Pub Date : 2024-05-30DOI: 10.1186/s12941-024-00710-6
Hong Zhang, Heng Zou, Chanyu Zhang, Shen Zhang
Background: Chronic endometritis (CE) is associated with poor reproductive outcomes, yet the role of endometrial microbiota in patients with recurrent implantation failure (RIF) and CE remains unclear. This study aims to characterize endometrial microbiota in RIF patients with CE and assess its implications for reproductive outcomes.
Methods: In this prospective study, we enrolled RIF patients both with and without CE. Endometrial and cervical samples were collected for 16 S rRNA gene sequencing. Microbiota composition was compared between groups using diversity indices, phylum, and genus-level analysis. Canonical correlation analysis (CCA) and Spearman's correlation coefficients were used to assess relationships between CE, reproductive outcomes, and microbiota. Predictive functional profiling was performed to evaluate metabolic pathways associated with CE.
Results: Endometrial microbiota in CE patients exhibited greater diversity and evenness compared to non-CE patients. Principal coordinates analysis (PCoA) revealed distinct clustering between CE and non-CE groups. Linear discriminant analysis (LDA) identified Proteobacteria, Aminicenantales, and Chloroflexaceae as characteristic of CE, while Lactobacillus, Acinetobacter, Herbaspirillum, Ralstonia, Shewanela, and Micrococcaceae were associated with non-CE. CCA demonstrated associations between CE, adverse reproductive outcomes, and specific bacterial taxa. Microbial metabolic pathways significantly differed between CE and non-CE groups, with enrichment in pathways related to cofactors, vitamins, secondary metabolites, and the immune system in CE patients.
Conclusion: RIF patients with CE exhibit distinct endometrial microbiota compositions associated with adverse reproductive outcomes. The increased microbial diversity and altered metabolic pathways in CE suggest a potential correlation with reproductive outcomes, although further studies are necessary to elucidate the causal relationship between microbiota alterations and fertility. Modulating the endometrial microbiome may represent a novel therapeutic strategy to improve IVF outcomes in patients with CE.
背景:慢性子宫内膜炎(CE)与不良生殖结局相关,但子宫内膜微生物群在复发性种植失败(RIF)和CE患者中的作用仍不清楚。本研究旨在描述RIF合并CE患者子宫内膜微生物群的特征,并评估其对生殖结局的影响:在这项前瞻性研究中,我们招募了有和没有 CE 的 RIF 患者。收集子宫内膜和宫颈样本,进行 16 S rRNA 基因测序。使用多样性指数、门和属级分析比较不同组间的微生物群组成。采用典型相关分析(CCA)和斯皮尔曼相关系数评估 CE、生殖结果和微生物群之间的关系。预测性功能分析用于评估与 CE 相关的代谢途径:结果:与非 CE 患者相比,CE 患者的子宫内膜微生物群表现出更高的多样性和均匀性。主坐标分析(PCoA)显示 CE 组和非 CE 组之间存在明显的聚类。线性判别分析(LDA)发现,变形杆菌、氨基链球菌和绿藻科(Chloroflexaceae)是 CE 的特征,而乳酸杆菌、醋酸杆菌、草吸菌、Ralstonia、Shewanela 和微球菌科(Micrococcaceae)则与非 CE 相关。CCA显示了CE、不良生殖结果和特定细菌类群之间的关联。CE组和非CE组之间的微生物代谢途径存在显著差异,CE患者与辅因子、维生素、次级代谢产物和免疫系统有关的途径更为丰富:结论:患有 CE 的 RIF 患者表现出与不良生殖结局相关的独特子宫内膜微生物群组成。子宫内膜异位症患者体内微生物多样性的增加和代谢途径的改变表明,这可能与生殖结果有关,但要阐明微生物群改变与生育能力之间的因果关系,还需要进一步的研究。调节子宫内膜微生物群可能是改善 CE 患者试管受精结果的一种新型治疗策略。
{"title":"Chronic endometritis and the endometrial microbiota: implications for reproductive success in patients with recurrent implantation failure.","authors":"Hong Zhang, Heng Zou, Chanyu Zhang, Shen Zhang","doi":"10.1186/s12941-024-00710-6","DOIUrl":"10.1186/s12941-024-00710-6","url":null,"abstract":"<p><strong>Background: </strong>Chronic endometritis (CE) is associated with poor reproductive outcomes, yet the role of endometrial microbiota in patients with recurrent implantation failure (RIF) and CE remains unclear. This study aims to characterize endometrial microbiota in RIF patients with CE and assess its implications for reproductive outcomes.</p><p><strong>Methods: </strong>In this prospective study, we enrolled RIF patients both with and without CE. Endometrial and cervical samples were collected for 16 S rRNA gene sequencing. Microbiota composition was compared between groups using diversity indices, phylum, and genus-level analysis. Canonical correlation analysis (CCA) and Spearman's correlation coefficients were used to assess relationships between CE, reproductive outcomes, and microbiota. Predictive functional profiling was performed to evaluate metabolic pathways associated with CE.</p><p><strong>Results: </strong>Endometrial microbiota in CE patients exhibited greater diversity and evenness compared to non-CE patients. Principal coordinates analysis (PCoA) revealed distinct clustering between CE and non-CE groups. Linear discriminant analysis (LDA) identified Proteobacteria, Aminicenantales, and Chloroflexaceae as characteristic of CE, while Lactobacillus, Acinetobacter, Herbaspirillum, Ralstonia, Shewanela, and Micrococcaceae were associated with non-CE. CCA demonstrated associations between CE, adverse reproductive outcomes, and specific bacterial taxa. Microbial metabolic pathways significantly differed between CE and non-CE groups, with enrichment in pathways related to cofactors, vitamins, secondary metabolites, and the immune system in CE patients.</p><p><strong>Conclusion: </strong>RIF patients with CE exhibit distinct endometrial microbiota compositions associated with adverse reproductive outcomes. The increased microbial diversity and altered metabolic pathways in CE suggest a potential correlation with reproductive outcomes, although further studies are necessary to elucidate the causal relationship between microbiota alterations and fertility. Modulating the endometrial microbiome may represent a novel therapeutic strategy to improve IVF outcomes in patients with CE.</p>","PeriodicalId":8052,"journal":{"name":"Annals of Clinical Microbiology and Antimicrobials","volume":"23 1","pages":"49"},"PeriodicalIF":5.7,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11140900/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141178689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-27DOI: 10.1186/s12941-024-00704-4
Mohamed A Elhosseini, Tarek E El-Banna, Fatma I Sonbol, Maisra M El-Bouseary
Background: Proteus mirabilis is a significant nosocomial pathogen that is frequently associated with a wide range of infections, necessitating heightened attention to mitigate potential health risks. Hence, this study was performed to investigate the impact of sub-minimum inhibitory concentrations (MICs) of ciprofloxacin (CIP) on Proteus mirabilis clinical isolates.
Methods: The sub-MICs of CIP were selected using the growth curve approach. The untreated and treated isolates with sub-MICs of CIP were assessed for their biofilm development, motilities on agar, and other virulence factors. The cell morphology of untreated and treated isolates with sub-MIC of CIP was explored using electron microscope. Moreover, the expression levels of the virulence genes in isolates were measured using quantitative real-time PCR.
Results: Data revealed that sub-MICs of CIP significantly (p < 0.05), in a concentration-dependent manner, inhibited biofilm formation and other virulence factors in the selected isolates. Electron microscope analysis showed cell enlargement and various abnormalities in the cell wall and membrane integrity.
Conclusion: Sub-MICs of CIP exhibited inhibition of virulence and alterations in morphological integrity against P. mirabilis isolates.
{"title":"Potential antivirulence activity of sub-inhibitory concentrations of ciprofloxacin against Proteus mirabilis isolates: an in-vitro and in-vivo study.","authors":"Mohamed A Elhosseini, Tarek E El-Banna, Fatma I Sonbol, Maisra M El-Bouseary","doi":"10.1186/s12941-024-00704-4","DOIUrl":"10.1186/s12941-024-00704-4","url":null,"abstract":"<p><strong>Background: </strong>Proteus mirabilis is a significant nosocomial pathogen that is frequently associated with a wide range of infections, necessitating heightened attention to mitigate potential health risks. Hence, this study was performed to investigate the impact of sub-minimum inhibitory concentrations (MICs) of ciprofloxacin (CIP) on Proteus mirabilis clinical isolates.</p><p><strong>Methods: </strong>The sub-MICs of CIP were selected using the growth curve approach. The untreated and treated isolates with sub-MICs of CIP were assessed for their biofilm development, motilities on agar, and other virulence factors. The cell morphology of untreated and treated isolates with sub-MIC of CIP was explored using electron microscope. Moreover, the expression levels of the virulence genes in isolates were measured using quantitative real-time PCR.</p><p><strong>Results: </strong>Data revealed that sub-MICs of CIP significantly (p < 0.05), in a concentration-dependent manner, inhibited biofilm formation and other virulence factors in the selected isolates. Electron microscope analysis showed cell enlargement and various abnormalities in the cell wall and membrane integrity.</p><p><strong>Conclusion: </strong>Sub-MICs of CIP exhibited inhibition of virulence and alterations in morphological integrity against P. mirabilis isolates.</p>","PeriodicalId":8052,"journal":{"name":"Annals of Clinical Microbiology and Antimicrobials","volume":"23 1","pages":"48"},"PeriodicalIF":5.7,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11131287/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141157861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-25DOI: 10.1186/s12941-024-00708-0
Corentin Deckers, Florian Bélik, Olivier Denis, Pierre Bogaerts, Isabel Montesinos, Catherine Berhin, Warda Bouchahrouf, Martin Hoebeke, Stephanie Evrard, Nicolas Gilliard, Merve Okur, Te-Din Huang
Aztreonam-avibactam (ATM-AVI) combination shows promising effectiveness on most carbapenemase-producing Gram-negatives, yet standardized antibiotic susceptibility testing (AST) methods for evaluating the combination in clinical laboratories is lacking. We aimed to evaluate different ATM-AVI AST approaches. 96 characterized carbapenem-resistant clinical isolates belonging to 9 Enterobacterales (EB; n = 80) and P. aeruginosa (PA; n = 16) species, including 90 carbapenemase producers and 72 strains resistant to both CAZ-AVI and ATM, were tested. Paper disk elution (DE; Bio-Rad) and E-test gradient strips stacking (SS; bioMérieux) were performed for the ATM + CAZ-AVI combination. MIC Test Strip (MTS; Liofilchem) was evaluated for ATM-AVI MIC determination. Results were interpreted applying ATM clinical breakpoints of the EUCAST guidelines and compared to the broth microdilution method (Sensititre, Thermofisher). According to broth microdilution method, 93% of EB and 69% of PA were tested susceptible to ATM-AVI. The synergistic effect of ATM-AVI was of 95% for EB, but of only 17% for PA. The MTS method yielded higher categorical and essential agreement (CA/EA) rates for both EB (89%/91%) and PA (94%/94%) compared to SS, where the rates were 87%/83% for EB and 81%/81% for PA. MTS and SS yielded 2 and 3 major discrepancies, respectively, while 3 very major discrepancies each were observed for both methods. Concerning the DE method, CA reached 91% for EB and 81% for PA, but high number of very major discrepancies were observed for EB (n = 6; 8%) and for PA (n = 3; 19%). The ATM-AVI association displayed excellent in vitro activity against highly resistant clinical Enterobacterales strains. MTS method offers accurate ATM-AVI AST results, while the SS method might serve as better alternative then DE method in assessing the efficacy of ATM + CAZ-AVI combination. However, further investigation is needed to confirm the methods' ability to detect ATM-AVI resistance.
{"title":"Comparison of testing methods assessing the in vitro efficacy of the combination of aztreonam with avibactam on multidrug-resistant Gram-negative bacilli","authors":"Corentin Deckers, Florian Bélik, Olivier Denis, Pierre Bogaerts, Isabel Montesinos, Catherine Berhin, Warda Bouchahrouf, Martin Hoebeke, Stephanie Evrard, Nicolas Gilliard, Merve Okur, Te-Din Huang","doi":"10.1186/s12941-024-00708-0","DOIUrl":"https://doi.org/10.1186/s12941-024-00708-0","url":null,"abstract":"Aztreonam-avibactam (ATM-AVI) combination shows promising effectiveness on most carbapenemase-producing Gram-negatives, yet standardized antibiotic susceptibility testing (AST) methods for evaluating the combination in clinical laboratories is lacking. We aimed to evaluate different ATM-AVI AST approaches. 96 characterized carbapenem-resistant clinical isolates belonging to 9 Enterobacterales (EB; n = 80) and P. aeruginosa (PA; n = 16) species, including 90 carbapenemase producers and 72 strains resistant to both CAZ-AVI and ATM, were tested. Paper disk elution (DE; Bio-Rad) and E-test gradient strips stacking (SS; bioMérieux) were performed for the ATM + CAZ-AVI combination. MIC Test Strip (MTS; Liofilchem) was evaluated for ATM-AVI MIC determination. Results were interpreted applying ATM clinical breakpoints of the EUCAST guidelines and compared to the broth microdilution method (Sensititre, Thermofisher). According to broth microdilution method, 93% of EB and 69% of PA were tested susceptible to ATM-AVI. The synergistic effect of ATM-AVI was of 95% for EB, but of only 17% for PA. The MTS method yielded higher categorical and essential agreement (CA/EA) rates for both EB (89%/91%) and PA (94%/94%) compared to SS, where the rates were 87%/83% for EB and 81%/81% for PA. MTS and SS yielded 2 and 3 major discrepancies, respectively, while 3 very major discrepancies each were observed for both methods. Concerning the DE method, CA reached 91% for EB and 81% for PA, but high number of very major discrepancies were observed for EB (n = 6; 8%) and for PA (n = 3; 19%). The ATM-AVI association displayed excellent in vitro activity against highly resistant clinical Enterobacterales strains. MTS method offers accurate ATM-AVI AST results, while the SS method might serve as better alternative then DE method in assessing the efficacy of ATM + CAZ-AVI combination. However, further investigation is needed to confirm the methods' ability to detect ATM-AVI resistance.","PeriodicalId":8052,"journal":{"name":"Annals of Clinical Microbiology and Antimicrobials","volume":"34 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141152276","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}
Pub Date : 2024-05-24DOI: 10.1186/s12941-024-00705-3
Maggi ElTaweel, Heba Shehta Said, Rasha Barwa
Background: Proteus mirabilis is an opportunistic pathogen that has been held responsible for numerous nosocomial and community-acquired infections which are difficult to be controlled because of its diverse antimicrobial resistance mechanisms.
Methods: Antimicrobial susceptibility patterns of P. mirabilis isolates collected from different clinical sources in Mansoura University Hospitals, Egypt was determined. Moreover, the underlying resistance mechanisms and genetic relatedness between isolates were investigated.
Results: Antimicrobial susceptibility testing indicated elevated levels of resistance to different classes of antimicrobials among the tested P. mirabilis clinical isolates (n = 66). ERIC-PCR showed great diversity among the tested isolates. Six isolates (9.1%) were XDR while all the remaining isolates were MDR. ESBLs and AmpCs were detected in 57.6% and 21.2% of the isolates, respectively, where blaTEM, blaSHV, blaCTX-M, blaCIT-M and blaAmpC were detected. Carbapenemases and MBLs were detected in 10.6 and 9.1% of the isolates, respectively, where blaOXA-48 and blaNDM-1 genes were detected. Quinolone resistant isolates (75.8%) harbored acc(6')-Ib-cr, qnrD, qnrA, and qnrS genes. Resistance to aminoglycosides, trimethoprim-sulfamethoxazole and chloramphenicol exceeded 80%. Fosfomycin was the most active drug against the tested isolates as only 22.7% were resistant. Class I or II integrons were detected in 86.4% of the isolates. Among class I integron positive isolates, four different gene cassette arrays (dfrA17- aadA5, aadB-aadA2, aadA2-lnuF, and dfrA14-arr-3-blaOXA-10-aadA15) and two gene cassettes (dfrA7 and aadA1) were detected. While class II integron positive isolates carried four different gene cassette arrays (dfrA1-sat1-aadA1, estXVr-sat2-aadA1, lnuF- dfrA1-aadA1, and dfrA1-sat2).
Conclusion: P. Mirabilis ability to acquire resistance determinants via integrons may be held responsible for the elevated rates of antimicrobial resistance and emergence of XDR or even PDR strains limiting the available therapeutic options for management of infections caused by those strains.
{"title":"Emergence of extensive drug resistance and high prevalence of multidrug resistance among clinical Proteus mirabilis isolates in Egypt.","authors":"Maggi ElTaweel, Heba Shehta Said, Rasha Barwa","doi":"10.1186/s12941-024-00705-3","DOIUrl":"10.1186/s12941-024-00705-3","url":null,"abstract":"<p><strong>Background: </strong>Proteus mirabilis is an opportunistic pathogen that has been held responsible for numerous nosocomial and community-acquired infections which are difficult to be controlled because of its diverse antimicrobial resistance mechanisms.</p><p><strong>Methods: </strong>Antimicrobial susceptibility patterns of P. mirabilis isolates collected from different clinical sources in Mansoura University Hospitals, Egypt was determined. Moreover, the underlying resistance mechanisms and genetic relatedness between isolates were investigated.</p><p><strong>Results: </strong>Antimicrobial susceptibility testing indicated elevated levels of resistance to different classes of antimicrobials among the tested P. mirabilis clinical isolates (n = 66). ERIC-PCR showed great diversity among the tested isolates. Six isolates (9.1%) were XDR while all the remaining isolates were MDR. ESBLs and AmpCs were detected in 57.6% and 21.2% of the isolates, respectively, where bla<sub>TEM</sub>, bla<sub>SHV</sub>, bla<sub>CTX-M</sub>, bla<sub>CIT-M</sub> and bla<sub>AmpC</sub> were detected. Carbapenemases and MBLs were detected in 10.6 and 9.1% of the isolates, respectively, where bla<sub>OXA-48</sub> and bla<sub>NDM-1</sub> genes were detected. Quinolone resistant isolates (75.8%) harbored acc(6')-Ib-cr, qnrD, qnrA, and qnrS genes. Resistance to aminoglycosides, trimethoprim-sulfamethoxazole and chloramphenicol exceeded 80%. Fosfomycin was the most active drug against the tested isolates as only 22.7% were resistant. Class I or II integrons were detected in 86.4% of the isolates. Among class I integron positive isolates, four different gene cassette arrays (dfrA17- aadA5, aadB-aadA2, aadA2-lnuF, and dfrA14-arr-3-bla<sub>OXA-10</sub>-aadA15) and two gene cassettes (dfrA7 and aadA1) were detected. While class II integron positive isolates carried four different gene cassette arrays (dfrA1-sat1-aadA1, estXVr-sat2-aadA1, lnuF- dfrA1-aadA1, and dfrA1-sat2).</p><p><strong>Conclusion: </strong>P. Mirabilis ability to acquire resistance determinants via integrons may be held responsible for the elevated rates of antimicrobial resistance and emergence of XDR or even PDR strains limiting the available therapeutic options for management of infections caused by those strains.</p>","PeriodicalId":8052,"journal":{"name":"Annals of Clinical Microbiology and Antimicrobials","volume":"23 1","pages":"46"},"PeriodicalIF":5.7,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11127457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141092462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: The population structure and the correlation between antimicrobial resistance (AMR) phenotypes and genotypes in Aeromonas species isolated from patients with gastroenteritis are not well understood. The aims of the study were to: (1) investigate the antimicrobial susceptibility profiles of Aeromonas species isolated from patients with gastroenteritis; (2) explore the relationship between AMR genes and resistance phenotypes; and (3) describe the population structure of these isolates and provide evidence of transmission events among them.
Methods: This microbiological survey was performed at the Microbiology Laboratory of the Emek Medical Center in Afula, Israel. Cultivation of Aeromonas was attempted from stool samples that tested positive by PCR. Antimicrobial susceptibility testing (AST) was performed using the Sensititre GN3F microdilution panel. Whole genome sequencing (WGS) was done using the Illumina NextSeq500/550 system. Phylogenetic studies involved multi-locus sequence typing (MLST) and core genome (cg) MLST. Resistance mechanisms were identified using the Comprehensive Antibiotic Resistance Database and compared with the AST results.
Results: The study included 67 patient-unique isolates. The species that were identified included A. caviae (n = 58), A. dhakensis (n = 3), A. media (n = 2), A. veronii (n = 2) and A. hydrophila (n = 2). Isolates were almost uniformly susceptible to amikacin, gentamicin, aztreonam, cefepime, ceftazidime, ciprofloxacin and meropenem. All isolates with the exception of 1-2 isolates were resistant to ampicillin, cefazolin and ampicillin-sulbactam which was compatible with the presence of the blaOXA genes. Variable resistance rates were observed to cefuroxime, cefoxitin, ceftriaxone, piperacillin-tazobactam that were not correlated with the presence of other β-lactamase genes. Resistance to tetracycline and trimethoprim-sulfamethoxazole correlated with the presence of tetA and sul1, respectively. The population structure of A. caviae was highly diverse with the minority of the isolates (16/57) clustering into six defined sequence types. A cgMLST-based distance of four genes was found in one pair of isolates, suggesting common source transmission.
Conclusions: A. caviae is the dominant species related to gastroenteritis and is characterized by a diverse population structure, with almost no evidence for common-source transmission. Resistance rates to most antimicrobial agents were low and partially matched with the presence of resistance genes.
{"title":"Phenotypic and genotypic analysis of antimicrobial resistance and population structure of gastroenteritis-related Aeromonas isolates.","authors":"Dana Sagas, Yizhak Hershko, Katia Levitskyi, Merav Strauss, Matan Slutzkin, Bibiana Chazan, Amos Adler","doi":"10.1186/s12941-024-00706-2","DOIUrl":"10.1186/s12941-024-00706-2","url":null,"abstract":"<p><strong>Background: </strong>The population structure and the correlation between antimicrobial resistance (AMR) phenotypes and genotypes in Aeromonas species isolated from patients with gastroenteritis are not well understood. The aims of the study were to: (1) investigate the antimicrobial susceptibility profiles of Aeromonas species isolated from patients with gastroenteritis; (2) explore the relationship between AMR genes and resistance phenotypes; and (3) describe the population structure of these isolates and provide evidence of transmission events among them.</p><p><strong>Methods: </strong>This microbiological survey was performed at the Microbiology Laboratory of the Emek Medical Center in Afula, Israel. Cultivation of Aeromonas was attempted from stool samples that tested positive by PCR. Antimicrobial susceptibility testing (AST) was performed using the Sensititre GN3F microdilution panel. Whole genome sequencing (WGS) was done using the Illumina NextSeq500/550 system. Phylogenetic studies involved multi-locus sequence typing (MLST) and core genome (cg) MLST. Resistance mechanisms were identified using the Comprehensive Antibiotic Resistance Database and compared with the AST results.</p><p><strong>Results: </strong>The study included 67 patient-unique isolates. The species that were identified included A. caviae (n = 58), A. dhakensis (n = 3), A. media (n = 2), A. veronii (n = 2) and A. hydrophila (n = 2). Isolates were almost uniformly susceptible to amikacin, gentamicin, aztreonam, cefepime, ceftazidime, ciprofloxacin and meropenem. All isolates with the exception of 1-2 isolates were resistant to ampicillin, cefazolin and ampicillin-sulbactam which was compatible with the presence of the bla<sub>OXA</sub> genes. Variable resistance rates were observed to cefuroxime, cefoxitin, ceftriaxone, piperacillin-tazobactam that were not correlated with the presence of other β-lactamase genes. Resistance to tetracycline and trimethoprim-sulfamethoxazole correlated with the presence of tetA and sul1, respectively. The population structure of A. caviae was highly diverse with the minority of the isolates (16/57) clustering into six defined sequence types. A cgMLST-based distance of four genes was found in one pair of isolates, suggesting common source transmission.</p><p><strong>Conclusions: </strong>A. caviae is the dominant species related to gastroenteritis and is characterized by a diverse population structure, with almost no evidence for common-source transmission. Resistance rates to most antimicrobial agents were low and partially matched with the presence of resistance genes.</p>","PeriodicalId":8052,"journal":{"name":"Annals of Clinical Microbiology and Antimicrobials","volume":"23 1","pages":"45"},"PeriodicalIF":5.7,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11119697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141086437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<p><strong>Background: </strong>Due to their resistance and difficulty in treatment, biofilm-associated infections are problematic among hospitalized patients globally and account for 60% of all bacterial infections in humans. Antibiofilm peptides have recently emerged as an alternative treatment since they can be effectively designed and exert a different mode of biofilm inhibition and eradication.</p><p><strong>Methods: </strong>A novel antibiofilm peptide, BiF, was designed from the conserved sequence of 18 α-helical antibiofilm peptides by template-assisted technique and its activity was improved by hybridization with a lipid binding motif (KILRR). Novel antibiofilm peptide derivatives were modified by substituting hydrophobic amino acids at positions 5 or 7, and both, with positively charged lysines (L5K, L7K). These peptide derivatives were tested for antibiofilm and antimicrobial activities against biofilm-forming Staphylococcus epidermidis and multiple other microbes using crystal violet and broth microdilution assays, respectively. To assess their impact on mammalian cells, the toxicity of peptides was determined through hemolysis and cytotoxicity assays. The stability of candidate peptide, BiF2_5K7K, was assessed in human serum and its secondary structure in bacterial membrane-like environments was analyzed using circular dichroism. The action of BiF2_5K7K on planktonic S. epidermidis and its effect on biofilm cell viability were assessed via viable counting assays. Its biofilm inhibition mechanism was investigated through confocal laser scanning microscopy and transcription analysis. Additionally, its ability to eradicate mature biofilms was examined using colony counting. Finally, a preliminary evaluation involved coating a catheter with BiF2_5K7K to assess its preventive efficacy against S. epidermidis biofilm formation on the catheter and its surrounding area.</p><p><strong>Results: </strong>BiF2_5K7K, the modified antibiofilm peptide, exhibited dose-dependent antibiofilm activity against S. epidermidis. It inhibited biofilm formation at subinhibitory concentrations by altering S. epidermidis extracellular polysaccharide production and quorum-sensing gene expression. Additionally, it exhibited broad-spectrum antimicrobial activity and no significant hemolysis or toxicity against mammalian cell lines was observed. Its activity is retained when exposed to human serum. In bacterial membrane-like environments, this peptide formed an α-helix amphipathic structure. Within 4 h, a reduction in the number of S. epidermidis colonies was observed, demonstrating the fast action of this peptide. As a preliminary test, a BiF2_5K7K-coated catheter was able to prevent the development of S. epidermidis biofilm both on the catheter surface and in its surrounding area.</p><p><strong>Conclusions: </strong>Due to the safety and effectiveness of BiF2_5K7K, we suggest that this peptide be further developed to combat biofilm infections, particularly those
{"title":"Dual-function antimicrobial-antibiofilm peptide hybrid to tackle biofilm-forming Staphylococcus epidermidis.","authors":"Mathira Wongchai, Saharut Wongkaewkhiaw, Sakawrat Kanthawong, Sittiruk Roytrakul, Ratchaneewan Aunpad","doi":"10.1186/s12941-024-00701-7","DOIUrl":"https://doi.org/10.1186/s12941-024-00701-7","url":null,"abstract":"<p><strong>Background: </strong>Due to their resistance and difficulty in treatment, biofilm-associated infections are problematic among hospitalized patients globally and account for 60% of all bacterial infections in humans. Antibiofilm peptides have recently emerged as an alternative treatment since they can be effectively designed and exert a different mode of biofilm inhibition and eradication.</p><p><strong>Methods: </strong>A novel antibiofilm peptide, BiF, was designed from the conserved sequence of 18 α-helical antibiofilm peptides by template-assisted technique and its activity was improved by hybridization with a lipid binding motif (KILRR). Novel antibiofilm peptide derivatives were modified by substituting hydrophobic amino acids at positions 5 or 7, and both, with positively charged lysines (L5K, L7K). These peptide derivatives were tested for antibiofilm and antimicrobial activities against biofilm-forming Staphylococcus epidermidis and multiple other microbes using crystal violet and broth microdilution assays, respectively. To assess their impact on mammalian cells, the toxicity of peptides was determined through hemolysis and cytotoxicity assays. The stability of candidate peptide, BiF2_5K7K, was assessed in human serum and its secondary structure in bacterial membrane-like environments was analyzed using circular dichroism. The action of BiF2_5K7K on planktonic S. epidermidis and its effect on biofilm cell viability were assessed via viable counting assays. Its biofilm inhibition mechanism was investigated through confocal laser scanning microscopy and transcription analysis. Additionally, its ability to eradicate mature biofilms was examined using colony counting. Finally, a preliminary evaluation involved coating a catheter with BiF2_5K7K to assess its preventive efficacy against S. epidermidis biofilm formation on the catheter and its surrounding area.</p><p><strong>Results: </strong>BiF2_5K7K, the modified antibiofilm peptide, exhibited dose-dependent antibiofilm activity against S. epidermidis. It inhibited biofilm formation at subinhibitory concentrations by altering S. epidermidis extracellular polysaccharide production and quorum-sensing gene expression. Additionally, it exhibited broad-spectrum antimicrobial activity and no significant hemolysis or toxicity against mammalian cell lines was observed. Its activity is retained when exposed to human serum. In bacterial membrane-like environments, this peptide formed an α-helix amphipathic structure. Within 4 h, a reduction in the number of S. epidermidis colonies was observed, demonstrating the fast action of this peptide. As a preliminary test, a BiF2_5K7K-coated catheter was able to prevent the development of S. epidermidis biofilm both on the catheter surface and in its surrounding area.</p><p><strong>Conclusions: </strong>Due to the safety and effectiveness of BiF2_5K7K, we suggest that this peptide be further developed to combat biofilm infections, particularly those ","PeriodicalId":8052,"journal":{"name":"Annals of Clinical Microbiology and Antimicrobials","volume":"23 1","pages":"44"},"PeriodicalIF":5.7,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11100219/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140955914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-10DOI: 10.1186/s12941-024-00702-6
Nathalie Yepes Madrid, Luis Fernando Mejia, José Fernando Gomez Urrego
Background: Shewanella putrefaciens is a gram-negative, nonfermenting, oxidase-positive, hydrogen sulfide-producing bacillus and a halophilic bacterium, known for causing unusual infections in humans and often regarded as an opportunistic pathogen. Its diverse symptoms have a significant impact on human health, with 260 documented disorders reported in the literature over the last 40 years, highlighting its potential danger.
Case presentation: We present the case of a previously healthy 15-year-old male patient who sustained a self-inflicted sharp-object injury while working in the field, resulting in secondary septic monoarthritis due to Shewanella putrefaciens.
Conclusions: This case highlights the bacteriological and clinical characteristics, as well as the antibiogram, of Shewanella spp. Given the recent increase in notifications of Shewanella infections, predominantly by S. algae and S. putrefaciens, it is essential to consider these pathogens in patients with a history of contact with bodies of water. Special attention must be paid to their resistance patterns in patient management to prevent the development of intrinsic antimicrobial resistance.
{"title":"Left knee septic monoarthritis in a pediatric patient due to shewanella putrefaciens: case report and literature review.","authors":"Nathalie Yepes Madrid, Luis Fernando Mejia, José Fernando Gomez Urrego","doi":"10.1186/s12941-024-00702-6","DOIUrl":"10.1186/s12941-024-00702-6","url":null,"abstract":"<p><strong>Background: </strong>Shewanella putrefaciens is a gram-negative, nonfermenting, oxidase-positive, hydrogen sulfide-producing bacillus and a halophilic bacterium, known for causing unusual infections in humans and often regarded as an opportunistic pathogen. Its diverse symptoms have a significant impact on human health, with 260 documented disorders reported in the literature over the last 40 years, highlighting its potential danger.</p><p><strong>Case presentation: </strong>We present the case of a previously healthy 15-year-old male patient who sustained a self-inflicted sharp-object injury while working in the field, resulting in secondary septic monoarthritis due to Shewanella putrefaciens.</p><p><strong>Conclusions: </strong>This case highlights the bacteriological and clinical characteristics, as well as the antibiogram, of Shewanella spp. Given the recent increase in notifications of Shewanella infections, predominantly by S. algae and S. putrefaciens, it is essential to consider these pathogens in patients with a history of contact with bodies of water. Special attention must be paid to their resistance patterns in patient management to prevent the development of intrinsic antimicrobial resistance.</p>","PeriodicalId":8052,"journal":{"name":"Annals of Clinical Microbiology and Antimicrobials","volume":"23 1","pages":"43"},"PeriodicalIF":4.6,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11088002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140904025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-06DOI: 10.1186/s12941-024-00700-8
Mariana Guedes, David Gathara, Inmaculada López-Hernández, Pedro María Martínez Pérez-Crespo, María Teresa Pérez-Rodríguez, Adrian Sousa, Antonio Plata, Jose María Reguera-Iglesias, Lucía Boix-Palop, Beatriz Dietl, Juan Sevilla Blanco, Carlos Armiñanzas Castillo, Fátima Galán-Sánchez, Clara Natera Kindelán, Alfredo Jover-Saenz, Josune Goikoetxea Aguirre, Ana Alemán Alemán, Teresa Marrodán Ciordia, Alfonso Del Arco Jiménez, Jonathan Fernandez-Suarez, Luis Eduardo Lopez-Cortes, Jesús Rodríguez-Baño
Background: Klebsiella aerogenes has been reclassified from Enterobacter to Klebsiella genus due to its phenotypic and genotypic similarities with Klebsiella pneumoniae. It is unclear if clinical outcomes are also more similar. This study aims to assess clinical outcomes of bloodstreams infections (BSI) caused by K. aerogenes, K. pneumoniae and Enterobacter cloacae, through secondary data analysis, nested in PRO-BAC cohort study.
Methods: Hospitalized patients between October 2016 and March 2017 with monomicrobial BSI due to K. aerogenes, K. pneumoniae or E. cloacae were included. Primary outcome was a composite clinical outcome including all-cause mortality or recurrence until 30 days follow-up. Secondary outcomes were fever ≥ 72 h, persistent bacteraemia, and secondary device infection. Multilevel mixed-effect Poisson regression was used to estimate the association between microorganisms and outcome.
Results: Overall, 29 K. aerogenes, 77 E. cloacae and 337 K. pneumoniae BSI episodes were included. Mortality or recurrence was less frequent in K. aerogenes (6.9%) than in E. cloacae (20.8%) or K. pneumoniae (19.0%), but statistical difference was not observed (rate ratio (RR) 0.35, 95% CI 0.08 to 1.55; RR 0.42, 95% CI 0.10 to 1.71, respectively). Fever ≥ 72 h and device infection were more common in K. aerogenes group. In the multivariate analysis, adjusted for confounders (age, sex, BSI source, hospital ward, Charlson score and active antibiotic therapy), the estimates and direction of effect were similar to crude results.
Conclusions: Results suggest that BSI caused by K. aerogenes may have a better prognosis than E. cloacae or K. pneumoniae BSI.
背景:由于其表型和基因型与肺炎克雷伯菌相似,产气克雷伯菌已从肠杆菌属重新分类为克雷伯菌属。目前尚不清楚临床结果是否也更为相似。本研究旨在通过二级数据分析,嵌套于PRO-BAC队列研究,评估产气荚膜克雷伯菌、肺炎克雷伯菌和泄殖腔肠杆菌引起的血流感染(BSI)的临床结局。方法:纳入2016年10月至2017年3月期间因产气荚膜克雷伯菌、肺炎克雷伯菌或泄殖腔肠杆菌引起单微生物BSI的住院患者。主要结果为综合临床结果,包括全因死亡率或随访30天前的复发率。次要结果为发热≥72小时、持续菌血症和二次设备感染。多层次混合效应泊松回归用于估计微生物与结果之间的关联:结果:总共纳入了 29 例产气荚膜杆菌、77 例衣霉菌和 337 例肺炎双球菌 BSI 病例。与丁香杆菌(20.8%)或肺炎双球菌(19.0%)相比,产气荚膜杆菌(6.9%)的死亡率或复发率较低,但未观察到统计学差异(比率比(RR)分别为 0.35,95% CI 0.08 至 1.55;RR 0.42,95% CI 0.10 至 1.71)。在产气荚膜杆菌组中,发热≥72 h和器械感染更为常见。在对混杂因素(年龄、性别、BSI来源、病房、Charlson评分和积极抗生素治疗)进行调整后的多变量分析中,估计值和效应方向与粗略结果相似:结果表明,与丁香杆菌或肺炎双球菌引起的BSI相比,产气荚膜杆菌引起的BSI预后可能更好。
{"title":"Differences in clinical outcomes of bloodstream infections caused by Klebsiella aerogenes, Klebsiella pneumoniae and Enterobacter cloacae: a multicentre cohort study.","authors":"Mariana Guedes, David Gathara, Inmaculada López-Hernández, Pedro María Martínez Pérez-Crespo, María Teresa Pérez-Rodríguez, Adrian Sousa, Antonio Plata, Jose María Reguera-Iglesias, Lucía Boix-Palop, Beatriz Dietl, Juan Sevilla Blanco, Carlos Armiñanzas Castillo, Fátima Galán-Sánchez, Clara Natera Kindelán, Alfredo Jover-Saenz, Josune Goikoetxea Aguirre, Ana Alemán Alemán, Teresa Marrodán Ciordia, Alfonso Del Arco Jiménez, Jonathan Fernandez-Suarez, Luis Eduardo Lopez-Cortes, Jesús Rodríguez-Baño","doi":"10.1186/s12941-024-00700-8","DOIUrl":"10.1186/s12941-024-00700-8","url":null,"abstract":"<p><strong>Background: </strong>Klebsiella aerogenes has been reclassified from Enterobacter to Klebsiella genus due to its phenotypic and genotypic similarities with Klebsiella pneumoniae. It is unclear if clinical outcomes are also more similar. This study aims to assess clinical outcomes of bloodstreams infections (BSI) caused by K. aerogenes, K. pneumoniae and Enterobacter cloacae, through secondary data analysis, nested in PRO-BAC cohort study.</p><p><strong>Methods: </strong>Hospitalized patients between October 2016 and March 2017 with monomicrobial BSI due to K. aerogenes, K. pneumoniae or E. cloacae were included. Primary outcome was a composite clinical outcome including all-cause mortality or recurrence until 30 days follow-up. Secondary outcomes were fever ≥ 72 h, persistent bacteraemia, and secondary device infection. Multilevel mixed-effect Poisson regression was used to estimate the association between microorganisms and outcome.</p><p><strong>Results: </strong>Overall, 29 K. aerogenes, 77 E. cloacae and 337 K. pneumoniae BSI episodes were included. Mortality or recurrence was less frequent in K. aerogenes (6.9%) than in E. cloacae (20.8%) or K. pneumoniae (19.0%), but statistical difference was not observed (rate ratio (RR) 0.35, 95% CI 0.08 to 1.55; RR 0.42, 95% CI 0.10 to 1.71, respectively). Fever ≥ 72 h and device infection were more common in K. aerogenes group. In the multivariate analysis, adjusted for confounders (age, sex, BSI source, hospital ward, Charlson score and active antibiotic therapy), the estimates and direction of effect were similar to crude results.</p><p><strong>Conclusions: </strong>Results suggest that BSI caused by K. aerogenes may have a better prognosis than E. cloacae or K. pneumoniae BSI.</p>","PeriodicalId":8052,"journal":{"name":"Annals of Clinical Microbiology and Antimicrobials","volume":"23 1","pages":"42"},"PeriodicalIF":5.7,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11071190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140849588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Infections caused by linezolid-resistant enterococci (LRE) are clinically difficult to treat and threaten patient health. However, there is a lack of studies on long time-span LRE strains in China. For this reason, our study comprehensively revealed the resistance mechanisms of LRE strains collected in a Chinese tertiary care hospital from 2011 to 2022. Enterococcal strains were screened and verified after retrospective analysis of microbial data. Subsequently, 65 LRE strains (61 Enterococcus faecalis and 4 Enterococcus faecium, MIC ≥ 8 µg/ml), 1 linezolid-intermediate Enterococcus faecium (MIC = 4 µg/ml) and 1 linezolid-susceptible Enterococcus faecium (MIC = 1.5 µg/ml) were submitted for whole-genome sequencing (WGS) analysis and bioinformatics analysis. The optrA gene was found to be the most common linezolid resistance mechanism in our study. We identified the wild-type OptrA and various OptrA variants in 98.5% of LRE strains (61 Enterococcus faecalis and 3 Enterococcus faecium). We also found one linezolid-resistant Enterococcus faecium strain carried both optrA and cfr(D) gene, while one linezolid-resistant Enterococcus faecium only harbored the poxtA gene. Most optrA genes (55/64) were located on plasmids, with impB-fexA-optrA, impB-fexA-optrA-erm(A), fexA-optrA-erm(A), and fexA-optrA segments. A minority of optrA genes (9/64) were found on chromosomes with the Tn6674-like platform. Besides, other possible linezolid resistance-associated mechanisms (mutations in the rplC and rplD genes) were also found in 26 enterococcal strains. Our study suggested that multiple mechanisms of linezolid resistance exist among clinical LRE strains in China.
{"title":"Genomic epidemiology reveals multiple mechanisms of linezolid resistance in clinical enterococci in China","authors":"Ziran Wang, Danping Liu, Jingjia Zhang, Lingli Liu, Zeming Zhang, Chang Liu, Songnian Hu, Linhuan Wu, Zilong He, Hongli Sun","doi":"10.1186/s12941-024-00689-0","DOIUrl":"https://doi.org/10.1186/s12941-024-00689-0","url":null,"abstract":"Infections caused by linezolid-resistant enterococci (LRE) are clinically difficult to treat and threaten patient health. However, there is a lack of studies on long time-span LRE strains in China. For this reason, our study comprehensively revealed the resistance mechanisms of LRE strains collected in a Chinese tertiary care hospital from 2011 to 2022. Enterococcal strains were screened and verified after retrospective analysis of microbial data. Subsequently, 65 LRE strains (61 Enterococcus faecalis and 4 Enterococcus faecium, MIC ≥ 8 µg/ml), 1 linezolid-intermediate Enterococcus faecium (MIC = 4 µg/ml) and 1 linezolid-susceptible Enterococcus faecium (MIC = 1.5 µg/ml) were submitted for whole-genome sequencing (WGS) analysis and bioinformatics analysis. The optrA gene was found to be the most common linezolid resistance mechanism in our study. We identified the wild-type OptrA and various OptrA variants in 98.5% of LRE strains (61 Enterococcus faecalis and 3 Enterococcus faecium). We also found one linezolid-resistant Enterococcus faecium strain carried both optrA and cfr(D) gene, while one linezolid-resistant Enterococcus faecium only harbored the poxtA gene. Most optrA genes (55/64) were located on plasmids, with impB-fexA-optrA, impB-fexA-optrA-erm(A), fexA-optrA-erm(A), and fexA-optrA segments. A minority of optrA genes (9/64) were found on chromosomes with the Tn6674-like platform. Besides, other possible linezolid resistance-associated mechanisms (mutations in the rplC and rplD genes) were also found in 26 enterococcal strains. Our study suggested that multiple mechanisms of linezolid resistance exist among clinical LRE strains in China.","PeriodicalId":8052,"journal":{"name":"Annals of Clinical Microbiology and Antimicrobials","volume":"13 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140839381","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}
Pub Date : 2024-05-03DOI: 10.1186/s12941-024-00697-0
Bing Zhao, Huiwen Zheng, Juliano Timm, Zexuan Song, Shaojun Pei, Ruida Xing, Yajie Guo, Ling Ma, Feina Li, Qing Li, Yan Li, Lin Huang, Chong Teng, Ni Wang, Aastha Gupta, Sandeep Juneja, Fei Huang, Yanlin Zhao, Xichao Ou
Pretomanid is a key component of new regimens for the treatment of drug-resistant tuberculosis (TB) which are being rolled out globally. However, there is limited information on the prevalence of pre-existing resistance to the drug. To investigate pretomanid resistance rates in China and its underlying genetic basis, as well as to generate additional minimum inhibitory concentration (MIC) data for epidemiological cutoff (ECOFF)/breakpoint setting, we performed MIC determinations in the Mycobacterial Growth Indicator Tube™ (MGIT) system, followed by WGS analysis, on 475 Mycobacterium tuberculosis (MTB) isolated from Chinese TB patients between 2013 and 2020. We observed a pretomanid MIC distribution with a 99% ECOFF equal to 0.5 mg/L. Of the 15 isolates with MIC values > 0.5 mg/L, one (MIC = 1 mg/L) was identified as MTB lineage 1 (L1), a genotype previously reported to be intrinsically less susceptible to pretomanid, two were borderline resistant (MIC = 2–4 mg/L) and the remaining 12 isolates were highly resistant (MIC ≥ 16 mg/L) to the drug. Five resistant isolates did not harbor mutations in the known pretomanid resistant genes. Our results further support a breakpoint of 0.5 mg/L for a non-L1 MTB population, which is characteristic of China. Further, our data point to an unexpected high (14/475, 3%) pre-existing pretomanid resistance rate in the country, as well as to the existence of yet-to-be-discovered pretomanid resistance genes.
{"title":"Prevalence and genetic basis of Mycobacterium tuberculosis resistance to pretomanid in China","authors":"Bing Zhao, Huiwen Zheng, Juliano Timm, Zexuan Song, Shaojun Pei, Ruida Xing, Yajie Guo, Ling Ma, Feina Li, Qing Li, Yan Li, Lin Huang, Chong Teng, Ni Wang, Aastha Gupta, Sandeep Juneja, Fei Huang, Yanlin Zhao, Xichao Ou","doi":"10.1186/s12941-024-00697-0","DOIUrl":"https://doi.org/10.1186/s12941-024-00697-0","url":null,"abstract":"Pretomanid is a key component of new regimens for the treatment of drug-resistant tuberculosis (TB) which are being rolled out globally. However, there is limited information on the prevalence of pre-existing resistance to the drug. To investigate pretomanid resistance rates in China and its underlying genetic basis, as well as to generate additional minimum inhibitory concentration (MIC) data for epidemiological cutoff (ECOFF)/breakpoint setting, we performed MIC determinations in the Mycobacterial Growth Indicator Tube™ (MGIT) system, followed by WGS analysis, on 475 Mycobacterium tuberculosis (MTB) isolated from Chinese TB patients between 2013 and 2020. We observed a pretomanid MIC distribution with a 99% ECOFF equal to 0.5 mg/L. Of the 15 isolates with MIC values > 0.5 mg/L, one (MIC = 1 mg/L) was identified as MTB lineage 1 (L1), a genotype previously reported to be intrinsically less susceptible to pretomanid, two were borderline resistant (MIC = 2–4 mg/L) and the remaining 12 isolates were highly resistant (MIC ≥ 16 mg/L) to the drug. Five resistant isolates did not harbor mutations in the known pretomanid resistant genes. Our results further support a breakpoint of 0.5 mg/L for a non-L1 MTB population, which is characteristic of China. Further, our data point to an unexpected high (14/475, 3%) pre-existing pretomanid resistance rate in the country, as well as to the existence of yet-to-be-discovered pretomanid resistance genes.","PeriodicalId":8052,"journal":{"name":"Annals of Clinical Microbiology and Antimicrobials","volume":"45 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140839385","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}