Unresolved sepsis

Unresolved sepsis and antibiotic treatment failure

Reviewed and revised 17 December 2015

OVERVIEW

  • When a ‘septic’ patient fails to improve despite initial therapy, it is important to ‘stop and think’ and systematically consider the multiple possible reasons why ‘the antibiotic is not working’
  • The mnemonic CCDHB (i.e. ‘Capital Coast District Health Board’) is a useful checklist of the possible reasons
  • Antibiotic treatment failure is more common with empiric therapy (e.g. too narrow coverage) than with directed therapy

ANTIBIOTIC TREATMENT FAILURE

  • no consensus definition exists
  • rates vary from 6 to 60%, depending on the study and the type of infection (e.g. pneumonia vs serious soft tissue infection vs intra-abdominal infection)
  • various criteria may be used to indicate antibiotic treatment failure
    • patient based (e.g. early death, physical manifestations of sepsis, organ dysfunction)
    • treatment based (e.g. change/ addition of antibiotics, ICU admission, additional organ support, operative intervention)
    • test based (e.g. in vitro resistance, persistent elevation of septic biomarkers, non-resolving/ worsening CXR infiltrates)
  • the time point of assessment is also undefined; 48 to 72h is commonly used for antibiotic treatment failure in pneumonia
  • antibiotic treatment failure, in various infections, is associated with:
    • increased mortality
    • increased hospital LOS
    • increased duration of antibiotic therapy
    • increased cost

POSSIBLE REASONS FOR UNRESOLVED SEPSIS (CCDHB)

Cause

  • Is the diagnosis correct?
  • Consider non-infectious causes of fever (e.g. due to drugs, VTE, malignancy, autoimmune condition and hyperthermia)
  • Inadequate source control? (e.g. abscess drainage, debridement)
  • Toxin production? (e.g. patient may remain sick even after the organism has been destroyed, due to the persistent effects of previously produced toxins)

Complications

  • e.g. metastatic sepsis, collection, secondary nosocomial infection?

Drug

  • wrong antibiotic, route, timing, dose or inadequate blood levels? (e.g. impaired oral absorption)
  • drug antagonism/ interaction?
  • decreased penetration to site? (e.g. ischaemic toe with poor blood supply, IV vancomycin for C. difficile instead of the oral form)

Host

  • immunodeficient or compromised?
  • foreign body or prosthesis present?
  • hidden places: sinusitis, endocarditis, retroperitoneum, neuroaxial infection?

Bug

  • multi-resistant organism?
  • unusual organism? (e.g. fungi)
  • polymicrobial infection?
  • infectious agent not amenable to antimicrobials? (e.g. virus, prion)

SECONDARY NOSOCOMIAL INFECTIONS

Consider the following sources of secondary nosocomial infections

  • lines
  • lungs and thoracic cavity
  • urine (e.g. IDC)
  • wounds and invasive procedures
  • prostheses
  • gastrointestinal (e.g. C. difficile, norovirus)
  • respiratory viruses (e.g. influenza)

References and links

LITFL

Journal articles

  • Garrod LP. Causes of failure in antibiotic treatment. British medical journal. 4(5838):473-6. 1972. [pubmed] [free full text]
  • Sánchez García M. Early antibiotic treatment failure. International journal of antimicrobial agents. 34 Suppl 3:S14-9. 2009. [pubmed] [free full text]

CCC 700 6

Critical Care

Compendium

Chris is an Intensivist and ECMO specialist at The Alfred ICU, where he is Deputy Director (Education). He is a Clinical Adjunct Associate Professor at Monash University, the Lead for the  Clinician Educator Incubator programme, and a CICM First Part Examiner.

He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives. He was one of the founders of the FOAM movement (Free Open-Access Medical education) has been recognised for his contributions to education with awards from ANZICS, ANZAHPE, and ACEM.

His one great achievement is being the father of three amazing children.

On Bluesky, he is @precordialthump.bsky.social and on the site that Elon has screwed up, he is @precordialthump.

| INTENSIVE | RAGE | Resuscitology | SMACC

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