List the factors which result in failure in resolution of sepsis despite antibiotic therapy.

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College Answer

List the factors which result in failure in resolution of sepsis despite antibiotic therapy.

•        wrong antibiotic choice
•        delayed administration of antibiotics
•        Inadequate source control
•        inadequate antimicrobial blood levels
•        inadequate penetration of the antimicrobial to the target site,
•        antimicrobial neutralization or antagonism,
•        superinfection or unsuspected secondary bacterial infection,
•        nonbacterial infection, and
•        noninfectious source of illness

Discussion

In 1972, Garrod Pollock and Cargill all published separate articles in the same edition of the British Medical Journal, exploring the reasons behind antibiotic failure.

In short, they came up with this list:

  • Wrong antibiotics
  • Inadequate dose of the right antibiotic
  • Inappropriately infrequent administration of antibiotics
  • Wrong route (poor absorption)
  • Enhanced metabolism (eg. due to drug interaction or CYP450 activation)
  • Increased clearance (eg. due to dialysis)
  • Inadequate source control
  • Poor tissue penetration of an otherwise sensible antibiotic (eg. daptomycin might be a great choice for VRE, but it is useless in the lung where it becomes inactivated by surfactant)
  • Development of in-vivo resistance (eg. the way Klebsiella seems to suddenly develop a resistance to β-lactams)
  • There is no infection, or the infection is not bacterial.

The Garrod article is beautiful. In a literary manner more consistent with earlier times, Garrod writes of chloramphenicol: "Chloramphenicol is the only antibiotic which when given in the normal way to apparently normal people is capable of killing them". Today's lame robotic authors should take heed.

A more extensive exploration of the reasons behind antibiotic treatment failure can be found in the Required Reading section.

References

Garrod, L. P. "Causes of failure in antibiotic treatment." British medical journal4.5838 (1972): 473.

Pollock, A. V. "Causes of failure in antibiotic treatment." British medical journal4.5843 (1972): 790.

Cargill, J. S. "Causes of failure in antibiotic treatment." British medical journal4.5843 (1972): 791.