Intravenous Antibiotics in the Community Lilian Li Principal Microbiology Pharmacist Imperial College Healthcare NHS Trust St Mary’s Hospital Thanks to Jan Hitchcock, Dr Hand & Dr Conlon

Aim & Objectives To improve knowledge on intravenous (IV) antibiotics used in the community Become familiar with some of the infections treated Become familiar with some of the pathogenic micro-organisms involved List the ideal properties of a suitable antibiotic for use in the community List the most common antibiotics used State how to administer those antibiotics Be familiar the side-effects associated with these antibiotics to be monitored List sources of support

Lactose-fermenting coliforms E coli, Klebsiella, Enterobacter Gram +ve Cocci (spherical) Staphylococci Streptococci Enterococci Peptococci/Peptostreptococci* Gram -ve Cocci Neisseria meningitidis Neisseria gonorrhoea Moraxella catarrhalis Acinetobacter (coccobacillus) Gram +ve Rods Clostridia* Corynebacteria (diphtheroids) Listeria Bacillus *Anaerobes Gram -ve Rods Bacteroides* Lactose-fermenting coliforms E coli, Klebsiella, Enterobacter Non lactose-fermenting coliforms Proteus, Salmonella, Shigella Pseudomonas Haemophilus Helicobacter, Campylobacter Legionella Start off with basic understanding of classification of bacteria as will use these terms later

Generally... Gram -ve GI-tract Anaerobes Mouth, teeth, throat, sinuses & lower bowel Gram +ve Skin & mucous membranes Atypicals Chest and genito-urinary Cert

The perfect IV antibiotic for use in the community Efficacy, safety, cost Ease of administration bolus vs. infusion Pharmacokinetics long half-life allows once or twice daily dosing Stability dry or diluted room temperature or refrigerated Compatibility with other antibiotics with saline and heparin flushes

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

Pattern of Activity Antibiotics Goal of Therapy PK/PD Parameter Type I Concentration-dependent killing & Prolonged persistent effects Aminoglycosides Daptomycin Fluoroquinolones Ketolides Maximize concentrations 24h-AUC/MIC Peak/MIC Type II Time-dependent killing and Minimal persistent effects Carbapenems Cephalosporins Erythromycin Linezolid Penicillins Maximize duration of exposure T>MIC Type III Time-dependent killing and Moderate to prolonged persistent effects. Azithromycin Clindamycin Oxazolidinones Tetracyclines Vancomycin Maximize amount of drug 24h-AUC/MIC

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

Which antibiotics? Ceftriaxone Teicoplanin Ertapenem Ceftazidime Meropenem Gentamicin

Ceftriaxone 3rd generations cephalosporin Activity: Gram negative and positive bacteria 5-10% cross sensitivity to penicillins Side-effects GI upset, diarrhoea, n&v (precipitation in gall bladder) Administration Bolus reconstitute 1g with 10ml WFI & infuse over 3-5 minutes Intermittent infusion Reconstitute 2g with 40ml N/Saline & infuse over 30 minutes

Teicoplanin Glycopeptide Activity: Serious Gram positive infection resistant to other antibiotics Contra-indicated if patient vancomycin allergic Side-effects Rash, n&v, hearing impairment, renal impairment Administration Bolus Reconstitute vial with 3ml WFI, roll & rest. Infuse over 3-5 minutes

Ertapenem Carbapenem Activity: broad spectrum (Gram +ve/-ve and anaerobes) CARE! Sodium valproate / valproic acid Contra-indication Anaphylaxis to β-lactams Side-effects Rash, n&v,  LFTs,  platelets Administration Reconstitute 1g with 10ml WFI, dilute up to 50ml with N/Saline. Infuse over 30 minutes.

Ceftazidime 3rd generations cephalosporin Activity: Gram -ve and +ve bacteria 5-10% cross sensitivity to penicillins Side-effects GI upset, diarrhoea, n&v Administration Bolus reconstitute with 10ml WFI or N/Saline & infuse over 3-5 minutes

Meropenem Carbapenem Activity: broad spectrum (Gram +ve/-ve and anaerobes) Contra-indication Anaphylaxis to β-lactams Side-effects GI upset, injection site reactions, headache Administration Reconstitute @ 500mg vial with 10ml WFI, infuse over 5 minutes.

Gentamicin Aminoglycoside Activity: Gram -ve Side-effects Ototoxicity, nephrotoxicity Administration Dilute 1g with 10ml N/Saline, infuse over 3-5 minutes. TDM Pre-dose = trough Aim < l mg/L

If one dose is given… peak Serum concentration trough time Dose Tds dosing If sample taken an hour post dose t = 8-1 = 7 hours trough time Dose

What we want… Serum concentration trough time Dose Dose Dose Dose Dose Tds dosing If sample taken an hour post dose t = 8-1 = 7 hours time Dose Dose Dose Dose Dose

If doses too close together Serum concentration trough Tds dosing If sample taken an hour post dose t = 8-1 = 7 hours time Dose Dose Dose Dose Dose Dose

How often should gentamicin be given

Infusion Devices Human with syringe and needle Gravity drip IVAC pump Syringe driver Elastomeric device (e.g. Intemate) CADD (programmable portable device)

OPAT complications Drug-associated Line-associated Other GI upset Rash Fever Neutropenia Anaphylaxis Renal Line-associated Infection Leakage Phlebitis Thrombosis Other Rx related Unrelated

OPAT team BNF Microbiology Pharmacists Medicines information Drug monographs Community chemist CNS Nurses Anu Viljanen Jan Hitchcock Microbiology Pharmacists Tracy Lyons Lilian Li Medicines information 020 7886 1203

Summary Safe and effective Saves thousands of bed days Highly dependent on liaison nurses Number of nurses are rate-limiting High patient satisfaction A model for NHS hospital / community cooperation