TABLE 2.

Magnitudes of avibactam exposures associated with stasis and killing of P. aeruginosa in the neutropenic mouse thigh infection model in the background of q2h dosing of ceftazidime^a

Strainb	MIC (mg/liter)		Exptf	Avibactam %fT>1 mg/literc yielding:
	CAZd	CAZ-AVIe		Stasis	1-log10 kill
1	128	8	Codosing	37.2	65.7
5	128	8	Codosing	14.1	32.9
7	64	4	AVI fractionation	74.1	Not reported
			Codosing	50.4	65.3
11	128	16	Codosing	29.1	37.5
18	32	2	AVI fractionation	30.2	Not reported
			Codosing	24.2	33.2
19	64	4	Codosing	62.5	67.2
Mean				40.2	50.3
SD				20	17

^aData were retabulated from Berkhout et al. (44).

^bResistance summaries for the strains used in this experiment are as follows. Strain 1, nitrocefinase activity, ++; AmpC transcript, overexpressed; β-lactamase genotype, bla_AmpC; class A⁻, class B⁻; strain 5: nitrocefinase activity, ++++; AmpC transcript, overexpressed; β-lactamase genotype, bla_AmpC; class A⁻, class B⁻; strain 7: nitrocefinase activity, +++; AmpC transcript, overexpressed; β-lactamase genotype, bla_AmpC; class A⁻, class B⁻; strain 11: OprD⁻, AmpC^con, class A⁻, class B⁻; strain 18: OprD⁻, AmpC_ind?, class A⁻, class B⁻; strain 19: OprD⁻, AmpC^con, class A⁻, class B⁻.

^cTimes are expressed as the percentages of the dosing interval.

^dCAZ, ceftazidime.

^eAVI, avibactam.

^fCodosing, ceftazidime and avibactam were codosed but the amount of avibactam was varied, without fractionating any given total daily dose; AVI fractionation, avibactam dose fractionation experiments.