Cmax/MIC Ratio Calculator

The peak-to-MIC ratio — the classical aminoglycoside target, from human studies in the 1980s and 1990s — with the published graded response, the modern argument that fAUC/MIC has replaced it, and the one-dilution bracket.

Last updated 8 Oct 2026

Cmax/MIC ratio

Peak / MIC

Peak concentration (mg/L)The post-distribution peak, drawn at least 30 minutes after the end of the infusion. A peak drawn earlier catches the distribution phase and overstates the true value. Calculate a half-life from a paired peak and trough on the aminoglycoside half-life calculator.

MIC (mg/L)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.

10.0Cmax/MICExample

peak 20 mg/L, MIC 2 mg/L

Formula

Cmax/MIC = peak concentration ÷ MIC

Cmax: the post-distribution peak at steady state, in mg/L. Not the concentration at the end of the infusion, which is still distributing: aminoglycoside peaks are conventionally drawn 30 minutes or more after the infusion ends
free or total: for the aminoglycosides the distinction barely matters, and that is itself worth knowing. EUCAST’s amikacin rationale document gives a fraction unbound of 89 to 100%, so the free and total concentrations are within about a tenth of each other. The same cannot be said of the highly bound agents
the 8-10 figure: a human-study figure, not an animal one: Moore 1987 (236 patients, clinical response) and Kashuba 1999 (78 patients, temperature and white-cell resolution), both tabulated by Bland, Pai and Lodise in 2018. Bland and colleagues also note that the 1980s in-vitro and animal support came from studies in which dosing was not humanised
what EUCAST uses instead: fAUC/MIC. The amikacin rationale document v3.1 gives median neutropenic-mouse-thigh targets of 21.4 for stasis and 62.5 for a 1-log10 kill against Enterobacterales, 55.4 and 74.3 against P. aeruginosa, and 41.4 and 90.4 against S. aureus. No Cmax/MIC target appears in it at all

Worked example

peak 20 mg/L, MIC 2 mg/L
20 ÷ 2 = 10.0, the upper of the two values the classical human studies identified
One doubling dilution up, at an MIC of 4 mg/L: 20 ÷ 4 = 5.0
One dilution down, at an MIC of 1 mg/L: 20 ÷ 1 = 20.0
So the reported MIC's own one-dilution bracket spans 5.0 to 20.0 — straddling the 8-to-10 region entirely
To reach a ratio of 10 at an MIC of 2 mg/L the peak has to be 20 mg/L; at an MIC of 4 it has to be 40 mg/L, which is above the peaks extended-interval gentamicin regimens produce
That last point is the practical one: at higher MICs the ratio cannot be reached by raising the peak within the range the drug tolerates, which is why the published target and the achievable exposure part company

The Moore 1987 graded response, as Bland 2018 tabulates it

236 patients with suspected gram-negative sepsis; the endpoint is clinical response, not microbiological cure or mortality. This is a graded association across bands in an observational cohort from 1987, not a threshold from a randomised comparison, and the spacing of the bands is where the familiar “8 to 10” comes from.
Cmax/MIC band	Clinical response
4 to under 6	about 70%
6 to under 8	about 84%
8 to under 10	about 88%
10 or more	about 92%

Which index belongs to which class, and on which basis

Matching a class to the wrong index is the error this category exists to prevent. A Cmax/MIC of 10 says nothing useful about a beta-lactam, and an fT>MIC of 70% says nothing useful about gentamicin. The PK/PD target interpreter walks the pairing.
Class	Index	Published target	Basis
Aminoglycosides (classical)	Cmax/MIC	8-10	Total drug, human cohorts (Moore 1987, Kashuba 1999)
Aminoglycosides (EUCAST)	fAUC/MIC	21.4-55.4 stasis, 62.5-90.4 for 1-log kill	Free drug, neutropenic mouse thigh
Beta-lactams	%fT>MIC	about 40-70% for a 1-log kill	Free drug, neutropenic murine models
Fluoroquinolones	AUC/MIC	125 clinical, 13.1-68.7 murine	Total drug clinically, free drug in the murine data
Vancomycin	AUC24/MIC	400-600	Total drug, observational human cohorts

A human-derived target, and the argument that it is the wrong one

Aminoglycosides kill faster as the concentration rises, and they keep suppressing growth for a while after the concentration has fallen below the MIC — the post-antibiotic effect. Both properties point the same way: give a large dose infrequently, let the peak go high and let the trough fall. The index that was fitted to that behaviour is the ratio of the post-distribution peak to the MIC, and the familiar target of 8 to 10 is unusual among PK/PD targets in resting on human data rather than on mice. Moore, Lietman and Smith reported a graded response across Cmax/MIC bands in 236 patients in 1987; Kashuba and colleagues found the ratio the single most important predictor of clinical and microbiological resolution in 78 patients with gram-negative nosocomial pneumonia in 1999.

That is the case for the index. The case against it is now at least as strong, and a page that quotes 8 to 10 without it is out of date. Bland, Pai and Lodise’s 2018 reappraisal notes that the in-vitro and animal work of the 1980s used dosing that was not humanised, which may itself explain why the peak looked decisive, and sets out the human data supporting an area-based index instead: an AUC₀₋₂₄/MIC of 110 or more associated with higher cure in 23 patients on tobramycin monotherapy, and fAUC/MIC correlating with lung-function improvement in 13 patients with cystic fibrosis. EUCAST has gone further: its amikacin rationale document sets breakpoints against fAUC/MIC and contains no Cmax/MIC target at all. Two reputable sources therefore disagree about which index aminoglycoside dosing should be judged by, and this page prints both rather than choosing silently.

The practical consequence of the MIC’s resolution is sharper here than anywhere else in this category, because the ratio is a plain division with nothing to damp it. At a peak of 20 mg/L and a reported MIC of 2 mg/L the ratio is 10.0; one dilution either way gives 5.0 and 20.0. And unlike a beta-lactam, where a longer infusion can buy time above the MIC without a higher peak, the only lever on a Cmax/MIC ratio is the peak itself, which aminoglycoside toxicity limits. At higher MICs the published target simply cannot be reached at a dose the kidney and the inner ear will tolerate, and the honest answer is that the arithmetic has run out rather than that the number should be chased.

This page takes the peak and the MIC as given. The dosing arithmetic is built elsewhere on this site and is not repeated here: the aminoglycoside half-life calculator derives a half-life from a paired peak and trough, the Hartford nomogram checker says whether the extended-interval chart applies to a given patient at all, and the dosing weight selection interpreter settles which body weight the dose should have been calculated on. 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 Cmax/MIC ratio is the aminoglycoside target?

8 to 10 is the figure in general use. It comes from two human studies tabulated by Bland, Pai and Lodise in 2018: Moore 1987, where clinical response rose through roughly 70%, 84%, 88% and 92% across bands of 4 to under 6, 6 to under 8, 8 to under 10 and 10 or more in 236 patients, and Kashuba 1999, where a ratio of 10 or more carried a 90% probability of temperature resolution in 78 patients.

Is Cmax/MIC still the right index for aminoglycosides?

It is contested, and the page prints both sides. EUCAST’s amikacin rationale document v3.1 sets breakpoints against fAUC/MIC and gives no Cmax/MIC target; Bland and colleagues set out human data supporting an area-based index, including an AUC24/MIC of 110 or more in 23 patients on tobramycin. The classical peak-based target remains in wide clinical use. Neither source is obviously wrong and the disagreement is real.

Which peak should I enter?

The post-distribution peak at steady state, drawn at least 30 minutes after the end of the infusion. A sample taken at the end of the infusion is still in the distribution phase and reads high, which inflates the ratio. The time the sample was drawn, relative to both the dose and the start of therapy, has to be recorded for the number to mean anything.

Does protein binding matter for this ratio?

Very little for the aminoglycosides, and that is worth knowing because it is unusual. EUCAST gives amikacin’s fraction unbound as 89 to 100%, so free and total concentrations are nearly the same number. For a highly bound agent such as ceftriaxone, at 95% bound falling to 85% at high concentrations, the distinction dominates the answer.

Why does the calculator show peaks needed at other MICs?

To make the ceiling visible. Reaching a ratio of 10 needs a peak of 10 times the MIC, so at an MIC of 4 mg/L that is 40 mg/L — above what extended-interval gentamicin regimens produce. The arithmetic says what exposure the published target would require, and sometimes the answer is an exposure the drug’s toxicity does not permit.

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.

Related calculators

References

Bland CM, Pai MP, Lodise TP. Reappraisal of contemporary pharmacokinetic and pharmacodynamic principles for informing aminoglycoside dosing. Pharmacotherapy. 2018;38(12):1229-1238. Source for the Moore 1987 and Kashuba 1999 figures quoted on this page, which it tabulates.
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).
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.
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.
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/