AUC24/MIC Ratio Calculator

AUC24/MIC Ratio Calculator

Divide a 24-hour area under the concentration-time curve by the MIC — the exposure target for vancomycin and the fluoroquinolones — and see what the ratio becomes one doubling dilution either side of the reported MIC.

AUC24/MIC ratio

AUC24 / MIC
The 24-hour area under the concentration-time curve. This page does not estimate one: for vancomycin, the vancomycin AUC24 calculator does that from the total daily dose and the creatinine clearance, and Bayesian software does it from measured concentrations.
In mg/L, exactly as the susceptibility report states it. MICs come in doubling dilutions — 0.125, 0.25, 0.5, 1, 2, 4, 8, 16 — because that is how the test is set up, so the reported value is the lowest dilution that inhibited growth and the true MIC lies between it and the dilution below. See the MIC doubling-dilution uncertainty calculator for what that does to the answer. The 2020 vancomycin consensus guideline specifies broth microdilution and says to assume 1 mg/L unless broth microdilution shows otherwise.
500AUC24/MICExample

AUC₀₋₂₄ 500 mg·h/L, MIC 1 mg/L

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Formula

AUC24/MIC = AUC₀₋₂₄ ÷ MIC
AUC₀₋₂₄
the area under the concentration-time curve across 24 hours, in mg·h/L. For a linear drug it is simply the total daily dose divided by the clearance, which is why a proportional dose change moves it proportionally
the units
mg·h/L divided by mg/L leaves hours, so the ratio is dimensionally a time. It is conventionally quoted as a bare number and that is how every target is written
free or total
this matters and the sources differ. The vancomycin consensus target of 400-600 is built on serum concentrations, which assays report as total drug; vancomycin is about 55% protein bound. EUCAST’s quinolone targets are explicitly fAUC/MIC, free drug. Forrest’s clinical AUC:MIC of 125 is total drug. A target and a measurement must be on the same basis
the MIC’s resolution
one doubling dilution doubles or halves the ratio. IDSA guidance reported by Brusamarello and colleagues treats an AUC/MIC of 200-400 against a gradient-strip MIC as roughly equivalent to 400-600 against a broth microdilution MIC — a factor of two, which is exactly one dilution, written into a guideline

Worked example

AUC₀₋₂₄ 500 mg·h/L, MIC 1 mg/L
500 ÷ 1 = 500, inside the 400 to 600 window the 2020 vancomycin consensus guideline recommends
Now move the MIC one doubling dilution up, to 2 mg/L: 500 ÷ 2 = 250, below 400
And one dilution down, to 0.5 mg/L: 500 ÷ 0.5 = 1,000, above 600
So the same measured exposure spans 250 to 1,000 across the one-dilution bracket the MIC measurement itself carries — a fourfold range that crosses both edges of the guideline window
The AUC needed for a ratio of 400 is 400 × the MIC: 400 mg·h/L at an MIC of 1, but 800 at an MIC of 2 and 1,600 at an MIC of 4
The highest MIC at which an AUC of 500 reaches 400 is 500 ÷ 400 = 1.25 mg/L, which is between two dilutions and therefore not a value any report will ever print
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Published AUC/MIC targets, with what each was derived against

AgentTargetFree or totalDerivation
Vancomycin400-600Total (serum concentrations; about 55% bound)2020 ASHP/IDSA/PIDS/SIDP consensus guideline, for serious invasive MRSA infection, MIC by broth microdilution assumed 1 mg/L. The guideline states the target derives largely from retrospective single-centre observational studies of MRSA bloodstream infection, with the earliest targets from animal models
Ciprofloxacin, clinical125TotalForrest 1993 in hospital-acquired pneumonia, named as the source by EUCAST’s ciprofloxacin rationale document v2.0
Ciprofloxacin, murine stasis13.1-35.8Free (fAUC/MIC)Neutropenic mouse thigh: 35.6 Enterobacterales, 34.8 P. aeruginosa, 35.8 S. aureus, 13.1 S. pneumoniae (EUCAST v2.0)
Ciprofloxacin, murine 1-log kill21.0-68.7Free (fAUC/MIC)Same model: 67.4, 47.3, 68.7 and 21.0 for the four organisms above (EUCAST v2.0)
Amikacin, murine21.4-55.4 stasis, 62.5-90.4 for 1-log killFree (fAUC/MIC)Neutropenic mouse thigh medians, attributed to USCAST (Ambrose 2019), in EUCAST’s amikacin rationale document v3.1
The free-drug murine numbers and the total-drug clinical numbers are not interchangeable and are an order of magnitude apart for the same drug. Check which basis a target is on before comparing it with anything.

What the ratio becomes across the one-dilution bracket

Reported MIC (mg/L)Ratio at AUC24 = 500One dilution lowerOne dilution higher
0.252,0004,0001,000
0.51,0002,000500
15001,000250
2250500125
412525063
Every figure is this calculator’s own arithmetic at an AUC24 of 500 mg·h/L. Read down the middle column: the ratio changes by a factor of two per row, which is the same factor as the measurement’s own reproducibility. A ratio quoted to three significant figures is false precision.

An exposure target, and the measurement that limits it

Vancomycin and the fluoroquinolones kill in proportion to total exposure rather than to peak height or to time above a threshold, so their pharmacodynamic index is the 24-hour area under the concentration-time curve divided by the MIC. The arithmetic is trivial — one division — and the whole difficulty is in the two numbers going into it.

The numerator is not measured directly. For a drug with linear kinetics the 24-hour AUC is the total daily dose divided by the clearance, which is how the population estimate on this site’s vancomycin AUC24 calculator works; the 2020 consensus guideline’s preferred method is instead two measured concentrations fitted with Bayesian software, which uses the patient’s own pharmacokinetics rather than a population average. Either way the AUC carries the error of whichever clearance estimate produced it, and clearance in acute illness is a moving target. This page takes the AUC as given and does not estimate one; the vancomycin dose adjustment calculator handles the proportional change in the other direction.

The denominator is worse, and this is where most pages stop short. The consequence is specific and checkable: at an AUC of 500 mg·h/L and a reported MIC of 1 mg/L the ratio is 500, comfortably inside the 400-600 window; at the dilution above it is 250 and at the dilution below it is 1,000. The same exposure, the same patient, the same organism, and a fourfold range of answers that crosses both edges of the window. Mouton and colleagues put a number on the underlying variation — a log2 standard deviation of about 0.3 to 0.5 of a dilution on repeat testing in one laboratory, rising to 0.5 to 1 dilution or more between laboratories — and concluded that using an individual MIC value to modify a dosing regimen is not justified. That conclusion sits uneasily beside a guideline that asks for an individualised ratio, and a reader of either deserves to know the other exists.

The method matters as well as the measurement. IDSA guidance, as Brusamarello and colleagues report it, treats an AUC/MIC of 200 to 400 measured against a gradient-strip MIC as roughly equivalent to 400 to 600 against a broth microdilution MIC — a factor of two written into a guideline because the two methods systematically differ by about a dilution. This page does not hold a breakpoint table. EUCAST and CLSI publish them, they are revised two or three times a year, and the laboratory that issued your report has already applied its own version. Take the MIC and the interpretive category from the report; this page does the arithmetic that sits on top of them.

Frequently asked questions

What AUC/MIC should I aim for with vancomycin?

The 2020 ASHP/IDSA/PIDS/SIDP consensus guideline recommends an individualised AUC/MIC of 400 to 600 for suspected or definitive serious invasive MRSA infection, with the MIC determined by broth microdilution and assumed to be 1 mg/L unless broth microdilution shows otherwise. The same guideline states that trough-only monitoring with a target of 15 to 20 mg/L is no longer recommended.

Is the vancomycin AUC/MIC target free drug or total drug?

Total. The guideline builds the target on serum concentrations, which assays report as total drug, and vancomycin is about 55% serum protein bound by ultrafiltration according to its label. EUCAST’s quinolone and aminoglycoside targets, by contrast, are explicitly fAUC/MIC — free drug — and are numerically much smaller. The two cannot be compared.

What is the AUC/MIC target for a fluoroquinolone?

There is more than one, on different bases. EUCAST’s ciprofloxacin rationale document names a total-drug AUC:MIC of 125 from Forrest 1993 in hospital-acquired pneumonia, and separately gives free-drug murine thigh targets of 35.6 for stasis and 67.4 for a 1-log10 kill against Enterobacterales, with S. pneumoniae needing much less (13.1 and 21.0).

Why does the calculator show the ratio at other MICs?

Because the reported MIC is a doubling-dilution bracket rather than a point value, and the ratio moves by a factor of two per dilution. At an AUC of 500 and a reported MIC of 1 mg/L the ratio spans 250 to 1,000 across the accepted one-dilution reproducibility. Showing only the middle number implies a precision the measurement does not have.

Can I compute the AUC from a single trough?

Not reliably. A single concentration does not determine an area without an assumed clearance and volume, which is what the population equation on the vancomycin AUC24 page supplies. The 2020 guideline’s preferred approach is two concentrations fitted with Bayesian software, and it names haemodynamic instability and rapidly changing renal function as the settings where the population estimate should not be trusted.

Does this page tell me whether the organism is susceptible?

No. This page cannot say whether an organism is susceptible: that is a laboratory interpretation against a versioned breakpoint table, and the laboratory that issued the report has already made it.

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References

  1. Rybak MJ, Le J, Lodise TP, et al. Therapeutic monitoring of vancomycin for serious methicillin-resistant Staphylococcus aureus infections: a revised consensus guideline and review of ASHP, IDSA, PIDS and SIDP. Am J Health-Syst Pharm. 2020;77(11):835-864.
  2. Brusamarello C, Daley AJ, Zhu X, Landersdorfer C, Gwee A. How important are MIC determination methods when targeting vancomycin levels in patients with Staphylococcus aureus infections? J Antimicrob Chemother. 2021;76(6):1641-1643. Source for the CLSI M07-A9 one-dilution criterion and the IDSA method equivalence quoted here.
  3. European Committee on Antimicrobial Susceptibility Testing. Ciprofloxacin rationale document, version 2.0, 1 January 2021. Source for the fAUC/MIC targets, the fraction unbound, and the total-drug AUC:MIC of 125 that it attributes to Forrest et al. 1993.
  4. Mouton JW, Muller AE, Canton R, Giske CG, Kahlmeter G, Turnidge J. MIC-based dose adjustment: facts and fables. J Antimicrob Chemother. 2018;73(3):564-568. Source for the log2 variability figures, the ISO 20776-2 criterion and the stated conclusion that individual MIC-based dose adjustment is not justified.
  5. European Committee on Antimicrobial Susceptibility Testing. Amikacin rationale document, version 3.1, September 2024. Source for the fAUC/MIC targets and the fraction unbound; attributes the murine data to the USCAST evaluation (Ambrose et al. 2019).
  6. Vancomycin hydrochloride for injection, USP. US prescribing information, Clinical Pharmacology. Source for about 55% binding by ultrafiltration and a half-life of 4 to 6 hours.
  7. European Committee on Antimicrobial Susceptibility Testing. Breakpoint tables for interpretation of MICs and zone diameters, version 16.1, 2026, stated valid 24 June to 31 December 2026. https://www.eucast.org. Cited rather than reproduced.
  8. Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing. 35th ed. CLSI supplement M100-Ed35. Wayne, PA: CLSI; January 2025. A commercial standard whose front matter requires express written consent for any reproduction; cited here, never reproduced or paraphrased.

Not medical advice. For healthcare professionals and education. Reference intervals vary by laboratory and assay — always use your own laboratory's. Never base a dose or a treatment decision on this page alone. Full disclaimer at calcengines.com/disclaimer/