Dr Steve Holden Consultant Microbiologist Nottingham University Hospitals NHS Trust

Dr Steve Holden Consultant Microbiologist Nottingham University Hospitals NHS Trust

Clinical Case 38 yrold man Renal replacement (CAPD) since 2011 Unexplained ESRF Visited Pakistan for 3 months end of 2014 Hospitalised in Pakistan with respiratory illness Empyema; central line inserted for HD Taken back to UK by relatives Admitted to Nottingham City Hospital

Multi-resistant Klebsiellapneumoniae NDM-1 and OXA-48 carbapenemase enzymes Treated with IV colistin Resistance emerged on treatment Eventually died December 2015 Positive blood cultures anti-mortem Untreatable infection

Antimicrobial resistance is a ticking time bomb as big a risk as terrorism. CMO Prof Dame Sally Davies Projected deaths due to AMR in 2050 Source: Review on Antimicrobial Resistance 2014, HMG and UK Wellcome Trust

Health & Social Care Act 2008 21 Code of practice relating to health care associated infections (1)The Secretary of State may issue a code of practice about compliance with any requirements of regulations under section 20 which relate to the prevention or control of health care associated infections. (2)The code may (a)operate by reference to provisions of other documents specified in it (whether published by the Secretary of State or otherwise); (b)provide for any reference in it to such a document to take effect as a reference to that document as revised from time to time; (c)make different provision for different cases or circumstances. (3)The Secretary of State must keep the code under review and may from time to time (a)revise the whole or any part of the code, and (b)issue a revised code.

Code of Practice Updated July 2015 Previously vague section on stewardship in Criterion 9 New Criterion 3 Ensure appropriate antimicrobial use to optimise patient outcomes and to reduce the risk of adverse events and antimicrobial resistance. Use of Start Smart then Focus and TARGET Antimicrobial Stewardship Committee reporting to Trust board

In other news NICE: Systems and Processes for Effective Antimicrobial Use (NG15, August 2015) Note recommendations for commissioners, providers and prescribers Patient Safety Alert 18 August 2015 Implement Antimicrobial Stewardship Programme Comply with new Code of Practice by SSTF / TARGET by 31 st March 2016.

What does this mean for the acute physician? Pressures Make a diagnosis as soon as possible? Timely discharge of patients Ensure severe sepsis treated urgently Available results: microbiology results are slow. Competing priorities e.g. falls/vte assessments etc All that is asked... Right antibiotic at the right time Documented in notes and drug charts Hold off antibiotics whilst investigating in stable patients? Appropriate samples taken before antibiotics Allergy history taken properly and documented

Temperature = Vitamin T

Areas of focus Penicillin allergy Incorrect initial diagnoses Hard to unstick diagnostic labels UTI and CAP Misuse of urine dipsticks Laboratory sampling Sepsis vs antimicrobial stewardship Antagonists? Long term antimicrobial prophylaxis 80% of antibiotic prescribing in community

Penicillin allergy 10% of population report penicillin allergy <10% have any genuine allergy to penicillin Cohort study (Macy E, Contreras R: J Allergy Clin Immunol 2013) 51,582 penicillin allergy patients vs matched controls More bed days More MRSA, VRE and C. difficile infections More likely to receive broad-spectrum antibiotics known to select out MR pathogens. Every effort to explore the nature of the allergy should be made before prescribing an allergic regimen. Recent NICE allergy guidelines Patients with documented allergy to betalactamsshould be referred to allergy service if likely to require betalactams in future

Acute medicine/hcop UTI audit High HSMR for UTI 2013 and 2014 Previous case note review revealed over-diagnosis and coding issues. Real-time audit of UTI diagnosis Dec 2014/Jan 2015 108 patients over 10 days, 10 wards (acute med & HCOP) Four diagnostic categories: Classic UTI signs / symptoms Signs / symptoms of infection, urinary tract possible source Non-specific symptoms e.g. new confusion No features of possible infection at all asymptomatic

Results Mean age 80 years; male:female= 30:78 16.5% of patients diagnosed with UTI had no documented evidence of a UTI. At least 7 of these had asymptomatic bacteriuria, which was being treated with antibiotics (approximately 6.5% of the total cohort). 39% of patients diagnosed with a UTI had non-specific features e.g. confusion but no definite evidence for UTI. For the above 55.5% of patients, a positive dipstick was used to justify the diagnosisin just over half (53%) despite the poor PPV in this patient group. Only 12% of the cohort had features of severe sepsis.

Admissions ED UTI audit 47% 21% Urinary Symptoms Collapse? Cause Sepsis? Cause 27% Confusion? Cause 100 urine samples sent to microbiology, Dec 2013 Retrospective review of ED notes Audit against Trust protocols for sending urine MC&S, treatment of UTI and asymptomatic bacteriuria 47 had no signs/symptoms suggestive of UTI 5 started on abx based on dipstick results 4 further pts treated for ASB inappropriately. 2% 3% Other

UTI: The unexacting diagnosis Samples easy to send to microbiology Poor PPV of urine dipsticks Should be used to exclude not make diagnoses Diagnosis may be made or corroborated by finding of asymptomatic bacteriuria Up to 50% of women in long term care facilities have ASB 20% of elderly patients in the community 100% with long term catheters and ureteric stents Challenge UTI diagnoses

Long term prophylaxis May be picked up on admission Urosepsis with MR pathogen Long term trimethoprim prophylaxis in face of resistance Drives multi-resistance Generally only appropriate for defined periods Agents with minimal effect on gut flora e.g. nitrofurantoin Review susceptibility results

20% cut-off for empirical use recommended by IDSA guidelines

Laboratory reporting Are we part of the problem? Mandate doctor ordering? Electronic requests with minimum information required? Withhold all CSU AST results? If labelled as urine, ASTs suppressed with comment to make e-referral explaining need for results. From 9 th March to 23 rd July 2015 565 reports issued like this Less than 20 requests for AST

What else would be helpful? Diagnostics POCT CRP or, better, procalcitonin? Rapid detection of resistance in pathogens molecular technology E-prescribing Ensure linked to laboratory system/results Infection ward rounds on acute areas Specialist review OPAT referral Thoughts?

What are ideal agents? What do we need? Low rate of resistance Unique mode of action Highly concentrated at the site of infection e.g. urine Minimal impact of normal flora Low rate of allergy, intolerance and contra-indications Cheap and easily available Easy to test in the laboratory for sensitivity

Some new or re-emerged drugs Pivmecillinam Betalactam; minimal effect on gut flora, low rates of resistance; highly concentrated in urine. Colistin IV form for treating serious infection Last line of defence against MR-GNB Ceftolozane/tazobactam Potent anti-pseudomonal compound

Discussion How can we work together to ensure reasonable antimicrobial use yet treat individual patients effectively? Improvement in initial diagnosis? Allergy pathway? Wider problem of access to suitable drugs Needs investment and strategic work with pharma on national/international scale