7. Antibiotics Flashcards by Zahraa Alzoubeidi

How much of antibiotic use is inappropriate?

50% of antbiotic therapy - baring in mind 25% of inpatients are on antibiotics and 2/3 will be put on antibiotics at some stage

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Antibiotic misuse and relationship consequences

MRSA, VRE
C. diff
Resistant Enterobacteriaceae esp E. coli and K. pneumonieae
- Extended spectrum Beta-lactamase (ESBL) producers
Carbapenemase producing enterobacteriaceae (CPE)
Klebsiella producing carbapenemases (KPC)

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Does antibiotic use affect patients on an individual basis

places individual patients at risk of resistant infection - including UTIs and RTIs

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key agents which bacteria can be resistant to?

co-amoxiclav, ciprofloxacin, piperacillin-tazobactam, gentamicin

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Which bacteria are antibiotic resistances most common in?

Gram negatives like E. coli

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Principles of safe and rational prescribing of antibiotics - the initial prescribing decision

Microbial aetiology - where the infection is, where they caught it (hosp vs community) - focus and exposure

Antimicrobial resistance - epidemiology and exposure

Patient factors - predisposition and severity

Antibiotic knowledge

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Rational use of antibiotics demands consideration of:

The aetiological agent (AMR potential)

The patient

The drug (mechanism of action-> spectrum of activity
mechanisms of resistance
key pharmacology

Monitoring

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What is antimicrobial stewardship?

Using antibiotics wisely and responsibly taking into account the long-term effects of antimicrobial selection, dosage, and duration of treatment on resistance developing

Key feature of health policy in the NHS
enforced by the 2008 health and social care act

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Aims of antimicrobial stewardship

enhance health outcomes
reduce antibiotic resistance
decrease unnecessary costs

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What is TARGET?

An Antibiotics toolkit that helps to influence prescribers’ and patient’s personal attitudes, social norms and perceived barriers to optimal antibiotic prescribing

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Are inpatients or outpatients more at risk from infection?

Inpatients, need to be especially on the lookout for prompt recognition and treatment of sepsis

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Sepsis signs

Systolic BP <90mmHg
Lactate >2mmol/l
Heart rate > 130 per minute
Resp rate>25 per mintue
O2 sats <91%
Responds only to voice or pain/unresponsive
purpuric rash

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Sepsis treatment

Give IV antibiotics in the first hour according to trust policy (TAKE ALLERGY HX FIRST)

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Start smart part of start smart then focus

Do not start antibiotics in absence of clinical evidence of bacterial infection
Take drug allergy hx, give w/i 1 hour of infection, local antimicrobial guidelines, document clinical indication, dose and route on drug chart and in notes, include duration and review/stop date, obtain cultures before therapy

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Focus part of start smart then focus

Clinical review & decision after 48-72 hours
Clinical review, check micro and make clear plan, document the decision

Stop
Switch IV to oral
Change antibiotic
Continue
OPAT (outpatient parenteral antibiotic therapy)

Document all decisions

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Drivers to stop antibiotics

Toxicity

Risk of AMR

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Drivers to continue antibiotics

Personal responsibility
Reluctance to interfere
patient outcome

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Most common outcome of focussing antibiotics?

95% of review and revise decisions are to continue Abx treatment

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Things to keep in mind when you review?

Remember antibiotics are harmful?
Did they ever have an infection?
Are they better now?
Do the risks of continuing outweigh the benefits?

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Key points about rational antibiotics antibiotic prescribing decisions

Two moments

Initial prescription:
- microbial aetiology
- patient factors
- antimicrobial resistance issues
- knowledge
- guidelines - choice of agent, duration of therapy
Review and revise

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Amoxicillin

An aminopenicillin

particularly strong against Gram negative bacteria

used to treat S. pyogenes infections (sore throat, skin infections), pneumococcal infections(RTIs), coliform/UTI

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Mechanism of action of amoxicillin

Inhibition of bacterial cell wall synthesis

Standard dose of amoxicillin, side effects and drug interactions

250-1000mg 8 hourly

allergy, damage to commensal microflora

Interactions: can increase levels of other protein bound drugs

Amoxicillin

good oral bioavailability
Protein binding 20%
Metabolism not significant
Half-life 1 hour
Excretion 1 hour

Beta-lactam antibiotics

Penicillins - penicillin G, penicillin V, Amoxicillin, coamoxiclav, flucloxacillin, piperacillin Cephalosporins e.g. cephalexin and cefuroxime carbapenams e.g. meropenem

the easy oral pencillin

Amoxicillin

Amox protected against beta-lactamases

co-amoxiclav

The penicillin for Staph aureus

flucloxacillin

Penicillin for pseudomonas

piperacillin

Beta lactam allergy

``` Penicillin allergy - a class effect - immediate/ accelerate - type 1 (0.02% of courses) Delayed - mixed mechanism (2-3% of courses) ```

Type 1 penicillin allergy

Immediate - 0-72hrs after exposure IgE mediated, mast cell mediated Urticaria, wheeze, life threatening 0.02% of courses

Delayed penicillin allergy

2-3% of courses >72 after exposure Will worsen with repeated exposure does not become immediate type

Cephalosporin allergy

Very complicated - lots of potential haptens involved Not a class effect Penicillin X-reactivity more with 1st and 2nd generations Risk ~8% if previous penicillin allergy Less with 3rd generation

History of beta-lactam allergy

When was it? What happened - time course and severity? What was the drug? Might they have had glandular fever? Have they had a different beta lactam since? good history of anaphylaxis - avoid all beta lactams Weak history or of delayed reaction - consider rechallenge

Clarithromycin

Macrolide w similar spectrum of action to amoxicillin Used for pts with penicillin allergy to treat S. pyogenes infections (sore throat and skin infections) pneumococcal infections (respiratory tract) coliform infections (UTIs) Also against cell-wall deficient bacteria e.g. chlamydia which causes penumonia and GU infections

Clarithromycin pharmacokinetics

``` Good oral bioavailability high protein binding hepatic metabolism 1-6 hours half Excretion as metabolites in bile ```

Clarithromycin mechanism of action

inhibition of protein synthesis bacterial ribosome (50s subunits)

Adverse effects and interactions of clarithromycin

Nausea and diarrhoea, may alter cardiac conduction - arrhythmias interactions - inhibits enzymes (cytochrome p450 enzymes) involved in the metabolism of other drugs

Standard dose of clarythromycin

500mg 12 hourly

Vancomycin

a glycopeptide active only against Gram-positive bacteria and is active against resistance strains including MRSA

Vancomycin pharmacokinetics

``` V low oral bioavailability 50% protein binding No metabolism 4-8 hours half life Excreted as urine ```

Mechanism of action of vancomycin

inhibits bacterial cell wall (peptidoglycans) formation by a different target to beta lactams

Standard dose

500-1500mg 12 hourly Narrow therapeutic window (levels needed to kill the bacteria v close to level toxic to pt) Dose by drugs level in blood

Adverse effects and interaction

Nephrotoxic and ototoxic | Interacts w other ototoxic and nephrotoxic drugs

Doxycycline

A tetracycline w good activity against Gram positive e.g. Streps and Staphs against some Gram negs e.g. haemophilus Active against cell-wall deficient bacteria e.g. chlamydia which cause pneumonia and genitourinary infections Poor against Enterobacteriaceae, anaerobes Used for skin, resp tract, genital tract infections Loe C diff risk

Mechanism of action of doxycycline

Inhibition of protein synthesis in the bacterial ribosome (30s subunit)

Adverse effects and interactions of doxycycline

Dyspepsia, photosensitivity, avoid in pregnancy/children (teeth) Interactions: competes for protein binding - warfarin, digoxin etc

Doxycycline

``` good oral bioavaialbity Moderate protein binding No metabolism Half-life 6-12 hours Excreted in urine and bile ```

Standard dose of doxycycline

100-200mg daily

Nitrofurantoin

Only nitrofuran Wide spectrum - esp E. coli and other enterobactericeae, enterococci, staphs, some streps Use for lower UTIs only too little tissue penetration elsewhere

Mechanism of action of nitrofurantoin

complex. Damages bacterial DNA | High resistance threshold

Adverse effects of nitrofurantoin

V well tolerated Safe in early pregnancy - avoid late Avoid in renal impairment - peripheral neuropathy, doesn't uterine if eGFR low no major interactions

Standard dose of nitrofurantoin

50mg qds