in Intravenous Drug Users Dr James Stone Consultant Medical Microbiologist Gloucester Royal Hospital BACKGROUND Three IVDU patients diagnosed with infective endocarditis within less than 6 months February April and June 2018 ID: 747857
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Case four:MRSA Infective Endocarditisin Intravenous Drug Users
Dr James Stone
Consultant Medical Microbiologist
Gloucester Royal HospitalSlide2
BACKGROUNDThree IVDU patients diagnosed with infective endocarditis within less than 6 months (February, April and June 2018)
All were actively taking intravenous drugs at time of diagnosis
Two patients deceased (female aged 37 and second female aged 44
).
Male
aged
39 survived.
All had positive blood cultures with MRSA
All (ultimately) received intravenous antimicrobial therapy with activity against the MRSA strains isolated
Range of complications related to the infectionsSlide3
POINTS FOR DISCUSSIONTreatment of MRSA infective endocarditis in a non-compliant IVDU patientEfficacy of intravenous v oral antimicrobial therapy in MRSA endocarditis
Possible cross-infection in community or hospital?
Value (
or otherwise)
of typing MRSA strains
Relative virulence of different strains of MRSA and their propensity to cause infective endocarditis
Screening for MRSA in high-risk populations such as IVDUs and role of interventions (if any) to reduce risk of infection in this population group.
Importance of involving Drug Liaison Team to assist with compliance and future management.Slide4
CASE - 144 year old femalePresented 13th April 2018
Admitted via A&E with left-sided neck pain
radiating into
left
hand side and chest
.
Known IVDU
using neck
for venous access.
Also suffering from frequency and
dysuria.Slide5
Case – 1: Past Medical HistoryIVDU – previous MRSA bacteraemia August 2015 and August 2016. Abscesses (multiple)
– groin and leg from injections.
DVT’s
- on
Rivaroxaban
Leg ulcers
Previously treated for Infective Endocarditis with MRSA (August 2015). Did not undergo cardiac surgery.
Known Hepatitis
C +
ve
Previous lumbar spine abscess
MRSA
colonised (in the past) – current MRSA screen status awaited following swabs being taken on admission
Peripheral Neuropathy
Asthma
Fractured Skull
Sciatica since spine abscess
Bronchitis.Slide6
Case 1: Progress following admissionCannula inserted into
r
ight
upper
arm, replaced with central line inserted into right internal jugular vein in theatre the next day (14.04.18).
Screened
for MRSA
colonisation (nose and groin).
Leg
ulcers
(to
both
legs) not
screened
until 15.04.18 (2 days after admission).
Absconded from ward following insertion of CVC and returned having clearly taken iv drugs.
Antibiotic therapy with Co-
amoxiclav
given.Slide7
Case 1: Progress - continued15.04.18 = Raised temperature 38.6. Neck
pain left
sided,
tender to touch
.
No evidence of deep abscess/collection on CT scan.
Absconded again.
R
eturned
to
ward.
B
ecame
unresponsive. Naloxone infusion and observations performed.
Thought
to be opioid n
arcosis.
Diagnosis at this stage: “Strong
possibility of deep seated infection ? infective
endocarditis
. Neck swelling and pain could represent
pyomyositis
.”Slide8
What would you do next?Investigations?Treatment?Slide9
Investigations PerformedMultiple blood culturesEchocardiogramMRISlide10
Case 1: Progress - continuedBlood cultures taken (multiple sets) Co-amoxiclav
continued.
Echocardiogram arranged
MRI spine booked for 17.04.18Slide11
Case 1: Progress - continuedMRI: No evidence of discitis or vertebral osteomyelitis (although commented that there was “multi-level disc disease”.
CVC - line removed (repeated absconding and using for self-administration of opiates).Slide12
What would you do next?Further investigations?Change to antimicrobial therapy?Slide13
Case 1: Progress - continued17.04.2018:Increasingly drowsy.
Heart rate 86. BP 94/50mmHg.
Sats
90% on air (refused oxygen). Temp 35.2 C.
Antimicrobial therapy changed to:
Daptomycin
700mg/day iv – but issues with administration following line removal
Clindamycin 450mg
qds
oral
Amoxicillin 1g
qds
oral
Hibiscrub
and
Naseptin
commenced (no
Bactroban
available – national shortage)
Leg ulcer swabs reported as being MRSA positive
CRP 159. WCC 5.2.Slide14
Case 1: Progress - continued18.04.18: Transthoracic Echocardiogram = “No obvious
SBE” (Refused TOE)
Again absconded from ward. On return admitted to using iv drugs and smoked 3 bags heroin.
Left-sided neck lump (3cm x 3cm) developed with pus pointing at needle entry point
Multiple blood cultures positive: MRSA and Streptococcus
parasanguinis
from all bottles
USS of neck booked.Slide15
Case 1: Progress - continuedPatient non-compliant with antimicrobial therapy.Accepted single dose of iv
Dalbavancin
(Microbiologist suggested 4 to 6 weeks of weekly
Dalbavancin
at 1.5g/week and to add oral co-
trimoxazole
960mg BD to Clindamycin).
Refused further investigations and treatment.
Self-discharged from ward.
Later re-admitted.
Clinically endocarditis had now developed (
hepatosplenomegaly
, new murmur, heart failure) but she refused further investigations or treatment (and considered to have capacity).
Developed renal failure and the heart failure became more severe.
Died.
MRSA typing performed.Slide16
Case - 237 year old femalePresented on 1
st
June 2018
Admitted via Emergency Department
Known IVDU – heroin and cocaine
Severely cachectic (weighed around 40kg)
Feeling unwell for 5 days with central chest pain (
pleuritic
in nature) and increasing shortness of breath. No cough. Body pain – “all over”.
Lived alone in supported housing
HR 85. BP 95/55 mmHg. No murmurs.
Resp
rate 19.
S
ats
97% on air. Inspiratory crackles bilaterally. Hypothermic (Temperature 34.7 C).Slide17
Case 2: ContinuedInitial diagnosis in ED: ? PE, ? Chest infectionInvestigations:
Bloods (including blood cultures)
ECG
CXR
Transferred to admitting medical teamSlide18
Case 2: ContinuedCXR: Wedge-shaped infarct left mid-zone
Multiple opacities in both lungs
For CTPA and/or CT Chest
Clinical Review by Medical
T
eam:
Loud systolic murmur (new),
Slight hepatomegaly
Bloods: WCC 17.8, Platelets 33, CRP 262.
Alb
16.
Creatinine
335, Urea 28.8.
D
-dimer 7324.
Blood gases: acidotic. Lactate 1.2.Slide19
Case 2: ContinuedRevised differential diagnosis:Sepsis ? Bacterial endocarditis – murmur and multifocal chest lesions
AKI
Thrombocytopaenia
secondary to sepsis
“Needs: blood cultures x3 sets, iv antibiotics, ECHO, HIV/Hep-B and C”
IV
Vancomycin
(1g) and Gentamicin (1mg/kg) startedSlide20
Case 2: Continued (day 2 – 2nd June)
Admitted to ward but then transferred to HDU
Developed generalised severe abdominal pain – mesenteric infarction considered likely
Lactate increased to 14.
Echocardiogram:
“Very large vegetation on tricuspid valve”
Transfer advised to cardiac centre
Blood cultures: Staphylococcus
aureus
(sensitivities pending) result telephoned.
Hepatitis-C positive.
Vancomycin
(1g od) and gentamicin (40mg od – 1mg/kg) to continue.
Discharging abscess noted overlying right MTPJ
Rifampicin addedSlide21
Case 2: Continued (day 3)Staphylococcus
aureus
isolated from blood cultures identified as MRSA – sensitive to
vancomycin
, gentamicin and rifampicin.
Suggestion by microbiologist to consider adding rifampicin to current therapy with
vancomycin
and gentamicin.
Staphylococcus
aureus
also isolated from MPTJ pus (subsequently identified as MRSA).
Observations getting worse:
Resp
rate 24,
sats
94% on 4L. Capillary refill 5sec. But: HR 92 and BP 112/70.
Later: increasing
o
xygen requirements to maintain saturations. GCS fallen to 14.
Resp
rate increasing further to 35/min.Slide22
Case 2: continued (day 4)Rapid deterioration during the day – hypoxic (on 15L), hypotensive, deteriorating renal function - became anuric, ventilated.Cardiothoracic team contacted – decided not to pursue operative
approach.
Deceased
MRSA sent for typingSlide23
Case-339 year old malePresented on 23rd
February 2018
Admitted via Emergency Department
Known IVDU (heroin)
Injecting into right groin
Noticed red rash and “strange feeling” in right leg
Swelling of right leg
Weight loss of 1
st
over last 3 months
Recent prison term and mental health issuesSlide24
Case 3: continuedOn examination: EmaciatedHole in right groin - groin hard, tender but no redness or pus. Petechial rash on right leg. Right calf oedema.
Observations:
Resp
rate 14,
Sats
98.1% on air, BP 110/60, HR 75. Temp 36.4.
Chest clear.
No splinter haemorrhages/murmurs/splenomegaly
CRP 300
Initially given stat dose of Co-
amoxiclav
1.2g iv in the EDSlide25
Case 3: continuedBlood cultures taken – 3 setsLeg USS and Echocardiogram bookedFlucloxacillin
1g
qds
started
Co-amoxicillin stopped
Provisional diagnosis: cellulitis
Note: “Need to rule out DVT and SBE”Slide26
Case 3: continuedWhat antimicrobial therapy would you consider giving at this stage?
Any further investigations?
Patient temporarily absconds from ward but returns in the evening. How might this behaviour influence your management plan?
(He missed USS of leg and Echocardiogram)Slide27
Case 3: continued (24th February Day 2)
Blood cultures (provisional result telephoned 11:20am): “Gram positive
cocci
in all bottles, look like staphylococci.”
Discussion with medical microbiologist: “Start iv
Daptomycin
od”
Previous results reviewed - indicate known screening test positive for MRSA in previous year but not clinically infected t that point
Clinically more unwell: BP falling (95/60),
Resp
rate increasing (18)
Splinter haemorrhages right thumb and middle finger
Increasing pain right legSlide28
Case 3: continuedWould you consider daptomycin monotherapy as reasonable at this stage?
Given previous positive screening tests for MRSA, what else would you do at this point?Slide29
Case 3: continued (25th February Day 3)
Staphylococcus
aureus
in blood cultures identified as MRSA
Weight loss now checked and would appear to be up to 2st in last few weeks (now 48kg)
Echo and USS re-booked
Daptomycin
as
monotherapy
continued
Spike in fever to 39.7 C
BP fallen to 95/54 mmHg. HR 96Slide30
Case 3: continuedGiven spike in fever and clinical deterioration, would you consider adding any additional antimicrobial agent(s) at this stage?
What dose of
Daptomycin
would be appropriate for an individual with a weight of 48kg and a potential infective endocarditis with MRSA?
Any further investigations?Slide31
Case 3: continuedHe was continued on iv daptomycin at a dose of 350mg/day, giving a dose of 7.3mg/kg/day.Slide32
Case 3: continued (26th February Day 4)
Echocardiogram: “No obvious SBE from views obtained. AV and PV not well seen”
USS: Abscess right groin (now starting to discharge)
Infection Control Team: “Needs MRSA decolonisation therapy”
Daptomycin
continued
Microbiologist comment: “Treat as intravascular infection +/- IE. For 4 weeks of IV
Daptomycin
if possible (assess suitability for OPAT given IVDU history). Take swab from discharging groin sinus”Slide33
Case 3: continued (Day 11)Referred to Drug Liaison TeamInitially some improvement from day 4.
Planning for discharge home
Then:
CXR: Patchy consolidation ?
Cavitating
lesions
Persistent cough
Temp spike to 38.6 C
BP fall to 95/51Slide34
Case 3: continuedWhat is you differential list of diagnoses at this stage?What investigations would you consider appropriate?
How may you antimicrobial therapy recommendations change? (e.g. questionable efficacy of
Daptomycin
in treatment of staphylococcal lower respiratory tract infection?)Slide35
Case 3: continuedThe medical team in fact added oral co-amoxiclav 625mg tds orally on day 11 (reported indication given on the drug chart for this was “infected groin wound”). It was continued for 10 days.Slide36
Case 3: continued (day 12)Medical Team Differential Diagnosis:
? TB
?
Vasculitic
infection
Plan:
Sputum culture (including for TB)
T-spot
CT Thorax
Respiratory referralSlide37
Case 3: continued (Day 13)CT scan: Multiple bilateral cavitating lung lesions
Bloods: CRP fallen steadily from 300 on admission to 89.
WCC: 8.5 (was 12.0 on admission)
Right groin – decreasing discharge
IV
Daptomycin
continuedSlide38
Case 3: continued (Day 18)T-spot positiveAwaiting TB sputum culture but AAFB smear –
ve
BCG scar present
Awaiting TOE (previous echocardiogram was TTE)Slide39
Case 3: continued (outcome)Completed 6 weeks of iv daptomycin
as an inpatient
TOE was ultimately not done, therefore uncertain as to whether he actually had IE
Lung lesions slowly resolved
?Latent TB was not treated. Sputum was culture negative
In late July 2018 he had a recurrence of his groin abscess which grew MRSA again but was treated successfully with
Daptomycin
MRSA sent for typing.Slide40
TYPING RESULTS FOR MRSA ISOLATES(as of August 2018)
Case 1:
MRSA typing: MLST Allelic Profile:
1,4,1,4,12,1,10
Case 2:
MRSA typing: MLST
Allelic Profile: 1,4,1,4,12,1,10 (same as case 1)
Case 3:
MRSA typing: MLST Allelic Profile: 1,4,
2
,4,12,1,10
BUT:
Genotyping suggested strains were different.Slide41
TYPING RESULTS FOR MRSA ISOLATES:UPDATE OCTOBER
Case 1:
MRSA typing: MLST Allelic Profile:
1,4,1,4,12,1,10
Case 2:
MRSA typing: MLST Allelic Profile: 1,4,1,4,12,1,10 (same as case 1
)
Case 3:
MRSA typing: MLST Allelic Profile:
1,4,
2 (re-reported as 1)
,4,12,1,10
Case 4 (14/07/2018):
Profile as above
Case 5 (13/09/2018):
Profile as above
Case 6 (24/09/2018):
Profile as above
(
Note, last 3 cases are all
bacteraemias
but not all confirmed as having endocarditis currently
)Slide42
POINTS FOR DISCUSSIONTreatment of MRSA infective endocarditis in a non-compliant IVDU patientEfficacy of intravenous v oral antimicrobial therapy in MRSA endocarditis
Possible cross-infection in community or hospital?
Value (
or otherwise)
of typing MRSA strains
Relative virulence of different strains of MRSA and their propensity to cause infective endocarditis
Screening for MRSA in high-risk populations such as IVDUs and role of interventions (if any) to reduce risk of infection in this population group.
Importance of involving Drug Liaison Team to assist with compliance and future management.