Unresolved sepsis and antibiotic treatment failure
Reviewed and revised 17 December 2015
- 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)
- 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)
- e.g. metastatic sepsis, collection, secondary nosocomial infection?
- 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)
- immunodeficient or compromised?
- foreign body or prosthesis present?
- hidden places: sinusitis, endocarditis, retroperitoneum, neuroaxial infection?
- 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
- lungs and thoracic cavity
- urine (e.g. IDC)
- wounds and invasive procedures
- gastrointestinal (e.g. C. difficile, norovirus)
- respiratory viruses (e.g. influenza)
References and links
- 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]