Intravenous Antibiotics in Intravenous Antibiotics in the Community the Community

Lilian Li Lilian Li

Principal Microbiology PharmacistPrincipal Microbiology Pharmacist

Imperial College Healthcare NHS Trust Imperial College Healthcare NHS Trust

St Mary’s HospitalSt Mary’s Hospital

Thanks to Jan Hitchcock, Dr Hand & Dr ConlonThanks to Jan Hitchcock, Dr Hand & Dr Conlon

Aim & ObjectivesAim & Objectives

To improve knowledge on intravenous (IV) To improve knowledge on intravenous (IV) antibiotics used in the communityantibiotics used in the community

Become familiar with some of the infections treatedBecome familiar with some of the infections treated Become familiar with some of the pathogenic micro-Become familiar with some of the pathogenic micro-

organisms involved organisms involved List the ideal properties of a suitable antibiotic for use List the ideal properties of a suitable antibiotic for use

in the communityin the community List the most common antibiotics usedList the most common antibiotics used State how to administer those antibioticsState how to administer those antibiotics Be familiar the side-effects associated with these Be familiar the side-effects associated with these

antibiotics to be monitoredantibiotics to be monitored List sources of supportList sources of support

Gram +ve Cocci (spherical)Gram +ve Cocci (spherical)

StaphylococciStaphylococci

StreptococciStreptococci

EnterococciEnterococci

Peptococci/Peptostreptococci*Peptococci/Peptostreptococci*

Gram -ve CocciGram -ve Cocci

Neisseria meningitidisNeisseria meningitidis

Neisseria gonorrhoeaNeisseria gonorrhoea

Moraxella catarrhalisMoraxella catarrhalis

Acinetobacter (coccobacillus)Acinetobacter (coccobacillus)

Gram +ve RodsGram +ve Rods

Clostridia*Clostridia*

Corynebacteria (diphtheroids)Corynebacteria (diphtheroids)

ListeriaListeria

BacillusBacillus

*Anaerobes*Anaerobes

Gram -ve RodsGram -ve Rods

Bacteroides*Bacteroides*

Lactose-fermenting coliformsLactose-fermenting coliforms E coli, Klebsiella, EnterobacterE coli, Klebsiella, Enterobacter

Non lactose-fermenting coliformsNon lactose-fermenting coliforms Proteus, Salmonella, ShigellaProteus, Salmonella, Shigella

PseudomonasPseudomonas

HaemophilusHaemophilus

Helicobacter, CampylobacterHelicobacter, Campylobacter

LegionellaLegionella

CertCert

Gram +ve Skin & mucous

membranes

Gram -ve GI-tract

AnaerobesMouth, teeth,

throat, sinuses & lower bowel

Generally...

AtypicalsChest and

genito-urinary

The perfect IV The perfect IV antibiotic for use in antibiotic for use in the communitythe community Efficacy, safety, costEfficacy, safety, cost Ease of administrationEase of administration

– bolus vs. infusionbolus vs. infusion PharmacokineticsPharmacokinetics

– long half-life allows once or twice daily dosinglong half-life allows once or twice daily dosing StabilityStability

– dry or diluteddry or diluted– room temperature or refrigeratedroom temperature or refrigerated

CompatibilityCompatibility– with other antibioticswith other antibiotics– with saline and heparin flusheswith saline and heparin flushes

http://www.rxkinetics.com/antibiotic_pk_pd.htmlhttp://www.rxkinetics.com/antibiotic_pk_pd.html

Pattern of Pattern of ActivityActivity

AntibioticsAntibiotics Goal of Goal of TherapyTherapy

PK/PD PK/PD ParameteParameterr

Type IType IConcentration-Concentration-dependent dependent killing & killing & Prolonged Prolonged persistent persistent effects effects

AminoglycosidesAminoglycosidesDaptomycinDaptomycinFluoroquinolonesFluoroquinolonesKetolides Ketolides

Maximize Maximize concentrationconcentrations s

24h-24h-AUC/MICAUC/MICPeak/MIC Peak/MIC

Type IIType IITime-Time-dependent dependent killing and killing and Minimal Minimal persistent persistent effects effects

CarbapenemsCarbapenemsCephalosporinsCephalosporinsErythromycinErythromycinLinezolidLinezolidPenicillins Penicillins

Maximize Maximize duration of duration of exposure exposure

T>MIC T>MIC

Type IIIType IIITime-Time-dependent dependent killing andkilling andModerate to Moderate to prolonged prolonged persistent persistent effects. effects.

AzithromycinAzithromycinClindamycinClindamycinOxazolidinonesOxazolidinonesTetracyclinesTetracyclinesVancomycin Vancomycin

Maximize Maximize amount of amount of drug drug

24h-24h-AUC/MIC AUC/MIC

Extract from Table 5. Tice AD et al. CID 2004, 38:1651-72Extract from Table 5. Tice AD et al. CID 2004, 38:1651-72

Duration of stability, by storage temperaturea

Drug

Half-life in h

Phlebitis risk

ratingb

Optimal dilution, mg/mLc

-20°C 5°C 25°C

Penicillin Gf 0.4 0.9 2 0.2 84 d 14 d 2 d

Ceftazidime 1.4 2 1 1 40 90 d 21 d 2 d

Ceftriaxone 5.4 10.9 1 10 40 180 d 10 d 3 d

Imipenem-cilastatin 0.8 1.3 2 2.5 5 ND 2 d 10 h

Meropenem 1.5 1 5 20 ND 24 h 4 h

Ertapenem 4 2 20 ND 24 h 6 h

Gentamicin 2 3 1 0.6 1 30 d 30 d 30 d

Vancomycin 4 6 2 5 63 d 63 d 7 d

Amphotericin B 24-360 3 0.1 ND 35 d 5 d

Which antibiotics?Which antibiotics?

CeftriaxoneCeftriaxone TeicoplaninTeicoplanin ErtapenemErtapenem CeftazidimeCeftazidime MeropenemMeropenem GentamicinGentamicin

CeftriaxoneCeftriaxone

33rdrd generations cephalosporin generations cephalosporin Activity: Gram negative and positive bacteriaActivity: Gram negative and positive bacteria 5-10% cross sensitivity to penicillins5-10% cross sensitivity to penicillins Side-effectsSide-effects

– GI upset, diarrhoea, n&v (precipitation in gall GI upset, diarrhoea, n&v (precipitation in gall bladder)bladder)

AdministrationAdministration– Bolus Bolus

reconstitute 1g with 10ml WFI & infuse over 3-5 minutesreconstitute 1g with 10ml WFI & infuse over 3-5 minutes– Intermittent infusion Intermittent infusion

Reconstitute 2g with 40ml N/Saline & infuse over 30 Reconstitute 2g with 40ml N/Saline & infuse over 30 minutesminutes

TeicoplaninTeicoplanin

GlycopeptideGlycopeptide Activity: Serious Gram positive infection Activity: Serious Gram positive infection

resistant to other antibioticsresistant to other antibiotics Contra-indicated if patient vancomycin Contra-indicated if patient vancomycin

allergicallergic Side-effectsSide-effects

– Rash, n&v, hearing impairment, renal impairmentRash, n&v, hearing impairment, renal impairment AdministrationAdministration

– BolusBolus Reconstitute vial with 3ml WFI, roll & rest. Infuse over Reconstitute vial with 3ml WFI, roll & rest. Infuse over

3-5 minutes3-5 minutes

ErtapenemErtapenem

CarbapenemCarbapenem Activity: broad spectrum Activity: broad spectrum

(Gram +ve/-ve and anaerobes)(Gram +ve/-ve and anaerobes) CARE! Sodium valproate / valproic acidCARE! Sodium valproate / valproic acid Contra-indicationContra-indication

– Anaphylaxis to Anaphylaxis to ββ-lactams-lactams Side-effectsSide-effects

– Rash, n&v, Rash, n&v, LFTs, LFTs, platelets platelets AdministrationAdministration

– Reconstitute 1g with 10ml WFI, dilute up to 50ml Reconstitute 1g with 10ml WFI, dilute up to 50ml with N/Saline. Infuse over 30 minutes.with N/Saline. Infuse over 30 minutes.

CeftazidimeCeftazidime

33rdrd generations cephalosporin generations cephalosporin Activity: Gram -ve and +ve bacteriaActivity: Gram -ve and +ve bacteria 5-10% cross sensitivity to penicillins5-10% cross sensitivity to penicillins Side-effectsSide-effects

– GI upset, diarrhoea, n&v GI upset, diarrhoea, n&v AdministrationAdministration

– Bolus Bolus reconstitute with 10ml WFI or N/Saline & infuse reconstitute with 10ml WFI or N/Saline & infuse

over 3-5 minutesover 3-5 minutes

MeropenemMeropenem

CarbapenemCarbapenem Activity: broad spectrum Activity: broad spectrum

(Gram +ve/-ve and anaerobes) (Gram +ve/-ve and anaerobes) Contra-indicationContra-indication

– Anaphylaxis to Anaphylaxis to ββ-lactams-lactams Side-effectsSide-effects

– GI upset, injection site reactions, headacheGI upset, injection site reactions, headache AdministrationAdministration

– Reconstitute @ 500mg vial with 10ml WFI, Reconstitute @ 500mg vial with 10ml WFI, infuse over 5 minutes.infuse over 5 minutes.

GentamicinGentamicin

AminoglycosideAminoglycoside Activity: Gram -veActivity: Gram -ve Side-effectsSide-effects

– Ototoxicity, nephrotoxicityOtotoxicity, nephrotoxicity AdministrationAdministration

– Dilute 1g with 10ml N/Saline, infuse over Dilute 1g with 10ml N/Saline, infuse over 3-5 minutes.3-5 minutes.

TDMTDM– Pre-dose = troughPre-dose = trough– Aim < l mg/LAim < l mg/L

peak

trough

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time

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nIf one dose is given…If one dose is given…

Do

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nWhat we want…What we want…

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Do

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time

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If doses too close If doses too close togethertogether

Do

se

Do

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se

Do

se

Do

se

trough

How often should How often should gentamicin be givengentamicin be given

Infusion DevicesInfusion Devices

Human with syringe and needleHuman with syringe and needle Gravity dripGravity drip IVAC pumpIVAC pump Syringe driverSyringe driver Elastomeric device (e.g. Intemate)Elastomeric device (e.g. Intemate) CADD (programmable portable CADD (programmable portable

device)device)

OPAT complicationsOPAT complications

Drug-associatedDrug-associated GI upsetGI upset

RashRash

FeverFever

NeutropeniaNeutropenia

AnaphylaxisAnaphylaxis

RenalRenal

Line-associatedLine-associated InfectionInfection

Leakage Leakage

PhlebitisPhlebitis

ThrombosisThrombosis

OtherOther Rx relatedRx related

UnrelatedUnrelated

OPAT teamOPAT team

BNFBNF Drug monographsDrug monographs Community chemistCommunity chemist CNS NursesCNS Nurses

– Anu ViljanenAnu Viljanen– Jan HitchcockJan Hitchcock

Microbiology PharmacistsMicrobiology Pharmacists– Tracy LyonsTracy Lyons– Lilian LiLilian Li

Medicines informationMedicines information– 020 7886 1203020 7886 1203

SummarySummary

Safe and effectiveSafe and effective Saves thousands of bed daysSaves thousands of bed days Highly dependent on liaison nursesHighly dependent on liaison nurses

– Number of nurses are rate-limitingNumber of nurses are rate-limiting High patient satisfactionHigh patient satisfaction

A model for NHS hospital / community cooperationA model for NHS hospital / community cooperation