The impact of 24hr infusions on clinical practice

Tim HillsNottingham University Hospitals NHS Trust

Outline• Why use CIV beta-lactam antibiotics?• Drug-stability work stream• Initial experience of CIV beta-lactams• Clinical Outcomes of there use in OPAT• Future plans

PK/PD consideration

• Meropenem 1.5g load then 1g tdsvs 500mg load then 3g/24hr CIV (3 x 8h infusions)

• Higher plasma and subcut. levels (black) with CIV.

Roberts et al JAC 2009

(Doses expressed as piperacillin content) Roberts et al critical care med 2009

• Piperacillin bolus 4g 6hrly vs 12-16g/24hr CIV

• Higher likelihood of PK/PD target attainment with CIV dosing in critically ill with normal renal function. (bolus target =60% T>MIC, CIV = 100% T>MIC)

þFlucloxacillinýMeropenem

National Advice• Advice for clinicians, pharmacy and

nursing staff on considerations for OPAT services– Drug stability, including design of studies– Use of buffers– Compounding– Procurement– Storage– Administration

Mark Santillo, Abi Jenkins and Conor Jamiesonhttps://www.sps.nhs.uk/wp-content/uploads/2018/07/OPAT-v1-April-18.pdf

Citrate Buffer

3Ca2+

Ca2+- O-

O-

O-Ca2+

Ca2+

6Na+

Citrate Buffer – potential issues

Monitored blood results

• N = 11• No patient required CIV interruption

• Low Ca2+: 1 x deranged LFTs, 1 x Low Vitamin D

Study 2:Clinical Outcomes• Design: Retrospective obervational study• Inclusion: Patient episodes treated with buffered CIV beta-lactams

on OPAT from July 2017-October 2018.• Outcomes: based on BSAC NORS Infection Outcomes

– Cured: Completed OPAT duration with resolution of infection and no long-term antibiotics

– Improved: Completed OPAT with partial resolution of infection but need for further follow-up OR required escalation of antimicrobial therapy.

– Failure: Progression or non-response of infection despite OPAT, required admissions, surgical intervention or died for any reason.

CIV Flucloxacillin (8g or 12g/24hours) Primary Infective Diagnosis

Discitis without metalwork (MW)

Discitis with MW

Epidural abscess

Infected total knee replacement

Infective Endocarditis

Malignant otitis externa

Post op wound infection

Psoas abscess

Septicaemia

Spinal infection assoc with MW

Wound infection post op

Osteomyelitis surgically related

N= 18

Benzylpenicillin• Single patient-episode of vascular surgery infection

treated with benzylpenicillin 9.6g/24hr (2 x 4.8g concurrent via a dual lumen PICC).

Pip/taz 13.5g/24 hour CIV Primary Infective Diagnosis

0

2

4

6

8

10

12

14

16

Bronchiectasis DF NO OM DFOM Empyema Lung abscess Vascular graftinfection

Outcomes

0

2

4

6

8

10

12

14

16

18

BenPen 4.8g/24h Fluclox 12g/24h Fluclox 8g/24h PipTaz 13.5g/24h

Cured

Fail

Improved

Hills and Snape Poster #2141

Comparison with Historic CohortPiperacillin/tazobactamdose and indication Number Male % Mean age

Proportion “improved” or

“cured”13.5g/24 hours CIV Bronchiectasis 15 53.3% 74.2 years 86.7%*

4.5g three times a day Bronchiectasis 53 41.5% 69.5 years 83.3%*

13.5g/24 hours CIV Diabetic foot osteomyelitis

11 63.6% 62.9 years 81.8%**

4.5g three times a day Diabetic foot osteomyelitis

28 63.0% 61.0 years 60%**

*p=0.73 **p=0.21(Chi squared test) .

Clinical outcomes: Study 3• 35 Patient episodes piperacillin/tazobactam

elastomeric CIV treating PsA infections Jan 2015-Dec 2017 on OPAT.

• Resp 42.9%, SSTI 34.6%, Urinary 25.7%, OA 2.9%

J Ferreiro et al Poster #2140

J Ferreiro et al Poster #2140

Where are we now and for the future?

• Bringing aseptic dispensing of CIVs in-house.– Pilot 7 week study annualised saved us 170 bed days, £5k

• Review of need for additional bloods as limited effects seen (with current citrate loads).– ?Focus on higher risk patient– ?Continue with adjusted calcium monitoring?

• Drug stability work on Piperacillin/Tazobactam and Ceftazidime

Summary• CIV beta lactams are a rational, efficacious option

which support OPAT patient care and service delivery.• Stability data is required to support their use

particularly in body-worn devices

• Any Questions?