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Identifying the Causative Bacterium in an Infection

1Why Identification Matters and What the Question Really Asks2Getting a Usable Specimen3Direct Examination: Seeing the Organism Before Culturing It4Culture: Amplifying and Isolating the Organism5From Isolated Colony to Species6Determining Susceptibility and Confirming the Causative Role7Rapid and Molecular Methods When Culture Is Not Enough
Determining Susceptibility and Confirming the Causative Role

Intrinsic and Acquired Resistance Are Not the Same Problem

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Think about what a resistant report is telling you. With intrinsic resistance, the whole species is resistant because of something built into its chromosome, like the beta-lactamase that makes Klebsiella pneumoniae resistant to ampicillin, or the low permeability and efflux pumps of Pseudomonas aeruginosa. That kind of resistance is predictable, so laboratories often skip testing those drugs altogether. Acquired resistance is the opposite situation: a normally susceptible species has picked up resistance in some of its isolates, either by mutation or by taking in a resistance gene on a plasmid. That is why it has to be measured for each isolate, why it can spread to other organisms, and why it can appear during treatment when a resistant subpopulation survives and expands. When you see resistance, ask which of these two you are looking at, because only the acquired kind changes what the drug could have done.
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Intrinsic resistance is a predictable, species-wide property that is not transmitted between organisms; acquired resistance is a variable property of a subset of isolates that can spread horizontally and can emerge during treatment. The same resistant report means different things depending on which one produced it.

Intrinsic resistance in practice

Klebsiella pneumoniae carries a chromosomal beta-lactamase that hydrolyzes ampicillin, so every isolate is resistant to that drug. Pseudomonas aeruginosa combines low outer-membrane permeability with efflux pumps, making it intrinsically resistant to several agents. Laboratories often omit these drugs from the panel rather than report a predictable result.

Acquired resistance in practice

A previously susceptible Escherichia coli isolate acquires a plasmid carrying an extended-spectrum beta-lactamase and becomes resistant to cephalosporins. The resistance is not shared by all E. coli, it can transfer to other organisms, and it can appear in a patient who was initially infected with a susceptible strain.

Comparing the two origins

Intrinsic resistance

  • Present in essentially all isolates of the species
  • Encoded in the chromosome and stable
  • Not transferred between organisms
  • Predictable, so often not tested or reported

Acquired resistance

  • Present in a subset of isolates of a normally susceptible species
  • Arises by mutation or by acquisition of a resistance gene
  • Can spread horizontally on mobile genetic elements
  • Must be measured for each isolate and can emerge during therapy

A resistant result is not automatically a therapeutic problem. If the drug was never active against the species, the result simply confirms what was already known. The clinically important signal is acquired resistance in a normally susceptible organism, because that is the situation the drug might otherwise have been expected to cover.

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