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OPAT management of SAB
Claire Mackintosh
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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
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SAB incidence
HPS
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NHS Lothian SAB incidence
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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
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PHE - HCAI_thirty_day_all_cause_fatality_report_2016_2017.pdf
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PHE - HCAI_thirty_day_all_cause_fatality_report_2016_2017.pdf
Thirty-day all-cause case fatality rate by NHS Region following MSSA bacteraemia
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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
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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
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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
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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
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Daptomycin } Cyclic lipropeptide – once daily administration
} Bactericidal activity against most GPC incl MSSA and MRSA
} Approved for: cSSTI, SAB, R-sided endocarditis
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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
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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.
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OPAT referrals
Cardiothoracic surgery
Neurosciences
Dermatology
Rheumatology
Vascular surgery
Urology
General surgery
GI/ Liver transplant
Cardiology
Oncology
Orthopaedics
RIDU
Medicine
75 episodes were identified
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29%
71%
female
male
Age
(ye
ars)
0 5 10 15 20 25 30 35 40
60
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Co-morbidities
0 10 20 30 40 50 60
Nil
Diabetes
Cancer
CKD
Cardiac failure
Prosthesis
Liver disease
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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)
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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%)
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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
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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
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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)
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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
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} 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
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} 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
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} 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
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} 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
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} 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
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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%)
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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%)
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} 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
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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
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} 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