What is the difference between in vitro (laboratory-determined) resistance and in vivo (within the human body) resistance in the context of antibiotic treatment?

Understanding In Vitro vs In Vivo Resistance

In vitro resistance refers to bacterial resistance demonstrated in laboratory testing, while in vivo resistance refers to clinical treatment failure in actual patients—and critically, these two do not always correlate. 1

In Vitro (Laboratory) Resistance

In vitro resistance is defined by laboratory testing methods that measure bacterial susceptibility to antibiotics outside the human body. 1

• Microbiologically resistant organisms possess any resistance mechanism demonstrated phenotypically or genotypically in laboratory conditions 1
• Resistance is typically determined by minimum inhibitory concentration (MIC) breakpoints measured through standardized testing methods 1
• These laboratory definitions are based on consensus interpretations of the antibiotic's properties and pharmacokinetics, particularly concentrations attainable at infection sites 1
• The critical limitation: surveillance data from in vitro testing are often based on selective samples (frequently from hospitalized patients), are not real-time, and are not representative of the situation at the point of prescribing 1

In Vivo (Clinical) Resistance

In vivo resistance represents actual clinical treatment failure in patients—what clinicians call "antibiotic-resistant disease"—which may have causes beyond simple laboratory resistance. 1

• Clinical resistance is assessed indirectly through treatment failure in patients who have not responded to appropriate antibiotic therapy with documented adherence 1
• This assessment is influenced by patient demography, comorbidities, and previous therapy—making it imprecise but clinically relevant 1
• The clinician is fundamentally more concerned with "antibiotic-resistant disease" rather than antibiotic-resistant organisms 1

The Critical Disconnect

In vitro definitions of resistance do not always correlate well with clinical outcomes, creating a credibility gap between prescribers and epidemiologic resistance data. 1

Why the Discrepancy Exists:

• MIC breakpoints must be interpreted relative to antibiotic concentration and pharmacodynamic effects at specific infection sites 1
• Original breakpoints for β-lactam resistance in S. pneumoniae were established for meningitis (due to poor CSF penetration) and may not apply to respiratory infections where β-lactams achieve far higher concentrations in blood and lung tissue 1
• β-lactams can eradicate even "nonsusceptible" strains from the lungs despite in vitro resistance, because achievable tissue concentrations exceed MIC breakpoints 1
• Evidence from multiple continents demonstrates that penicillin nonsusceptibility (MIC > 0.1 mg/L) does not significantly impair efficacy in treating pneumococcal pneumonia 1

Clinical Implications:

• Bacteria with low-level microbiological resistance mechanisms may be clinically susceptible (sometimes called "borderline susceptible") 1
• The problem is managing resistant infections, not just resistant bacteria 1
• No evidence supports reliably treating S. aureus infections with antibiotics showing in vitro resistance, as this results in worse clinical outcomes 2

Important Caveat:

Higher-level resistance (MIC > 4 mg/L) is more likely to produce clinical failure, and there are limited data on oral antibiotic effectiveness for outpatient treatment in these cases 1