Transcript Document

Acute Medicine
Training Day
3rd Apirl, 2014
Dr Julian Sutton
Consultant in Infectious Diseases and Medical Microbiology
Case 1
• 30M, IT worker
• PMH: Asthma & Severe eczema
• Prednisolone 10mg OD & Methotrexate
• 2 days: Fever, chills, headache
• 1 day: Vomiting, neck stiffness, worsening severity headache
• T38.2, P110, BP 115/75, Sats 97%
• Hb 156, Wbc 13.8, nø 12.8, lø 0.4, Plt 150
• U+E normal, alb 35, bili 16, ALT 74, ALP 106, CRP341
Case 1
Case 1
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Blood cultures taken
Commenced on CNS dose Cefotaxime, Amoxicillin, Aciclovir
Urinalysis ++ protein, +++ ketones, +++ blood
CT brain without contrast…..
Case 1
• Small lateral and 3rd ventricles
• Global effacement of cerebral sulci
• Exaggerated grey/white matter differentiation c/w diffuse oedema
• Cerebellar tonsils extend into but not through the foramen magnum
• Conclusion: diffuse brain swelling c/w meningitis or meningoencephalitis
• D/w Neurosurgery if considering LP
Case 1
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Admission blood cultures, gram positive cocci, both bottles at 24hrs
R/v by Infection team
Small ulcer on tongue
No splinters, possible vascultic lesion L hand, loud PSM
Alert and orientated, no meningism
• Imp: features c/w meningoencephalitis in IC’d host
• Need to exclude Infective endocarditis (though headache and cerebral
oedema not explained by uncomplicated IE)
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Urgent echocardiogram
MRI brain w contrast
Neurology r/v re ability to perform LP
BC, EDTA blood for pneumococcal & meningococcal PCR, urine
pneumococcal ag, serum CrAg, HIV test
Case 1
• Echocardiogram
– 1.2cm x 1cm mobile structure on post MV leaflet
– Mild / Moderate MR
– Normal bi-ventricular function
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Following day BCs confirmed as S. aureus (MSSA)
CNS dose cefotaxime continued
Amoxicillin and Aciclovir stopped
MR brain w contrast awaited….
• Pneumococcal & meningococcal PCR on blood negative
• HSV, VZV and Enterovirus PCR on mouth ulcer negative
• HIV negative, serum CrAg negative
Case 1
Case 1
Case 1
• lesions in the left side of the corpus callosum.
• right parietal white matter
• both lesions show modest peripheral enhancement
• no additional parenchymal, meningeal or dural enhancement
• cerebellar tonsils not low lying, cortical sulci not effaced
Case 1
• Rifampicin 600mg BD added day 10
• Minimum of 4 weeks iv antibiotics
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LP performed day 14 admission
N opening pressure,
CSF WBC 222 (44% polymorphs, 56% mononuclear)
CSF RBC 17
CSF/serum Glucose 4.2/6.0
CSF protein 984 mg/L (0-500)
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Diagnosis: MSSA MV IE with meningoencephalitis and embolic cerebral
abscesses
MV repair after 4 weeks iv antibiotics
Excellent recovery. Completed 6weekss antibiotics
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The ARREST trial
Adjunctive Rifampicin to Reduce Early
mortality from STaphylococcus aureus
bacteraemia: a multi-centre, randomised,
blinded, placebo controlled trial
United Kingdom Clinical Infection Research Group
UKCIRG
Hypotheses:
1) There is a population of bacteria, in blood and/or infected tissues, which is
relatively ‘resistant’ to killing by standard antibiotics (beta-lactams/glycopeptides).
2) Antibiotics with enhanced penetration and activity within cells, tissues and biofilms,
will enhance killing of S. aureus early in the course of antibiotic treatment, sterilise
infected foci and blood faster, and thereby reduce the risk of dissemination,
metastatic infection and death.
Co-primary outcome measures
1.
All-cause mortality up to 14 days
2.
Death or microbiologically confirmed treatment failure
or disease recurrence up to 12 weeks from
randomisation
Microbiologically confirmed treatment failure is:
(1)symptoms and signs of infection ongoing for longer than 14 days from
randomisation
AND
(2) the isolation of same strain of S. aureus (confirmed by genotyping) from either
blood or another sterile site (e.g. joint fluid, pus from tissue) indicating blood-born
dissemination of the bacteria
Microbiologically confirmed disease recurrence:
the isolation of the same strain of S. aureus from a sterile site after >7 days of
apparent clinical improvement
Study design
Parallel group, randomised (1:1), blinded, placebo-controlled multi-centre
trial
Standard IV antibiotic ‘backbone’
+ 14 days placebo
Vs
Standard IV antibiotic ‘backbone’
+ 14 days rifampicin
12-week follow-up
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Doses
<60kg: 600mg rifampicin OD for 14 days
≥60kg: 900mg rifampicin OD for 14 days
Inclusion criteria
• Adults (18 years or older)
• Staphylococcus aureus (meticillin-susceptible or resistant)
grown from at least one blood culture
• Less than 96 hours of active* antibiotic therapy for the
current infection, not including rifampicin
• Patient or legal representative (LR) provides written informed
consent
* Defined by in vitro susceptibility testing
Exclusion criteria
• Infection not caused by S. aureus alone in the opinion of the infection
specialist (e.g. S. aureus is considered a blood culture contaminant, or
polymicrobial culture with another organism likely to be contributing
clinically to the current infection)
• Sensitivity results already available and demonstrate rifampicin
resistant S. aureus
• Infection specialist, in consultation with the treating physician,
considers rifampicin is contraindicated for any reason
• Infection specialist, in consultation with the treating physician,
considers rifampicin treatment is mandatory for any reason
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Infection specialist suspects active infection with Mycobacterium tuberculosis
Previously been randomised in ARREST for a prior episode of S. aureus
bacteraemia
The aim
Lab result:
S. aureus in
Blood culture
Visit patient
11.00hrs
Screen
1400hrs
15.00hrs
Consent
Randomise
< 96 hours of active treatment
Complete within 6 hours
16.00hrs
Start study drug
S. aureus bacteraemia at Southampton,
2006-2012
COMMUNITY
Mean Resistance
Sensitive
% of Hospital
Total Hospital Acquired Isolates
Acquired Isolates
Resistant to
Rifampicin
Sensitive
2006
0
18
18
0%
2
51
53
4%
2007
0
10
10
0%
0
30
30
0%
2008
0
3
3
0%
0
13
13
0%
2009
0
4
4
0%
0
4
4
0%
2010
0
4
4
0%
0
7
7
0%
2011
0
6
6
0%
1
2
3
33%
2012
0
4
4
0%
0
1
1
0%
0%
5%
2006
0
40
40
0%
0
68
68
0%
2007
1
47
48
2%
0
53
53
0%
2008
0
44
44
0%
0
40
40
0%
2009
0
37
37
0%
0
22
22
0%
2010
1
50
51
2%
0
25
25
0%
2011
0
56
56
0%
0
23
23
0%
2012
1
55
56
2%
0
31
31
0%
Mean Resistance
Combined MRSA &
MSSA
Resistant
Resistant
Mean Resistance
MSSA
% of
Community
Isolates
Resistant to
Rifampicin
Total Community
Acquired Isolates
Year
MRSA
HOSPITAL
1%
0%
2006
0
58
58
0%
2
119
121
2%
2007
1
57
58
2%
0
83
83
0%
2008
0
47
47
0%
0
53
53
0%
2009
0
41
41
0%
0
26
26
0%
2010
1
54
55
2%
0
32
32
0%
2011
0
62
62
0%
1
25
26
4%
2012
1
59
60
2%
0
32
32
0%
1%
2012: n=92 S. aureus bacteraemias
64% were community-acquired, 87 MSSA, 5 MRSA
1%
Trial duration
• 4 years funding. July 1st 2012 to June 31st 2016
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Expected recruitment duration: 3 years
October/November 2012 to November 2015
Approval for UHS to begin recruitment due April 2014
UHS Consultant for patient will be contacted for permission to
approach patient to gain consent for entry into the trial
Acute sepsis
 Each hour of delay in
antimicrobial
administration over
the 6 hrs following
onset of hypotension
was associated with
an average decrease
in survival of 7.6%.
Kumar A, Roberts D, Wood KE, et al. Duration of hypotension before initiation of effective
antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care
Med. 2006;34(6):1589-1596
Acute sepsis
Is there sepsis, severe sepsis or septic shock?
• Systemic Inflammatory Response Syndrome
(SIRS). 2 or more = SIRS
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Temp >38°C or < 36°C
Heart Rate > 90 bpm
Respiratory Rate > 20 breaths/min
WBC > 12 or < 4x109/L
Acutely altered mental status
Hyperglycaemia (glucose >6.6 mmol/L) (unless diabetic)
– Are there symptoms or signs suggestive of new infection?
– SIRS + evidence of infection = sepsis
Is there sepsis, severe sepsis or septic shock?
• Severe sepsis screen:
– Any of the following present and new to the patient?
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SBP <90 or mean < 65mmHg
New or increased O2 requirement to maintain SpO2 >90%
Creatinine >180 umol/L or UO <0.5ml/kg/hour for 2 hours
Bilirubin >34 umol/L
Platelets <100 x109/L
Lactate > 2 mmol/L
Coagulopathy: INR >1.5 or APTT>60s
Is there sepsis, severe sepsis or septic shock?
• Severe sepsis diagnosed – Sepsis 6:
– 1. Oxygen 100%
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2. Blood Cultures
3. IV antibiotics
4. Fluids
5. Measure lactate and Hb
6. Urinary catheter and monitor UO
– Must check all relevant past Microbiology results – e.g.
previous ESBL infection, MRSA colonisation
– Consult specialist in Infection - Microbiology/Infectious
Diseases
– Piperacillin/tazobactam 4.5g qds
– Meropenem if non-severe penicillin allergy
– Add Vancomycin if high risk for invasive MRSA infection
Is there sepsis, severe sepsis or septic shock?
• Septic shock screen:
– Severe Sepsis with Hypotension, despite adequate
fluid resuscitation or lactate >4 mmol/L
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Sepsis 6 PLUS….
Add Gentamicin 3-5mg/kg
Consider antifungal
Refer for vasopressor support
Is there sepsis, severe sepsis or septic shock?
To diagnose Severe Sepsis patients must reach all three of the following criteria. Follow top
of guideline overleaf.
1. Known infection or clinical evidence suggestive of infection
2. Meet 2 or more of SIRS criteria?
Tachycardia ≥90
RR> 20 or PaCO2 <4.3
WCC >10 or <4
Temp ≤36 or ≥38
3. Evidence of end organ hypo-perfusion
Systolic BP <90 or MAP <65
Cr >180 or U/O <0.5ml/kg for 2 hours
Lactate >2
Bili > 35, Plt < 100, SpO2 <90%, Acute confusion
If your patients meets all three criteria they have Severe Sepsis.
If they are fluid therapy resistant, then they have Septic Shock
Audit of implementation of the sepsis 6 at UHS
Mamadou Jallow, Pre-registration Pharmacist
Kieran Hand, Consultant Pharmacist
• Aim to identify patients with severe sepsis and septic shock
and evaluate whether sepsis six interventions are
implemented in a timely manner
• CCOT database searched from October 2011 to September
2012 for patients with a systolic blood pressure (≤90mmHg)
and a body temperature of >38.3C or <36C to identify
patients with potential severe sepsis
• Case notes reviewed
Audit of implementation of the sepsis 6 at UHS
2612 patients identified from CCOT
records from Sept 2011 to Oct 2012
Filters applied (temp. >38.3 or
<36°C and low BP with systolic)
<90
53 patients with hypothermia /
hyperthermia and BP <90 mmHg
5 case notes unavailable
40 case notes retrieved
8 case notes retrieved
and reviewed
late
24 patients met definition of severe
16 patients did not meet definition
sepsis / shock
of severe sepsis / shock
Audit of implementation of the sepsis 6 at UHS
% of patients given IV Antibiotics
< 1 hour
21%
Implemented < 1
hour
Implemented
between 1-6 hours
after onset
79%
Audit of implementation of the sepsis 6 at UHS
E. coli resistance rates in UHS inpatient urine
samples 2008 – 2013
Initial Empiric antibiotic therapy
• Is there severe sepsis or septic shock?
• What is the source of infection?
– Respiratory tract / urinary tract / SSTI / intra-abdominal / CNS /
uncertain
• For sepsis of uncertain chest and/or urinary origin, combine
treatments for RTI and UTI, and if meets criteria for severe
sepsis, ensure gentamicin is included, if no renal failure
• Empiric therapy must take account of relevant recent
Microbiology results
Initial Empiric antibiotic therapy
• Have relevant urgent investigations been done?
– Blood culture
– Urine culture
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EDTA blood for meningococcal/pneumococcal PCR
CSF
Sputum / bacterial throat swab / viral throat swab
Wound swabs if appropriate
• Guidelines are there to help promote patient safety but
use intelligently
– If in doubt consult with an Infection specialist
Case 2: ‘A case of urinary sepsis’
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76M NH resident, COPD, AF, schizophrenia
Previous CAUTIs
Dysuria and constipation
Hb 124, WBC 20, Plts 87, U 20.2, Creat 181, CRP 181,
lactate 1.3
• Afebrile, nomotensive
• Commenced on empiric iv gentamicin
Case 2: ‘A case of urinary sepsis’
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Blood cultures – not done on admission
1st Urine culture – not processed
Severe sepsis not recognised
Previous gentamicin – resistant E. coli in urine within the last
6 months
• Delayed (day 3 of admission) blood culture – Group B
Streptococcus
Antimicrobial stewardship –
‘start smart then focus’
Potential harm caused by antimicrobials…
• Adverse drug reaction
• Selection pressure for resistant organisms
– Particularly within the hospital environment
• Risk factor for C. difficile infection (CDI)
0
Apr-07
Jan-08
SUHT
SHA Trajectory
5
Jan-10
13
10
Mar-10
13
Feb-10
6
Dec-09
12 10
Nov-09
Oct-09
7
Sep-09
8
Aug-09
8
Jul-09
9
Jun-09
15
May-09
22
Apr-09
Mar-09
28
Feb-09
19
Jan-09
22
Dec-08
Nov-08
Oct-08
25 25
Sep-08
20
23
Aug-08
10
27
Jul-08
29
Jun-08
20
Apr-08
31
May-08
30
Mar-08
37
Feb-08
38
Dec-07
64
Oct-07
61
Nov-07
40
Sep-07
50
Aug-07
57
Jul-07
Jun-07
60
May-07
No. of Cases
UHS: monthly C. difficile cases 2007 - 2010
SUHT Number of C. difficile Cases (>2 Yrs)
Including SHA Trajectory
70
63
56
46
34
38
25
17
14
UHS: monthly C. difficile cases 2012 - 2013
Community C.diff cases 2012/13 (As per HPA Definition)
16
16
14
14
12
12
10
10
No of Cases
No of Cases
SUHT C.diff cases 2012/13 (As per HPA Definition)
8
6
16
13
6
11
10
4
4
6
2
8
3
3
2
3
3
4
4
5
2
8
5
1
April
May
June
July
August
3
September October November December January
February
May
June
July
August September October November December January
March
Community
SUHT
Target
2012/13
Target
Actual
Qtr 1
15
8
Qtr 2
12
12
4
0
0
April
5
4
3
0
9
Qtr 3
8
11
Qtr 4
11
6
February
March
Antimicrobial stewardship –
‘start smart then focus’
• Section A – intended for use by
frontline staff in acute healthcare
settings.
• Section B – intended for use and
consideration during the planning
and implementation phases at
board / executive level.
• Section C – intended for risk
assessment and public information
• Section D – Glossary
Countries and regions with reported high prevalence
of healthcare-associated carbapenemase-producing
Enterobacteriaceae
UK NRL-confirmed carbapenemase producing
Enterobacteriaceae
No. of isolates
Imported & ‘home grown’
Early cases often imported
43
AMRHAI unpublished data
No. of labs referring carbapenemase-producing
Enterobacteriaceae to AMRHAI
AMRHAI unpublished data
Occurrence of carbapenemase-producing Enterobacteriaceae (CPE) (all types of
isolates) based on self-assessment by national experts, EuSCAPE project, 38
European countries, March 2013
http://www.ecdc.europa.eu/en/eaad/Documents/EuSCAPE-summary-CPE-CRA.pdf
Acute trust – patient admission flow chart for infection prevention
and control (IP&C) of carbepenemase-producing Enterobacteriaceae
Early recognition of individuals who may be colonised / have an infection.
Risk Assessment
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IN THE LAST 12 MONTHS HAS THE PATIENT:
Been an inpatient in a hospital abroad
OR
Been an inpatient in a UK hospital known to have had problems with spread of
carbapenemase-producing Enterobacteriaceae
OR
Previously been colonised or had an infection with carbapenemase-producing
Enterobacteriaceae or close contact (see glossary) with a person who has, if
known
If one or more of above applies then:
The patient is considered to meet the criteria for being a suspected case of
carbapenemase-producing Enterobacteriaceae colonisation or infection (as
applicable)
AND REQUIRES IMMEDIATE ISOLATION, PLUS:
instigation of strict standard precautions to prevent possible spread
screening to assess current status for colonisation or infection
assessment for appropriate treatment (applies to infection only)
Summary
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Good antimicrobial stewardship is part of the process to optimise patient care
and reduce risk of harm requiring….
– Clinical judgment
– Sending appropriate diagnostic tests
– Review of relevant previous information – Microbiology results
• There are signifiant threats to our ability to Rx serious infectons
including CPE