International Journal of Antimicrobial Agents最新文献

{"title":"Clinical outcomes of a twice daily metronidazole dosing strategy for Bacteroides bloodstream infections.","authors":"Sunish Shah, Kathleen Adams, Lloyd Clarke, Justin Ludwig, Dayna McManus, Minh-Hong Nguyen, Jeffrey E Topal, Ryan K Shields","doi":"10.1016/j.ijantimicag.2024.107403","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2024.107403","url":null,"abstract":"<p><strong>Objective: </strong>The optimal metronidazole dose for the treatment of Bacteroides spp. has not been well-defined.</p><p><strong>Methods: </strong>This study was a multicenter, retrospective chart review of adult patients with bacteremia secondary to Bacteroides spp. between October 2010 and March 2024. Clinical outcomes of patients who received 500mg of metronidazole twice daily were compared to those who received 500mg of metronidazole thrice daily. Clinical failure defined as a composite of 30-day recurrent infection due to Bacteroides spp. or all-cause mortality.</p><p><strong>Results: </strong>Of the 242 patients who met the inclusion criteria, 76 received metronidazole 500mg twice daily and 166 received metronidazole 500mg thrice daily. Patients who received metronidazole twice daily did not have significantly different rates of clinical failure (15% vs 18%, P=0.561) or 30-day mortality (15% vs 17%, P=0.638) compared to those who received metronidazole thrice daily. After applying full-cohort matching, patients who received metronidazole twice daily were not at an increased risk of clinical failure [OR=0.859; 95% CI (0.283-2.606); P= 0.801] or 30-day mortality [OR = 0.897, 95% CI (0.292-2.752) P=0.8573].</p><p><strong>Conclusions: </strong>In the largest study to date of patients with Bacteroides spp. bacteremia treated with metronidazole, twice daily dosing strategies were not associated with worse outcomes compared to thrice daily metronidazole dosing strategies.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"107403"},"PeriodicalIF":4.9,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817552","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}

{"title":"Analysis of time-to-positivity data in tuberculosis treatment studies: Identifying a new limit of quantification.","authors":"Suzanne M Dufault, Geraint R Davies, Elin M Svensson, Derek J Sloan, Andrew D McCallum, Anu Patel, Pieter Van Brantegem, Paolo Denti, Patrick P J Phillips","doi":"10.1016/j.ijantimicag.2024.107404","DOIUrl":"10.1016/j.ijantimicag.2024.107404","url":null,"abstract":"<p><strong>Background: </strong>The BACTEC Mycobacteria Growth Indicator Tube (MGIT) machine is the standard globally for detecting viable mycobacteria in patients' sputum. Samples are observed for no longer than 42 days, at which point the sample is declared \"negative\" for tuberculosis (TB). This time to detection of bacterial growth, referred to as time-to-positivity (TTP), is increasingly of interest not solely as a diagnostic tool, but as a continuous biomarker wherein change in TTP can be used for comparing the bactericidal activity of different TB treatments. However, as a continuous measure, there are oddities in the distribution of TTP values observed, particularly at higher values.</p><p><strong>Methods: </strong>We explored whether there is evidence to suggest setting an upper limit of quantification for modeling purposes (ULOQ_M) lower than the diagnostic limit of detection (LOD) using data from several TB-PACTS randomized clinical trials and PanACEA MAMS-TB.</p><p><strong>Results: </strong>Across all trials, less than 7.1% of weekly samples returned TTP measurements between 25 and 42 days. Further, the relative absolute prediction error (%) was highest in this range. When modeling with ULOQ_Ms of 25 and 30 days, estimator precision improved for 23 of 25 regimen-level slopes compared to models using the LOD. Discrimination between regimens based on Bayesian posteriors also improved.</p><p><strong>Conclusions: </strong>While TTP measurements between 25 days and the diagnostic LOD may be important for diagnostic purposes, TTP values in this range may not contribute meaningfully to its use as a quantitative measure, particularly when assessing treatment response, and may lead to under-powered clinical trials.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"107404"},"PeriodicalIF":4.9,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142800553","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}

{"title":"ANAKINRA EFFICACY IN COVID-19 PNEUMONIA GUIDED BY SOLUBLE UROKINASE PLASMINOGEN ACTIVATOR RECEPTOR: ASSOCIATION WITH THE INFLAMMATORY BURDEN OF THE HOST.","authors":"Evdoxia Kyriazopoulou, Karolina Akinosoglou, Eleni Florou, Elli Kouriannidi, Artemis Bogosian, Olga Tsachouridou, Konstantinos N Syrigos, Nikolaos Gatselis, Haralampos Milionis, Ilias C Papanikolaou, Styliani Sympardi, Maria Dafni, Antonia Alevizou, Alexia-Vasiliki Amvrazi, Errika Alexandrou, Kyprianos Archontoulis, Katerina Argyraki, Zoi Alexiou, Yakinthi Georgiou, Dimitra Gkogka, Foteini Kyrailidi, Vassiliki Kalyva, Triantafilli Nikolopoulou, Sofia Ioannou, Petros Bakakos, Georgia Karathanassiou, Kyriakos Koklanos, Dionysios-Nikolaos Miletis, Anna-Maria Tili, Lampros Vakkas, Ioanna Vila, Periklis Panagopoulos, Michael Samarkos, George Chrysos, George N Dalekos, Garyphallia Poulakou, Symeon Metallidis, Evangelos J Giamarellos-Bourboulis","doi":"10.1016/j.ijantimicag.2024.107405","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2024.107405","url":null,"abstract":"<p><p>Anakinra was approved by the European Medicines Agency and received Emergency Use Authorization by the Food and Drug Administration of the United States for patients with COVID-19 pneumonia at risk for severe respiratory failure (SRF) with blood levels of suPAR (soluble urokinase plasminogen activator receptor) ≥ 6 ng/ml. We report the final results of the phase II open-label single-arm SAVE trial in a large population. Patients with COVID-19 pneumonia and suPAR levels ≥6 ng/ml received subcutaneously anakinra 100mg once daily for 10 days. The primary outcome was the incidence of SRF by day 14. Secondary outcomes were 30-day mortality, incidence of SRF according to time delay for start of treatment, safety and associations with the inflammatory burden of the host. From March 2020 to March 2022, 992 patients were enrolled. The incidence of SRF was 18.8% similar to the results of the phase III pivotal trial. The overall 30-day mortality was 9.5%. Participants were divided into four subgroups of time delay between symptoms onset and start of anakinra. The incidence of SRF was similar for all subgroups. Serious adverse events were reported in 15.4%; only 3 were possibly related to anakinra. The most common adverse event was increased liver function tests. A post-hoc comparison with the pivotal phase III trial showed similar anakinra outcomes among patients' subgroups by levels of inflammatory mediators and D-dimers. Results support similar efficacy of anakinra with the pivotal registrational trial for COVID-19 pneumonia. The lack of a comparator group is a limitation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04357366.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"107405"},"PeriodicalIF":4.9,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794597","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}

{"title":"Clarithromycin For Improved Clinical Outcomes in Community-Acquired Pneumonia: A Subgroup Analysis of the ACCESS Study.","authors":"Karolina Akinosoglou, Konstantinos Leventogiannis, Elisavet Tasouli, Nikolaos Kakavoulis, Georgios Niotis, Sarantia Doulou, Lamprini Skorda, Konstantina Iliopoulou, Anna Papailiou, Paraskevi Katsaounou, Vassiliki Rapti, George Chrysos, Theodoros Seferlis, Styliani Gerakari, Konstantina Dakou, Ilias C Papanikolaou, Haralampos Milionis, Samantha Kewitz, Sara Georgiadou, Theano Kontopoulou, Vasiliki Tzavara, Antonio Torres, Michael S Niederman, Evangelos J Giamarellos-Bourboulis","doi":"10.1016/j.ijantimicag.2024.107406","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2024.107406","url":null,"abstract":"<p><strong>Background: </strong>In the ACCESS trial the addition of clarithromycin to standard-of-care (SoC) antibiotics enhanced early clinical response and attenuated the inflammatory burden in adults with community-acquired pneumonia (CAP) requiring hospitalization. A post-hoc analysis was performed to investigate the benefit in specific subgroups.</p><p><strong>Methods: </strong>The primary endpoint comprised two conditions to be met during the first 72 hours: ≥50% decrease of respiratory symptom severity score; and any of ≥30% decrease of SOFA score and favourable change of kinetics of procalcitonin (defined as ≥80% PCT decrease or PCT <0.25 ng/ml). In this exploratory post-hoc analysis achievement of the study composite primary endpoint was compared between the two treatment groups within subsets differentiated by demographic characteristics, comorbidities, CAP severity, baseline laboratory findings and corticosteroid co-administration. The impact of clarithromycin treatment on the need for mechanical ventilation (MV) in all subgroups was also analysed.</p><p><strong>Results: </strong>The addition of clarithromycin significantly increased the proportion of patients achieving the primary endpoint across all subgroups and decreased the need for MV in many subgroups. For instance, the primary endpoint was attained by 32.7% of placebo-treated patients and in 67% of clarithromycin-treated patients with CURB-65 score ≥2 (p<0.0001) whereas MV was required in 18.8% and 7.4% respectively (p=0.022). The addition of corticosteroids alone was not as clinically advantageous as the use of clarithromycin alone.</p><p><strong>Conclusion: </strong>Adding clarithromycin to SoC in the ACCESS study achieved early clinical anti-inflammatory responses and decreased the need for MV in subgroups of hospitalized patients with CAP.</p><p><strong>Registration: </strong>EudraCT 2020-004452-15; ClinicalTrials.gov NCT04724044.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"107406"},"PeriodicalIF":4.9,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794599","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}

{"title":"Novel active Trp- and Arg-rich antimicrobial peptides with high solubility and low red blood cell toxicity designed using machine learning tools.","authors":"Bridget A B Henson, Fucong Li, José Ausencio Álvarez-Huerta, Poornima G Wedamulla, Arianna Valdes Palacios, Max R M Scott, David Thiam En Lim, W M Hayden Scott, Monica T L Villanueva, Emily Ye, Suzana K Straus","doi":"10.1016/j.ijantimicag.2024.107399","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2024.107399","url":null,"abstract":"<p><p>Given the rising number of multidrug-resistant (MDR) bacteria, there is a need to design synthetic antimicrobial peptides (AMPs) that are highly active, non-hemolytic, and highly soluble to act as alternatives to antibiotics that are either no longer effective or used as drugs of last resort. Machine learning tools allow the straightforward in silico identification of non-hemolytic antimicrobial peptides. Here, we utilized a number of these tools to rank the best peptides from two libraries: 1) 8192 peptides with sequence bhxxbhbGAL, where b is the basic amino acid R or K, h is a hydrophobic amino acid, i.e. G, A, L, F, I, V, Y, or W and x is Q, S, A, or V; and 2) 512 peptides with sequence RWhxbhRGWL, where b and h are as for the first library and x is Q, S, A, or G. The top 100 sequences from each library, as well as 10 peptides predicted to be active but hemolytic (for a total of 220 peptides), were SPOT synthesized and their IC₅₀ values were determined against S. aureus USA 300 (MRSA). Of these, 6 AMPs with low IC₅₀'s were characterized further in terms of: MICs against MRSA, E. faecalis, K. pneumoniae, E.coli and P. aeruginosa; RBC lysis; secondary structure in mammalian and bacterial model membranes; and activity against cancer cell lines HepG2, CHO, and PC-3. Overall, the approach yielded a large family of active antimicrobial peptides with high solubility and low red blood cell toxicity. It also provides a framework for future designs and improved machine learning tools.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"107399"},"PeriodicalIF":4.9,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791657","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}

{"title":"LL-37, the master Antimicrobial Peptide, its multifaceted role from combating infections to cancer immunity.","authors":"Anand K Keshri, Suraj S Rawat, Anubha Chaudhary, Swati Sharma, Ananya Kapoor, Parul Mehra, Rimanpreet Kaur, Amit Mishra, Amit Prasad","doi":"10.1016/j.ijantimicag.2024.107398","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2024.107398","url":null,"abstract":"<p><p>Antimicrobial peptides (AMPs) represent a unique group of naturally occurring molecules having diverse biological activities, including potent antimicrobial properties. Among them, LL-37 has emerged as a significant player, demonstrating its multifaceted roles during bacterial, fungal, and viral infections, as well as exhibiting intriguing implications in cancer. This review delves into the versatile functions of LL-37, elucidating its mechanisms of action against microbial pathogens and its potential to modulate immune responses. We explored the efficacy of LL-37 in disrupting bacterial membranes, inhibiting fungal growth, and interfering with viral replication, highlighting its potential as a therapeutic agent against a wide array of infectious diseases. Furthermore, we discussed the emerging role of LL-37 in cancer immunity, where its immunomodulatory effects and direct cytotoxicity towards cancer cells offer novel avenues for cancer therapy in the near future. We provided a comprehensive overview of the activities of LL-37 across various diseases and underscored the importance of further research into harnessing the therapeutic potential of this potential antimicrobial peptide along with other suitable candidates.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"107398"},"PeriodicalIF":4.9,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791640","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}

{"title":"Developing a human monoclonal antibody combination CRM25 to prevent rabies after exposure.","authors":"Caifeng Long, Wenbo Wang, Jialiang Du, Gangling Xu, Chuanfei Yu, Lan Wang","doi":"10.1016/j.ijantimicag.2024.107383","DOIUrl":"10.1016/j.ijantimicag.2024.107383","url":null,"abstract":"<p><strong>Objective: </strong>Immunization against rabies post-exposure prophylaxis requires passive immunization with either monoclonal antibody (mAb) or blood-derived rabies immunoglobin (RIG). Currently, replacing traditional RIG with emerging mAb or mAb combinations is highly recommended due to the limited supply and potential safety risks of RIG.</p><p><strong>Methods: </strong>We developed a mAb combination named CRM25 by combining two human mAbs, RM02 and RM05, at a 1:1 mass ratio.</p><p><strong>Results: </strong>RM02 and RM05 were non-competing and non-overlapping mAbs targeting epitopes I and III, respectively. K226 and G229 were found to be the critical amino acid sites for RM02 neutralization, but the mutant I338T displayed decreased susceptibility to RM05 neutralization. Notably, CRM25 was capable of cross-neutralizing rabies virus (RABV) strains containing K226M or I338T mutations. CRM25 additionally showed an inhibitory effect on the infection of all tested common RABVs and non-RABV phylogroup I lyssaviruses. CRM25 not only exhibited neutralizing activity but also exhibited antiviral effects via Fc-mediated effector functions. Importantly, CRM25 was comparable to human RIG in terms of its capacity to protect Syrian golden hamsters from lethal RABV challenges.</p><p><strong>Conclusions: </strong>These findings promote more thorough research on CRM25's antiviral properties in cells and in vivo to enhance its clinical applicability and suggest that it may be a viable candidate medication for rabies post-exposure prophylaxis.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"107383"},"PeriodicalIF":4.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619961","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}

{"title":"Acquired bla_CfxA-3 carried by a conjugative transposon or duplicated intrinsic bla_CME-3 mediates cefiderocol resistance in Elizabethkingia anophelis clinical isolates.","authors":"Ya-Sung Yang, Yu-Lin Lee, Yuag-Meng Liu, Chen-Feng Kuo, Mei-Chen Tan, Wei-Cheng Huang, Shu-Yuan Hsu, Yea-Yuan Chang, Hung-Sheng Shang, Shu-Chen Kuo","doi":"10.1016/j.ijantimicag.2024.107378","DOIUrl":"10.1016/j.ijantimicag.2024.107378","url":null,"abstract":"<p><strong>Objectives: </strong>Elizabethkingia spp. are resistant to multiple antibiotics. This study aimed to determine in vitro and in vivo activities of cefiderocol against Elizabethkingia spp. and to investigate resistance mechanisms.</p><p><strong>Methods: </strong>Bloodstream isolates were collected from four hospitals. In vitro and in vivo activities were determined using broth microdilution and the wax moth model, respectively. Genome comparison and gene editing were used to confirm the contribution of target genes. Conjugation experiments and serial passage were used to determine transferability and stability, respectively. A MIC of ≤4 mg/L was designated as the susceptibility breakpoint.</p><p><strong>Results: </strong>Among 228 non-duplicated isolates, 226 exhibited a MIC of ≤4 mg/L with MIC_50/90 of 1/2 mg/L. Two isolates had a MIC of 128 mg/L; both patients had multiple comorbidities, were ventilator-dependent and had not received cefiderocol previously. Resistance was attributable to acquisition of bla_CfxA-3, carried by a conjugative transposon from Prevotella jejuni, and duplication of intrinsic bla_CME-3, which led to its overexpression. tetQ coexisted with bla_CfxA-3 in this conjugative transposon and minocycline facilitated its transfer among E. anophelis. Antibiotics prescribed for source patients did not induce bla_CME-3 duplication. The stabilities of bla_CfxA-3 and double bla_CME-3 were 100% and > 90%, respectively, after 10-day serial passage. Cefiderocol failed to rescue moth larvae infected with resistant strains, but removal of resistance mechanisms restored in vivo efficacy.</p><p><strong>Conclusions: </strong>Cefiderocol was in vitro and in vivo active against Elizabethkingia spp. but resistance may emerge due to the availability, transferability, and/or stability of resistance mechanisms.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"107378"},"PeriodicalIF":4.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603809","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}

{"title":"PK/PD modelling and simulation of longitudinal meropenem in vivo effects against Escherichia coli and Klebsiella pneumoniae strains with high MICs.","authors":"Raphaël Saporta, Elisabet I Nielsen, Jon U Hansen, Edgars Liepinsh, Iris K Minichmayr, Lena E Friberg","doi":"10.1016/j.ijantimicag.2024.107389","DOIUrl":"10.1016/j.ijantimicag.2024.107389","url":null,"abstract":"<p><strong>Background: </strong>Carbapenem-resistant bacteria pose a threat to public health. Characterising the pharmacokinetics-pharmacodynamics (PKPD) of meropenem longitudinally in vivo against resistant bacteria could provide valuable information for development and translation of carbapenem-based therapies.</p><p><strong>Objectives: </strong>To assess the time course of meropenem effects in vivo against strains with high MIC to predict PK/PD indices and expected efficacy in patients using a modelling approach.</p><p><strong>Methods: </strong>A PKPD model was built on longitudinal bacterial count data to describe meropenem effects against six Escherichia coli and Klebsiella pneumoniae strains (MIC values 32-128 mg/L) in a 24 h mouse thigh infection model. The model was used to derive PK/PD indices from simulated studies in mice and to predict the efficacy of different infusion durations with high-dose meropenem (2 g q8 h/q12 h for normal/reduced kidney function) in patients.</p><p><strong>Results: </strong>Data from 592 mice were available for model development. The estimated meropenem concentration-dependent killing rate was not associated with differences in MIC. The fraction of time that unbound concentrations exceeded EC₅₀ (fT_>EC50, EC₅₀ = 1.01 mg/L) showed higher correlations than fT_>MIC. For all investigated strains, bacteriostasis at 24 h was predicted for prolonged infusions of high-dose meropenem monotherapy in >90% of patients.</p><p><strong>Conclusions: </strong>The developed PKPD model successfully described bacterial growth and meropenem killing over time in the thigh infection model. For the investigated strains, the MIC, determined in vitro, or MIC-based PK/PD indices, did not predict in vivo response. Simulations suggested prolonged infusions of high-dose meropenem to be efficacious in patients infected by the studied strains.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"107389"},"PeriodicalIF":4.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647987","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}

{"title":"Monitoring of the cerebrospinal fluid voriconazole level in a patient with recurrent Candida meningitis after pituitary surgery.","authors":"Mete Ucdal, Emre Kara, Mustafa Berker, Aslı Pinar, Dolunay Gulmez, Sevtap Arikan-Akdagli, Ahmet Cağkan Inkaya, Gokhan Metan","doi":"10.1016/j.ijantimicag.2024.107379","DOIUrl":"10.1016/j.ijantimicag.2024.107379","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"107379"},"PeriodicalIF":4.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619971","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}