International Journal of Antimicrobial Agents最新文献

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Comparing ceftazidime/avibactam and polymyxin B for treating carbapenem-resistant organisms infections: a propensity score-matched retrospective cohort study.
IF 4.9 2区 医学
International Journal of Antimicrobial Agents Pub Date : 2024-12-20 DOI: 10.1016/j.ijantimicag.2024.107418
Chunmei Liu, Bing Leng, Maoyu Xie, Shuangyan Jiang, Xiaoyan Guan, Jiahui Xu, Yuqing Guo, Jinjiao Jiang, Juan Zeng
{"title":"Comparing ceftazidime/avibactam and polymyxin B for treating carbapenem-resistant organisms infections: a propensity score-matched retrospective cohort study.","authors":"Chunmei Liu, Bing Leng, Maoyu Xie, Shuangyan Jiang, Xiaoyan Guan, Jiahui Xu, Yuqing Guo, Jinjiao Jiang, Juan Zeng","doi":"10.1016/j.ijantimicag.2024.107418","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2024.107418","url":null,"abstract":"<p><strong>Background and aim: </strong>Comparative studies of Ceftazidime/avibactam(CAZ/AVI) versus polymyxin B (PMB) for carbapenem-resistant organisms (CRO) infections are limited. We aims to compare the efficacy and safety of CAZ/AVI and PMB in treating CRO infections.</p><p><strong>Methods: </strong>This single-center, propensity score-matched (PSM) retrospective cohort study involved adult patients with CRO infections. Patients who received a CAZ/AVI-based regimen were included in the cohort group, while those prescribed with a PMB-based regimen were in the control group. The primary outcome was 28-day all-cause mortality.</p><p><strong>Results: </strong>Among 298 eligible patients, 96 patients in each group were included in the PSM cohort. The CAZ/AVI group showed no improvement in 28-day or 14-day all-cause mortality, nor in 14-day clinical response, compared to the PMB group. However, the CAZ/AVI-based regimen showed higher 14-day clinical response rates than PMB-based regimen in subgroups of carbapenem-resistant Pseudomonas aeruginosa (CRPA) infections and monotherapy. The CAZ/AVI group achieved more CRO eradication than the PMB group (crude OR 1.658; 95% CI, 1.108-2.480; P=0.014; adjusted OR 1.718; 95% CI, 1.055-2.798; P=0.030). This advantage in CRO eradication with CAZ/AVI was consistent in most subgroups including septic shock, bloodstream infection and lower respiratory tract infection. The CAZ/AVI and PMB groups had comparable nephrotoxicity (crude OR 0.577; 95% CI, 0.306-1.089; P=0.090, adjusted OR, 0.741; 95% CI, 0.361-1.521; P= 0.414).</p><p><strong>Conclusion: </strong>CAZ/AVI-based and PMB-based regimens demonstrated similar clinical efficacy and nephrotoxicity in treating CRO infections. However, CAZ/AVI was superior to PMB in CRO eradication and treating CRPA infections. CAZ/AVI monotherapy was more effective than PMB monotherapy for CRO infections.</p><p><strong>Trial registration: </strong>ChiCTR2300078790 prospectively registered on Dec 19, 2023 (https://www.chictr.org.cn).</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"107418"},"PeriodicalIF":4.9,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Assessment of actual renal function in critically ill patients with severe infections: moving towards a personalized approach.
IF 4.9 2区 医学
International Journal of Antimicrobial Agents Pub Date : 2024-12-20 DOI: 10.1016/j.ijantimicag.2024.107417
Oliva A, Volpicelli L, Gigante A
{"title":"Assessment of actual renal function in critically ill patients with severe infections: moving towards a personalized approach.","authors":"Oliva A, Volpicelli L, Gigante A","doi":"10.1016/j.ijantimicag.2024.107417","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2024.107417","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"107417"},"PeriodicalIF":4.9,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Integrons are key players in the spread of beta-lactamase-encoding genes.
IF 4.9 2区 医学
International Journal of Antimicrobial Agents Pub Date : 2024-12-20 DOI: 10.1016/j.ijantimicag.2024.107421
Rafael D S Tavares, Marta Tacão, Isabel Henriques
{"title":"Integrons are key players in the spread of beta-lactamase-encoding genes.","authors":"Rafael D S Tavares, Marta Tacão, Isabel Henriques","doi":"10.1016/j.ijantimicag.2024.107421","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2024.107421","url":null,"abstract":"<p><p>Integrons mediate the acquisition and expression of gene cassettes (GCs). The production of beta-lactamases (BLs) is the most relevant mechanism of beta-lactams resistance. To explore the role of integrons in BL genes dissemination, we retrieved sequences and metadata from the INTEGRALL database and performed literature review. Integrons (mostly class 1) carrying ≥1 BL-encoding genes (n = 1,981) were detected in 37 bacterial genera and encoded BLs from 18 families. We identified 159 BL-encoding gene cassettes (BLGCs) representing all Ambler classes, being bla<sub>OXA</sub>-, bla<sub>VIM</sub>- and bla<sub>IMP</sub>-carrying integrons the most prevalent. bla<sub>GES</sub>, bla<sub>BEL</sub> and most metallo-BLs were exclusively associated to integrons. BL genes from 13 families were identified as genes captured by ISCR1 in complex integrons (n = 234), namely bla<sub>NDM</sub>, bla<sub>CTX-M</sub> and bla<sub>TEM</sub>. Frequently co-detected GCs encoded resistance to all major classes of antibiotics, namely aminoglycosides, phenicols and trimethoprim. Most BLGCs encoded resistance to carbapenems (n = 90) and Pseudomonas aeruginosa was the most frequent host. Most bla-carrying integrons were from clinical contexts while wastewater was the richest environmental compartment. The frequent association of BLs and integrons suggests a significant role in beta-lactams resistance dissemination. Considering that integrons are (i) low-cost structures often associated with other mobile elements, and that (ii) often carry multiple GCs (interchangeable according to environmental stimuli), the association of BL genes with integrons should always be considered a risk factor in beta-lactam resistance spread when performing surveillance and epidemiological studies. Further studies monitoring integrons prevalence and diversity, particularly across non-clinical environments, will draw a more comprehensive picture of integron-associated beta-lactams resistance dissemination.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"107421"},"PeriodicalIF":4.9,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The longitudinal trend and driving factors of antimicrobial resistance among Streptococcus pneumoniae worldwide.
IF 4.9 2区 医学
International Journal of Antimicrobial Agents Pub Date : 2024-12-20 DOI: 10.1016/j.ijantimicag.2024.107415
Liqin Shi, Haitao Yuan, Jie Xu, Jinzhao Long, Fang Liu, Yuefei Jin, Shuaiyin Chen, Jingyuan Zhu, Guangcai Duan, Haiyan Yang
{"title":"The longitudinal trend and driving factors of antimicrobial resistance among Streptococcus pneumoniae worldwide.","authors":"Liqin Shi, Haitao Yuan, Jie Xu, Jinzhao Long, Fang Liu, Yuefei Jin, Shuaiyin Chen, Jingyuan Zhu, Guangcai Duan, Haiyan Yang","doi":"10.1016/j.ijantimicag.2024.107415","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2024.107415","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"107415"},"PeriodicalIF":4.9,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
FL058, a novel β-lactamase inhibitor, increases the anti-Mycobacterium abscessus activity of imipenem.
IF 4.9 2区 医学
International Journal of Antimicrobial Agents Pub Date : 2024-12-20 DOI: 10.1016/j.ijantimicag.2024.107414
Zhili Tana, Yani Lin, Junsheng Fan, Yaping Jia, Shansong Zheng, Xinmei Wang, Cong Gao, Zhemin Zhang, Bing Li, Haiqing Chu
{"title":"FL058, a novel β-lactamase inhibitor, increases the anti-Mycobacterium abscessus activity of imipenem.","authors":"Zhili Tana, Yani Lin, Junsheng Fan, Yaping Jia, Shansong Zheng, Xinmei Wang, Cong Gao, Zhemin Zhang, Bing Li, Haiqing Chu","doi":"10.1016/j.ijantimicag.2024.107414","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2024.107414","url":null,"abstract":"<p><strong>Background: </strong>β-lactams are crucial for anti-Mycobacterium abscessus complex (MABC) therapy. Treating infections is challenging since MABC produces a class A β-lactamase (Bla<sub>Mab)</sub> , which is capable of hydrolyzing β-lactams thus causing drug resistance. Diazabicyclooctane (DBO) β-lactamase inhibitors (BLIs) can inhibit Bla<sub>Mab</sub>. FL058 is a novel DBO BLI; the anti-MABC activity of FL058 combined with β-lactams remains unknown.</p><p><strong>Methods: </strong>The activities of ten β-lactams (imipenem, meropenem, faropenem, tebipenem, cefoxitin, cefepime, ceftazidime, cefdinir, cefuroxime, and amoxicillin) combined with three DBO BLIs (FL058, avibactam, and relebactam) toward two MABC reference strains were determined by broth microdilution assay. The anti-MABC activities of imipenem combined with three BLIs against 193 clinical isolates were also evaluated. The activity of imipenem combined with FL058 was also tested against intracellular MABC residing in macrophages and in a mouse model. Finally, the Bla<sub>Mab</sub> mutations in clinical isolates were analyzed using sequence alignment to determine whether Bla<sub>Mab</sub> mutations are associated with DBO BLIs sensitivity.</p><p><strong>Results: </strong>FL058, avibactam and relebactam significantly increased the anti-MABC activity of β-lactams, especially imipenem, against reference strains and clinical isolates. The anti-MABC activity of imipenem combined with FL058 was superior to its activity when combined with either avibactam or relebactam. The combination of imipenem and FL058 significantly reduced the numbers of intracellular organisms in cultured macrophages, and of viable bacteria in the lungs of MABC-infected mice. Rough morphotypes tended to be more resistant than smooth morphotype. A Bla<sub>Mab</sub> T141A mutation may reduce the susceptibility of MABC to imipenem-BLIs.</p><p><strong>Conclusion: </strong>The elevated anti-MABC activity exhibited by imipenem combined with FL058 suggests a potential new approach to treating MABC infections.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"107414"},"PeriodicalIF":4.9,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Individualized Antimicrobial Therapy using Antibiotic Combination Testing and Therapeutic Drug Monitoring to Treat Carbapenem-Resistant Acinetobacter baumannii Infection.
IF 4.9 2区 医学
International Journal of Antimicrobial Agents Pub Date : 2024-12-19 DOI: 10.1016/j.ijantimicag.2024.107410
Nathalie Grace Sy Chua, Kelvin Kau-Kiat Goh, Tze Peng Lim, Sarah Silin Tang, Winnie Lee, Candice Yuen Yue Chan, Andrea Layhoon Kwa
{"title":"Individualized Antimicrobial Therapy using Antibiotic Combination Testing and Therapeutic Drug Monitoring to Treat Carbapenem-Resistant Acinetobacter baumannii Infection.","authors":"Nathalie Grace Sy Chua, Kelvin Kau-Kiat Goh, Tze Peng Lim, Sarah Silin Tang, Winnie Lee, Candice Yuen Yue Chan, Andrea Layhoon Kwa","doi":"10.1016/j.ijantimicag.2024.107410","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2024.107410","url":null,"abstract":"<p><p>Treatment of multidrug resistant infections is challenging due to limited therapeutic options. To maximise treatment success of such infections, our infectious disease-trained pharmacists employ a two-pronged approach, using both in vitro antibiotic combination testing and therapeutic drug monitoring, to individualise antibiotic combination regimens for our patients, akin to precision medicine. This approach ensures that the most optimal antibiotic combination and dosing regimens are prescribed for our patients with multidrug resistant infection, to ensure adequate antibiotic exposure and maximal clinical efficacy. We describe the implementation of such 2-pronged approach in two of our patients infected with extensively drug-resistant Acinetobacter baumannii infections. Doses higher than manufacturer-approved regimens were administered. Both cases achieved treatment success with no adverse effects.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"107410"},"PeriodicalIF":4.9,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Molecular investigation of an epidemic dissemination of vancomycin-resistant Enterococcus faecium sequence type 80 in Guangdong Province, China.
IF 4.9 2区 医学
International Journal of Antimicrobial Agents Pub Date : 2024-12-19 DOI: 10.1016/j.ijantimicag.2024.107412
Lianghui Peng, Jingjie Song, Hongli Sun, Xiwei Zhang, Yulan Huang, Shihan Zeng, Zhuoyang Zhou, Xiaoyan Li, Chao Zhuo
{"title":"Molecular investigation of an epidemic dissemination of vancomycin-resistant Enterococcus faecium sequence type 80 in Guangdong Province, China.","authors":"Lianghui Peng, Jingjie Song, Hongli Sun, Xiwei Zhang, Yulan Huang, Shihan Zeng, Zhuoyang Zhou, Xiaoyan Li, Chao Zhuo","doi":"10.1016/j.ijantimicag.2024.107412","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2024.107412","url":null,"abstract":"<p><strong>Objectives: </strong>The detection rate of vancomycin-resistant Enterococcus faecium (VREfm) displayed a dramatically increase in Guangdong, China from 2021 to 2023, for which the molecular epidemiology and genomic characteristics remain largely unexplored. In this study, we investigated the genetic features and epidemiology of VREfm isolates in Guangdong.</p><p><strong>Methods: </strong>A total of 54 Guangdong VREfm isolates were collected from three tertiary hospitals in Guangdong. We preformed antimicrobial susceptibility test, whole genome sequencing, risk factor analysis, and bioinformatics analysis to conduct this research.</p><p><strong>Results: </strong>Our investigation indicated that VREfm isolates were highly clonal and multidrug-resistant ST80 Enterococcus faecium harboring vanA-positive plasmid. The phylogenetic analysis based on single-nucleotide polymorphisms (SNPs) demonstrated that VREfm isolates exhibited minimal genetic similarity to previously reported E. faecium in China, whereas exhibited high genomically similar to an India strain A10290 isolated in 2019 and Hiroshima isolates detected in 2020, indicative of a possible exogeneous import. The genetic environment of cps region showed a novel type of wzy gene cluster involved in capsule polysaccharide (CPS) biosynthesis flanked by ISEf1 and IS16 was identified in VREfm isolates, which displayed a remarkably divergence from the downstream of putative cpsABCD region in other sequence types (STs) E. faecium. Heat map of plasmid-mediated virulence factors suggested several predicted proteins including Cag pathogenetic island proteins existed in VREfm isolates at a high frequency.</p><p><strong>Conclusions: </strong>This study highlighted the importance of ongoing surveillance to track the dynamic dissemination of multidrug-resistant ST80 VREfm isolates harboring multiple virulence genes in Guangdong province, China.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"107412"},"PeriodicalIF":4.9,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Prophylactic Phage Aerosols for Nosocomial Infection Control in an Extracorporeal Membrane Oxygenation Unit: A 4-Year Prospective Study of Temporospatially Designed Phage Cocktails.
IF 4.9 2区 医学
International Journal of Antimicrobial Agents Pub Date : 2024-12-19 DOI: 10.1016/j.ijantimicag.2024.107413
Chun-Chieh Tseng, Li-Kuang Chen, Hsiu-Tzu Chu, Yi-Ting Chen, Hui-Li Jiang, Hui-Hua Yang, Chin-Cheng Chang, Sankhla Debangana, Lee-Mei Ponge, Min-Xiu Li, Ying-Hao Chin, Jui-Chih Chang
{"title":"Prophylactic Phage Aerosols for Nosocomial Infection Control in an Extracorporeal Membrane Oxygenation Unit: A 4-Year Prospective Study of Temporospatially Designed Phage Cocktails.","authors":"Chun-Chieh Tseng, Li-Kuang Chen, Hsiu-Tzu Chu, Yi-Ting Chen, Hui-Li Jiang, Hui-Hua Yang, Chin-Cheng Chang, Sankhla Debangana, Lee-Mei Ponge, Min-Xiu Li, Ying-Hao Chin, Jui-Chih Chang","doi":"10.1016/j.ijantimicag.2024.107413","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2024.107413","url":null,"abstract":"<p><p>Phage-based decontamination has rarely been explored in real-world settings, particularly in the environments of patients undergoing extracorporeal membrane oxygenation (ECMO). This four-year prospective study aimed to evaluate the effectiveness of aerosolized phage cocktails tailored to combat target antibiotic-resistant species of Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia. The decontamination procedure with phage aerosols was proactively implemented before the admission of ECMO patients based on a thorough analysis of phage typing results from bacterial species isolated from prospective patient areas during the preceding two months. The phage cocktail formulation design also accounted for phage resistance development, phage families, and plaque characteristics. Throughout the study, 85 ECMO patients were monitored, with the environments of 22 patients undergoing phage decontamination. Fifty phage cocktails were prepared to target the identified species. Respiratory infections were most common among ECMO patients, accounting for 71.4%. The ECMO duration for patients infected with the targeted species was significantly longer than that for noninfected patients (p = 0.019), with peak infection incidence occurring between 3-7 days of ECMO treatment (67.1 per 1000 ECMO days). Notably, none of the patients in phage-treated environments contracted infections from the targeted species. However, the overall incidence of bacterial infections did not significantly correlate with phage decontamination efforts, as phages are effective only against their specific hosts. This study demonstrates the potential of prophylactic phage decontamination to prevent specific infections, aligning with One Health principles by offering a sustainable alternative to antibiotics, potentially significantly reducing antibiotic use.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"107413"},"PeriodicalIF":4.9,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Characterization of a Novel KPC-2 Variant, KPC-228, Conferring Resistance to Ceftazidime-Avibactam in an ST11-KL64 Hypervirulent Klebsiella pneumoniae.
IF 4.9 2区 医学
International Journal of Antimicrobial Agents Pub Date : 2024-12-19 DOI: 10.1016/j.ijantimicag.2024.107411
Peiyao Zhou, Haojin Gao, Meilan Li, Chunyang Wu, Weihua Han, Cailing Wan, Li Shen, Xinru Yuan, Junhong Shi, Yu Huang, Jianbo Lv, Ying Zhou, Fangyou Yu
{"title":"Characterization of a Novel KPC-2 Variant, KPC-228, Conferring Resistance to Ceftazidime-Avibactam in an ST11-KL64 Hypervirulent Klebsiella pneumoniae.","authors":"Peiyao Zhou, Haojin Gao, Meilan Li, Chunyang Wu, Weihua Han, Cailing Wan, Li Shen, Xinru Yuan, Junhong Shi, Yu Huang, Jianbo Lv, Ying Zhou, Fangyou Yu","doi":"10.1016/j.ijantimicag.2024.107411","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2024.107411","url":null,"abstract":"<p><p>With the widespread clinical use of ceftazidime-avibactam (CZA), reports of resistance have increased continuously, posing immense threats to public health worldwide. In this study, we explored the underlying mechanisms leading to the development of CZA resistance in an ST11-KL64 hypervirulent Klebsiella pneumoniae CRE146 that harbored the bla<sub>KPC-228</sub> gene. Twelve carbapenem-resistant Klebsiella pneumoniae (CRKP) strains were isolated from the same patient, including K. pneumoniae CRE146. Whole genome sequencing (WGS), phylogenetic analysis, bla<sub>KPC</sub> gene cloning and pACYC-KPC construction assays were conducted to further explore the molecular mechanisms of CZA resistance. Quantitative siderophore production assay, string test, capsule quantification and Galleria mellonella in vivo infection model were applied to verify the level of pathogenicity of K. pneumoniae CRE146. This strain carried key virulence factors, iutA-iucABCD operon and rmpA gene. Compared to the wild-type KPC-2 carbapenemase, the novel KPC-228 enzyme exhibited a deletion of four amino acids in the Ω-loop (del_167-170_ELNS). In addition, the emergence of CZA resistance appeared to be associated with drug exposure, and we observed the in vivo evolution of wild-type KPC-2 to KPC-228 and then the reversion to its original wild-type KPC-2. The bla<sub>KPC-228</sub> gene was located within the double IS26 flanking the ISKpn6-bla<sub>KPC-228</sub>-ISKpn27 core structure and carried on an IncFII/IncR-type plasmid. Notably, CRE146 exhibited high-level resistance to CZA (64/4 mg/L) but increased susceptibility to meropenem (1 mg/L) and imipenem (0.5 mg/L) respectively. PACYC-KPC plasmids were constructed and expressed in K. pneumoniae ATCC13883. Compared to K. pneumoniae ATCC13883 harboring bla<sub>KPC-2</sub>, K. pneumoniae ATCC13883 harboring bla<sub>KPC-228</sub> exhibited a high-level resistance to CZA (32/4 mg/L) and increased susceptibility to meropenem (1 mg/L) and imipenem (0.5 mg/L). Interestingly, K. pneumoniae ATCC13883 harboring bla<sub>KPC-228</sub> showed a significant decrease in their resistance to all β-lactamases tested except CZA and ceftazidime. In conclusion, we reported a novel KPC variant, KPC-228, in a clinical ST11-KL64 hypervirulent K. pneumoniae strain, which conferred CZA resistance, possibly through enhancing ceftazidime affinity and reducing avibactam binding. The bla<sub>KPC-228</sub> can mutate back to bla<sub>KPC-2</sub> under carbapenem pressure, which was very detrimental to clinical treatment. This strain carried both resistance and virulence genes, posing a major challenge in clinical management.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"107411"},"PeriodicalIF":4.9,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
In vitro antimicrobial activity of six novel β-lactam and β-lactamase inhibitor combinations and cefiderocol against NDM-producing Enterobacterales in China.
IF 4.9 2区 医学
International Journal of Antimicrobial Agents Pub Date : 2024-12-11 DOI: 10.1016/j.ijantimicag.2024.107407
Xinmeng Liu, Ziyao Li, Feilong Zhang, Xinrui Yang, Zichen Lei, Chen Li, Yongli Wu, Jiankang Zhao, Yulin Zhang, Yanning Hu, FangFang Shen, Pingbang Wang, Junwen Yang, Yulei Liu, Huihui Shi, Binghuai Lu
{"title":"In vitro antimicrobial activity of six novel β-lactam and β-lactamase inhibitor combinations and cefiderocol against NDM-producing Enterobacterales in China.","authors":"Xinmeng Liu, Ziyao Li, Feilong Zhang, Xinrui Yang, Zichen Lei, Chen Li, Yongli Wu, Jiankang Zhao, Yulin Zhang, Yanning Hu, FangFang Shen, Pingbang Wang, Junwen Yang, Yulei Liu, Huihui Shi, Binghuai Lu","doi":"10.1016/j.ijantimicag.2024.107407","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2024.107407","url":null,"abstract":"<p><strong>Introduction: </strong>To date, the global prevalence of New Delhi metallo-β-lactamase (NDM) in carbapenem-resistant Enterobacterales (CRE) has been of concern, which is not inhibited by classical β-lactamase inhibitors (BLIs). In this study, we investigated the newly developed antimicrobial agents or inhibitors against NDM-producing Enterobacterales (NPEs).</p><p><strong>Methods: </strong>The in vitro activities of cefiderocol, cefepime/taniborbactam, meropenem/taniborbactam, cefepime/zidebactam, meropenem/nacubactam, aztreonam/nacubactam and aztreonam/avibactam were analyzed in 204 NPE strains collected in China. The potential resistance mechanisms were identified by whole genome sequencing.</p><p><strong>Results: </strong>Of 204 NPE strains, 18.1% (37/204) were resistant to cefiderocol, in which cirA deleterious alteration, PBP3 insertion and NDM production were taken as potential resistance mechanisms; 28.9% (59/204) were resistant to cefepime/zidebactam, involving K. pneumoniae with ompK35 deleterious alteration; 22.5% (46/204) were resistant to cefepime/taniborbactam, in which YRIN or YRIK inserted in PBP3 and altered ompC are more frequently detected in the resistant E. coli isolates; 27.9% (57/204) were resistant to meropenem/taniborbactam. Aztreonam/avibactam and aztreonam/nacubactam exhibited excellent activity against NPE. However, meropenem/nacubactam had the lowest activity, with only 49.0% (100/204) of all isolates having MICs of <4/4 mg/L.</p><p><strong>Conclusions: </strong>Aztreonam/avibactam and aztreonam/nacubactam showed the highest activity against NPE. The potential resistance mechanisms of novel antimicrobial agents against NPE should be under active surveillance.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"107407"},"PeriodicalIF":4.9,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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