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
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
time
Ser
um
co
nce
ntr
atio
n
If doses too close If doses too close togethertogether
Do
se
Do
se
Do
se
Do
se
Do
se
Do
se
trough
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