended testing criteria to age 16 and 40 years and date of arrival in the United Kingdom (UK) to 10 years at a Bangladeshi Islamic centre.

Screening was also undertaken at ESOL (English for speakers of other languages) classes in Sandwell College. Testing criteria was further extended by Sandwell Local Authority and SWB CCG to screen students from countries with a TB incidence of ≥40/100,000 population, to include Eastern Europe.

Results: At the Bangladeshi centre, 9/17 (52.94%) tested positive for LTBI; only one of these met the original screening criteria.

Results from the ESOL screening showed: 23/194 positive (11.86%), 2 equivocal, and 169/194 negative. Eight positives would have been excluded on the basis of country of origin (4 from Eastern Europe) and 10 excluded on age. 7/23 would have been excluded on the basis of age AND country of origin. Of the negatives and equivocal results, 57/171 would have been excluded on age and 100/171 excluded on country of origin. Twenty-nine would have been excluded on age AND country of origin.

Using original NHSE criteria would have increased the positivity rate to 21.82% (12/43).

Discussion: Using extended testing criteria gave conflicting results for the two centres. Eastern European populations are considered to be high risk for drug resistant TB, making treatment for LTBI problematic. However, Armenia, Bulgaria, Estonia, Georgia, Latvia and Lithuania are no longer on the World Health Organisation’s (WHO) MDR-TB (Multidrug resistant TB) list of high burden countries (WHO, 2016). In Sandwell and West Birmingham, patients from Eastern Europe with active TB tend to have more complications and burden of disease. In 2016, 7 patients born in an Eastern European country were treated for active TB in Sandwell and West Birmingham Hospitals NHS Trust. All were smear positive at presentation, 5/7 had cavitary lesions on chest X ray or CT (computerised tomography) and 2/7 had disseminated disease. Two patients died from their TB and only 1/7 had MDR-TB.

Our results show it might be beneficial to modify testing criteria to allow for demographic variations in high incidence areas. Long term follow-up is required to determine if extending screening criteria for LTBI to include Eastern European migrants in Sandwell and West Birmingham is cost effective and preventative.

More evidence is required to see if extending screening programmes help manage the burden of TB disease at a local level. However, our data suggests that in our high TB incidence, area with high complication rates, tailoring the screening programme to fit the needs of the local population might be beneficial.

 

 

196
The use of Interferon Gamma Release Assay (IGRA) testing for latent Mycobacterium tuberculosis prior to commencing immune-modulating drugs and the subsequent management of identified cases of latent M. tuberculosis

Abstract - 196

Poster 196

The use of Interferon Gamma Release Assay (IGRA) testing for latent Mycobacterium tuberculosis prior to commencing immune-modulating drugs and the subsequent management of identified cases of latent M. tuberculosis

Alice Maxwell, Emmanuel Nsutebu, Geraint Davies
Royal Liverpool and Broadgreen University Hospitals NHS Trust

Introduction: The risk of reactivation of latent tuberculosis in patients commencing TNF-α blockers has been well-established and there are clear recommendations on the screening and management of these patients. Currently clear guidance does not exist for other forms of immune-modulating drugs. It is not known what the current practice is for these drugs and whether it differs between different specialities.

This audit looked at the number of tests being carried out and the rationale behind testing. Following on from these results we wanted to look at how the positive results were acted upon, whether the patients were investigated and treated appropriately and whether advice was sought.

The cost of the IGRA test is not insignificant and is another factor to consider when looking at the number and rationale for the testing. Further analysis was carried out looking at the costs of testing and potential cost saving.

Methods: Data was collected from all IGRA tests performed within one year in Royal Liverpool and Broadgreen University Hospital. This amounted to over 1000 tests. 100 results were analysed using electronic notes and ordering system to determine: indication, underlying diagnosis, demographic information, number of tests per patient and department ordering the test. This information was extrapolated to estimate the overall characteristics.

Following this the 37 positive results were analysed again using electronic notes and ordering system. The same characteristics as described for the sample were determined, then the sample was analysed to determine if appropriate investigations had been carried out, whether advice regarding treatment was sought and finally what treatment patients went on to have and whether they completed treatment.

Results: Of the 1000 tests it was found that 46% were ordered by Dermatology, the other departments with high ordering numbers were Gastroenterology at 20% and Rheumatology at 19%. In terms of indication only 10% were ordered with the specific indication of being prior to commencing an anti-TNF-α medication, although a further 33% stated the indication as prior to commencing immune-modulating medications. 33% stated in the indication that they were for ongoing immune-modulating medications. 39% of the tests were multiple and the average number of tests per patient was 2.

Looking at the 37 positive results all had appropriate liver function testing carried out but 6 did not have a chest x-ray and in 13 cases no advice was sought from the Infectious Diseases department regarding treatment. For the 23 patients managed by the Infectious Diseases team, 9 patients were not treated largely due to the high burden of co-morbidities. 3 patients were unable to complete treatment due to side-effects.

Looking at cost saving analysis if only the duplicate tests were eliminated, £14,869 could have been saved over one year.

Discussion: The results of this audit elicited some surprising findings, both with the number of IGRA tests that were being carried out and the indications for testing. Clearly there are cost-saving opportunities highlighted by this project. There are also the implications of inappropriate management of positive test results and potential patient harm. This has precipitated design of guidelines for latent M. tuberculosis testing and directs clinicians to the referral process for a positive result. This audit has also been used as an opportunity to change the electronic requesting process so that prompts inform the clinician of the implications of a positive result and reminds clinicians not to order duplicate tests.

197
Mycobacterium abscessus; lessons learnt from a complex case

Abstract - 197

Poster 197

Mycobacterium abscessus; lessons learnt from a complex case

Francesca Knapper, Alexander May, Kirsten MacGregor, Izak Heys, Charlotte Hall
Southmead Hospital, North Bristol NHS Trust

Introduction: A 27-year-old female presented with a tender lump in the right buttock following a steroid injection for rheumatoid arthritis in a European city. MRI pelvis demonstrated a multifocal fluid collection confined to the adipose tissue, the largest collection measured 4x3cm. There was no osteomyelitis or extension beyond the deep fascia.

Methods: Culture of tissue obtained during initial surgical debridement yielded Mycobacterium abscessus. Treatment was commenced pending sensitivity results. Meropenem, Azithromycin, and Amikacin were given for a month with subsequent switch to oral Moxifloxacin, Azithromycin, and Doxycyline. A week into the oral phase of treatment the initial sensitivities reported that the isolate was resistant to Moxifloxacin, Co-trimoxazole, Tobramycin, Doxycycline, and Clarithromycin (inducible). At this point treatment was held pending further sensitivities and investigations.

Additional sensitivities showed a Tigecycline MIC 0.25, Imipenem MIC 16, Minocycline MIC >8 (regarded as resistant), and Linezolid MIC 32 (regarded as resistant). Clofazamine was not tested. MRI showed a moderate reduction in size of the right buttock abscess with no new fluid collections identified. Further surgical debridement was undertaken (this was limited in extent due to lack of a distinct area of diseased tissue at operation) followed by repeated antimicrobial therapy with Tigecyline, Azithromycin, Amikacin and Clofazamine.

Treatment was complicated by significant intolerance; Clofazamine was discontinued after a few days at the patient’s request due to concern regarding pigmentary change. Tigecyline caused significant nausea despite antiemetics and advice from the palliative care team. There was a temporary decline in renal function, and Amikacin repeatedly had to be held and then dose reduced. Although hearing tests did not demonstrate any hearing loss, the patient reported mild tinnitus. The patient also developed a transaminitis.

Results: Histology from the second debridement suggested that the abscess had been completely excised with Ziehl-Neelsen, Grocott, Gram and DPAS stains for microorganisms negative. At 42 days mycobacterium cultures remained negative. At this point the decision was made to stop treatment. An MRI at this point, and subsequent scans, revealed a marked improvement with only a residual linear signal abnormality. At nearly six months post treatment cessation there has no sign of recurrence.

Discussion: Patients with rheumatoid arthritis are at increased risk of both TB and non-tuberculous mycobacterial infections. M. abscessus is a nontuberculous mycobacterium that is multidrug resistant; interpretation of susceptibility testing is challenging as in vitro results do not always predict clinical response. The complex treatment regimes are often difficult to tolerate and require a significant monitoring. Debridement has a central role in these patients and a multidisciplinary approach to care is essential. Given the fact that we were unable to culture M. abscessus following the second debridement despite the short course of antimicrobial therapy, initial surgery was likely key to management in this case.

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