Consider the patient, the drug and the device how do you choose?

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Consider the patient, the drug and the device how do you choose? Tim Hills Lead Pharmacist Antimicrobials and Infection Control Nottingham University Hospitals NHS Trust

OPAT Recommendations Drug Therapy 3.2 The treatment plan is the responsibility of the OPAT infection specialist, following discussion with the referring clinician. It should include choice and dose of antimicrobial agent, frequency of administration and duration of therapy, and where appropriate should take into account flexibility based on clinical response. 3.3 Antimicrobial choice within OPAT programmes should be subject to review by the local antimicrobial stewardship programme

Microbiology The treatment plan is the responsibility of the OPAT infection specialist, following discussion with the referring clinician Important to get appropriate specimens for culture and sensitivities. Effective treatment for the infection site/sensitivities.

Ideal Drug for OPAT Fits microbiology/sensitivities/allergies Good evidence base for treating infection Ease of dosing and administration Low toxicity/limited monitoring Cost effective

Ease of Administration Once Daily Twice Daily Three Times a Day Direct injection Ceftriaxone 1g Teicoplanin Daptomycin Infusion Ertapenem Ceftriaxone 2g Gentamicin/tobramycin Direct injection Aztreonam Amikacin Infusion Vancomycin Direct injection Meropenem 1g Piperacillin/tazobactam Co-amoxiclav Ceftazidime 1g Colistimethate Sodium (colistin) * Infusion Ceftazidime 2g Meropenem 2g *Totally implantable intravenous access device

Ceftriaxone Broad spectrum Short once daily injection (1g)/infusion (2g) Licensed in pneumonia, Bone and Joint, Meningitis, SSTI Good evidence in IE, PJI, Diabetic foot, CNS infection. Well tolerated, Standard monitoring -weekly bloods Cheap Higher risk for CDI (OPAT ~0.1% 1 ) 1. Int J Clin Pharm (2012) 34:410 417

Clinical Infectious Diseases 2004; 38:1651 72

Ceftriaxone Broad spectrum Short once daily infusion Licensed in pneumonia, Bone and Joint, Meningitis, SSTI Experience in IE, PJI, Diabetic foot, CNS infection. Well tolerated, Standard monitoring -weekly bloods Higher risk for CDI (OPAT ~0.1% 1 ) 1 st dose at discharge 1. Int J Clin Pharm (2012) 34:410 417

Teicoplanin Once daily bolus Licensed for sensitive Gram +ve infections where penicillins/cephalosporins can t be used. Suboptimal outcomes SSTI 1, IE 2 and?pji Rashes and malaise common, Blood dyscrasias occur. Therapeutic Drug Monitoring Required Aim 10-20mg/L SSTI 20-60mg/L for bone/joint/deepseated Standard 400mg dose Potential underdosing 4. 600mg BD for 3 doses OD, if no renal impairment. 1. Seaton RA et al IJAA 38;3 :243-8 2. Duncan CJ et al JAC 2013. 68;7:1650-4) 3. Mackintosh CL et al JAC 2011; 66: 408 415 4. Matthews P. J Infection 2013.

Teicoplanin 3 x Weekly - Loading Dose Lamont et al Journal of Antimicrobial Chemotherapy (2009) 64, 181 187

Teicoplanin 3 x Weekly- Maintenance Dose Lamont et al Journal of Antimicrobial Chemotherapy (2009) 64, 181 187

Daptomycin Gram +ve Once daily bolus Licensed cssti (4mg/kg OD), Right sided IE, S.aureus bacteraemia (6mg/kg OD) Experience in bone/joint/ PJI/L-sided IE ( 6mg/kg OD) Higher doses ( 8mg/kg OD) for Enterococci Consider dose rounding for self/carer admin? 350/500/700/850/1000mg or nearest 50mg. Myositis - weekly CK levels, monitor for eosinophilic pneumonitis.

Ertapenem Broad spectrum (not pseudomonas) Short once daily infusion Licensed for CAP, Abdo, Gynae SSTI of DFI Published experience in OM, DFI, cuti Well tolerated

OPAT Recommendations - Patient 2.1 It is the responsibility of the infection specialist to agree specific infection-related inclusion and exclusion criteria for OPAT. These should incorporate specific infection severity criteria where appropriate. 2.2 There should be agreed and documented OPAT patient suitability criteria incorporating physical, social and logistic criteria. These should be documented for each patient.

NUH Patient Inclusion Age 16 years or above Independent with daily contact with relative/friend Have telephone access If the patient is to self-administer antibiotics they must: Be psychologically stable Have no significant visual impairment Have no significant problems affecting manual dexterity Consent to training to administer own IVs Suitable venous access device in place which is functional and reliable (Home situation cleanliness)

NUH Patient Exclusion Patients with significant co-morbidities Patients with unstable LFTs / U&Es Current intravenous drug users Patients who have known allergies to named treatments Patients who are medically unstable and require in-patient course of therapy

OPAT Recommendations - Administration 3.6 Storage, reconstitution and administration of antimicrobials must comply with published RCN standards and with local hospital clinical pharmacy standards. 3.9 A member of the OPAT team with the appropriate competencies is responsible for selection of the drug delivery device, and use of these must comply with published RCN standards and local hospital guidelines.

Flow restrictors Infusion Bags and Pumps Often poor tolerance values for accurate administration. Not for vancomycin/ drugs where rate important. Electronic pumps and giving set. Can be harder to learn More accurate Syringe driver 24hour infusion via infusion centre model

Closed-admixture bags Simplifies number of steps. Still requires dexterity for attaching giving-set. Flow-restrictor/pump still needed. Option if stability short.

Elastomeric Devices Homepump Easypump /Eclipse Intermate /Infusor Surefuser Reasonable options of all OPAT drugs (inc. vancomycin?). 24hr infusion option available

Factors Affecting Elastomeric Flow Rates Built-in flow restrictor- main variable as per manufacturer Viscosity - Temperature 10 o C change can 20-30% viscosity change check calibration temps. 100ml 6 hours out of fridge before use (Home pump eclipse ) 6 hours Intermate large volume 4 hours Intermate small volume Drug concentration viscosity

Factors Affecting Elastomeric Flow Rates Pressure gradient Underfill/overfill Height of administration Potential overall fluctuation of +/-40% Patient education on correct use essential

Obtaining prefilled devices Local pharmacy sterile production department Under supervision of a pharmacist special (max 7 days) Manufacturing licence (longer expiry but batch manufacturer and QC) Penicillins Stability data for device required Other NHS Trust production department Private/Homecare provider BSAC Project

NUH service (Oct12-Apr13) Method of administration Taught Self/Carer administered % of total episodes (6 months) 76% Taught using prefilled 10% HCW delivered in patient home 4% Ward based infusion centre 10% Plumbers vs Academics!

Acknowledgements Amanda Bort, Lead OPAT nurse, and the Nottingham OPAT team.