Antimicrobial therapy Laura Whitney Sept 2010. Limitations of this session Prescribing practice only – not micro teaching Not covering why prudent prescribing.

Antimicrobial therapy

Laura Whitney

Sept 2010

Limitations of this session

Prescribing practice only – not micro teaching Not covering why prudent prescribing is a key

Trust and national priority or principles of good prescribing

Adults only Prescribing principles apply to paediatrics, just not

drug choices/doses

What this session will cover

Prescribing in allergies Reviewing antimicrobials IV to Oral Switch Gentamicin and Vancomycin prescribing and

monitoring

Review of Anitbiotic Therapy

Patient referred to the ward from MAU

67 year old male with CAP

CURB-65 score = 2

On the Drug chart

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Penicillin allergy Hx of allergy given by 5% to 20% of pts

reactions range from mild rashes to life-threatening anaphylaxis

Anaphylactic reactions rare (< 0.05%) BUT penicillins are the most common form of drug induced

anaphylaxis (5-10% of cases are fatal) Up to 10% of patients with a true penicillin allergy

will also be allergic to cephalosporins and carbapenems.

Patients who have experienced side-effects e.g. nausea, diarrhoea etc. should not be labelled penicillin allergic the medical notes, drug chart and patient wrist band should

be corrected to reflect this. A detailed clinical history is important to identify

patients with TRUE penicillin allergy. Salkind AR et al. Is this patient Allergic to Penicillin? An Evidence-Based Analysis of the Likelihood

of Penicillin Allergy. JAMA 2001; 285: 2498-2505.

Taking a history

What was the patient’s age at the time of the reaction? Does the patient remember what happened? If not,

who informed them of it? How long after beginning penicillin did the reaction

begin? What were the characteristics of the reaction? What was the route of administration? Why was the patient taking the penicillin? What other medications was the patient taking? Why

and when were they prescribed? What happened when the penicillin was stopped? Has the patient taken antibiotics similar to penicillin

after the reaction? If so, what happened? Salkind AR et al. Is this patient Allergic to Penicillin? An Evidence-Based Analysis of the Likelihood

of Penicillin Allergy. JAMA 2001; 285: 2498-2505.

Allergies – what to do

Allergy Reaction Document Sign

Determining the nature of the allergy

Immediate (<1hours) or accelerated (<72hours) reactions Often associated with systemic manifestations of anaphylaxis

diffuse erythema, pruritis, urticaria, angioedema, laryngeal oedema, bronchospasm, hypotension or cardiac arrhthymias

Patients reporting such reactions must not receive any β-lactam antibiotics.

The use of cephalosporins and carbapenems should be avoided, where possible.

Delayed reactions (>72hours) Patients with a history of minor rash (i.e. non-confluent rash

restricted to a small area of the body) or a rash that occurs more than 72 hours after penicillin are probably not hypersensitive to penicillin.

Avoid β-lactams Reasonable to administer a cephalosporin or carbapenem

Salkind AR et al. Is this patient Allergic to Penicillin? An Evidence-Based Analysis of the Likelihood of Penicillin Allergy. JAMA 2001; 285: 2498-2505.

Common mistakes in allergic pts

Side-effect not allergy Appropriate history not taken

Drug, Reaction, Timeframe, Rechallenges?

Unsure what is safe Betalactams Carbapenems/Cephalosporins Other classes

Use of brand names Augmentin® and Tazocin® Augmentin = Co-amoxiclav Tazocin = Piperacillin-Tazobactam

Fatal mistakes in penicillin-allergic patients

Local Audit data 2009

Audit of penicillin allergy 9% in-patients labelled penicillin-allergic Endorsement complete (drug and reaction) in only

45% charts Allergies

Angiodema/anaphylaxis = 15% Rash = 31% Side-effects only = 10% Unsure = 40%

Amend the Drug chart

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Reviewing Antibiotics

When to review ≤ 48 hrs

Was the diagnosis substantiated? Response to therapy? Any side effects of treatment? Any positive cultures? Continued treatment required? De-escalate Narrower spectrum possible?

IV to oral switch?

How to review

IV to oral switch criteria

• Temp <38°C for 48hours

• No unexplained tachycardia (HR<90bpm for 48 hrs)

• Tolerates oral foods/fluids with no malabsorption

• Patient is clinically stable

• Improving clinical parameters• WCC, CRP

• Not treating conditions requiring high tissue penetration such as meningitis or endocarditis

Can we switch Mr DB to orals?

Day 3 of admission for CAP Clinical improvement seen. IV

fluids discontinued, pt eating and drinking.

BCs negative so far Urinary legionella and

pneumococcal antigens = negative

Can we switch Mr DB to orals?

8/9 9/9 10/9

WCC 14.2 13.5 13.2

Neut 12.8 12.1 12.2

CRP 102 62 48

IV to oral switch criteria

• Temp <38°C for 48hours

• No unexplained tachycardia (HR<90bpm for 48 hrs)

• Tolerates oral foods/fluids with no malabsorption

• Patient is clinically stable

• Improving clinical parameters• WCC, CRP

• Not treating conditions requiring high tissue penetration such as meningitis or endocarditis

What did you prescribe?

Why?

• ↓ adverse effects associated with IV therapy• Phlebitis, administration errors, nosocomial infections

• ↑ Ease of administration• Patient preference, ↓ nursing time, ↓ LOS

• ↓ Cost • ↓ acquisition costs, ↓ LOS, ↓ costs associated with HCAIs

Studies have demonstrated that PO therapy can be as effective as IV in the treatment of infections ranging from

mild to severe

Local Audit data – June 2010

18-21% of in-patients on IV antibiotics 16% of patients on IV abx met the criteria for

an IV to oral switch No patients who met the switch criteria had

microbiology results indicating that an oral treatment option was unavailable

61% of patients who met the switch criteria were not on any other IV medicines or fluids at the time of the audit

Did you remember to document indication and duration?

• Assists in regular review• Ensures optimum treatment duration• Prevents overuse of anti-infectives

Remember to document in medical notes too

Local Audit data

0%

20%

40%

60%

80%

100%

Date

Perc

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Indication in notes

Indication on drugchartStop/Review dateon drug chartCompliance withguidelinesDual-approvalagents approved

Extended interval aminoglycosides

AG of choice is Gentamicin @ 5mg/kg OD Amikacin 15-20mg/kg OD used in certain indications

(neutropenic sepsis) or on micro advice

Benefits of extended interval dosing Concentration-dependent killing Post antibiotic effect Drug free period reduces renal toxicity More convenient to administer and monitor

But… Few trials included patients with pre-existing renal

impairment No evidence for use in endocarditis Altered PK in ascities, pregnancy and burns

These pts are excluded from policy – contact pharmacy for advice

Extended Interval AG

Gentamicin prescribing Seek advice if unsure

Not very fat soluble - adjust dose in obese patients Use dose determining weight (DDW) if actual weight (ABW)

>120% ideal body weight (IBW) IBW (kg) = 50/45kg + (2.3 x every inch over 5ft) 50 = male 45 = female DDW (kg) = IBW + 0.4 (ABW – IBW)

Or just remember to cap pt wt at 100kg

Dose = 5 mg/kg ↓ in renal impairment - See guidelines

But not always necessary in severe sepsis

Miss LC

46 year old patient being treated for abdominal sepsis already on amoxicillin 1g IV tds and metronidazole 500mg IV tds.

You are asked to Rx the gentamicin Weight = 95kg Height = 5ft 4” Serum Creatinine = 74mmol/L What do you prescribe?

Miss LC IBW (kg) = 45kg + 2.3 kg x 4 = 45 + 9.2 55kg

>120% IBW

DDW (kg) = 55 + 0.4 (95 – 55) = 55 + 16 = 71kg

Renal function normal – Dose = 5mg/kg = 360mg

If not adjusted 95 x 5 = 475 mg

What did you prescribe?

Gentamicin monitoring Aim for trough<1mg/L

must be taken 18-24h post first dose Document sampling time on blood form

Peak levels not required

Only wait for levels to come back before giving 2nd dose in Elderly patients Patients with renal impairment If previous levels were high

If trough high reduce dose or increase dosing interval If trough within range and renal function normal monitor

levels twice weekly More frequent monitoring may be required in elderly patients or

those with renal impairment

Call from Staff nurse 9/9/10 2pm

Answer??

Pt LC was off the ward when bloods were done this morning shall we give the 2pm dose?

But take bloods before the dose – We’ll check the results later

Pt is under 65 with good renal function

Vancomycin

Glycopeptide antibiotic in use for 50yrs Early use associated with adverse effects as impure

compound

Standard practice in the UK is to monitor levels to assure efficacy and prevent toxicity evidence for this is lacking and this approach is

controversial

IDSA guidelines 2009

Vancomycin blood concentrations

IDSA guidelines 2009 cont..

Vancomycin prescribing Therapeutic range = 10-15mg/L

Higher levels may be required in severe infections on micro advice

Give loading dose (LD) to ensure therapeutic concentrations achieved on day 1 If unsure about calculating CrCl/MD just give LD

and contact pharmacy for advice You have at least 12 hrs to sort this out!

Pt MH – treatment with vancomycin is required cellulitis as pt is MRSA colonised

.

Mr MH Age 76 Weight = 75kg Height = 5ft 10 Serum Creatinine = 105μmol/L (stable)

CrCl = (140-76) x 1.23 x 75 = 56ml/min 105

What do you prescribe?

What did you prescribe?

Vancomycin monitoring Trough levels (0-60 minutes

pre-dose) must be taken at steady state Document sampling time on

blood form

Peak levels not required

Do not wait for levels to come back before giving dose unless dialysis pt

Only need to check levels twice weekly if renal function stable

Call from Staff nurse 9/9/10 10pm

What is your response?

Pt MH had vanc levels taken this morning? The result came back at

36mg/L. I’m not going to give the dose

When was the level taken?

The phlebotomist was late this morning so they

weren’t done till 11am

Local Audit data 2008

Audit of Vanc, gent & amikacin prescribing, administration and monitoring 14% doses inappropriately omitted 32% levels sent without sampling time 32% levels taken at incorrect time = 34% levels useful

Although some not needed 67% appropriately timed levels acted on

appropriately Inappropriate actions more common when levels taken at

the wrong time

Top Tips Antibiotic Prescribing

1 Documentationensure that you record the indication for therapy on the prescription chart and in the medical notes, along with any specific monitoring parameters or plan for review

2 Durationensure that you record either a proposed review date (ideally within 72 hours of starting therapy) or a proposed stop date on the prescription chart at the time of prescribing

3 De-escalationwhen further information on the causative organism or diagnosis becomes available, change therapy from broad-spectrum empiric antimicrobials to a more narrow-spectrum choice, if appropriate

4 Dosingchoose a dose and route of antimicrobial appropriate for the patient’s severity of illness – convert from IV therapy to oral as soon as is practical and appropriate

5 Don’tdon’t treat colonisation – treat infection; don’t treat contamination – treat infection; don’t routinely use ciprofloxacin empirically – it can predispose to MRSA and Clostridium difficile

Top Tips Antibiotic Therapeutic Drug Monitoring

PK/PD properties of vanc and gent are very different – different prinicples apply to dosing and monitoring

Vancomycin Therapy

Top Tips Antibiotic Therapeutic Drug Monitoring cont

Samples must be taken at the correct time Always document sampling time on blood

forms Avoid unnecessary dose omissions Interpret results carefully No need to do levels every day in every

patient