point of care testing for influenza dr jen kok centre for

ANTIBIOTIC ESSENTIALS Intern Orientation 21ST Jan 2019 MATTHEW O’SULLIVAN | INDY SANDARADURA| JON IREDELL ANGELA NETLUCH

icpmr Centre for Infectious Diseases and Microbiology

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THE ANTIMICROBIAL TIMELINE


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THE PIPELINE IS RUNNING DRY • Antimicrobial use inevitably leads to antimicrobial resistance

• Ongoing drug development is required to combat resistance development to older agents

• Disappointing sales of recently launched antibiotics

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THE PIPELINE IS RUNNING DRY

4 icpmr Centre for Infectious Diseases and Microbiology

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INAPPROPRIATE ANTIMICROBIAL USE Numerous studies have found

a large percentage of antimicrobials prescribed are inappropriate – No bacterial infection

– Ineffective antibiotic

– Inappropriate antibiotic Antimicrob Agents Chemo 51:864

J Hosp Inf 71:108

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Euro Surveill. 2007;12(41):pii=3284.


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ANTIMICROBIAL STEWARDSHIP (AMS)

• Systematic approach to optimising use of antimicrobials

• Aim: – Reduce inappropriate antimicrobial use – Improve patient outcomes – Reduce adverse effects/toxicity – Reduce development of antimicrobial resistance – Reduce costs

Clin Micro Rev 18:638


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The AMS Team • AMS Ward Rounds

– Mondays, Wednesdays & Fridays @ 10:30am

Doctors • Matthew O’Sullivan, Matthew Watts, Indy

Sandaradura, Trish Ferguson + 7 other ID Drs AMS Pharmacist • Angela Netluch Infection Prevention & Control Team • Wednesday Rounds

What we do? • Education • Interpreting microbiology results • Therapeutic Drug Monitoring (TDM) • Advice

– De-escalation – Dose optimisation – IV to Oral Switch – Appropriate duration – Other investigations – Cessation – Directed therapy/Broadening cover – Formal ID consult

• Conflict Resolution

Don’t be shy!

Always happy to answer

ID/Micro/AMS questions on the

round!

There are no dumb questions

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RED ANTIBIOTICS Infectious Diseases/Microbiology input is advocated for these agents PRIOR to use because they may either: - Be very broad spectrum agents which should

only be used when difficult-to-treat multi-resistant organisms are suspected/present; and/or

- Lead to increased rates of antimicrobial resistance if overused; and/or

- Require therapeutic drug monitoring to ensure efficacy and avoid toxicity; and/or

- Be expensive; and/or - Possibly have life threatening drug

interactions/adverse effects.

RESTRICTED ANTIMICROBIALS


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GREEN ANTIBIOTICS Infectious Diseases/Microbiology input is not essential for these agents because they may either: - Be narrow spectrum agents which are

suitable for directed therapy and are less likely to promote antimicrobial resistance

- Do not require therapeutic drug monitoring

- Less likely to have life threatening drug interactions/adverse effects.


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UNRESTRICTED ANTIMICROBIALS

ANTIMICROBIAL ADVICE AND APPROVALS

11 icpmr Centre for Infectious Diseases and Microbiology, Westmead Hospital

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• Electronic decision support and approval system – MANDATORY to obtain approvals for restricted

antimicrobials

• Training for interns – 24/01 and 25/01

Medical Officer Responsibilities

12 icpmr Centre for Infectious Diseases and Microbiology, Westmead Hospital

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• To log use of restricted antimicrobials on Guidance MS as soon as you wish to prescribe the antimicrobial

• To select an appropriate indication – NOT TO FALSIFY MEDICAL RECORDS

• To write APPROVAL NUMBER on the medication chart • To discontinue antimicrobials when appropriate

Charting Antimicrobials • Drug in generics – important for allergies • Indication • Date therapy was started or Day 1, 2, 3 • Review date – mandatory for eMeds (2019) • Guidance approval number • TDM – indicate when to take level

Spectrum What is the spectrum? • Gram Positive • Gram Negative • Anaerobes • Atypicals

Acknowledge Dr Craig Boutlis - http://www.boutlis.com/files/AntibioticPrescribing.pdf

Narrow vs Broad Spectrum What’s the difference? Which one is better?

http://www.boutlis.com/files/AntibioticPrescribing.pdf

What lives where?

Surgical Prophylaxis

• Read the Surgical Antibiotic Prophylaxis Guidelines available on the ABCs of Antibiotics Intranet Page

• Postoperative surgical prophylaxis SHOULD NOT extend beyond 24 hrs

– >24hrs = no further benefit & ↑ adverse effects

• The recommended surgical prophylaxis dose of cephazolin is 2g

• Timing

Simple principles

Special Attention to those doing - Ortho, Vascular, Cardiothoracic, Colorectal, Neurosurgery, Plastics, Urology or Upper GI terms

CASE STUDY 1 • 50 yo woman presents with lower abdominal and left

loin pain, dysuria, frequency and lethargy • NKDA • PR 98, BP 90/55, Temp 38.9ºC • Urine dipstick: WBC 3+, protein 2+, nitrites 2+ • WCC 19, CRP 230, Cr 60 • MSU and blood cultures collected

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Ampicillin 2g IV 6th hourly and gentamicin 5mg/kg What is your empiric antibiotic therapy?


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CASE STUDY 1

What is your treatment plan?

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Change to oral amoxycillin 500mg tds once improving and temp <38ºC for 24 hours

› Blood culture negative

› Urinary tract ultrasound normal


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IV-ORAL SWITCH


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• It’s 2am • Called by a nurse on one of the wards • “Mrs Smith has a temperature of 39 degrees.

Can you please come assess her?”


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CASE STUDY 2

You go to the ward and assess Mrs Smith: • What do you want to know?


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CASE STUDY 2

• 61 year old lady • NKDA • Had an open cholecystectomy 8 days ago • Was in HDU for 3 days post-op due to blood loss • Complaining of feeling short of breath, cough

with some sputum production Other medical problems: • Type II Diabetes Mellitus • Hypertension


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CASE STUDY 2

O/E • Alert and oriented • Heart rate = 98 • Blood pressure = 150/90 • Respiratory Rate = 25 • Temp = 39


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CASE STUDY 2

• Respiratory examination: Coarse crackles in right base

• Cardiovascular examination: Normal • Abdominal examination: Wound looks ok,

drain in situ

• Peripheral cannula in situ, inserted yesterday, site looks clean


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CASE STUDY 2

• What do you do next?


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CASE STUDY 2

• Take Blood cultures!!

• Other blood tests as necessary

• Sputum microscopy and culture

• Chest Xray

What next? icpmr Centre for Infectious Diseases and Microbiology

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CASE STUDY 2

How will you choose which antibiotic to give?


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CASE STUDY 2

How will you choose which antibiotic to give? Call your registrar/senior and/or


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CASE STUDY 2

How will you choose which antibiotic to give? Call your registrar/senior and/or Call Infectious Diseases if it is tricky! (e.g. resistance, allergies etc.) and/or Use the available online resources to guide your choice

Which are found…


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CASE STUDY 2


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Links to important antimicrobial information

Quick links to useful pages such as eTGs, AUC calculator, text page function, SydPath website

eTGs


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Let’s change the story a little… •You’ve seen Mrs Smith in the Emergency Department.

•No recent surgery, but presents from home with precisely the same symptoms and signs.

•What’s the difference?


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CASE STUDY 2 part 2

Community Acquired Pneumonia

1. Common organisms 2. Severity scores 3. Investigations 4. Treatment


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COMMUNITY ACQUIRED PNEUMONIA GUIDELINES


∼ Green = Typical Blue = Atypical


• Pneumonia severity scores – Several scores available – Predict likelihood of death – Can be used as an aid to determine severity and help

decide: • Outpatient vs inpatient therapy

• Oral vs IV therapy

• Broad spectrum vs targeted therapy


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∼ Red = Needs Guidance Approval



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Red = Needs Guidance approval



∼ Red = Needs Guidance approval



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Red= Needs Guidance approval

Adverse reactions to antibiotics are common

Adverse reactions may involve any organ: • cutaneous • haematological (eg cytopenias) • renal (eg interstitial nephritis) • hepatic (eg hepatitis) • gastrointestinal (eg pseudomembraneous colitis) • neurological (eg encephalopathy) • cardiac (eg prolonged QT interval)


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ANTIBIOTICS AND ALLERGIES

CUTANEOUS REACTIONS • around 2% of hospitalised patients develop a cutaneous drug reaction and

antibiotics account for ~55% of cases

• 5% of the population have an antibiotic allergy but 15% of patients report one, and it may be difficult to clarify which patients have a true allergy

• an immediate (IgE mediated) reaction to penicillin can be predicted by a positive skin test

• a negative skin test does not exclude the development of a delayed maculopapular rash


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In the UK (1992-1997): • 12 deaths due to antibiotic anaphylaxis

• 6 of these followed cephalosporin administration

• …and 3 of these had a history of anaphylaxis to penicillins

Patients with a history of anaphylaxis to a penicillin should NOT be given a cephalosporin .

Risk of cross reactivity with carbapenems is 0.01%


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• Patients who develop a maculopapular rash to a penicillin should NOT receive any penicillin

• Cross-reactivity between penicillin and cephalosporins is OVERESTIMATED

• Only 1% of those with a delayed penicillin allergy will also develop a rash with a 1st generation cephalosporin

• Therefore may be given a cephalosporin with care Campagna et al, J Emerg Med. 2012;42(5):612-20.


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Natural penicillins Penicillin G (benzylpenicillin) Penicillin G procaine Penicillin G benzathine Phenoxymethyl penicillin (V) Penicillinase resistant Flucloxacillin Dicloxacillin Aminopenicillins Ampicillin Amoxicillin

Beta lactamase inhibitor combinations

Amoxicillin-clavulanate (Augmentin®)

Ticarcillin-clavulanate (Timentin®) Piperacillin-tazobactam (Tazocin®)


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First-generation Oral Cephalexin IV Cefazolin Cephalothin Second-generation Cefuroxime Cefoxitin Cefaclor

Third-generation (Cefotaxime) Ceftriaxone Third-generation Ceftazidime Fourth-generation Cefepime Fifth-generation Ceftaroline


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• An injecting drug user presents with fever and the CXR pictured • Blood cultures are positive with Gram positive cocci


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Case 3

• Sepsis (and likely endocarditis) due to Staphyloccus aureus is

suspected

• The medical registrar recommends you commence flucloxacillin

Thoughts about dose and spectrum?


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Case 3

Which of the following reason(s) would be a contraindication to commencing flucloxacillin?

1. the patient developed a maculopapular rash while on piperacillin-tazobactam during a previous admission

2. the patient developed a urticaria and wheeze after he was given cephalexin by a GP

3. the patient has chronic active hepatitis due to HCV


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Case 3

• A 34 yo male presents to the emergency department with 24 hours of fevers and chills

• BP 95/60, PR 110, Temp 38.4°C • No clear source of infection on examination • Urine dipstick is clear • He has a history of face swelling minutes after being given

amoxycillin • You take bloods (including blood cultures) • Blood pressure remains low despite fluid boluses • What antibiotics would you commence?


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Charting Exercise

• Using the medication chart provided, please chart vancomycin and gentamicin for this patient. He weighs 80kg, 185cm tall. Assume normal renal function.

Name: John Smith, MRN 1234567, DOB 12/1/1981 • Should we use ideal or actual body weight to calculate the

doses?

Charting Exercise


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TG: antibiotic via CIAP “search ideal body weight”

ANSWERS


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• Chart gentamicin in the ‘once-only’ or ‘variable-dose’ section of the medication chart

• Chart vancomycin loading dose in the ‘once-only’ and maintenance dosing in the regular section of the medication chart (not variable dose section)

– Need two charts if use variable = unsafe

• Round doses to the nearest half-vial. Vials are: – 80mg for gentamicin – 500mg and 1g for vancomycin

• Don’t forget: – Patient identifiers – Allergies – Indication – Approval number – Trough level on day 3 of vancomycin dosing – Write a time of administration not STAT


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Key Points from Charting Exercise

Vancomycin and Gentamicin dosing and monitoring


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INDICATIONS FOR VANCOMYCIN Infections caused by Gram positive organisms:

• suspected or confirmed MRSA infection

• Enterococcal infection (not VRE)

• surgical prophylaxis in known colonizer

• severe C. difficile infection (oral)

• penicillin hypersensitivity icpmr

Centre for Infectious Diseases and Microbiology

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• Dosing is based on – WEIGHT (actual body weight) – RENAL FUNCTION – SEVERITY OF INFECTION

• loading dose of 25-30 mg/kg (only for patients with severe sepsis)

• Round dose to the nearest 250 mg • Adjust dose based on trough levels


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VANCOMYCIN DOSING

Loading dose

Kidney

Therapeutic level

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Loading with vancomycin

Without loading dose With loading dose

Target concentration

12 hours to reach target steady state

Target concentration

Reach target steady state after

the 1st dose

VANCOMYCIN GUIDELINES

• Full details in the WSLHD vancomycin guidelines:

icpmr Centre for Infectious Diseases and Microbiology, Westmead Hospital

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Maintenance intermittent dose: Creatinine Clearance (mL/min) Initial maintenance IV dose

≥ 90 15 to 20 mg/kg/dose 12-hourly 60 to 90 15 mg/kg/dose 12-hourly 20 to 60 15 mg/kg/dose 24-hourly

< 20 15 mg/kg/dose 48-hourly On renal replacement therapy Refer to guideline

Where to find the guideline?


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Dosing in obesity • Definition: body mass index (BMI) ≥30 kg/m2 or an

actual body weight ≥100 kg AND an actual body weight (ABW) of ≥140% of the ideal body weight (IBW)

• Using actual body weight for obese patients for standard doses (ie 15-20 mg/kg dose) supra-therapeutic conc – So 10mg/kg/dose is recommended

• Still use ACTUAL BODY WEIGHT

Creatinine Clearance Loading doses Maintenance IV dose Timing of trough

> 60 mL/min 20 mg/kg/dose 10 mg/kg/dose 12-hourly Before the 4th dose

20 to 60 mL/min No loading dose 10 mg/kg/dose 24-hourly Before the 3rd dose

< 20 mL/min No loading dose 10 mg/kg/dose 48 to 96 hourly 48 hours after the last dose

TDM for intermittent Vancomycin

Target trough concentration Uncomplicated infections 10 to 20 mg/L Complicated infections: (e.g. bacteraemia, septic shock, endocarditis, osteomyelitis, meningitis, necrotising fasciitis, and pneumonia)

15 to 20 mg/L (up to 25 mg/L in meningitis)

TDM for intermittent Vancomycin • When is a trough?

– Within 60 mins before the next dose is due – VERY IMPORTANT!

• Has the level been taken too early?

– Steady state

• Do not withhold subsequent doses whilst waiting for trough level (unless CrCl < 20 mL/min)

Vancomycin dose adjustment

For example: • 50 kg patient is on vancomycin 750 mg 12-hourly • Measured trough level was 7.5 mg/L (Target trough 15

mg/L) • 15 mg/L ÷ 7.5 mg/L = 2 previous dose (750 mg 12-hourly) x 2 = 1.5 g 12-hourly Practice tips • <10 mg/L consider changing patient to continuous

infusion

• >25 mg/L check timing of collection, withhold icpmr Centre for Infectious Diseases and Microbiology

If your level is twice what it should be … halve the dose

• Similar efficacy and tolerance for continuous infusion vs. intermittent infusion

• Required for patients on PACC (Hospital In The Home *HITH*)

• Dose similar to that of intermittent infusion

• Target level higher (20-25 mg/L) since it is not a trough level


∼ Wysocki Antimicrob Agents Chemother 2001

Vancomycin Infusions

INDICATIONS FOR GENTAMICIN

Infections caused by Gram negative organisms • intra-abdominal sepsis • febrile neutropenia • synergy in enterococcal endocarditis • limit use to no more than 48 hrs when given as

empirical therapy


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GENTAMICIN DOSING • Initial dose of 4 – 7 mg/kg daily (up to 640 mg)

– Higher doses appropriate for sepsis

• Doses based on Ideal Body Weight – Exceptions exist to this including obesity

• Seek advice from Infectious Diseases or Pharmacy

• Round dose to the nearest multiple of 40mg – They come as 80mg vials *easier for

administration*


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TG:Antibiotic via CIAP “search ideal body weight”

• No need for monitoring if only used for < 72 hrs • For once daily dosing estimate AUC and subsequent dose using

computer program – Requires 2 plasma levels (1 hour and 6 – 14 hrs after start of dose

administration) • Angela Netluch(AMS Pharmacist; pager 8926) • Trough concentrations are not useful for once daily dosing


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GENTAMICIN MONITORING

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GENTAMICIN TOXICITY

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GENTAMICIN TOXICITY

Wobblers.com

Febrile Neutropenia

• 47 year old AML patient presents with fevers, chills and rigors after receiving chemotherapy 10 days ago

• NKDA • not known to be colonized with any multi-

resistant organisms – Screening was recent and no recent hospitalisations

• Hickman’s line in situ, otherwise examination normal

• neutrophil count 0.2 x 109/L


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Case 4

after collecting BC, what antibiotics would you prescribe assuming normal renal function?

a. piperacillin-tazobactam b. gentamicin c. piperacillin-tazobactam + gentamicin d. piperacillin-tazobactam + gentamicin + vancomycin e. meropenem f. amikacin


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Case 4

after collecting BC, what antibiotics would you prescribe assuming normal renal function?

a. piperacillin-tazobactam b. gentamicin c. piperacillin-tazobactam + gentamicin d. piperacillin-tazobactam + gentamicin + vancomycin e. meropenem f. Amikacin

NOTE: There is a piperacillin-tazobactam shortage – cefepime is an alternative agent


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Case 4

Where can I learn more?


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JMO Oncall contains tips for

antimicrobial prescribing

• Should be used in conjunction with locally endorsed policies and guidelines

• We welcome feedback on this resource as we continue to develop it

Acknowledgments: Ms Kristin Xenos for her contribution to these slides

point of care testing for influenza dr jen kok centre for

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