Pathogens最新文献

{"title":"For Better or Worse: Type I Interferon Responses in Bacterial Infection.","authors":"Aihong Xia, Xin Li, Changjing Zhao, Xiaojing Meng, Gulmela Kari, Yongjuan Wang","doi":"10.3390/pathogens14030229","DOIUrl":"10.3390/pathogens14030229","url":null,"abstract":"<p><p>Type I interferons (IFNs) are pleiotropic cytokines, primarily comprising IFN-α and IFN-β, and their effect in host defense against viral infection has been extensively studied and well-established. However, in bacterial infection, the role of type I IFNs is more complex, exhibiting multifaceted effects that depend on several factors, such as the pathogen species, the specific cell populations, and the routes of infection. In this review, we summarize research progress on host type I interferon responses triggered by specific bacteria and their immune regulation function in order to better understand the role of type I IFNs in bacterial infection and provide insights for adjuvant therapies tailored to treat specific bacterial infections.</p>","PeriodicalId":19758,"journal":{"name":"Pathogens","volume":"14 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11945191/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731039","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":"Case Report: Shift from Aggressive Periodontitis to Feline Chronic Gingivostomatitis Is Linked to Increased Microbial Diversity.","authors":"Claire A Shaw, Maria Soltero-Rivera, Rodrigo Profeta, Bart C Weimer","doi":"10.3390/pathogens14030228","DOIUrl":"10.3390/pathogens14030228","url":null,"abstract":"<p><p>Aggressive Periodontitis (AP) and Feline Chronic Gingivostomatitis (FCGS) are two oral inflammatory diseases in cats with unknown etiology. Both conditions present with severe inflammation of the oral cavity and in FCGS it is found with additional deterioration of the non-keratinized mucosa. The oral microbiome is increasingly implicated in disease progression, but little is known about shifts in the microbial community during the AP and FCGS progression. To that end, we used deep metagenomic sequencing with total RNA on three longitudinal samples of the oral microbiome in a cat first diagnosed with AP that progressed to FCGS. This deep sequencing approach revealed that increased diversity at both the genus and species levels marked the shift from AP to FCGS, including increases in <i>Porphyromonas</i> and <i>Treponema</i> species, and decreased <i>Streptobacillus</i> species. The metatranscriptomes were then probed for expression of antimicrobial resistance genes and virulence factors. Disease-related genes that include <i>cheY</i>, and <i>ompP5</i> were expressed in early AP and FCGS, while others like <i>galU</i> were only expressed in one or the other disease state. Both genus and species-level shifts were observed along the longitudinal microbiome samples with a noted increase in species diversity in the FCGS-associated microbiome. Corroborating that functional shifts accompany taxonomic changes, the AMR and virulence factor expression similarly changed between the sampling points. Together, these taxonomic and functional shifts indicate that AP and FCGS are potentially linked and may be marked by changes in the oral microbiome, which supports the development of microbial-based clinical diagnostics and therapeutics.</p>","PeriodicalId":19758,"journal":{"name":"Pathogens","volume":"14 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944619/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731048","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":"Characterization of the Antibiotic and Copper Resistance of Emergent Species of Onion-Pathogenic <i>Burkholderia</i> Through Genome Sequence Analysis and High-Throughput Sequencing of Differentially Enriched Random Transposon Mutants.","authors":"Jonas J Padilla, Marco A S da Gama, Inderjit Barphagha, Jong Hyun Ham","doi":"10.3390/pathogens14030226","DOIUrl":"10.3390/pathogens14030226","url":null,"abstract":"<p><p>The prevalence of antimicrobial resistance (AMR) in bacterial pathogens resulting from the intensive usage of antibiotics and antibiotic compounds is acknowledged as a significant global concern that impacts both human and animal health. In this study, we sequenced and analyzed the genomes of two emergent onion-pathogenic species of <i>Burkholderia</i>, <i>B</i>. <i>cenocepacia</i> CCRMBC56 and <i>B</i>. <i>orbicola</i> CCRMBC23, focusing on genes that are potentially associated with their high level of antibiotic and copper resistance. We also identified genes contributing to the copper resistance of <i>B</i>. <i>cenocepacia</i> CCRMBC56 through high-throughput analysis of mutated genes in random transposon mutant populations that were differentially enriched in a copper-containing medium. The results indicated that genes involved in DNA integration, recombination, and cation transport are important for the survival of <i>B. cenocepacia</i> CCRMBC56 in copper-stressed conditions. Furthermore, the fitness effect analysis identified additional genes crucial for copper resistance, which are involved in functions associated with the oxidative stress response, the ABC transporter complex, and the cell outer membrane. In the same analysis, genes related to penicillin binding, the TCA cycle, and FAD binding were found to hinder bacterial adaptation to copper toxicity. This study provides potential targets for reducing the copper resistance of <i>B. cenocepacia</i> and other copper-resistant bacterial pathogens.</p>","PeriodicalId":19758,"journal":{"name":"Pathogens","volume":"14 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11946587/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731054","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":"One Health: Action in Brazilian Cases of Sporotrichosis in Humans and Cats.","authors":"Geovana Thaís Motta, Aline Fernanda Dos Santos, Paulo Henrique Campos, Flavio Luiz de Oliveira, Margarete Schinemann, Nariany Pollyane da Silva, Pricila Regina Sikora Bruger, Kauane Oliveira Campos, Luciana Dalazen Dos Santos, Carla Fredrichsen Moya, Meire Christina Seki, Adriano de Oliveira Torres Carrasco","doi":"10.3390/pathogens14030225","DOIUrl":"10.3390/pathogens14030225","url":null,"abstract":"<p><p>This study aims to report the number of animal cases identified in the central-south region of Paraná. It also seeks to correlate these findings with human diagnoses, thereby underscoring the importance of the One Health approach in implementing prophylactic measures and protocols for evaluating both positive and suspected cases. In August 2023, a cat diagnosed with sporotrichosis was presented at the UNICENTRO Veterinary School Clinic. Accompanying the cat was its guardian, who exhibited characteristic lesions of the disease. An epidemiological study was then initiated and spanned from August 2023 to March 2024. Cytological tests were performed on the suspected cases. From the epidemiological survey, 21 animals were tested. A total of 15 cats were confirmed to have sporotrichosis; all were unneutered males of the moggy breed with access to outdoor environments. Some pet owners also displayed symptoms and lesions consistent with sporotrichosis. Considering the recent surge in sporotrichosis cases in Brazil, along with its zoonotic potential and significance for public health-and considering its status as a notifiable disease-epidemiological studies such as this one are vital. They help in understanding the spread of the disease and are crucial for the development and implementation of prophylactic measures to protect human and animal health.</p>","PeriodicalId":19758,"journal":{"name":"Pathogens","volume":"14 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11946085/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731116","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":"Integrated One Health Surveillance of West Nile Virus and Usutu Virus in the Veneto Region, Northeastern Italy, from 2022 to 2023.","authors":"Federica Gobbo, Giulia Chiarello, Sofia Sgubin, Federica Toniolo, Francesco Gradoni, Lidia Iustina Danca, Sara Carlin, Katia Capello, Giacomo De Conti, Alessio Bortolami, Maria Varotto, Laura Favero, Michele Brichese, Francesca Russo, Franco Mutinelli, Stefania Vogiatzis, Monia Pacenti, Luisa Barzon, Fabrizio Montarsi","doi":"10.3390/pathogens14030227","DOIUrl":"10.3390/pathogens14030227","url":null,"abstract":"<p><p>West Nile virus (WNV) and Usutu virus (USUV) are neurotropic mosquito-borne orthoflaviviruses maintained in an enzootic cycle, in which birds are amplifying/reservoir hosts, while humans and equids are dead-end hosts. As northern Italy, especially the Veneto Region, is considered an endemic area for WNV and USUV circulation, a surveillance plan based on a One Health approach has been implemented since 2008. This work reports the results of entomological, veterinary and human surveillances for WNV and USUV in the Veneto Region in 2022 and 2023, through virological and/or serological examinations. In 2022, 531 human WNV infections were recorded, and 93,213 mosquitoes and 2193 birds were virologically tested, showing infection rates (IRs) of 4.85% and 8.30%, respectively. The surveillance effort in 2023 provided these results: 56 human WNV infections were confirmed, and 133,648 mosquitoes and 1812 birds were virologically tested, showing IRs of 1.78% and 4.69%, respectively. This work highlights the exceptional circulation of WNV in the Veneto Region, due to the new re-introduction of WNV lineage 1 and co-circulation with WNV lineage 2. This paper confirms the efficacy of integrated surveillance for early warning of viral circulation and gives new insights about avian hosts involved in the enzootic cycle of orthoflavivirus in the endemic region of Italy.</p>","PeriodicalId":19758,"journal":{"name":"Pathogens","volume":"14 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11945005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731076","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":"Characterization of Early Lesions of Human Post-Primary Tuberculosis and Its Progression to Necrosis Using Archival Material of the Pre-Antibiotic Era.","authors":"Syeda Mariam Riaz, Kurt Hanevik, Lisbet Sviland, Tehmina Mustafa","doi":"10.3390/pathogens14030224","DOIUrl":"10.3390/pathogens14030224","url":null,"abstract":"<p><p>Primary and post-primary TB are distinct entities. Primary TB occurs when the patient is infected with Mycobacterium tuberculosis (MTB) for the first time without prior immunity, and post-primary TB occurs when the patient has developed immunity against the primary infection. Post-primary TB occurs only in humans. It accounts for 80% of all clinical cases and nearly 100% of transmissions of infection. Early lesions of post-primary TB are reversible, and studying it using modern immunological tools holds the key to developing preventive or treatment strategies. Human lung tissue from untreated TB patients was acquired from pathology archives stored at the Gades Institute of Pathology, Haukeland University Hospital, Bergen, Norway, from 1931 to 1947. Manual immunohistochemistry was performed for macrophage (CD68, CD64 and CD163), T cells (CD3 and CD8), matrix metalloproteinases (MMP-9), and markers for programmed death-pathway PD/PDL-1. Digital quantification was performed using Qupath software. In early lesions of post-primary TB, macrophages showed mixed-phenotype M1 and M2, expressed PDL-1, and were compartmentalized in the alveolar space. T-cells expressed PD-1 and were compartmentalized in the interstitial wall surrounding early lesions. MTB antigens and MMP-9 were also found in early lesions. As the lesion progressed towards necrosis, macrophages showed predominant M1 morphology, and expressions of PDL-1, PD-1, CD8⁺ cells, and MTB antigens increased. In the early lesions of post-primary TB, the compartmentalization of macrophages in the alveoli and T cells in the interstitium was shown. The PDL-PD1 pathway probably facilitated the mycobacterial growth by evading host immunity.</p>","PeriodicalId":19758,"journal":{"name":"Pathogens","volume":"14 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731049","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":"Unraveling the Dynamics of Human Filarial Infections: Immunological Responses, Host Manifestations, and Pathogen Biology.","authors":"Anuradha Rajamanickam, Subash Babu","doi":"10.3390/pathogens14030223","DOIUrl":"10.3390/pathogens14030223","url":null,"abstract":"<p><p>Lymphatic filariasis (LF), or elephantiasis, is a neglected tropical disease caused by filarial worms, primarily <i>Wuchereria bancrofti</i>, transmitted through mosquito bites. It often begins in childhood but may not show symptoms until later, leaving many individuals asymptomatic for long periods. LF disrupts the lymphatic system, causing severe swelling in the limbs and genitals, leading to deformities and disabilities. The World Health Organization estimates that around 51 million people are affected globally, with 36 million suffering from chronic conditions like lymphedema and hydrocele. In 2021, approximately 882.5 million people in 44 countries required preventive chemotherapy, making LF the second leading parasitic cause of disability, significantly impacting socioeconomic status. The immune response to filarial parasites is complex, involving both innate and adaptive immune cells. A key feature of LF immunology is the antigen-specific Th2 response, expansion of IL-10-producing CD4⁺ T cells, and a muted Th1 response. This T cell hypo-responsiveness is crucial for sustaining long-term infections with high parasite densities. While the correlates of protective immunity are not fully understood-due in part to a lack of suitable animal models-T cells, particularly CD4⁺ Th2 cells, and B cells, play essential roles in immune protection. Moreover, host immune responses contribute to the disease's pathological manifestations. A failure to induce T cell hypo-responsiveness can lead to exaggerated inflammatory conditions such as lymphedema, hydrocele, and elephantiasis. Filarial infections also induce bystander effects on various immune responses, impacting responses to other infectious agents. This intricate immune interplay offers valuable insights into the regulation of immune responses to chronic infections. This review explores recent immunological research on lymphatic filarial worms, highlighting their effects on both innate and adaptive immune responses in humans and the mechanisms underlying this neglected tropical disease.</p>","PeriodicalId":19758,"journal":{"name":"Pathogens","volume":"14 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11945129/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730920","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":"Prevalence and Antimicrobial Susceptibility of <i>Salmonella</i> in Retail Meat Collected from Different Markets in Sichuan, China.","authors":"Hang Zeng, Donghai Yang, Nanxi Huang, Yonglin Li, Jiazhen Chen, Zhongjia Yu, Jie Tang, Zhenju Jiang","doi":"10.3390/pathogens14030222","DOIUrl":"10.3390/pathogens14030222","url":null,"abstract":"<p><p><i>Salmonella</i> is one of the most significant zoonotic and foodborne pathogens, and it is the leading cause of bacterial diarrhea. In this study, 156 retail meat samples were collected from three supermarkets and one local wet market in Sichuan, China, including 96 chicken samples and 60 pork samples. The prevalence of <i>Salmonella</i> in these samples was analyzed, and 91 samples (58.33%) tested positive, with 60 (62.5%) positive chicken samples and 31 (51.67%) positive pork samples. From these positive samples, 190 <i>Salmonella</i> isolates were confirmed by double PCR. Subsequent serotyping identified nine serovars, with the predominant ones being <i>S.</i> London (58.94%), <i>S.</i> Typhimurium (12.58%), and <i>S.</i> Enteritidis (10.60%). Antibiotic susceptibility test revealed that 168 isolates (88.42%) were resistant to at least one antibiotic, and 150 isolates (78.95%) were resistant to three or more antibiotics. The highest resistance rates were observed for ampicillin (83.16%), followed by tetracycline (76.31%) and trimethoprim/sulfamethoxazole (67.37%). In the disinfectant susceptibility test, <i>Salmonella</i> isolates exhibited higher resistance rates to benzalkonium bromide (100%) and benzalkonium chloride (97.37%), while showing a lower resistance rate to potassium monopersulfate triple salt (33.6%). These findings highlight the high prevalence of <i>Salmonella</i> and its significant resistance to antibiotics and disinfectants, indicating that effective measures must be implemented to ensure the microbiological safety of retail meat.</p>","PeriodicalId":19758,"journal":{"name":"Pathogens","volume":"14 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731124","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":"Comparative In Vitro Drug Susceptibility Study of Five Oxazolidinones Against <i>Mycobacterium tuberculosis</i> in Hainan, China.","authors":"Jinhui Dong, Qian Cheng, Chuanning Tang, Yeteng Zhong, Jieying Wang, Meiping Lv, Zhuolin Chen, Peibo Li, Ming Luo, Hua Pei","doi":"10.3390/pathogens14030218","DOIUrl":"10.3390/pathogens14030218","url":null,"abstract":"<p><p>Oxazolidinones, novel synthetic antibacterials, inhibit protein biosynthesis and show potent activity against Gram-positive bacteria, including <i>Mycobacterium tuberculosis</i> (MTB). In this study, we aimed to compare the in vitro activity of linezolid (LZD) and four oxazolidinones, including tedizolid (TZD), contezolid (CZD), sutezolid (SZD), and delpazolid (DZD), against multidrug-resistant tuberculosis (MDR-TB) and pre-extensively drug-resistant tuberculosis (pre-XDR-TB) isolates from Hainan. We established their epidemiological cut-off values (ECOFFs) using ECOFFinder software and analyzed mutations in <i>rrl</i> (23S rRNA), <i>rplC</i>, <i>rplD</i>, <i>mce3R</i>, <i>tsnR</i>, <i>Rv0545c</i>, <i>Rv0930</i>, <i>Rv3331</i>, and <i>Rv0890c</i> genes to uncover potential mechanisms of oxazolidinone resistance. This study included 177 MTB isolates, comprising 67 MDR and 110 pre-XDR-TB isolates. Overall, SZD exhibited the strongest antibacterial activity against clinical MTB isolates, followed by TZD and LZD, with CZD and DZD showing equivalent but weaker activity (SZD_MIC50 = TZD_MIC50 < LZD_MIC50 < CZD_MIC50 = DZD_MIC50; SZD_MIC90 < TZD_MIC90 = LZD_MIC90 < CZD_MIC90 = DZD_MIC90). Significant differences in MIC distribution were observed for TZD (<i>p</i> < 0.0001), CZD (<i>p</i> < 0.01), SZD (<i>p</i> < 0.0001), and DZD (<i>p</i> < 0.0001) compared to LZD but not between MDR-TB and pre-XDR-TB isolates. We propose the following ECOFFs: SZD, 0.5 µg/mL; LZD, TZD, and CZD, 1.0 µg/mL; DZD, 2.0 µg/mL. No statistically significant differences in resistance rates were observed among these five drugs (<i>p</i> > 0.05). We found that eight MTB isolates (4.52% [8/177]) resisted these five oxazolidinones. Among these, only one isolate, M26, showed an amino acid substitution (Arg79His) in the protein encoded by the <i>rplD</i> gene, which conferred cross-resistance to TZD and CZD. Three distinct mutations were identified in the <i>mce3R</i> gene; notably, isolate P604 displayed two insertions that contributed to resistance against all five oxazolidinones. However, no significant correlation was observed between mutations in the <i>rrl</i>, <i>rplC</i>, <i>rplD</i>, <i>mce3R</i>, <i>tsnR</i>, <i>Rv0545c</i>, <i>Rv0930</i>, <i>Rv3331</i>, and <i>Rv0890c</i> genes with oxazolidinone resistance in the clinical MTB isolates tested. In summary, this study provides the first report on the resistance of MTB in Hainan to the five oxazolidinones (LZD, TZD, CZD, SZD, and DZD). In vitro susceptibility testing indicated that SZD exhibited the strongest antibacterial activity, followed by TZD and LZD, while CZD and DZD demonstrated comparable but weaker effectiveness. Mutations in <i>rplD</i> and <i>mce3R</i> were discovered, but further research is needed to clarify their role in conferring oxazolidinone resistance in MTB.</p>","PeriodicalId":19758,"journal":{"name":"Pathogens","volume":"14 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11945096/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731068","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":"Are New β-Lactam/β-Lactamase Inhibitor Combinations Promising Against Carbapenem-Resistant <i>K. pneumoniae</i> Isolates?","authors":"Ayşe Nur Ceylan, Selda Kömeç, Kamuran Şanlı, Beyza Öncel, Mehmet Akif Durmuş, Abdurrahman Gülmez","doi":"10.3390/pathogens14030220","DOIUrl":"10.3390/pathogens14030220","url":null,"abstract":"<p><strong>Background/objectives: </strong>Carbapenem-resistant <i>Klebsiella pneumoniae</i> (CRKP) infections present a significant clinical challenge due to limited therapeutic options and high transmission potential. This study aimed to identify the resistance genes associated with carbapenemase production in CRKP isolates and evaluate the in vitro activity of ceftazidime/avibactam (CZA) and meropenem/vaborbactam (MEV), among other β-lactam/β-lactamase inhibitor combinations.</p><p><strong>Methods: </strong>Between October 2021 and June 2022, a total of 504 CRKP isolates were grown from patient samples in intensive care units. When duplicate patient samples were removed, the remaining 89 isolates were included in the study. Bacterial identification and antimicrobial susceptibility testing were per-formed using MALDI-TOF, Phoenix M50, and disk diffusion methods, following EUCAST guidelines. PCR analyses identified carbapenemase genes such as OXA-48, NDM, and KPC.</p><p><strong>Results: </strong>The most prevalent carbapenemase gene was OXA-48 (79.8%), followed by NDM (21.4%) and KPC (17.9%). The susceptibility rate to CZA was 82.0%, significantly higher than MEV (10.1%). All isolates were resistant to piperacillin/tazobactam and ceftolozane/tazobactam. Among MEV-resistant isolates, most carried the OXA-48 gene, while NDM was common in CZA-resistant isolates.</p><p><strong>Conclusions: </strong>CZA demonstrates high efficacy against OXA-48-producing CRKP, making it a viable treatment option in settings where OXA-48 predominates. The limited activity of MEV in this study underscores the need for molecular surveillance of resistance mechanisms to guide empirical therapy.</p>","PeriodicalId":19758,"journal":{"name":"Pathogens","volume":"14 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944681/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731042","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}