Chemotherapy最新文献

{"title":"Cryoablation Combined with Programmed Cell Death Protein 1 Inhibitor Pembrolizumab for Advanced Non-small Cell Lung Cancer.","authors":"Li Wang, Kai Yang, Xinxin Xie, Hailiang Wei, Pengli Wang, Shaohui Wang","doi":"10.1159/000545185","DOIUrl":"https://doi.org/10.1159/000545185","url":null,"abstract":"<p><strong>Introduction: </strong>To evaluate the efficacy and safety of cryoablation combined with pembrolizumab treatment versus cryoablation alone in patients with advanced non-small cell lung cancer (NSCLC).</p><p><strong>Methods: </strong>This retrospective study was conducted from February 2018 and October 2021. A total of 90 patients with NSCLC (AJCC stage IIIB/IV) were included, with 36 patients receiving cryoablation combined with pembrolizumab (Group A) and 54 patients receiving cryoablation alone (Group B). The primary outcome measures included objective response rate (ORR), overall survival (OS), and progression-free survival (PFS), immune responses and adverse events serving as secondary endpoints. Risk factors for OS and PFS were identified using univariate and multivariate analyses.</p><p><strong>Results: </strong>No treatment related deaths were observed. Group A demonstrated a higher ORR (75.0% vs. 61.1%), longer median OS (28.1 months vs. 24.2 months), and longer median PFS (12.8 months vs. 8.4 months) compared to Group B. Additionally, Group A showed significant increases in CD3+, CD4+, and CD8+ T cells, and elevated levels of IL-2, IL-6, TNF-β, and IFN-γ. The multivariate analysis showed the combination of cryoablation and pembrolizumab was an independent prognostic factor for OS and PFS.</p><p><strong>Conclusions: </strong>Cryoablation combined with pembrolizumab significantly improves clinical outcomes in advanced NSCLC patients compared to cryoablation alone, highlighting the potential of this combination therapy in enhancing anti-tumor immunity and prolonging survival.</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":" ","pages":"1-24"},"PeriodicalIF":2.0,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Impacts of Active and Inactive Ghrelin on Cachexia and Immune Checkpoint Inhibitor Monotherapy in Patients with Non-Small Cell Lung Cancer.","authors":"Daiki Murata, Koichi Azuma, Yuuya Nishii, Kenta Murotani, Goushi Matama, Akihiko Kawahara, Takaaki Tokito, Tetsuro Sasada, Tomoaki Hoshino","doi":"10.1159/000543425","DOIUrl":"10.1159/000543425","url":null,"abstract":"<p><strong>Introduction: </strong>Identifying the underlying mechanisms of immune checkpoint inhibitor resistance in patients with cachexia is a current challenge. Ghrelin is a peptide hormone that plays an important role in the metabolism of patients with cancer cachexia. Despite the importance of ghrelin in cancer cachexia, most previous studies on the subject have not distinguished between the forms of ghrelin.</p><p><strong>Methods: </strong>We retrospectively screened patients with advanced or recurrent non-small cell lung cancer receiving PD-1/PD-L1 inhibitor monotherapy. Active and inactive ghrelin levels were measured in 100 patients with available plasma samples at immune checkpoint inhibitor initiation. Cancer cachexia was defined as weight loss of at least 5% during the past 6 months or weight loss of at least 2% with a BMI <20. We analyzed the associations of the active and inactive ghrelin levels and active-to-inactive ghrelin ratio (AIR) with cancer cachexia. The prognostic impact of the active and inactive ghrelin levels and AIR were also analyzed.</p><p><strong>Results: </strong>Among 100 patients, 35 were diagnosed with cancer cachexia. The active ghrelin level and AIR were significantly associated with cancer cachexia, whereas the inactive ghrelin level was not. The active and inactive ghrelin levels and AIR were not associated with patient prognosis.</p><p><strong>Conclusion: </strong>The active ghrelin level and AIR were associated with cancer cachexia but not with patient prognosis. The function of the active and inactive forms of ghrelin may differ in cancer patients. The form of ghrelin should be clearly mentioned in relevant studies on cancer cachexia.</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":" ","pages":"1-7"},"PeriodicalIF":2.0,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gaza's First Polio Case in 25 Years: Is Health Infrastructure Collapse Threatening Resilience?","authors":"Francesco Branda, Giancarlo Ceccarelli, Marta Giovanetti, Massimo Ciccozzi, Fabio Scarpa","doi":"10.1159/000541933","DOIUrl":"10.1159/000541933","url":null,"abstract":"","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":" ","pages":"9-11"},"PeriodicalIF":2.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Downregulation of Rad51 Expression and Activity Potentiates the Cytotoxic Effect of Osimertinib in Human Non-Small Cell Lung Cancer Cells.","authors":"Jen-Chung Ko, Jyh-Cheng Chen, Ching-Hsiu Huang, Pei-Jung Chen, Qiao-Zhen Chang, Bo-Cheng Mu, Jun-Jie Chen, Tzu-Yuan Tai, Kasumi Suzuki, Yi-Xuan Wang, Yun-Wei Lin","doi":"10.1159/000540867","DOIUrl":"10.1159/000540867","url":null,"abstract":"<p><strong>Introduction: </strong>Osimertinib (AZD9291) is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that has shown significant clinical benefits in patients with EGFR-sensitizing mutations or the EGFR T790M mutation. The homologous recombination (HR) pathway is crucial for repairing DNA double-strand breaks (DSBs). Rad51 plays a central role in HR, facilitating the search for homology and promoting DNA strand exchange between homologous DNA molecules. Rad51 is overexpressed in numerous types of cancer cells. B02, a specific small molecule inhibitor of Rad51, inhibits the DNA strand exchange activity of Rad51. Previous studies have indicated that B02 disrupted Rad51 foci formation in response to DNA damage and inhibited DSBs repair in human cells and sensitized them to chemotherapeutic drugs in vitro and in vivo. However, the potential therapeutic effects of combining osimertinib with a Rad51 inhibitor are not well understood. The aim of this study was to elucidate whether the downregulation of Rad51 expression and activity can enhance the osimertinib-induced cytotoxicity in non-small cell lung cancer (NSCLC) cells.</p><p><strong>Methods: </strong>We used the MTS, trypan blue dye exclusion and colony-formation ability assay to determine whether osimertinib alone or in combination with B02 had cytotoxic effects on NSCLC cell lines. Real-time polymerase chain reaction was conducted to measure the amounts of Rad51 mRNA. The protein levels of phosphorylated AKT and Rad51 were determined by Western blot analysis.</p><p><strong>Results: </strong>We found that osimertinib reduced Rad51 expression by inactivating AKT activity. Rad51 knockdown using small interfering RNA or AKT inactivation through the phosphatidylinositol 3-kinase inhibitor LY294002 or si-AKT RNA transfection enhanced the cytotoxic and growth inhibitory effects of osimertinib. In contrast, AKT-CA (a constitutively active form of AKT) vector-enforced expression could mitigate the cytotoxic and cell growth inhibitory effects of osimertinib. Furthermore, B02 significantly enhanced the cytotoxic and cell growth inhibitory effects of osimertinib in NSCLC cells. Compared to parental cells, the activation of AKT and Rad51 expression in osimertinib-resistant cells could not be significantly inhibited by osimertinib treatment. Moreover, the increased expression of Rad51 is associated with the resistance mechanism in osimertinib-resistant H1975 and A549 cells.</p><p><strong>Conclusion: </strong>Collectively, the downregulation of Rad51 expression and activity enhances the cytotoxic effect of osimertinib in human NSCLC cells.</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":" ","pages":"12-25"},"PeriodicalIF":2.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic Drug Monitoring of Imatinib: Is There a Rationale for Also Quantifying Its Active Metabolite?","authors":"Clara Eschalier, Thierry Lafont, Sabrina Marsili, Malika Yakoubi, Aurélie Brice, Fabienne Thomas, Mélanie White-Koning, Ben Allal, Etienne Chatelut","doi":"10.1159/000541936","DOIUrl":"10.1159/000541936","url":null,"abstract":"<p><strong>Introduction: </strong>Therapeutic drug monitoring of imatinib is widely performed to individualize imatinib dosage. While N-desmethyl imatinib is an active metabolite of imatinib, its concentrations are not routinely determined.</p><p><strong>Methods: </strong>Imatinib and N-desmethyl imatinib trough plasma concentrations at steady-state were obtained from 295 patients with either chronic myeloid leukemia or gastrointestinal stromal tumor to see whether N-desmethyl imatinib provided additional information. Pharmacokinetic data were analyzed using a nonlinear mixed effect approach. Correlations between several pharmacokinetic metrics of drug exposure were evaluated.</p><p><strong>Results: </strong>The mean value of the N-desmethyl imatinib/imatinib ratio of trough concentrations was 0.31 with half of the values between 0.23 and 0.37. N-desmethyl imatinib and total (i.e., N-desmethyl imatinib plus imatinib) trough plasma concentrations or area under the curve values were closely correlated with imatinib values. The distribution of imatinib or total concentrations between patients requiring imatinib dosage adjustment, or not, was similar.</p><p><strong>Conclusion: </strong>These results do not clearly support routine N-desmethyl monitoring since it does not provide additional information to imatinib data.</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":" ","pages":"26-36"},"PeriodicalIF":2.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disseminated Infection Caused by Nocardia cyriacigeorgica in Immunocompromised Patient Confirmed by Whole Genome Sequencing.","authors":"Dijana Varda Brkić, Jakša Babel, Ana Budimir, Iva Butić, Marija Gužvinec, Dragan Jurić, Ivana Ferenčak, Selma Bošnjak, Ivana Mareković","doi":"10.1159/000539977","DOIUrl":"10.1159/000539977","url":null,"abstract":"<p><strong>Introduction: </strong>Nocardia spp. is an opportunistic pathogen capable of causing localized and disseminated infections in immunocompromised hosts. It is critical for serious infections to have an early and accurate identification of this pathogen in order to enable timely and focused combination antimicrobial treatment.</p><p><strong>Case presentation: </strong>We describe the case of an 87-year-old patient previously treated for myasthenia gravis with corticosteroids and azathioprine. Patient was admitted at the emergency department with clinical signs of sepsis with cellulitis of right hand associated with injury acquired after gardening and trimming roses and did not respond to empirical antimicrobial treatment. Computerized tomography revealed pulmonary infiltrates with inflammatory etiology. Nocardia cyriacigeorgica was cultivated from blood culture, skin swab, abscess aspirate, and endotracheal aspirate and identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), 16S rRNA sequencing, and whole genome sequencing (WGS). Susceptibility testing was performed with E-test (bioMerieux, Marcy-l'Étoile, France), and corresponding resistance genes were detected by WGS. Resistance to amoxicillin-clavulanate, azithromycin, ciprofloxacin, and vancomycin was detected by both methods. Despite all interventions and the patient receiving antimicrobial treatment including imipenem-cilastatin, amikacin, and trimethoprim-sulfamethoxazole, the course and outcome of infection were unfavorable.</p><p><strong>Conclusion: </strong>We would like to emphasize the need to consider the possibility of disseminated Nocardia infection in immunocompromised patients, especially in patients receiving long-term corticosteroid treatment with skin infections and/or cavitary lung lesions, especially if these do not improve with standard antimicrobial treatment. Precise species identity provides a critical guide for physicians in the choice of targeted treatment. Thanks to MALDI-TOF MS, Nocardia spp. identification is now available in routine lab work. WGS is still inevitable for the identification of uncommon and novel species due to the high sequence similarities between closely related species and the genetic diversity of that genus.</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":" ","pages":"1-8"},"PeriodicalIF":2.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Meta-Analysis of the Efficacy and Safety of Pembrolizumab in the Treatment of Advanced Gastric Cancer and Gastroesophageal Junction Cancer.","authors":"Jingyun Yang, Weisheng Luo, Xiaocong Ma, Yinhang Cui, Jiacheng Xie, Chengzhen Pan, Ziyao Chen, Shuang Yang","doi":"10.1159/000540071","DOIUrl":"10.1159/000540071","url":null,"abstract":"<p><strong>Introduction: </strong>Pembrolizumab has been approved for the first-line treatment of patients with advanced gastric cancer (GC) and gastroesophageal junction (GEJ) cancer. However, the results of several clinical trials are not entirely consistent, and the dominant population of first-line immunotherapy for advanced GC/GEJ still needs to be precisely determined.</p><p><strong>Purpose: </strong>The aim of this meta-analysis was to assess the efficacy and safety of pembrolizumab in the treatment of advanced GC/GEJ.</p><p><strong>Methods: </strong>We conducted computerized searches across multiple databases, including PubMed, Cochrane Library, Web of Science, and Embase. We established the inclusion criteria to comprise randomized clinical trials examining the efficacy of pembrolizumab in late-stage GC/GCJ cancer. We conducted a meta-analysis of outcome measures using STATA 14.0 software.</p><p><strong>Results: </strong>A total of six studies involving 1,448 cases were included in this analysis. The results of the meta-analysis indicate that, when compared to chemotherapy, patients in the pembrolizumab group experienced a significant reduction in the risk of mortality in terms of overall survival (OS) (hazard ratio [HR] = 0.72, 95% confidence interval [CI]: 0.65-0.79, p < 0.01). In terms of progression-free survival (PFS), pembrolizumab was associated with a similar PFS as compared to chemotherapy (HR = 0.88, 95% CI: 0.73-1.07, p = 0.206). Subgroup analyses based on PD-L1 expression levels indicated a significantly longer PFS with pembrolizumab in subgroups of patients with PD-L1 CPS ≥10 but not in those with PD-L1 CPS ≥1 and PD-L1 CPS ≥5. Subgroup analyses based on distinct geographical regions revealed a comparable effect of PFS in patients residing in Asia or the USA Subgroup analysis based on tumor sites consistently demonstrated a similar effect of PFS in patients with EC/GEJ tumors and GC patients.</p><p><strong>Conclusion: </strong>Our findings demonstrated that pembrolizumab led to a significant extension in OS and objective response rate, along with a favorable tolerability profile compared to chemotherapy. Furthermore, the observed survival benefits were particularly pronounced in subgroup patients with a CPS of ≥10. Given the potential limitations inherent in our study, it is imperative to underscore the necessity for further large-scale RCTs to corroborate our results.</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":" ","pages":"37-52"},"PeriodicalIF":2.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and Efficacy of Dose-Dense Methotrexate, Vinblastine, Doxorubicin, and Cisplatin with Pegfilgrastim in Japanese Patients with Advanced or Metastatic Urothelial Carcinoma.","authors":"Takahiro Harano, Masaomi Ikeda, Shuhei Hirano, Soichiro Shimura, Masayoshi Toyoda, Satoshi Okuda, Dai Koguchi, Hideyasu Tsumura, Daisuke Ishii, Kazumasa Matsumoto","doi":"10.1159/000543333","DOIUrl":"10.1159/000543333","url":null,"abstract":"<p><strong>Introduction: </strong>Dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC) therapy is indicated as first-line or neoadjuvant chemotherapy (NAC) for patients with advanced or metastatic urothelial carcinoma (UC). However, no studies reported ddMVAC therapy with pegfilgrastim (3.6 mg) in Japanese patients. We investigated the safety and efficacy of ddMVAC therapy with pegfilgrastim in patients with advanced or metastatic UC.</p><p><strong>Methods: </strong>A total of 43 patients received ddMVAC therapy with pegfilgrastim (3.6 mg) from February 2021 to December 2023. Among them, 25 and 18 patients received this regimen as first-line chemotherapy and NAC, respectively. We assessed toxicity and efficacy using Common Terminology Criteria for Adverse Events version 4.0 and Response Evaluation Criteria in Solid Tumors version 1.1, respectively.</p><p><strong>Results: </strong>The median number of ddMVAC therapy cycles was 3 (range: 1-5), with a total of 131 cycles. Cisplatin at the full dose without reduction was administered to 24 (56%) patients. Grade ≥3 hematologic toxicity occurred in 15 (35%) patients. Among them, anemia, neutropenia, thrombocytopenia, and febrile neutropenia were 13.9%, 9.3%, 11.7%, and 7.0%, respectively. Regarding non-hematologic toxicity, grade 3 appetite loss was observed in 2 (5%) patients. Complete response was observed in 7 (16%) patients and partial response in 26 patients (60%), yielding an objective response rate of 76%. Pathologic complete response (pCR; ypT0pN0) was observed in 3 (16.7%) patients and downstaging occurred in 13 (72.2%) patients. The median progression-free survival and overall survival of first-line treatment with ddMVAC were 18.6 months and not reached, respectively.</p><p><strong>Conclusion: </strong>The ddMVAC with pegfilgrastim (3.6 mg) reduced injection-related patient burden, caused fewer grade ≥3 adverse events, and demonstrated similar efficacy when compared to the original ddMVAC regimen that used granulocyte colony-stimulating factor for 7 consecutive days.</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":" ","pages":"1-7"},"PeriodicalIF":2.0,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic Drug Monitoring, Population Pharmacokinetics Models, and External Validation of High-Dose Methotrexate in Pediatric Acute Lymphoblastic Leukemia.","authors":"Natalia Maximova, Pasquale Fabio Calabrò, Alice Cangialosi, Antonello Di Paolo","doi":"10.1159/000543181","DOIUrl":"10.1159/000543181","url":null,"abstract":"<p><strong>Introduction: </strong>High-dose methotrexate (MTX) is used to treat pediatric acute lymphoblastic leukemia (ALL). The drug has a low therapeutic index and a highly interindividual variability in systemic exposure. These characteristics necessitate dose adjustments and therapeutic drug monitoring protocols, while population pharmacokinetic (POP/PK) models may enable more precise drug dosing. Therefore, we assessed the performance of external POP/PK models in ALL children receiving high-dose MTX.</p><p><strong>Methods: </strong>We retrospectively harvested clinical and laboratory data from ALL children during their first two cycles of chemotherapy. A POP/PK model was elaborated using the Monolix suite 2024R1. External models were selected from PUBMED based on strict inclusion/exclusion criteria, and their fit to the actual data was assessed by calculating bias (percentage prediction error [PE%]) and precision (percentage root mean squared error [RMSE%]).</p><p><strong>Results: </strong>Thirty-seven ALL children participated in the study (18 males, median age 5.1 years, range 1.7-15.2 years), and six external POP/PK models were chosen. Except for one model (median PE% value, -97.45%), all models exhibited acceptable bias (median PE% values, -4.17%-2.67%), despite none of them demonstrating good precision (median RMSE% values, 89.19%-120.40%).</p><p><strong>Conclusion: </strong>External models should be accurately evaluated before they are implemented in clinical practice, even when patients share very similar characteristics.</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":" ","pages":"1-10"},"PeriodicalIF":2.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142852944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Time-Kill Curve Analysis of Fucoidan Combination with Conventional Antibiotics against Biofilms Formation of Methicillin-Resistant Staphylococcus aureus and Acinetobacter baumannii Clinical Isolates.","authors":"Mohsen Nazari, Mohammad Taheri, Fatemeh Nouri, Maryam Bahmanzadeh, Mohammad Yousef Alikhani","doi":"10.1159/000542826","DOIUrl":"10.1159/000542826","url":null,"abstract":"<p><strong>Introduction: </strong>This study investigates the efficacy of fucoidan combination with antibiotics, against single-species biofilms and mixed-species, individual planktonic, and coculture planktonic conditions of Methicillin-resistant Staphylococcus aureus (MRSA) and Acinetobacter baumannii by time-kill curve analysis.</p><p><strong>Materials and methods: </strong>Fucoidan, a sulfated polysaccharide, was purchased from Sigma-Aldrich, USA. Clinical isolates of MRSA and A. baumannii from diabetic foot ulcers (DFUs) were used, and single-species biofilms and mixed-species biofilms were developed to assess susceptibility to the treatments using MIC, MBC, minimum biofilm inhibitory concentration, minimum biofilm eradication concentration, and time-kill kinetics assays. Cytotoxicity was assessed using MTT assays on human skin fibroblast cells (HSF-PI 16).</p><p><strong>Results: </strong>The study determined the geometric mean MIC and MBC values for gentamicin, imipenem, and fucoidan in MRSA and A. baumannii cultures, both individually and in co-cultures. The MIC and MBC values were significantly lower under co-culture conditions, indicating enhanced antimicrobial efficacy. Synergy between fucoidan, gentamicin, and imipenem was confirmed through time-kill assays, which showed complete inhibition of bacterial growth and effective biofilm eradication, particularly in mixed-species biofilms. Fucoidan demonstrated low cytotoxicity at optimal concentrations, highlighting their potential as a therapeutic strategy against biofilm-associated infections in DFUs.</p><p><strong>Conclusion: </strong>The study concludes that fucoidan, in combination with gentamicin and imipenem, effectively disrupts mixed-species biofilms of MRSA and A. baumannii, suggesting fucoidan-based therapies could improve outcomes for DFU patients, warranting further clinical investigation.</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":" ","pages":"1-12"},"PeriodicalIF":2.0,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142779260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}