European Journal of Clinical Microbiology & Infectious Diseases最新文献

{"title":"The virulence toolkit of Staphylococcus aureus: a comprehensive review of toxin diversity, molecular mechanisms, and clinical implications.","authors":"Stefano Di Bella, Bruna Marini, Giacomo Stroffolini, Nicholas Geremia, Daniele Roberto Giacobbe, Floriana Campanile, Michele Bartoletti, Giulia Alloisio, Ludovica Di Risio, Giulia Viglietti, Luigi Principe, Venera Costantino, Marina Busetti, Verena Zerbato, Filippo Mearelli, Gianni Biolo, Alessio Nunnari, Claudia Maria Cafiero, Alessandra di Masi","doi":"10.1007/s10096-025-05148-y","DOIUrl":"https://doi.org/10.1007/s10096-025-05148-y","url":null,"abstract":"<p><strong>Purpose: </strong>This review examines the pathogenic mechanisms of Staphylococcus aureus, emphasizing its toxin-driven virulence factors, including pore-forming toxins, exfoliative toxins, and superantigens.</p><p><strong>Methods: </strong>This paper was conducted using the available literature (PubMed/MEDLINE/Google Scholar and books written by experts in pharmacology and infectious diseases).</p><p><strong>Results: </strong>Toxins are crucial in promoting tissue invasion, immune system evasion, and the development of systemic diseases. Notably, the qualitative and quantitative expression of these toxins influences the clinical presentation and severity of S. aureus infections. The paper explores toxins' role in S. aureus pathogenesis and clinical manifestations as well as current and emerging therapeutic strategies aimed at targeting these toxins, including antibiotics, monoclonal antibodies, and anti-inflammatory treatments. Additionally, it highlights the potential of novel inhibitors and vaccines to neutralize specific toxins and prevent toxin-mediated diseases.</p><p><strong>Conclusion: </strong>By combining antimicrobial therapies with approaches that neutralize toxins and modulate the immune response, clinicians can improve outcomes in patients affected by S. aureus infections.</p>","PeriodicalId":11782,"journal":{"name":"European Journal of Clinical Microbiology & Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144062471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibiotic de-escalation patterns and outcomes in critically ill patients with suspected pneumonia as informed by bronchoalveolar lavage results.","authors":"Mengou Zhu, Chiagozie I Pickens, Nikolay S Markov, Anna Pawlowski, Mengjia Kang, Luke V Rasmussen, James M Walter, Nandita R Nadig, Benjamin D Singer, Richard G Wunderink, Catherine A Gao","doi":"10.1007/s10096-025-05144-2","DOIUrl":"https://doi.org/10.1007/s10096-025-05144-2","url":null,"abstract":"<p><strong>Purpose: </strong>Antibiotic stewardship in critically ill pneumonia patients is crucial yet challenging, partly due to the limitations of noninvasive diagnostic tests. This study reports an antibiotic de-escalation pattern informed by bronchoalveolar lavage (BAL) results, incorporating quantitative cultures and multiplex PCR rapid diagnostic tests.</p><p><strong>Methods: </strong>We analyzed data from SCRIPT, a single-center prospective cohort study of mechanically ventilated patients who underwent a BAL for suspected pneumonia. We used the Narrow Antibiotic Therapy (NAT) score to quantify day-by-day antibiotic prescription patterns for each suspected pneumonia episode etiology (bacterial, viral, mixed bacterial/viral, microbiology-negative, and non-pneumonia control). The primary outcome was a composite of in-hospital mortality, discharge to hospice, or requiring lung transplantation during hospitalization, which we referred to as unfavorable outcomes. The secondary outcomes were duration of ICU stay, duration of intubation, and Clostridium difficile during admission. Outcomes were compared across pneumonia etiologies with the Mann-Whitney U test and Fisher's exact test.</p><p><strong>Results: </strong>Among 686 patients (409 men, 276 women) with 927 pneumonia episodes, NAT score analysis showed consistent antibiotic de-escalation in all pneumonia etiologies except resistant bacterial pneumonia. Microbiology-negative pneumonia was treated similarly to susceptible bacterial pneumonia. 44% viral episodes had antibiotic cessation by post-BAL day 5. Unfavorable outcomes were comparable across all pneumonia etiologies. Patients with viral and mixed bacterial/viral pneumonia had longer durations of ICU stay and intubation. Clostridium difficile was detected in 14 (2%) patients.</p><p><strong>Conclusions: </strong>BAL quantitative cultures and multiplex PCR rapid diagnostic tests resulted in prompt antibiotic de-escalation in critically ill pneumonia patients. There was no evidence of increased unfavorable outcomes.</p>","PeriodicalId":11782,"journal":{"name":"European Journal of Clinical Microbiology & Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Complicated pneumococcal pneumonia in the era of higher-valent pneumococcal conjugate vaccines: a systematic literature review and meta-analysis, 2001-2022.","authors":"Mark A Fletcher, Omar Okasha, Marc Baay, Maria Syrochkina, Kyla Hayford","doi":"10.1007/s10096-025-05114-8","DOIUrl":"https://doi.org/10.1007/s10096-025-05114-8","url":null,"abstract":"<p><strong>Purpose: </strong>To estimate pneumococcal conjugate vaccine (PCV) national program impact on pneumococcal complicated pneumonia (PnCP) based on changes in PnCP population-based incidence, PnCP proportion of all-cause complicated pneumonia (or invasive pneumococcal disease), and PnCP serotype distribution.</p><p><strong>Methods: </strong>MEDLINE, EMBASE, and Global Index Medicus articles (2001-March 2022) reporting laboratory-confirmed PnCP studies were stratified by age group, outcome measure, PCV program period(s) (pre-PCV, transition, and post-PCV), serotype distribution (based on serotyping methodology used), and PCV serotype formulation. Random effect meta-analysis of the total number of serotyped isolates within each study was used to calculate pooled serotype-specific percentages.</p><p><strong>Results: </strong>Of 1360 publications screened, the 134 studies included from 30 countries differed widely by methodological approaches. Pediatric PnCP incidence tended to decline from pre-PCV to post-PCV periods, as did PnCP as a proportion of all-cause complicated pneumonia from transition to post-PCV periods. Studies describing changes in serotype distribution by PCV program period applied detection methods that varied from pre-PCV period microbiological culture with Quellung serotyping to in the transition and post-PCV periods molecular methods like PCR. Meta-analysis revealed near elimination of pediatric PCV7-serotype PnCP between pre- and post-PCV, while the PCV13nonPCV7 percentage increased from 51.1% pre-PCV period to 76.5% in the transition period, remaining stable post-PCV period. Non-PCV13 serotypes increased slightly from low baseline numbers. Adult data were lacking or inconsistent.</p><p><strong>Conclusions: </strong>Although studies were heterogeneous, pediatric PnCP incidence and proportion tended to decline from pre-PCV to post-PCV periods, and PCV13nonPCV7 serotype distribution percentage remained unchanged from transition to post-PCV period. Standardization of PnCP surveillance methods, definitions, and reporting is needed to evaluate accurately PCV program impact.</p>","PeriodicalId":11782,"journal":{"name":"European Journal of Clinical Microbiology & Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Construction and validation of an interpretable XGBoost machine learning model to predict ESBL positivity rates based on urinalysis data.","authors":"Lulu Zhang, Shaokui Hua, Yu Zhang, Yan Jiang, Qunlian Huang, Baoyuan Chang, Dengke Li","doi":"10.1007/s10096-025-05155-z","DOIUrl":"https://doi.org/10.1007/s10096-025-05155-z","url":null,"abstract":"<p><strong>Background: </strong>Microbiological culture and drug susceptibility testing of urine samples have lengthy turnaround times, increasing the risk of extended-spectrum β-lactamase (ESBL)-positive urinary tract infection (UTI) patients progressing to sepsis.</p><p><strong>Objective: </strong>To develop an efficient machine learning model for the identification of ESBL positivity in UTI patients.</p><p><strong>Methods: </strong>This retrospective study included 528 samples that had undergone drug susceptibility testing, based on inclusion and exclusion criteria. Variables were screened using Lasso regression, with 70% of the samples used to construct nine machine learning models (XGBClassifier, LogisticRegression, LGBMClassifier, AdaBoostClassifier, SVC, MLPClassifier, ComplementNB, GaussianNB, and GradientBoostingClassifier). Model selection was based on criteria including accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), F1 score, Kappa score, and Area Under the Curve (AUC). The best model type was identified through ten-fold cross-validation, which was then built using the remaining 30% of the data as a test set. Interpretations of predictive results were provided using the SHAP model, clarifying the impact of each feature on predictions and enhancing model transparency and interpretability.</p><p><strong>Results: </strong>The variables selected by the Lasso regression model are as follows: gender + urinary protein + urobilinogen + leukocytes + occult blood + age + pH + specific gravity + leukocyte count + erythrocyte count + epithelial cell count + cast count.The XGBoost model outperformed others in ten-fold cross-validation, with scores on the validation set as follows: AUC (95%CI): 0.924 (0.860-0.989); cutoff: 0.664(0.637-0.690); accuracy: 0.862(0.839-0.885); sensitivity: 0.9(0.879-0.920); specificity: 0.725(0.618-0.832); PPV: 0.923(0.896-0.950); NPV: 0.667(0.626-0.707); F1 score: 0.911(0.896-0.925); Kappa: 0.603(0.527-0.679). The final model achieved an AUC of 0.968 and accuracy of 0.943 on the test set.</p><p><strong>Conclusion: </strong>This study developed a rapid and efficient machine learning model capable of identifying ESBL positivity based solely on routine urine test data.</p>","PeriodicalId":11782,"journal":{"name":"European Journal of Clinical Microbiology & Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143990656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beta-lactam combination treatment overcomes rifampicin resistance in Mycobacterium tuberculosis.","authors":"Diana H Quan, Trixie Wang, Elena Martinez, Hanna Y Kim, Vitali Sintchenko, Warwick J Britton, James A Triccas, Jan-Willem Alffenaar","doi":"10.1007/s10096-025-05062-3","DOIUrl":"10.1007/s10096-025-05062-3","url":null,"abstract":"<p><p>The significant global impact of tuberculosis (TB) on human health is exacerbated by the increasing prevalence of multi-drug resistant tuberculosis (MDR-TB) and the challenges of novel drug discovery for the treatment of drug-susceptible and drug-resistant strains of M. tuberculosis. Rifampicin is a key first-line TB drug and rifampicin resistance is a major obstacle to treating MDR-TB. Utilising existing antimicrobial drugs to supplement combination therapy and overcome rifampicin resistance is a promising solution due to their widespread availability and proven clinical safety profile. Therefore, this study aimed to explore the feasibility of using beta-lactam/beta-lactamase inhibitor combinations with rifampicin to inhibit the growth of multidrug-resistant M. tuberculosis. Based on inhibitory concentration (IC), oral bioavailability, pricing, commercial availability, five beta-lactams and the beta-lactamase inhibitor, clavulanate, were selected for testing. These were combined with rifampicin for in vitro testing against Mycobacterium tuberculosis H37Rv. Resazurin assays and colony forming unit (CFU) enumeration were used to quantify drug efficacy, Chou-Talalay calculations were performed to identify drug synergy and Chou-Martin calculations were performed to quantify drug dose reduction index (DRI). The combination of tebipenem-clavulanate/rifampicin and cephradine-clavulanate/rifampicin were found to be synergistic and highly effective against clinical isolates of MDR-TB, overcoming rifampicin resistance in vitro. Beta-lactam synergy may provide viable combination therapies with rifampicin to address the issue of drug resistance in TB.</p>","PeriodicalId":11782,"journal":{"name":"European Journal of Clinical Microbiology & Infectious Diseases","volume":" ","pages":"1279-1284"},"PeriodicalIF":3.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12062089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diversity of Mycoplasma genitalium strains in Australia: relationship with sexual networks and antimicrobial resistance.","authors":"Teck-Phui Chua, Jennifer A Danielewski, Emma L Sweeney, Erica L Plummer, Catriona S Bradshaw, David M Whiley, Dorothy A Machalek, Suzanne M Garland, Gerald L Murray","doi":"10.1007/s10096-025-05081-0","DOIUrl":"10.1007/s10096-025-05081-0","url":null,"abstract":"<p><strong>Purpose: </strong>Molecular typing can identify relationships between M. genitalium strains and antimicrobial resistance and demographic data. We examined the association of mgpB sequence types (STs) with sex/sexual orientation, antimicrobial resistance and geographical location for M. genitalium in Australia.</p><p><strong>Methods: </strong>Sequence data derived from previous studies in Victoria and Queensland were obtained from 170 M. genitalium samples for the mgpB, 23 S rRNA, and parC genes. An additional 55 M. genitalium samples from Victoria were sequenced for the same three genes in this study. A combined data set of 225 samples collected between 2017 and 2019 were examined for associations between mgpB ST and (i) sex/sexual orientation, (ii) macrolide and fluoroquinolone resistance, and (iii) geographical location using chi-square test.</p><p><strong>Results: </strong>Overall, 66 mgpB STs were identified; the most common were ST-7 (17.9%), ST-4 (11.6%), ST-105 (11.6%), and ST-2 (5.4%). There was a strong association between ST and sex/sexual orientation; ST-4 and ST-105 were most common among men-who-have-sex-with-men (p < 0.0001) while ST-7 among women (p < 0.0001). There was a strong association between ST and macrolide resistance (p = 0.0028). Fluoroquinolone resistance was less common (28.0%) and did not differ by STs (p = 0.20). There was no association between ST and geographic location (p = 0.056).</p><p><strong>Conclusion: </strong>In this Australian study, four mgpB STs were common and were strongly associated with sex/sexual orientation and macrolide resistance. This relationship was not seen for fluoroquinolone resistance nor geographic location. These findings highlight the sporadic nature of resistance, indicating a need for effective treatment approaches combined with routine antimicrobial resistance surveillance.</p>","PeriodicalId":11782,"journal":{"name":"European Journal of Clinical Microbiology & Infectious Diseases","volume":" ","pages":"1167-1175"},"PeriodicalIF":3.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12062162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of imipenem-relebactam susceptibility testing in carbapenem resistant Pseudomonas aeruginosa: comparison of sensititre microplates, disc diffusion, and MTS gradient strips with broth microdilution.","authors":"Adrien Biguenet, Léa Devoos, Julie Rousselot, Maxime Bour, Damien Fournier, Katy Jeannot","doi":"10.1007/s10096-025-05058-z","DOIUrl":"10.1007/s10096-025-05058-z","url":null,"abstract":"<p><p>Four commercial tests EUMDROXF^® Sensititre microplates, MTS gradient strips, and disc diffusion were evaluated for imipenem-relebactam susceptibility in 148 ceftazidime and imipenem-resistant Pseudomonas aeruginosa strains, using broth microdilution (BMD) as the reference. EUMDROXF^® Sensititre microplates showed the highest accuracy (CA = 93.2%, EA = 93.9%, and bias difference + 21.8%). While the MTS gradient strips showed acceptable performance (CA = 84.5%; EA = 89.9%, and difference of bias = 21.0%), the disc method misclassified 25.8% (16/62) of the resistant strains. Given these results, considering an Area of Technical Uncertainty (ATU) for disc diffusion (20-24 mm) in imipenem-relebactam testing is recommended for P. aeruginosa strains.</p>","PeriodicalId":11782,"journal":{"name":"European Journal of Clinical Microbiology & Infectious Diseases","volume":" ","pages":"1231-1237"},"PeriodicalIF":3.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro activity and resistance mechanisms of novel antimicrobial agents against metallo-β-lactamase producers.","authors":"Matteo Boattini, Paolo Gaibani, Sara Comini, Cristina Costa, Rossana Cavallo, Francesco Broccolo, Gabriele Bianco","doi":"10.1007/s10096-025-05080-1","DOIUrl":"10.1007/s10096-025-05080-1","url":null,"abstract":"<p><p>The carbapenemase-producing Gram-negative organisms represent an urgent clinical and public health concern, as they have been associated with increased mortality and high dissemination in healthcare settings. Although overall incidence rates of infections sustained by metallo-β-lactamase (MβL)-producers have remained lower than those sustained by other carbapenemase-producers, albeit with substantial geographic differences, a significant increase in the prevalence of MβL-producers has been observed over the last decade. The recent development of new antimicrobials expanded the armamentarium to counter the challenge of metallo-β-lactamase (MβL)-producers. Cefiderocol and aztreonam/avibactam are already clinically available and recommended by international guidelines. In addition, two new classes of β-lactam/ β-lactamase combinations are under clinical evaluation: (i) combination of β-lactam with novel boronic-derived inhibitors (e.g. taniborbactam and xeruborbactam), (ii) combination of β-lactam with last generation diazabicyclooctane β-lactamase inhibitors (e.g. zidebactam and nacubactam), active on most of serine-β-lactamases but also showing strong intrinsic activity on PBP-2. This review aims to provide up-to-date data on the characteristics, activity and emerging resistance mechanisms of the armamentarium of clinically available or soon-to-be introduced drugs for the treatment of MβL-producing Gram-negative organisms.</p>","PeriodicalId":11782,"journal":{"name":"European Journal of Clinical Microbiology & Infectious Diseases","volume":" ","pages":"1041-1068"},"PeriodicalIF":3.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12062158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering the genetic context of the emerging OXA-484-producing carbapenem-resistant Escherichia coli from ST167 high-risk clone in the United Arab Emirates.","authors":"Farah Al-Marzooq, Akela Ghazawi, Mushal Allam, Timothy Collyns","doi":"10.1007/s10096-025-05082-z","DOIUrl":"10.1007/s10096-025-05082-z","url":null,"abstract":"<p><strong>Purpose: </strong>The evolution of new carbapenemase variants is alarming. We aimed to investigate the genetic context and molecular epidemiology of the emerging OXA-484 carbapenemase in the United Arab Emirates, to decipher its resistance mechanisms and evolutionary relationships.</p><p><strong>Methods: </strong>Antimicrobial susceptibility testing was performed for an E. coli isolate recovered from an intrauterine contraceptive device of a patient returning to the UAE after a trip to Pakistan. Whole genome sequencing was used to characterize the genetic environment of bla_OXA-484, resistance and virulence determinants. Southern blotting was used to localize OXA-484 gene. Phylogenetic analysis established the sequence type (ST) and used to investigate relationships with global strains, and differences from other OXA-48-like types.</p><p><strong>Results: </strong>The strain demonstrated selective resistance against ertapenem while maintaining susceptibility to imipenem and meropenem. OXA-484 exhibited R214G substitution affecting the enzyme's activity and distinguishing it from closely related variants like OXA-181 (214R) and OXA-232 (214 S). bla_OXA-484 was located on two non-conjugative plasmids (∼ 65 and 100 kb) within a genetic environment containing multiple insertion sequences. It belonged to the high-risk clone ST167, recognized for its enhanced capacity to acquire and maintain resistance determinants. The gene was mostly prevalent in the Western part of the world with limited distribution in the Middle East.</p><p><strong>Conclusion: </strong>This study presents the first comprehensive characterization of OXA-484-producing E. coli ST167 in the UAE. The presence of bla_OXA-484 in high-risk clone warrants concern on its dissemination potential and underscores the importance of genomic surveillance and targeted infection control to prevent the spread of emerging resistance determinants.</p>","PeriodicalId":11782,"journal":{"name":"European Journal of Clinical Microbiology & Infectious Diseases","volume":" ","pages":"1155-1166"},"PeriodicalIF":3.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro synergistic effects of mefloquine combined with other antimicrobial agents on carbapenem-resistant Enterobacterales.","authors":"Chunhong Zou, Zixin Wen, Wen Wang, Ke Gao, Shimei Shen, Lisha Shang, Xue Li, Jie Yu, Jinyi Shen, Yujin Li, Liang Chen, Jianglin Wu, Jie Wei, Deqiang Wang, Siqiang Niu","doi":"10.1007/s10096-025-05060-5","DOIUrl":"10.1007/s10096-025-05060-5","url":null,"abstract":"<p><strong>Purpose: </strong>Human health is seriously threatened by carbapenem-resistant Enterobacterales (CRE) due to the lack of effective treatment. The purpose of this study is to examine the efficacy of mefloquine (MEF) together with multiple drugs against 96 clinical CRE isolates including 94 Klebsiella pneumoniae carbapenemase (KPC)-producers or Metallo-β-lactamases (MBLs)-producers and 2 colistin antibiotic resistance enzyme MCR-1-producers.</p><p><strong>Methods: </strong>Using the broth microdilution method, MICs of MEF in combination with multiple antimicrobial agents, including colistin (COL), imipenem, aztreonam-avibactam (ATM-AVI), ceftazidime-avibactam (CAZ-AVI) for 96 CRE isolates were determined. Time-kill assays were implemented for 3 colistin-resistant (COL-R) isolates to analyze in vitro synergistic impacts of COL combined with MEF.</p><p><strong>Results: </strong>MEF alone showed little antibacterial activity with MICs greater than 128 µg/mL for all the 96 clinical CRE isolates. The addition of MEF (32 µg/mL) increased the sensitivity of almost all strains (98.9%, 95/96) to COL, reducing the MICs range of COL from ≤ 0.0625->8 µg/mL to ≤ 0.004-0.5 µg/mL. In particular, we observed that COL-MEF combination therapy had a significant effect on COL-R isolates, reducing their MICs from resistance to susceptibility. Moreover, the MIC₅₀ and MIC₉₀ of imipenem were both reduced by 2-fold in almost all strains with the addition of MEF (32 µg/mL), and in single MBL-producers, the MIC₅₀ (from 16 to 4 µg/mL) and MIC₉₀ (from 128 to 32 µg/mL) were both reduced by 4-fold. In addition, the MIC₅₀ and MIC₉₀ values of 96 CRE isolates of CAZ-AVI and ATM-AVI did not decrease significantly after combined with MEF (32 µg/mL). For the time-kill assays of 3 COL-R isolates, COL or MEF alone had almost no killing effect, however, when MEF was combined with COL, the isolates were completely killed within 4 h, and NDM-5-producing Klebsiella pneumoniae did not regenerate within 24 h.</p><p><strong>Conclusions: </strong>According to our study, COL-MEF may offer a potential alternative for treating CRE infections, especially COL-R Gram-negative bacterial infections.</p>","PeriodicalId":11782,"journal":{"name":"European Journal of Clinical Microbiology & Infectious Diseases","volume":" ","pages":"1089-1097"},"PeriodicalIF":3.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143439637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}