Outcomes in participants with ventilated nosocomial pneumonia and organ failure treated with ceftolozane/tazobactam versus meropenem: a subset analysis of the phase 3, randomized, controlled ASPECT-NP trial

Martin-Loeches, Ignacio; Shorr, Andrew F.; Wunderink, Richard G.; Kollef, Marin H.; Timsit, Jean-François; Yu, Brian; Huntington, Jennifer A.; Jensen, Erin; Bruno, Christopher J.

doi:10.1186/s13613-022-01084-8

Annals of Intensive Care

Table 3 MIC summary of baseline LRT pathogens in participants with a baseline R-SOFA ≥ 2 or CV-SOFA ≥ 2 (mITT population)

From: Outcomes in participants with ventilated nosocomial pneumonia and organ failure treated with ceftolozane/tazobactam versus meropenem: a subset analysis of the phase 3, randomized, controlled ASPECT-NP trial

Pathogen	Respiratory SOFA component score ≥ 2		Cardiovascular SOFA component score ≥ 2
Pathogen	Ceftolozane/tazobactam (n = 222)	Meropenem (n = 219)	Ceftolozane/tazobactam (n = 53)	Meropenem (n = 72)
All Gram-negatives
n1	312	307	75	106
MIC range	< 0.064 to ≥ 256	< 0.064 to ≥ 256	< 0.064 to ≥ 256	< 0.064 to 128
MIC₅₀	0.5	< 0.064	0.5	< 0.064
MIC₉₀	16	1	8	0.5
Pseudomonas aeruginosa
n1	52	58	14	14
MIC range	0.25 to ≥ 256	< 0.064 to 16	0.25 to ≥ 256	0.125 to 2
MIC₅₀	1	0.5	1	0.5
MIC₉₀	4	8	2	1
AmpC overexpressing
n1	7	6	1	0
MIC range	1 to 8	0.25 to 16	2 to 2	N/a
MIC₅₀	2	8	2	N/a
MIC₉₀	8	16	2	N/a
Enterobacterales
n1	206	206	47	79
MIC range	0.125 to ≥ 256	< 0.064 to 16	0.125 to 128	< 0.064 to 0.25
MIC₅₀	0.5	< 0.064	0.5	< 0.064
MIC₉₀	16	0.25	16	< 0.064
ESBL + Enterobacterales
n1	77	74	15	19
MIC range	0.25 to ≥ 256	< 0.064 to 1	0.25 to 128	< 0.064 to < 0.064
MIC₅₀	4	< 0.064	4	< 0.064
MIC₉₀	128	1	64	< 0.064
Citrobacter koseri
n1	5	7	1	3
MIC range	0.125 to 1	< 0.064 to 0.25	0.125 to 0.125	< 0.064 to 0.25
MIC₅₀	0.25	< 0.064	0.125	< 0.064
MIC₉₀	1	0.25	0.125	0.25
Enterobacter cloacae
n1	16	13	5	10
MIC range	0.125 to 8	< 0.064 to < 0.064	0.25 to 8	< 0.064 to < 0.064
MIC₅₀	0.5	< 0.064	1	< 0.064
MIC₉₀	8	< 0.064	8	< 0.064
Escherichia coli
n1	47	38	9	14
MIC range	0.125 to 4	< 0.064 to 0.125	0.125 to 0.5	< 0.064 to < 0.064
MIC₅₀	0.25	< 0.064	0.25	< 0.064
MIC₉₀	1	< 0.064	0.5	< 0.064
Klebsiella aerogenes
n1	3	7	2	4
MIC range	0.125 to 0.25	< 0.064 to 1	0.125 to 0.25	< 0.064 to 0.25
MIC₅₀	0.125	0.25	0.125	0.125
MIC₉₀	0.25	1	0.25	0.25
Klebsiella oxytoca
n1	13	9	5	6
MIC range	0.125 to 2	< 0.064 to < 0.064	0.125 to 0.25	< 0.064 to < 0.064
MIC₅₀	0.25	< 0.064	0.25	< 0.064
MIC₉₀	0.25	< 0.064	0.25	< 0.064
Klebsiella pneumonia
n1	77	86	16	24
MIC range	0.25 to ≥ 256	< 0.064 to 16	0.25 to 128	< 0.064 to < 0.064
MIC₅₀	2	< 0.064	0.5	< 0.064
MIC₉₀	128	1	64	< 0.064
Proteus mirabilis
n1	21	19	3	6
MIC range	0.25 to 8	< 0.064 to 0.125	0.25 to 0.5	< 0.064 to 0.125
MIC₅₀	0.5	< 0.064	0.5	< 0.064
MIC₉₀	4	0.125	0.5	0.125
Serratia marcescens
n1	10	12	5	3
MIC range	0.5 to 4	< 0.064 to 0.125	0.5 to 8	< 0.064 to < 0.064
MIC₅₀	0.5	< 0.064	2	< 0.064
MIC₉₀	2	< 0.064	8	< 0.064
Acinetobacter baumannii
n1	18	12	3	1
MIC range	< 0.064 to ≥ 256	0.25 to ≥ 256	< 0.064 to 8	0.25 to 0.25
MIC₅₀	8	1	4	0.25
MIC₉₀	≥ 256	128	8	0.25
Haemophilus influenzae
n1	18	15	5	8
MIC range	< 0.064 to 0.5	< 0.064 to 0.125	< 0.064 to 0.5	< 0.064 to 0.125
MIC₅₀	0.125	< 0.064	0.125	< 0.064
MIC₉₀	0.25	0.125	0.5	0.125
All Gram-positive
n1	8	14	2	3
MIC range	< 0.064 to 32	< 0.064 to 1	0.25 to 4	< 0.064 to 1
MIC₅₀	0.25	< 0.064	0.25	< 0.064
MIC₉₀	32	1	4	1
Streptococcus pneumoniae
n1	4	7	1	2
MIC range	< 0.064 to 0.25	< 0.064 to 1	0.25 to 0.25	< 0.064 to < 0.064
MIC₅₀	0.064	< 0.064	0.25	< 0.064
MIC₉₀	0.25	1	0.25	< 0.064

n is the number of participants in the population
n1 is the number of pathogens with baseline MIC data available
MIC is reported in mg/L and was measured by broth microdilution testing
MIC₅₀ is the minimum inhibitory concentration required to inhibit the growth of 50% of the pathogens
MIC₉₀ is the minimum inhibitory concentration required to inhibit the growth of 90% of the pathogens
Pathogens with n ≥ 10 within organism species pooled across both treatment arms for any SOFA component score. ESBL + Enterobacterales reported collectively
Each pathogen was counted once per participant and where there were multiple values, the pathogen with the highest MIC was used
CV-SOFA cardiovascular SOFA component score, ESBL + extended-spectrum β-lactamase producing, LRT lower respiratory tract, MIC minimum inhibitory concentration, mITT microbiologic intention-to-treat, R-SOFA respiratory SOFA component score, SOFA Sequential Organ Failure Assessment

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