Content. In the beginning Antimicrobial Stewardship 2. Antimicrobial Prescribing with cases to cover

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1 Content Safe & Effective Prescribing of Antimicrobials: Whistle-stop update for non-medical prescribers Elaine Roberts Lead Pharmacist, Antimicrobials BCUHB East 1. Antimicrobial Stewardship 2. Antimicrobial Prescribing with cases to cover When to use IV treatment When to step down Therapeutic Drug Level Monitoring Management of clinically important drug/ drug and drug/disease interactions 11/03/ /04/16 2 Why is antibiotic stewardship so important? Antimicrobial stewardship embodies an organisational or healthcare-system wide approach to promoting and monitoring judicious use of antimicrobials In the beginning... Aids the delivery of consistent, optimal and evidence based infection management Reduces the risk of antibiotic-related morbidity e.g. C difficile Reduces rate of development of resistance 11/04/16 6 1

2 And now... Has the era of untreatable infections arrived? 11/04/16 7 Multi-resistant Klebsiella pneumoniae isolate from Wrexham within the last five years Antibiotics Approved Lethal drug-resistant organisms mean threat must be listed on register of civil emergencies, says chief medical officer Ian Sample, science correspondent, Thursday 24 January 2013, The Guardian 11/04/ /04/16 BCU monthly rates of C. difficile per 1,000 hospital admissions, Apr 10 to Feb 16 Start SMART Apr-10 May-10 Jun-10 Jul-10 Aug-10 Sep-10 Oct-10 Nov-10 Dec-10 Jan-11 Feb-11 Mar-11 Apr-11 May-11 Jun-11 Jul-11 Aug-11 Sep-11 Oct-11 Nov-11 Dec-11 Jan-12 Feb-12 Mar-12 Apr-12 May-12 Jun-12 Jul-12 Aug-12 Sep-12 Oct-12 Nov-12 Dec-12 Jan-13 Feb-13 Mar-13 Apr-13 May-13 Jun-13 Jul-13 Aug-13 Sep-13 Oct-13 Nov-13 Dec-13 Jan-14 Feb-14 Mar-14 Apr-14 May-14 Jun-14 Jul-14 Aug-14 Sep-14 Oct-14 Nov-14 Dec-14 Jan-15 Feb-15 Mar-15 Apr-15 May-15 Jun-15 Jul-15 Aug-15 Sep-15 Oct-15 Nov-15 Dec-15 Jan-16 Feb-16 C. difficile/1,000 hospital admissions 12 month moving average rate of C. difficile/1,000 hospital admissions Prompt effective treatment in life threatening infections Take cultures before starting antibiotic therapy where to do so will not delay prompt treatment in septic patients Use local guidance when prescribing Document allergies (including nature), indication, route, dose and duration on chart and in notes 11/04/ /04/

3 Then FOCUS Allergies At 48 hours Stop if no evidence of infection Consider IV to PO switch Change : de-escalation, substitution, addition Review again at 24 hours OPAT Does the patient really need to be in hospital for IV therapy 11/04/ /04/16 14 Allergies Check for allergies before every prescription Consider allergy versus intolerance Do not prescribe penicillin to patients with history of rash, anaphylaxis, swelling, hives You may cautiously prescribe cephalosporins and meropenem to patients with a history of non-urticarial (flat, not itchy) rash with penicillin Adverse effect Allergy 11/04/ /04/16 16 Penicillin (beta-lactam) allergy Self-reported beta-lactam allergy common (up to 20% hospitalised patients) Only 1-10% of these patients have type 1 hypersensitivity on testing Additional cost per penicillin allergic patient more hospital days over next 20 months 23.4% more likely to develop C difficile 30.1% more likely to have VRE Antibiotics 63 times more expensive in penicillin allergic patients Mirakian R et al. Management of allergy to penicillins and other beta-lactams. Clinical & Experimental Allergy 2015; 45, (Cochrane review) Good Antimicrobial Prescribing Patient not allergic to chosen agent Clear evidence of likely benefit and documented indication for use Local guidelines consulted (or deviations justified in medical record) Check cultures and narrow spectrum Think intravenous to oral switch Be open to challenge by all health care professionals 11/04/

4 Prescribing outside of guidance Warm up Should be clear justification for deviation in notes Deviation should be rational and cover likely causative organisms Refer if unsure EB, 56 year old male with confusion Complains of back pain. PMH: Epilepsy & recurrent UTIs DH: sodium valproate po, 800mg bd, cefalexin po 250mg nocte long term NKDA Prescribed co-amoxiclav po 625mg 8 hourly for UTI Had three doses 11/04/ /04/16 20 Is this prescription appropriate and safe? Sepsis Assessment LTC in situ (urologists 2 weeks ago) No other likely source of infection Cr 146 CRP 146 Previous micro: none available BP 105/60 mmhg, Pulse 95, Temp 35, WCC 14, RR 22 NEWs 4 Fluids: none prescribed Severe sepsis (2 or more SIRs criteria plus AKI) plus suspected source of infection PO to IV switch!!! LTC left on long term cephalexin risk of resistant organisms Poor response with co-amoxiclav (had 24hours) Choices: meropenem IV or fosfomycin IV 11/04/ /04/16 22 What would the specialists do? Oral co-amoxiclav to fosfomycin IV switch Why not meropenem? Stop long term cefalexin and ensure reason for this is communicated with GP Document review at 48 hours with response/culture results Outcome Catheter changed under fosfomycin cover Blood cultures positive for ESBL-producing Ecoli sensitive to meropenem and fosfomycin. NB blood cultures should be taken if evidence of SIRs not only if temperature spikes 11/04/ /04/

5 Indications for IV antibiotics ü Systemic Inflammatory Response Syndrome When to use IV antibiotics? ü Severe Sepsis ü Early Warning Score (NEWS) 4 ü Bacterial meningitis ü Osteomyelitis ü Septic arthritis ü Bacterial endocarditis ü Neutropenic sepsis ü Cellulitis ü Enteral absorption cannot be guaranteed Example 1: Appropriate or inappropriate? Rationale for IV meropenem Post-take consultant changes trimethoprim to meropenem for symptomatic patient with suspected UTI without evidence of ascending symptoms or pyelonephritis or SIRs What rationale might you expect to see in medical notes? No rationale chase team and clarify and get them to write in medical notes Likely to be previous history of resistant organisms in urine 11/04/ /04/16 28 Example 2: Appropriate or Inappropriate? Multiple infection sources Post-take consultant confirms no changes on chest x-ray, diagnoses LRTI but leaves amoxicillin IV 1g tds and clarithromycin po 500mg bd prescribed. No evidence of SIRs and CURB-65 on admission 2. LRTI =/- UTI Treat as sepsis?source until further information becomes available Encourage team to narrow diagnosis wherever possible Check culture results 11/04/ /04/

6 IV to PO : Why? Increased risk of line infection & bacteraemia Increased length of stay Increased expenditure Increased demands on nursing time Line related adverse events e.g. phlebitis (clarithromycin follow IV administration guidelines) URINARY TRACT INFECTIONS 11/04/ /04/16 32 Dispelling some UTI myths Definitions Asymptomatic patients should not be treated unless pregnant or immunecompromised Always check first if a patient has a long term catheter Positive urine dipstick UTI Cloudy urine in catheter bag UTI Smelly urine UTI Bacteriuria The presence of bacteria in the urine with or without consequent urinary tract infection. Pyuria The production of urine which contains white blood cells Bacteriuria in Catheterised patients High prevalence of recurrent bacterial entry.combined with the catheter as a focus of bacterial biofilm formation: Pyuria in Catheterised Patients Presence of catheter invariably induces pyuria. There is no relationship between the level of pyuria and infection. Make diagnosis of UTI difficult based on bacterial count alone. There is no evidence that detecting pyuria by dipstick is of any value in differentiating UTI from bacteriuria. 6

7 Symptoms of UTI in patients with catheters Supra-pubic discomfort and tenderness Change in character of urine Malaise Rigors Nausea & vomiting Fever may or may not be present Atypical presentations in elderly may include new onset delirium or confusion Summary - CAUTI Urine dipsticks should not be done routinely CSU should be prompted only by clinical symptoms of infection not positive dipstick State CSU on all lab request forms. Do not leave blank. Ensure cultures/sensitivity reports are checked Catheter should ideally be removed or changed within 24 hours of starting antibiotic therapy if in doubt refer! Case 1 Female 70 years old Therapeutic Drug Monitoring (TDM) PC : UTI, Ecoli sensitive to gentamicin Weight 102kg Height 5ft 5inches Consultant Microbiologist Please prescribe 5mg/kg gentamicin once daily 11/04/ /04/16 40 Questions to ask TDM which drugs? Is it safe to dose as per Consultant Microbiologist s instructions? What do you need to know about the patient? Where are the local gentamicin guidelines? Narrow therapeutic index drugs Toxicity Unpredictable dose response relationship Significant consequences from toxicity Readily available assays Correlation between serum levels and efficacy or toxicity 11/04/ /04/

8 TDM Sources of error TDM Sources of error Prescribing Overdosing in clinically obese patients Using inappropriate dosing method (inclusions/ exclusions) Administration Not documenting time given Failing to give on time Giving too early Monitoring Failure to monitor (levels and U&Es) Sampling Blood drawn at incorrect time Blood drawn before steady state Blood drawn from wrong site Failing to sample 11/04/ /04/16 44 Interactions What is the most likely cause of bleed? Drug/drug Drug/disease Remember always drug monograph and appendix 1 BNF PM admitted with GI bleed. INR 12. DH Amlodipine, warfarin Penicillin allergic Recent chest infection. Antibiotics from GP last week. Completed course yesterday. What is the likely cause of the bleed? 11/04/ /04/16 46 What is the most likely cause of seizures? Mrs JD 68 years. Admitted 3 days ago with severe urosepsis Cultures from GP: Ecoli. This is an ESBLproducer. PMH: epilepsy well controlled DH sodium valproate, phenytoin Prescribed meropenem IV 500mg tds 3 days ago for urosepsis Discuss - Which regime? An otherwise healthy young epileptic patient with chest x-ray evidence of pneumonia and evidence of severe sepsis. Recently stayed in UK hotel with air conditioning unit in room. No allergies. Takes carbamazepine MR 600mg bd and sodium valproate 300mg bd 1. Tazocin IV 4.5g tds (as per sepsis bundle) 2. Tazocin IV 4.5g + clarithromycin po 500mg bd 3. Amoxicillin IV 1g tds + doxycycline po 100mg bd 4. Amoxicillin IV 1g tds + clarithromycin po 500mg bd 5. Amoxicillin IV 1g tds + rifampicin po 600mg bd 6. Tazocin IV 4.5g tds plus rifampicin po 600mg bd 7. Teicoplanin IV 600mg 12 hourly + ciprofloxacin 500mg bd po 8. Amoxicillin IV 1g tds + ciprofloxacin IV 400mg bd 11/04/ /04/

9 Which regime? Medication related admissions A patient admitted with neutropenic sepsis. No evidence of systemic inflammatory response. Chest x-ray changes both bases. 11/04/ % of hospital admissions are due to avoidable medication-related harm 1 Local tracking of medication-related admissions 2 (April March 2011) (n=201) 16.4% (n=33) involved antimicrobials 2 1. Pirmohamed M, James S, Meakin S et al. BMJ 2004;329 (7456); Thomas J. Poster Session presented at Patient Safety Congress May 2011, Birmingham, UK. Avoidance-of-medication-related-admissions-pdf.pdf 11/04/16 50 Antimicrobial admissions data (1 April March 2013) n=94 Theme n (%) Drugs* involved *admissions may involve >1 drug Root Cause Analysis (RCA) Contributory factors included: Contra-indication 15 (16 %) Nitrofurantoin (n=15) Dose/choice 62 (66 %) Drug interactions 16 (17% ) Nitrofurantoin (n=1), Quinolones (n=6), co-amoxiclav (n=10), Penicillins (n=29), Cefalosporins (n=12), Macrolides (n=10), Warfarin (n=9), calcium (n=4), iron (n=1), calcium + iron (n=1), simvastatin (n=1) Access to specialist advice Lack of catheter change Lack of patient counselling Avoidable adr 1 (1% ) Ciprofloxacin-seizure Finally Diolch / Thank you 11/04/ /04/