头孢他啶/阿维巴坦对耐碳青霉烯类肺炎克雷伯菌的体外抗菌活性研究-现代医学

头孢他啶/阿维巴坦对耐碳青霉烯类肺炎克雷伯菌的体外抗菌活性研究

单位：1. 浙江大学医学院附属儿童医院遗传与代谢科, 浙江杭州 310000;
2. 昆明医科大学第一附属医院医学检验科, 云南昆明 650032

分类号：R378

出版年·卷·期（页码）：2024·52·第八期（1197-1204）

摘要：

目的: 明确头孢他啶/阿维巴坦(CZA)对耐碳青霉烯类肺炎克雷伯菌的体外抗菌活性。方法: 收集昆明医科大学第一附属医院2022年1至12月期间从临床各科室分离的非重复碳青霉烯类耐药肺炎克雷伯菌株(CRKP)，分析其临床分布特征和药敏信息；并进行耐药基因酶型检测，采用微量肉汤稀释法测定CZA对不同酶型菌株的MIC₅₀、MIC₉₀和MIC_range；另外，对产NDM型金属酶的CRKP采用微量棋盘稀释法和时间杀菌试验测定CZA联合氨曲南(ATM)体外协同作用。结果: 共收集到143株非重复CRKP，标本类型分布以呼吸道标本为主，科室分布主要集中在ICU；药敏结果显示对包括碳青霉烯类在内的多种抗生素耐药率＞95%；143株CRKP中bla_KPC阳性及bla_OXA-48阳性CRKP对CZA敏感率均为100%，bla_NDM阳性CRKP对CZA的耐药率为100%，但CZA+ATM联合用药对其具有较强的体外协同抑菌作用。结论: 使用CZA治疗CRKP所致感染时，有必要先明确其酶型，为临床抗感染治疗提供用药指导。

Objective: To analyze the antibacterial activity of ceftazidime/avibactam(CZA) against carbapenem-resistant Klebsiella pneumoniae(CRKP) in vitro. Methods: Non-repetitive CRKP strains isolated from clinical departments in the First Affiliated Hospital of Kunming Medical University from January to December 2022 were collected, analyze the clinical distribution and sensitivity of CRKP; PCR was used to detect common carbapenemase genes in CRKP, CZA MIC against CRKP carrying different carbapenemase was determined by the micro broth dilution method, expressed as MIC₅₀, MIC₉₀ and MIC_range; additionally, micro-checkerboard dilution method and time-kill assay were used to detect the antibacterial activity of CZA combined with aztreonam(ATM) on the NDM-producing CRKP. Results: A total of 143 non-repetitive CRKP strains were collected, the specimen was dominated by respiratory specimens, mainly concentrated in ICU; CRKP are characterized by extensive drug resistance, including resistance rate of Carbapenem was>95%;143 CRKP carrying bla_KPC and bla_OXA-48 were 100% sensitive to CZA, bla_NDM were 100% resistant to CZA, however, CZA combined with ATM showed a strong synergistic bactericidal effect on NDM-producing CRKP in vitro. Conclusion: It is necessary to detect the enzyme type of CRKP in the process of treatment with CZA, to provide drug guidance for clinical anti-infection treatment.

参考文献：

[1] KARAMPATAKIS T,TSERGOULI K,BEHZADI P.Carbapenem-resistant Klebsiella pneumoniae:virulence factors,molecular epidemiology and latest updates in treatment options[J].Antibiotics(Basel),2023,12(2):234.
[2] HOBSON C A,PIERRAT G,TENAILLON O,et al.Klebsiella pneumoniae carbapenemase variants resistant to ceftazidime-avibactam:an evolutionary overview[J].Antimicrob Agents Chemother,2022,66(9):e0044722.
[3] JALALVAND K,SHAYANFAR N,SHAHCHERAGHI F,et al.Evaluation of phenotypic and genotypic characteristics of carbapnemases-producing Enterobacteriaceae and its prevalence in a referral hospital in Tehran city[J].Iran J Pathol,2020,15(2):86-95.
[4] HO狟UL T,AYDOǦAN C N,KAYA S,et al.In vitroactivity of ceftazidime-avibactam and colistin against carbapenem-resistant Klebsiella pneumoniae clinical isolates[J].Mikrobiyol Bul,2022,56(2):218-229.
[5] LODISE T P,SMITH N M,O'DONNELL N,et al.Determining the optimal dosing of a novel combination regimen of ceftazidime/avibactam with aztreonam against NDM-1-producing Enterobacteriaceae using a hollow-fibre infection model[J].J Antimicrob Chemother,2020,75(9):2622-2632.
[6] ROMINA P E,LUCÍA A,LETICIA C,et al.In vitro effectiveness of ceftazidime-avibactam in combination with aztreonam on carbapenemase-producing enterobacterales[J].J Glob Antimicrob Resist,2023,35:62-66.
[7] ZHAO Y,LI C,ZHANG J,et al.The in vitro activity of polymyxin B and tigecycline alone and combination with other antibiotics against carbapenem-resistant enterobacter cloacae complex isolates,including high-risk clones[J].Ann Transl Med,2019,7(23):779.
[8] LI J,LI Y,SONG N,et al.Risk factors for carbapenem-resistant Klebsiella pneumoniae infection:a meta-analysis[J].J Glob Antimicrob Resist,2020,21:306-313.
[9] HU Y,LIU C,SHEN Z,et al.Prevalence,risk factors and molecular epidemiology of carbapenem-resistant Klebsiella pneumoniae in patients from Zhejiang,China,2008-2018[J].Emerg Microbes Infect,2020,9(1):1771-1779.
[10] SORIANO A,CARMELI Y,OMRANI A S,et al.Ceftazidime-avibactam for the treatment of serious gram-negative infections with limited treatment options:a systematic literature review[J].Infect Dis Ther,2021,10(4):1989-2034.
[11] SALES G T M,FORESTO R D.Drug-induced nephrotoxicity[J].Rev Assoc Med Bras,2020,66(suppl 1):s82-s90.
[12] CORNELY O A,CISNEROS J M,TORRE-CISNEROS J,et al.Pharmacokinetics and safety of aztreonam/avibactam for the treatment of complicated intra-abdominal infections in hospitalized adults:results from the REJUVENATE study[J].J Antimicrob Chemother,2020,75(3):618-627.
[13] TOOKE C L,HINCHLIFFE P,BRAGGINTON E C,et al.β-Lactamases and β-Lactamase Inhibitors in the 21st Century[J].J Mol Biol,2019,431(18):3472-3500.
[14] GIANI T,ANTONELLI A,SENNATI S,et al.Results of the Italian infection-Carbapenem Resistance Evaluation Surveillance Trial(iCREST-IT):activity of ceftazidime/avibactam against Enterobacterales isolated from urine[J].J Antimicrob Chemother,2020,75(4):979-983.
[15] KHAN A,ERICKSON S G,PETTAWAY C,et al.Evaluation of susceptibility testing methods for aztreonam and ceftazidime-avibactam combination therapy on extensively drug-resistant gram-negative organisms[J].Antimicrob Agents Chemother,2021,65(11):e0084621.
[16] DRAWZ S M,PAPP-WALLACE K M,BONOMO R A.New β-lactamase inhibitors:a therapeutic renaissance in an MDR world[J].Antimicrob Agents Chemother,2014,58(4):1835-1846.
[17] LODISE T P,O'DONNELL J N,BALEVIC S,et al.Pharmacokinetics of ceftazidime-avibactam in combination with aztreonam(COMBINE) in a phase 1,open-label study of healthy adults[J].Antimicrob Agents Chemother,2022,66(12):e0093622.
[18] LODISE T P,O'DONNELL J N,RAJA S,et al,Antibacterial Resistance Leadership Group.Safety of ceftazidime-avibactam in combination with aztreonam(combine) in a phase I,open-label study in healthy adult volunteers[J].Antimicrob Agents Chemother,2022,66(12):e0093522.

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