Ca-EDTA restores the activity of ceftazidime- avibactam or aztreonam against carbapenemase- producing Klebsiella pneumoniae infections

被引：10

作者：

Leshan, Dhammika ^{[1
,2
,3
,4
,5
,6
]}

Shein, Aye Mya Sithu ^{[2
,3
]}

Hurst, Cameron ^{[7
]}

Monk, Peter N. ^{[8
]}

Hongsing, Parichart ^{[9
,10
]}

Phattharapornjaroen, Phatthranit ^{[11
,12
]}

Ditcham, William Graham Fox ^{[4
]}

Ounjai, Puey ^{[13
]}

Saethang, Thammakorn ^{[14
]}

Chantaravisoot, Naphat ^{[15
,16
]}

Wapeesittipan, Pattama ^{[17
]}

Luk-in, Sirirat ^{[18
]}

Sae-Joo, Sasipen ^{[2
,3
]}

Nilgate, Sumanee ^{[2
,3
]}

Rirerm, Ubolrat ^{[2
,3
]}

Tanasatitchai, Chanikan ^{[2
,3
]}

Kueakulpattana, Naris ^{[2
,3
]}

Laowansiri, Matchima ^{[2
,3
]}

Liao, Tingting ^{[19
,20
]}

Kupwiwat, Rosalyn ^{[6
,21
]}

Rojanathanes, Rojrit ^{[22
]}

Ngamwongsatit, Natharin ^{[23
]}

Tungsanga, Somkanya ^{[24
,25
]}

Leelahavanichkul, Asada ^{[2
,26
]}

Ragupathi, Naveen Kumar Devanga ^{[6
,27
,28
]}

Badavath, Vishnu Nayak ^{[29
]}

Hosseini, S. M. Ali

Kanjanabuch, Talerngsak ^{[24
,32
,33
,34
]}

Hirankarn, Nattiya ^{[2
,31
]}

Storer, Robin James ^{[35
]}

Cui, Longzhu ^{[36
]}

Amarasiri, Mohan ^{[37
]}

Ishikawa, Hitoshi ^{[38
]}

Higgins, Paul G. ^{[39
,40
,41
,42
,43
]}

Stick, Stephen M. ^{[30
,31
,44
,45
,46
]}

Kicic, Anthony ^{[44
,45
,46
,47
]}

Chatsuwan, Tanittha ^{[2
,3
]}

Abe, Shuichi ^{[5
,6
]}

机构：

[1] Yamagata Prefectural Cent Hosp, Dept Infect Dis & Infect Control, Yamagata, Japan

[2] Chulalongkorn Univ, King Chulalongkorn Mem Hosp, Fac Med, Dept Microbiol,Thai Red Cross Soc, Bangkok, Thailand

[3] Chulalongkorn Univ, Fac Med, Ctr Excellence Antimicrobial Resistance & Stewards, Bangkok, Thailand

[4] Univ Western Australia, Sch Med, Fac Hlth & Med Sci, Nedlands, WA, Australia

[5] Univ Sheffield, Biofilms & Antimicrobial Resistance Consortium ODA, Sheffield, England

[6] Yamagata Prefectural Cent Hosp, Dept Infect Dis & Infect Control, Pathogen Hunters Res Team, Yamagata, Japan

[7] Charles Darwin Univ, Molly Wardaguga Res Ctr, Brisbane, Qld, Australia

[8] Univ Sheffield, Med Sch, Dept Infect Immun & Cardiovasc Dis, Sheffield, England

[9] Mae Fah Luang Univ, Chiang Rai, Thailand

[10] Mae Fah Luang Univ, Sch Integrat Med, Chiang Rai, Thailand

[11] Mahidol Univ, Fac Med, Ctr Excellence, Dept Emergency Med,Ramathibodi Hosp, Bangkok, Thailand

[12] Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Surg, S-40530 Gothenburg, Sweden

[13] Mahidol Univ, Fac Sci, Dept Biol, Bangkok, Thailand

[14] Kasetsart Univ, Fac Sci, Dept Comp Sci, Bangkok, Thailand

[15] Chulalongkorn Univ, Fac Med, Ctr Excellence Syst Biol, Res Affairs, Bangkok, Thailand

[16] Chulalongkorn Univ, Fac Med, Dept Biochem, Bangkok, Thailand

[17] Univ Bergen, Dept Clin Sci, Bergen, Norway

[18] Mahidol Univ, Fac Med Technol, Dept Clin Microbiol & Appl Technol, Bangkok, Thailand

[19] Chulalongkorn Univ, Fac Med, Dept Physiol, Bangkok, Thailand

[20] Chulalongkorn Univ, Fac Med, Ctr Excellence Microcirculat, Bangkok, Thailand

[21] Mahidol Univ, Fac Med, Dept Dermatol, Siriraj Hosp, Bangkok, Thailand

[22] Chulalongkorn Univ, Fac Sci, Ctr Excellence Mat & Biointerfaces, Bangkok, Thailand

[23] Mahidol Univ, Fac Vet Sci, Dept Clin Sci & Publ Hlth, Nakhon Pathom, Thailand

[24] Chulalongkorn Univ, Fac Med, Dept Med, Div Nephrol, Bangkok, Thailand

[25] Chulalongkorn Univ, Div Gen Internal Med Nephrol, Dept Med, Fac Med, Bangkok, Thailand

[26] Chulalongkorn Univ, Dept Microbiol, Translat Res Inflammat & Immunol Res Unit TRIRU, Bangkok, Thailand

[27] Univ Sheffield, Dept Chem & Biol Engn, Sheffield, England

[28] Christian Med Coll & Hosp, Dept Clin Microbiol, Vellore, India

[29] SVKMs Narsee Monjee Inst Management Studies NMIMS, Sch Pharm & Technol Management, Hyderabad 509301, India

[30] Univ Otago, Dept Microbiol & Immunol, Dunedin 9010, Otago, New Zealand

[31] Chulalongkorn Univ, Ctr Excellence Immunol & Immune Mediated Dis, Bangkok 10330, Thailand

[32] Chulalongkorn Univ, Fac Med, Ctr Excellence Kidney Metab Disorders, Bangkok, Thailand

[33] Chulalongkorn Univ, Fac Med, Sch Global Hlth, Dialysis Policy & Practice Program DiP3, Bangkok, Thailand

[34] King Chulalongkorn Mem Hosp, Peritoneal Dialysis Excellence Ctr, Bangkok, Thailand

[35] Chulalongkorn Univ, Fac Med, Off Res Affairs, Bangkok, Thailand

[36] Jichi Med Univ, Div Bacteriol, Sch Med, Tochigi, Japan

[37] Kitasato Univ, Sch Allied Hlth Sci, Dept Hlth Sci, Lab Environm Hyg, Sagamihara Minami, Kanagawa 2520373, Japan

[38] Yamagata Prefectural Univ Hlth Sci, Kamiyanagi, Yamagata 9902212, Japan

[39] Univ Cologne, Inst Med Microbiol Immunol & Hyg, Fac Med, Cologne, Germany

[40] Univ Cologne, Univ Hosp Cologne, Cologne, Germany

[41] German Ctr Infect Res, Partner Site Bonn Cologne, Cologne, Germany

[42] Univ Cologne, Fac Med, Ctr Mol Med Cologne, D-50935 Cologne, Germany

[43] Univ Cologne, Univ Hosp Cologne, D-50935 Cologne, Germany

[44] Univ Western Australia, Telethon Kids Inst, Nedlands, WA 6009, Australia

[45] Univ Western Australia, Ctr Cell Therapy & Regenerat Med, Med Sch, Nedlands, WA 6009, Australia

[46] Perth Childrens Hosp, Dept Resp & Sleep Med, Nedlands, WA 6009, Australia

[47] Curtin Univ, Sch Publ Hlth, Bentley, WA 6102, Australia

来源：

ISCIENCE | 2023年 / 26卷 / 07期

关键词：

PSEUDOMONAS-AERUGINOSA; COLISTIN-RESISTANT; ANTIBIOTIC-RESISTANCE; BIOFILM FORMATION; BETA-LACTAMASE; CALCIUM-EDTA; COMBINATION; EFFICACIES; INHIBITOR; MODEL;

D O I：

10.1016/j.isci.2023.107215

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Developing an effective therapy to overcome carbapenemase-positive Klebsiella pneumoniae (CPKp) is an important therapeutic challenge that must be ad-dressed urgently. Here, we explored a Ca-EDTA combination with aztreonam or ceftazidime-avibactam in vitro and in vivo against diverse CPKp clinical iso-lates. The synergy testing of this study demonstrated that novel aztreonam-Ca-EDTA or ceftazidime-avibactam-Ca-EDTA combination was significantly effective in eliminating planktonic and mature biofilms in vitro, as well as eradicating CPKp infections in vivo. Both combinations revealed significant therapeutic efficacies in reducing bacterial load in internal organs and protecting treated mice from mor-tality. Conclusively, this is the first in vitro and in vivo study to demonstrate that novel aztreonam-Ca-EDTA or ceftazidime-avibactam-Ca-EDTA combinations pro-vide favorable efficacy and safety for successful eradication of carbapenemase-producing Klebsiella pneumoniae planktonic and biofilm infections.

引用

页数：24

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