Diagnosing and assessing infection

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Diagnosing and assessing infection
Bill Lynn, Ealing Hospital London William.lynn_at_eht
.nhs.uk
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Promoting Good Antimicrobial Prescribing

• Avoid unnecessary antibiotic use
• No infection
• Infection that will not respond to antibiotics eg
  viral
• Infection that will be self-limited and
  antibiotics have minimal effect on outcome

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Febrile patient

• Clinical evaluation
• Does the patient have an infection?
• Organism?
• Will it kill them if I dont do anything soon?
• Site
• Severity
• Severe sepsis campaign
• Diagnostics

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Myocardial infarction

• ECG
• Markers with high sensitivity/specificity
  troponin, myoglobin, CPK etc
• Direct myocardial imaging echo, perfusion scans
• Diagnostic angiography
• Revascularisation pharmacological or physical
• Evidence-based drug interventions

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Infection

• Clinical diagnosis supported by non-specific
  tests eg WBC, CRP, radiology
• Guess what is the likely infecting organism
• Guess what antibiotic to use
• Wait to see if it works
• If it doesn't have another guess
• If it still doesnt ask micro/ID/pharmacy to
  guess as well

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Key Clinical Points

• Make a logical and reasoned clinical diagnosis
  and antibiotic decision
• Try and counter reflex antibiotic prescribing in
  A/E
• Presumptive diagnosis until microbiologically
  confirmed
• Review diagnosis when treatment failing
• Do not simply switch antibiotics more
  broad-spectrum cover

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Ideal supporting rapid diagnostics

• Nature of infecting organism
• Bacterial vs viral vs no-infection etc
• Identify specific organism
• Antibiotic sensitivities
• Severity/prognostic markers help inform
  admission, placement, route of administration etc
• Target other interventions

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Are acute phase markers useful?

• C-reactive protein
• Procalcitonin
• Cytokines IL-6, IL-8 among others
• Newer acute phase reactants
• LBP, TREM, manose binding proteins etc

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C-reactive protein

• Sensitive
• Good negative predictive value in established
  bacterial infection
• May be low early in acute severe infection
• Poor specificity
• Infective vs non-infective inflammation
• Bacterial vs non-bacterial infection
• Overused/abused in hospital setting
• Probably not sufficiently specific as a good
  prescribing adjunct

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Pro-calcitonin

• More specific than CRP
• Has some prognostic value in severe sepsis
• May be difficult to interpret
• Calibrate PCT cut off levels in different patient
  populations and/or scenarios
• Difficult to apply in non-specific setting ie DGH
• Slow adoption in UK

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CRP vs PCT in predicting bacterial infection

• Acute arthritis
• CRPgt50 sens 100, spec 40
• PCT gt0.5 sens 54 spec 94
• Systemic autoimmune disease with fever
• CRPgt50 not discriminatory
• PCT gt0.5 sens 75 spec 81
• Post operative infection
• CRPgt100 not discriminatory
• PCT gt1.1 sens 81 spec 72
• IL-6 gt310 sens 90 spec 58

Scire et al Clin Exp Rheum 2006
Martinot et al Clin Exp Rheum 2005
Mokart et al. Br J Anaesth 2005
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Potential for procalcitonin to target antibiotic
use

• 243 patients with suspected LRTI
• 119 standard care
• 124 PCT-guided care (cut off 0.25 microlog/l)
• PCT group rr antibiotic use
• 0.49 (0.44-0.55 plt0.001)
• Reduction in antibiotic use confined to the
  non-pneumonia patients

Christ-Grain et al Lancet 2004
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Nucleic acid recognition

• Gold standard for viral diagnostics
• Used for chlamydia screening
• Has potential to detect resistance
• Can be automated and rapid
• Disappointing lack of real-time application in
  common severe bacterial infections

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The future??

• Proteomics
• Detect specific bacterial protein signatures
• Detect biological response markers
• Protein microarrays

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Conclusions

• Clinical judgement, supported by basic diagnostic
  tests, continues to drive empirical antibiotic
  prescribing
• The role of biological markers in assisting
  prescribing decisions merits further study
• Better diagnostic technology is required to focus
  accurate prescribing