Antimicrobial Agents and Chemotherapy最新文献

{"title":"Restoring ceftolozane susceptibility: a role for diazabicyclooctane β-lactamase inhibitors?","authors":"Ava J Dorazio, Ellen G Kline, Kevin M Squires, Jason M Pogue, Daria Van Tyne, Ryan K Shields","doi":"10.1128/aac.01543-24","DOIUrl":"10.1128/aac.01543-24","url":null,"abstract":"<p><p>Paired baseline and post-exposure isolates from 34 patients who developed ceftolozane-tazobactam (TOL-TAZ) resistance following treatment of multidrug-resistant (MDR) <i>Pseudomonas aeruginosa</i> infections were analyzed to determine if ceftolozane with an alternative β-lactamase inhibitor could restore susceptibility. The median baseline TOL-TAZ MIC was 2 mg/L; 88% of post-exposure isolates harbored new <i>ampC</i> mutations. Median MIC fold-increase from baseline was 32-, 24-, 16-, and 6-fold for ceftolozane-tazobactam, ceftolozane-avibactam (AVI), ceftolozane-relebactam (REL), and ceftolozane-durlobactam (DUR), respectively. Enhanced ceftolozane-durlobactam activity was evident in specific <i>ampC</i> mutations.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0154324"},"PeriodicalIF":4.1,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143050989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Guidelines vs mindlines: a qualitative investigation of how clinicians' beliefs influence the application of rapid molecular diagnostics in intensive care.","authors":"Sarah-Jane F Stewart, Alyssa M Pandolfo, Yogini Jani, Zoe Moon, David Brealey, Virve I Enne, David M Livermore, Vanya Gant, Stephen J Brett, Rob Horne","doi":"10.1128/aac.01156-24","DOIUrl":"10.1128/aac.01156-24","url":null,"abstract":"<p><p>Rapid molecular diagnostic tests improve antimicrobial stewardship (AMS) by facilitating earlier refinement of antimicrobial therapy. The INHALE trial tested the application of the BioFire FilmArray Pneumonia Panel (Pneumonia Panel) for antibiotic prescribing for hospital-acquired and ventilator-associated pneumonias (HAP/VAP) in UK intensive care units (ICUs). We report a behavioral study embedded within the INHALE trial examining clinicians' perceptions of using these tests. Semi-structured interviews were conducted with 20 ICU clinicians after using the Pneumonia Panel to manage suspected HAP/VAP. Thematic analysis identified factors reinforcing perceptions of the necessity to modify antibiotic prescribing in accordance with test results and doubts/concerns about doing so. While most acknowledged the importance of AMS, the test's impact on prescribing decisions was limited. Concerns about potential consequences of undertreatment to the patient and prescriber were often more salient than AMS, sometimes leading to \"just-in-case\" antibiotic prescriptions. Test results indicating a broad-spectrum antibiotic were unnecessary often failed to influence clinicians to avoid an initial prescription or de-escalate antibiotics early as they considered their use to be necessary to protect the patient and themselves, \"erring on the side of caution.\" Some clinicians described cases where antibiotics would be prescribed for a sick patient regardless of test results because, in their opinion, it fits with the clinical picture-\"treating the patient, not the result.\" Our findings illustrate a tension between prescribing guidelines and clinicians' \"mindlines,\" characterized by previous experiences. This highlights the need for a \"technology plus\" approach, recognizing the challenges clinicians face when applying technological solutions to patient care.IMPORTANCERapid molecular diagnostic tests for pathogens and resistance genes may improve antibiotic-prescribing decisions and stewardship. However, clinicians' desire to protect their patients with antibiotics often overrides more distal concerns about possible resistance selection, limiting the application of these tests in practice. Findings underscore the challenge of changing prescribing decisions based on technical results or guidelines, highlighting factors such as clinicians' previous experience and \"knowledge in practice\" as more proximal drivers of these decisions. Implementation strategies for technological solutions to antimicrobial resistance must be \"behaviorally intelligent,\" recognizing the challenges facing clinicians when making \"life or death\" prescribing decisions.CLINICAL TRIALSThis study is registered with ISRCTN as ISRCTN16483855.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0115624"},"PeriodicalIF":4.1,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881570/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143187636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"β-Lactamase diversity in <i>Acinetobacter baumannii</i>.","authors":"Andrew R Mack, Andrea M Hujer, Maria F Mojica, Magdalena A Taracila, Michael Feldgarden, Daniel H Haft, William Klimke, Arjun B Prasad, Robert A Bonomo","doi":"10.1128/aac.00784-24","DOIUrl":"10.1128/aac.00784-24","url":null,"abstract":"<p><p><i>Acinetobacter baumannii</i> is a clinically important, Gram-negative pathogen responsible for a wide variety of nosocomial and community-acquired infections. Antibiotic resistance is a serious concern, as the organism has a wide variety of intrinsic resistance mechanisms, including chromosomal class C (<i>bla</i>_ADC) and D (<i>bla</i>_OXA-51 family) β-lactamases, and the ability to readily acquire additional β-lactamases. Surveillance studies can reveal the diversity and distribution of β-lactamase alleles, but are difficult and expensive to conduct. Herein, we describe an approach using publicly available data derived from whole genome sequences, to explore the diversity and distribution of β-lactamase alleles across 28,330 isolates. The most common intrinsic alleles at the time of writing were <i>bla</i>_ADC-73, <i>bla</i>_ADC-30, <i>bla</i>_ADC-222, <i>bla</i>_ADC-33, and <i>bla</i>_OXA-66, and the most common acquired allele was <i>bla</i>_OXA-23. Interestingly, only 63.0% of assigned <i>bla</i>_ADC alleles were encountered and the 10 most common <i>bla</i>_ADC and intrinsic <i>bla</i>_OXA alleles represented approximately 75% of their respective gene totals while dozens were extremely infrequent. Differences were observed over time and geography. Surprisingly, more distinct unassigned (i.e., lacking a <i>bla</i>_ADC or <i>bla</i>_OXA number) alleles were encountered than distinct, assigned alleles. Understanding the diversity and distribution of β-lactamase alleles helps to prioritize variants for further research, selects targets for drug development, and may aid in selecting therapies for a given infection.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0078424"},"PeriodicalIF":4.1,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum for Kar et al., \"Cimicifugin, a broad-spectrum inhibitor of <i>Theileria annulata</i> and <i>Plasmodium falciparum</i> CDK7\".","authors":"Prajna Parimita Kar, Prasanna Babu Araveti, Kanika Saxena, Atlanta Borah, Puran Sijwali, Anand Srivastava","doi":"10.1128/aac.01782-24","DOIUrl":"10.1128/aac.01782-24","url":null,"abstract":"","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0178224"},"PeriodicalIF":4.1,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881569/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum for Xu et al., \"Deoxyshikonin: a promising lead drug grass against drug resistance or sensitivity to <i>Helicobacter pylori</i> in an acidic environment\".","authors":"Jia-Yin Xu, Hui-Hua Dong, Li-Juan Liao, Shi-Xian Yang, Lu-Yao Wang, Hao Chen, Peipei Luo, Liang Huang, Ai-Xing Guan, Yan-Qiang Huang","doi":"10.1128/aac.01840-24","DOIUrl":"10.1128/aac.01840-24","url":null,"abstract":"","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0184024"},"PeriodicalIF":4.1,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881568/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of two gradient diffusion tests to determine susceptibility to aztreonam and ceftazidime-avibactam in combination.","authors":"Ayesha Khan, Carmila Manuel, Richard Maynard, Romney M Humphries","doi":"10.1128/aac.01736-24","DOIUrl":"10.1128/aac.01736-24","url":null,"abstract":"<p><p>The combination of aztreonam and ceftazidime-avibactam (ATM-CZA) is a last resort regimen against recalcitrant infections caused by metallo-β-lactamase (MBL)-producing organisms. Susceptibility testing is warranted due to emerging resistance to the combination, but there are no widely implemented methods for use in clinical laboratories. Here, we used a cohort of 100 Enterobacterales<i>, Pseudomonas aeruginosa</i>, and <i>Stenotrophomonas maltophilia</i> strains, including 68 MBL producers, to evaluate the performance of two ETEST strip-based synergy testing methods: the side-by-side (SS) method with an ATM ETEST placed next to a CZA ETEST (10 mm apart) and the strip cross (SX) method with a CZA ETEST placed perpendicularly on top of the ATM ETEST (at the 8 µg/mL mark). By reference broth microdilution (BMD), 89.1% (41/46) of the Enterobacterales, 15% (3/20) of the <i>P. aeruginosa</i>, and 97.1% (33/34) of the <i>S. maltophilia</i> isolates tested susceptible to the ATM-CZA combination. The SS method yielded 72% categorical agreement with BMD and 28 major errors (ME, 36.4%). Initial testing with the SX method yielded three ME , of which one was resolved upon repeat testing, yielding a final categorical agreement of 98% with BMD with two ME (2.6%). The SX method also yielded 100% reproducibility across three brands of Mueller Hinton agar (BD, Hardy, Remel). Our study demonstrates that the SX method is accurate, precise, and feasible for clinical laboratories to perform ATM-CZA susceptibility testing to guide use of the combination for treatment of multidrug-resistant gram-negative pathogens.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0173624"},"PeriodicalIF":4.1,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881574/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence and mortality associated with multidrug-resistant infections in adult intensive care units in Argentina (PREV-AR).","authors":"Wanda Cornistein, Carina Balasini, Yanina Nuccetelli, Viviana M Rodriguez, Norma Cudmani, Maria Virginia Roca, Graciela Sadino, Martín Brizuela, Analía Fernández, Soledad González, Damián Águila, Alejandra Macchi, Maria Inés Staneloni, Elisa Estenssoro","doi":"10.1128/aac.01426-24","DOIUrl":"10.1128/aac.01426-24","url":null,"abstract":"<p><p>Data from low and middle-income countries (LMICs) on multidrug-resistant microorganisms (MDROs) in intensive care units (ICUs) are scarce. Working in several ICUs in Argentina, we sought to estimate the prevalence and characteristics of MDRO infections and carbapenemase-producing Enterobacterales (CPE) colonization. Mortality associated with MDRO infection was also evaluated. The study was a 24-hour point prevalence study conducted in 164 adult ICUs in Argentina between 24 November and 28 November 2023. The main study outcome was in-ICU mortality and secondary outcomes included the prevalence of MDRO infections, the prevalence of CPE colonization (defined as CPE recovered from a rectal swab), and ICU length of stay (LoS). Mixed effects modeling was used to identify risk factors for in-ICU mortality. Among 1,799 patients, 933 (51.9%) had a reported infection; 599 infections (64.2%) were classified as definite (i.e., with positive cultures) and 334 (35.8%) as probable infection (i.e., negative cultures but signs of infection). Of the 933 patients with infection, 273 (29.2%) had an MDRO recovered with 344 total MDRO cultures recovered. Non-MDRO was recovered from 326 (34.9%) of the 933 patients. Among definite infections, 45.5% (273/599) were due to MDRO with an overall prevalence of MDRO of 15.1% (273 patients with MDRO infections/1,799 patients). CPE colonization, defined as a positive rectal swab taken during the incident hospitalization, occurred in 420/1,696 (24.7%) patients. The most frequent MDRO infection was ventilator-associated pneumonia (100/344; 29.1%). The most common MDRO recovered were carbapenem-resistant <i>Acinetobacter baumannii</i> and CPE (98/344, 28.5% each). In-ICU mortality was 27.1% (487/1,799); independent predictors were age (odds ratio [OR] 1.01 [1.00-1.02], <i>P</i> = 0.003), MDRO infection (OR 1.65 [1.18-2.43], <i>P</i> = 0.012), probable infection (OR 1.41 [0.97-2.04], <i>P</i> = 0.073), sepsis-related organ failure assessment (SOFA) score (OR 1.18 [1.13-1.23], <i>P</i> = 0.000), and hospital-acquired pneumonia (OR 1.84 [1.12-3.01], <i>P</i> = 0.016). Mortality also varied significantly by hospital (<i>P</i> < 0.001). LoS was significantly longer in patients with MDRO infections, 30.0 (interquartile range [IQR] 17-35) days vs 16.0 (IQR 8-33) in non-MDRO, <i>P</i> < 0.0001. Among 1,799 ICU patients in an LMIC, the prevalence of MDRO infection and CPE colonization was high. The presence of an MDRO infection was associated with increased mortality and prolonged ICU LoS.CLINICAL TRIALSThis study is registered with Clinicaltrials.gov as NCT06574776.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0142624"},"PeriodicalIF":4.1,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881575/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142999073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>In vitro</i> and <i>in vivo</i> activity of 1,2,3,4,6-O-pentagalloyl-glucose against <i>Candida albicans</i>.","authors":"Lu Gao, Hao Wu, Jia Feng, Yu Liu, Ruina Wang, Lan Yan, Quanzhen Lv, Yuanying Jiang","doi":"10.1128/aac.01775-24","DOIUrl":"10.1128/aac.01775-24","url":null,"abstract":"<p><p>Invasive fungal infections have become an increasingly serious threat to global human health, underscoring the urgent need for the development of new antifungal drugs. In this study, we found a natural polyphenolic compound 1,2,3,4,6-O-pentagalloyl-glucose (PGG), which is present in various plants and herbs. PGG showed broad-spectrum antifungal activities, enhancing the efficacy of fluconazole. Furthermore, PGG could protect mice against gastrointestinal and systemic infection with <i>Candida albicans</i>. Our mechanistic studies revealed that PGG exerts its antifungal effects partially by binding to the CaEno1 protein to inhibit its activity. As a crucial therapeutic target, Eno1 has been reported to be closely associated with cancer, hypertension, and infectious diseases. Our findings indicated that PGG, a new Eno1 inhibitor, is a potential candidate for further antifungal development.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0177524"},"PeriodicalIF":4.1,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881577/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Model-informed dose optimization for prophylactic piperacillin-tazobactam in perioperative pediatric critically ill patients.","authors":"Wen Rui Tan, Kei Irie, Carter McIntire, Julie Luna Torres, Rhonda Jones, Abigayle Gibson, Tomoyuki Mizuno, Sonya Tang Girdwood","doi":"10.1128/aac.01227-24","DOIUrl":"10.1128/aac.01227-24","url":null,"abstract":"<p><p>Piperacillin/tazobactam (PTZ) is frequently prescribed during the perioperative period as prophylaxis in critically ill patients. Current international guidelines recommend that the pediatric intraoperative dosing regimen for PTZ be 90-112.5 mg/kg (80-100 mg/kg as piperacillin [PIP]) administered every 2 hours (Q2H). Concerns have been raised not only about the risk of nephrotoxicity due to elevated PIP exposure but also regarding the practicality of adhering to a 2-h dosing interval in clinical settings. To address these concerns, we employed population pharmacokinetic (PK) modeling and simulation approaches to optimize PTZ dosing regimens in pediatric intraoperative patients. PIP plasma concentration data were obtained from 34 patients using an opportunistic sampling strategy. A two-compartment model was found to adequately describe the PK data. Creatinine clearance was identified as a significant covariate on clearance. The inclusion of inter-occasion variability significantly improved model fit. Simulations across body weights of 10-70 kg and creatinine clearance of 20-130 mL/min/1.73 m² demonstrated that 6-15 mg/kg Q2H, or a 10 mg/kg loading dose followed by 1.0-2.75 mg/kg/h continuous infusion would achieve free PIP concentrations being above the minimum inhibitory concentration (MIC) for 100% of the dosing interval (100% <i>f</i>T >1× MIC). For achieving 100% <i>f</i>T >4× MIC, 25-55 mg/kg Q2H or a 20 mg/kg loading dose followed by 3.25-9.25 mg/kg/h continuous infusion was derived. The model-informed simulations indicated that both lower Q2H doses and continuous infusion methods are clinically viable options and potentially resolve current clinical challenges during intraoperative dosing.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0122724"},"PeriodicalIF":4.1,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881557/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liposomal amphotericin B and complement activation-related pseudoallergy (CARPA).","authors":"George R Thompson, Gelina M Sani, Monica A Donnelley, Jaimie K Figueroa, Ryan Ciuffetelli, Kate Trigg, Juan Arredondo, Alan Koff, Marie Nearing, Ikaika C Loque, Derek J Bays, Satya Dandekar","doi":"10.1128/aac.01692-24","DOIUrl":"10.1128/aac.01692-24","url":null,"abstract":"<p><p>Infusion reactions (tachycardia, hypertension, fever, etc.) associated with liposomal amphotericin B are common. Animal models have found complement activation responsible, yet the pathophysiology has not been evaluated in human patients. We performed a prospective observational study and found complement activation-related pseudoallergy (CARPA) responsible in those with infusion reactions.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0169224"},"PeriodicalIF":4.1,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}