In vitro antibacterial activity of ceftazidime/avibactam alone and in combination with fosfomycin against carbapenem-resistant Gram-negative bacilli

doi:10.3969/j.issn.1673-8640.2020.10.006

Abstract

Abstract:

Objective To investigate in vitro antibacterial activity of a novel β-lactam/β-lactamase inhibitor ceftazidime（CAZ）/avibactam（AVI） alone and in combination with fosfomycin against carbapenem-resistant Gram-negative bacilli. Methods A total of 56 carbapenem-resistant Escherichia coli（CREC）,43 carbapenem-resistant Klebsiella pneumoniae（CRKP）,53 carbapenem-resistant Pseudomonas aeruginosa（CRPA）,51 carbapenem-susceptible Escherichia coli（CSEC）,43 carbapenem-susceptible Klebsiella pneumoniae（CSKP） and 51 carbapenem-susceptible Pseudomonas aeruginosa（CSPA） were collected from the First Affiliated Hospital of Wenzhou Medical University from 2014 to 2017. The minimum inhibitory concentration（MIC） against CAZ/AVI was determined by agar dilution method. The fractional inhibitory concentration index（FICI） of CAZ/AVI in combination with fosfomycin was determined by checkerboard method to evaluate the combined antibacterial effect. Results The total resistance rate of 297 Gram-negative bacilli to CAZ/AVI was 18.18%. The resistance rate of carbapenem-resistant Gram-negative bacilli to CAZ/AVI was 30.26%,which was higher than that of carbapenem-susceptible isolates（5.52%）（P<0.05）. The resistance rate of CRKP to CAZ/AVI was 9.3%,which was lower than those of CREC and CRPA（39.29% and 37.74%）（P<0.05）. CAZ/AVI in combination with fosfomycin showed synergistic effect on CRKP and CRPA and additive effect on CREC. Conclusions CAZ/AVI has a high in vitro antibacterial activity towards CRKP,and can be the first choice for clinical treatment of CRKP. CAZ/AVI in combination with fosfomycin may be a new treatment strategy for the treatment of 3 common carbapenem-resistant Gram-negative bacilli.

Key words: Carbapenem resistance, Gram-negative bacillus, Ceftazidime, avibactam, Fosfomycin, Drug combination

CLC Number:

R446.5

CHEN Tao, XU Ye, DONG Guofeng, ZHOU Cui, XU Wenya, ZHOU Tieli. In vitro antibacterial activity of ceftazidime/avibactam alone and in combination with fosfomycin against carbapenem-resistant Gram-negative bacilli[J]. Laboratory Medicine, 2020, 35(10): 988-993.

Figures/Tables 4

References 21

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菌株类型	菌株数/株	MIC₅₀/（μg/mL）	MIC₉₀/（μg/mL）	范围/（μg/mL）	耐药率/%
碳青霉烯耐药
CREC	56	8/4	≥128/4	≤0.12/4~>128/4	39.29^#
CRKP	43	4/4	8/4	0.5/4~128/4	9.30
CRPA	53	8/4	64/4	0.25/4~>128/4	37.74^#
碳青霉烯敏感
CSEC	51	≤0.12/4	1/4	≤0.12/4~128/4	1.96^*
CSKP	43	0.5/4	1/4	≤0.12/4~>128/4	6.98
CSPA	51	2/4	8/4	≤0.12/4~>128/4	7.84^*
合计					18.18

菌株类型	菌株数/株	MIC₅₀/（μg/mL）	MIC₉₀/（μg/mL）	范围/（μg/mL）	耐药率/%
碳青霉烯耐药
CREC	56	8/4	≥128/4	≤0.12/4~>128/4	39.29^#
CRKP	43	4/4	8/4	0.5/4~128/4	9.30
CRPA	53	8/4	64/4	0.25/4~>128/4	37.74^#
碳青霉烯敏感
CSEC	51	≤0.12/4	1/4	≤0.12/4~128/4	1.96^*
CSKP	43	0.5/4	1/4	≤0.12/4~>128/4	6.98
CSPA	51	2/4	8/4	≤0.12/4~>128/4	7.84^*
合计					18.18

菌株分类	菌株数	CAZ/AVI MIC
菌株分类	菌株数	<4/4/（μg/mL）	4/4~8/4/（μg/mL）
CREC	34	25^*	9^*
CRKP	39	16	23
CRPA	33	17	16

菌株分类	菌株数	CAZ/AVI MIC
菌株分类	菌株数	<4/4/（μg/mL）	4/4~8/4/（μg/mL）
CREC	34	25^*	9^*
CRKP	39	16	23
CRPA	33	17	16

表型/基因型	菌株数/株	MIC₅₀/（μg/mL）	MIC₉₀/（μg/mL）	范围/（μg/mL）	耐药率/%
NDM	31	>128/4	>128/4	≤0.12/4~>128/4	67.74
KPC-2	54	2/4	8/4	≤0.12/4~>128/4	7.41
IMP	1			1/4~1/4	0
KPC-2+IMP	2			1/4~4/4	0
不产酶	64	4/4	64/4	≤0.12/4~>128/4	32.81
合计	152				30.26