Dalbavancin The Glasgow Experience. Dr Neil Ritchie Consultant Physician, Infectious Diseases Queen Elizabeth University Hospital, Glasgow

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Dalbavancin The Glasgow Experience Dr Neil Ritchie Consultant Physician, Infectious Diseases Queen Elizabeth University Hospital, Glasgow

Financial Disclosures I have previously received an honorarium to prepare a presentation from Cardiome UK

Dalbavancin within the context of a comprehensive cellulitis service Expanding ambulatory care Overview Dalbavancin as an option for out-patient management of complex infection Rationale for use within Glasgow OPAT

Dalbavancin Lipoglycopeptide antibiotic with prolonged half life Suitable for extended interval dosing: Single dose and two dose regimens available for use in soft tissue infection Limited published experience on use for other indications

Nurse-led Cellulitis Care Admission Avoidance Open referral criteria: Direct referral from GPs Referral from nursing triage at immediate assessment unit Direct referral from ED Nurse-led assessment and management in hours First dose and discharge to return out of hours Facilitated Discharge Daily ward rounds of the medical receiving units Discharge on OPAT Antimicrobial stewardship Direct admission to ID unit Expedite ID physician review Facilitated discharge of patients with cellulitis from any inpatient area of the hospital

Service Overview First 6 months: 372 patients reviewed by the service 71 patients managed with oral antibiotics or no antibiotics at all 138 patients accepted for ambulatory management of cellulitis In-patient IV No IV required Ambulatory IV therapy

Service Overview Ceftriaxone First 6 months: 372 patients reviewed by the service 71 patients managed with oral antibiotics or no antibiotics at all 138 patients accepted for ambulatory management of cellulitis In-patient IV No IV required Ambulatory IV therapy Daptomycin Dalbavancin

Case 1 Mrs CE, 103 year old woman Nursing home resident Past history of heart failure, AF, hypertension Admitted to hospital with worsening right leg cellulitis Previous course of flucloxacillin from GP but failed to respond

Case 1 P97, Temp 37.6 WCC 15.4, CRP 167 Reviewed by OPAT nursing team: Medically suitable for OPAT but unable to attend daily Very keen to be discharged from hospital Given dalbavancin 1000mg and discharged Elected not to attend for review one week later as completely recovered

Dalbavancin for Cellulitis Patient selection by ID consultant after review on receiving unit/ medical ward All dalbavancin given via OPAT team Patients managed with initial dose of 1000mg dalbavancin Planned review at 1 week: Further 500mg or IVOST No patient received further IV dose Age Gender Reason for dalbavancin use Outcome 34 Male Injecting drug use, multiple skin popping abscesses/cellulitis Improved 37 Male Injecting drug use, soft tissue infection, anti-social behaviour DNA no readmission 82 Male House bound, failed on appropriate oral therapy Cure died 2/12 cssti 92 Female Unable to attend day unit, failed on appropriate oral therapy Cure 94 Female Nursing home resident, unable to arrange alternative OPAT Cure 103 Female Residential care home resident, unable to arrange alternative DNA telephone cured

Dalbavancin in OPAT Age Gender Diagnosis Microbiology Reason for Use 81 Male Prosthetic joint infection MRSA tissue Unable to manage daily OPAT 47 Female Recurrent line infection MSSA bacteraemia IV access, recurrent infection 35 Male Discitis and epidural collection MSSA bacteraemia Unsuitable for IV access in community 87 Female Prosthetic joint infection CNS tissue Lack of OPAT alternatives 52 Female Vascular graft infection Nil Intolerance of alternatives 42 Male Recurrent tricuspid endocarditis MSSA bacteraemia Risk of indwelling vascular access 44 Male Mitral valve endocarditis MSSA bacteraemia Unable to manage daily OPAT 55 Male Drug use associated sepsis MSSA bacteraemia Unsuitable for IV access in community

Dalbavancin in OPAT Age Gender Diagnosis Microbiology Reason for Use 81 Male Prosthetic joint infection MRSA tissue Unable to manage daily OPAT 47 Female Recurrent line infection MSSA bacteraemia IV access, recurrent infection 35 Male Discitis and epidural collection MSSA bacteraemia Unsuitable for IV access in community 87 Female Prosthetic joint infection CNS tissue Lack of OPAT alternatives 52 Female Vascular graft infection Nil Intolerance of alternatives 42 Male Recurrent tricuspid endocarditis MSSA bacteraemia Risk of indwelling vascular access 44 Male Mitral valve endocarditis MSSA bacteraemia Unable to manage daily OPAT 55 Male Drug use associated sepsis MSSA bacteraemia Unsuitable for IV access in community

Case 2 47 year old woman T1DM with diabetic nephropathy Admitted with challenging DKA Challenging IV access and PICC lines sited Repeated episodes of MSSA bacteraemia with relapse rapidly following withdrawal of antibiotic therapy

Case 2 Normal TOE Non-occlusive thrombus at origin of SVC Very challenging access and plan to insert Hickman line

Case 2 Normal TOE Non-occlusive thrombus at origin of SVC Very challenging access and plan to insert Hickman line Given single dose of dalbavancin 1000mg immediately prior to removing PICC line Maintained without access for as long as possible (managed 10 days) Hickman line inserted after access free period No evidence of recurrence at 7 months

Case 3 87 year old woman Nursing home resident with history of Alzheimer s dementia Admitted with painful right leg Found to have prosthetic joint infection with multiple isolates of MDR S. epidermidis Managed with washout and limited debridement Unable to tolerate lines, high risk of injury in hospital due agitation

Case 3 Received 2 weeks of vancomycin Switched to dalbavancin 1000mg weekly with oral rifampicin and discharged back to nursing home Developed rash and eosinophila after 72 hours resolved after withdrawal of rifampicin Completed 4 weeks of dalbavancin without further incident Switched to linezolid and tolerated 3 weeks No evidence of recurrence at 4 months Mobile in nursing home Refused blood monitoring

Case 4 42 year old man History of intra-venous drug use Admitted to ITU with tricuspid valve endocarditis and multiple intrapulmonary abscesses Given 6 weeks IV flucloxacillin and discharged on oral clindamycin

Case 4 Readmitted with sepsis Evidence of ongoing injecting Enlarging tricuspid vegetation MSSA and Group B strep bacteraemia Re-treated with amoxicillin and flucloxacillin Patient spending large amount of time off ward with concern about drug use within hospital

Case 4 Readmitted with sepsis Evidence of ongoing injecting Enlarging tricuspid vegetation MSSA and Group B strep bacteraemia Re-treated with amoxicillin and flucloxacillin Patient spending large amount of time off ward with concern about drug use within hospital Completed 3 weeks flucloxacillin as in-patient Discharged after 1500mg dalbavacin and given further 1500mg dose 1 week later No evidence of relapse after 4 months

Dalbavancin in OPAT Age Gender Diagnosis Microbiology Reason for Use 81 Male Prosthetic joint infection MRSA tissue Unable to manage daily OPAT 47 Female Recurrent line infection MSSA bacteraemia IV access, recurrent infection 35 Male Discitis and epidural collection MSSA bacteraemia Unsuitable for IV access in community 87 Female Prosthetic joint infection CNS tissue Lack of OPAT alternatives 52 Female Vascular graft infection Nil Intolerance of alternatives 42 Male Recurrent tricuspid endocarditis MSSA bacteraemia Risk of indwelling vascular access 44 Male Mitral valve endocarditis MSSA bacteraemia Unable to manage daily OPAT 55 Male Drug use associated sepsis MSSA bacteraemia Unsuitable for IV access in community

Summary Dalbavancin allows ambulatory management of patients with cellulitis otherwise not suitable for OPAT therapy Dalbavancin is an alternative treatment for the management of patients with complex infections: Those unsuitable for OPAT due to injecting drug use Those intolerant of OPAT alternatives or with challenging IV access Those whose physical frailty makes extended interval dosing useful Limited outcome data and data on dosing in extended courses

Dalbavancin Outcome Data 100% 69 20 15 12 8 7 3 4 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Overall PJI ABSSSI Osteomyelitis CR-Bacteraemia Endocarditis Intra-abdominal Other Bousa et al, IJAA 2017

Acknowledgements Glasgow OPAT Team: Andrew Seaton Beth White Lee Stuart Fiona Robb Claire Valance Claire Summerhill Lynne O Reilly Liz Collison ID/Microbiology/AIM StRs