OPAT management of SAB

Claire Mackintosh

Staph aureus bacteraemia }  Identified as the most common causative organism in the most recent

Scottish point prevalence study }  Serious systemic blood stream infection with significant morbidity and

mortality }  Frequently healthcare /hospital acquired

SAB incidence

HPS

NHS Lothian SAB incidence

SAB outcomes }  SAB are serious infections associated with serious morbidity and mortality.

}  2015 in Scotland – 30 day all cause mortality: }  MSSA bacteraemia 19.2% }  MRSA bacteraemia 26.2%

}  No change in mortality rates in Scotland between 2011 - 2015

HPS

PHE - HCAI_thirty_day_all_cause_fatality_report_2016_2017.pdf

PHE - HCAI_thirty_day_all_cause_fatality_report_2016_2017.pdf

Thirty-day all-cause case fatality rate by NHS Region following MSSA bacteraemia

Controversies }  Are once daily treatments good enough?

}  1st line therapy – anti-staphylococcal penicillins (flucloxacillin – 4 or 6 hrly)

}  2nd line therapy – glycopeptides }  (vancomycin – bd dosing with requirement for levels)

}  Eliminating multi-dose regimens – improved adherence and retention (high risk patients – PWID), reduce line complications, allow use of OPAT

Ceftriaxone }  Once daily 3rd generation cephalosporin

}  Sparse data }  In vitro: }  Narrow spectrum of activity against penicillin-binding proteins with lower

affinity to PBPs in MSSA cf fluclox

}  Ceftriaxone highly protein bound – modelling suggests serum proteins may impair activity of Ceftriaxone against MSSA

Palmer SM et al, Antimicrob Agents Chemother. 1995;39(8):1764-71 Carr Di et al, Open Forum infect Dis. 2015;2(1):620

Ceftriaxone }  Retrospective review – 541 pts }  Empiric (1st 48hrs illness) ceftriaxone/cefotaxime was associated with

higher 30 day mortality v fluclox/cefazolin: 50.5% v 22.1% (p

Ceftriaxone }  Retrospective review – 93 patients

}  Ceftriaxone v fluclox/cefazolin/vancomycin – MSSA bacteraemia

}  Microbiological cure rates: 94.1% v 95.2% (p=0.812) }  Clinical cure rates: 74.5% v 83.3% (p=0.303)

}  But: No randomisation, 24% received vancomycin, 64% (v 24%) of cef patients were treated via OPAT – suggesting more stable, less unwell patients.

Patel UC et al, Int J Clin Pharm2014;36:1282-9

Daptomycin }  Cyclic lipropeptide – once daily administration

}  Bactericidal activity against most GPC incl MSSA and MRSA

}  Approved for: cSSTI, SAB, R-sided endocarditis

Daptomycin }  Randomised control trial }  6mg/kg Daptomycin v standard therapy (fluclox/vancomycin)

}  MSSA bacteraemia + endocarditis:

}  Success rate 44.6% (dapto) v 48.6% (standard care)

}  Uncomplicated MSSA bacteraemia }  Success rate 57.1% (dapto) v 64.7% (standard care)

}  But: sample sizes were small (144 in endoc group and 36 in bacteraemia group overall), success rates seem low, dose of daptomycin possibly low as we know it exhibits concentration dependant killing

Fowler VG et al NEJM 2006;355(7):653-665

OPAT SAB management }  A retrospective series of all cases of SAB managed at the Edinburgh OPAT centre

between June 2011 and April 2015.

}  Data were collected from patient case records on patient demographics and diagnosis, microbiology and source of culture.

}  }  Data were also collected on antibiotic choice, duration and side effect, including

Clostridium Difficile up to 90 days post- discharge from OPAT.

}  Patient case records were reviewed, data extracted and entered into an SPSS database.

}  Only the first episode of OPAT treated SAB was included for each patient.

OPAT referrals

Cardiothoracic surgery

Neurosciences

Dermatology

Rheumatology

Vascular surgery

Urology

General surgery

GI/ Liver transplant

Cardiology

Oncology

Orthopaedics

RIDU

Medicine

75 episodes were identified

29%

71%

female

male

Age

(ye

ars)

0 5 10 15 20 25 30 35 40

60

Co-morbidities

0 10 20 30 40 50 60

Nil

Diabetes

Cancer

CKD

Cardiac failure

Prosthesis

Liver disease

0 5 10 15 20 25 30 35 40

Bone and joint

Skin and soft tissue

Endocarditis

Infected venflon

Hickman line infection

No source identified

Median duration Inpatient anbx (range; days) 8 (1-30)

7 (5-13)

9 (4-22)

31 (9-68)

18 (5-46)

6 (4-10)

Infective diagnosis Median duration OPAT anbx (range; days)

10 (4-35)

10 (7-17) 11 (5-17) 15 (5-35)

20(6-31) 33 (8-63)

Inpatient treatment

0.00 20.00 40.00 60.00 80.00 100.00

Flucloxacillin

Vancomycin

Daptomycin Median CRP on inpatient dc: 34 (2-198) Echo prior to dc: 68 (87.2%) MSSA 72/75 (96%) MRSA 3/75 (4%)

OPAT treatment

0.00 10.00 20.00 30.00 40.00 50.00 60.00 70.00 80.00

ceftriaxone

daptomycin

teicoplanin

Adverse event rate 2/5 patients (40%) – 1 rash, 1 CDI within 3/12 OPAT completion 1 readmission – worsening infection 3/11 patients (27.3%) – 2 rash, 1 non CDI diarrhoea, 1 readmission - rash 8/59 patients (13.6%) – 5 rash, 1 severe allergic reaction, 1 non CDI diarrhoea, 1 anaemia 2 readmissions – 1 worsening infection/surgical debridement, 1 rash

0.00 10.00 20.00 30.00 40.00 50.00 60.00 70.00 80.00

ceftriaxone

daptomycin

teicoplanin

Infective dx 2/5 patients -BJI, 1 venflon-assoc, 1 Hickman-assoc, 1 unknown source 4/11 patients BJI, 2 SSTI, 1 endocarditis, 1 venflon-assoc, 1 Hickman-assoc, 2 unknown source 9/59 patients BJI, 15 SSTI, 6 endocarditis, 1 venflon-assoc, 4 Hickman-assoc, 24 unknown source

OPAT treatment

OPAT treatment

0.00 10.00 20.00 30.00 40.00 50.00 60.00 70.00 80.00

ceftriaxone

daptomycin

teicoplanin

Unscheduled readmission rate 1/5 patients (20%) 1/11 patients (9.1%) 2/59 patients (3.4%)

IV drug switch – adverse event 0 patients 1 patient à ceftriaxone (rash) 1 patient à daptomycin (severe allergic reaction)

OPAT outcomes }  Success was defined as:

}  completion of the initial prescribed therapy with signs of clinical improvement, a reduction in inflammatory markers, and negative blood cultures.

}  no further iv therapy prescribed post-discharge

}  no unplanned readmission or serious adverse event within 4 weeks of completion of iv therapy

}  Early failure: }  (i) there was a need to continue iv therapy beyond the original prescribed course;

}  (ii) there was a need for unanticipated surgery to control the infection (e.g. surgical debridement, amputation) within 4 weeks of completion of the initial prescribed iv therapy;

}  (iii) the OPAT course was interrupted for any other reason (e.g. admission to hospital for a related or unrelated reason, any serious adverse event or side effect due to the antibiotic that required a change in therapy);

}  (iv) any evidence of relapse or recurrence of infection within 4 weeks of completion of the initial prescribed iv antimicrobial therapy.

OPAT outcomes

}  Late failure: }  evidence of recurrence of infection, relapse or reinfection ≥4

weeks after completing the initial prescribed iv therapy if the patient died for any reason.

OPAT outcomes

}  Whole cohort }  Success: 69/75 (92%) up until 4 weeks following end

of OPAT treatment

}  Early failure:

}  6 patients failed during or within 4 weeks of completing OPAT treatment

OPAT outcomes

}  6 early failures:

}  Median age 66 years (59-76) }  1 female, 5 male }  Median duration of inpatient anbx: 23

days (8-37)

}  Median CRP: 40 (11-198)

}  4 ceftriaxone }  1 teicoplanin }  1 daptomycin

}  Diagnoses: }  2 SSTI }  2 BJI }  2 unknown source

}  Comorbidities: }  2 Nil }  2 Diabetes (non foot) }  1 DFI +CKD }  1 cardiac disease +CKD

OPAT outcomes

}  Median duration of follow up: }  73 weeks (7-104)

}  A further 10 patients failed over follow up period:

}  Final success rate 59/75 (78.6%)

OPAT outcomes

OPAT outcomes

0 5 10 15 20 25 30 35 40

Bone and joint

Skin and soft tissue

Endocarditis

Infected venflon

Hickman line infection

No source identified

Success rate at 30 days 25/27 (92.6%) 6/6 (100%) 3/3 (100%) 7/7 (100%) 15/17 (88.2%) 13/15 (86.6%)

Overall success rate 18/27 (66.6%) 5/6 (83.3%) 2/3 (66.7%) 7/7 (100%) 15/17 (88.2%) 12/15 (80%)

OPAT outcomes

0.00 10.00 20.00 30.00 40.00 50.00 60.00 70.00 80.00

ceftriaxone

daptomycin

teicoplanin

Success rate at 30 days 4/5 (80%) 10/11 (93.2%) 55/59 (86.6%)

Overall success rate 3/5 (60%) 8/11 (72.7%) 49/59 (83.1%)

}  5 deaths in total }  4 – Unknown source }  1 – Hickman line infection

}  4 – cancer }  1 – diabetes (non foot)

}  3 died >26 weeks after completing OPAT treatment

}  2 died within 8 weeks

}  Median age 46 years (37-80) }  Median duration of OPAT: 9 days (7-24)

OPAT outcomes

Conclusions }  Highly select group of patients with SAB

}  Not directly comparable to inpatient group

}  Small numbers in some clinical sub-groups

}  Unknown source – likely very heterogenous group – needs more investigation

}  No deaths within 30 days (with national 30 day mortality rate in MSSA – 19.2% - we would have expected 14.4 deaths) – likely much fitter cohort (50% no-comorbidity)

}  Nevertheless – overall relatively good outcomes in this group }  OPAT management possible with appropriate clinical oversight and selection

}  Phoebe Makiello – Medical student University of Edinburgh

}  Dr Oliver Koch }  Ruth Armstrong }  Lyn Bennett

}  All the patients

}  OPAT Team: }  Sharon Watson }  Maureen Glendinning }  David Adams }  Katie McIntyre }  Clare McTear }  Danielle Godfrey }  Julie Murray }  Gillian Burton }  Gillian Quinn }  Jean Hudson

Thanks

Drawing courtesy of Louis Mackintosh