Clinical Infectious Diseases最新文献

{"title":"Safety and Tolerability of Pivmecillinam During More Than Four Decades of Clinical Experience: A Systematic Review.","authors":"Keith S Kaye,Anne Santerre Henriksen,Morten Sommer,Niels Frimodt-Møller","doi":"10.1093/cid/ciae621","DOIUrl":"https://doi.org/10.1093/cid/ciae621","url":null,"abstract":"The recent US Food and Drug Administration approval of pivmecillinam-an oral prodrug of the amidinopenicillin antibiotic mecillinam-presents a valuable opportunity to address the need for new treatments for uncomplicated urinary tract infection (uUTI). We report findings of a systematic literature review of the safety profile of pivmecillinam/mecillinam based on more than 40 years' experience, mainly in Europe and Canada, to describe its tolerability profile and identify any important safety signals. In total, 110 eligible publications were identified describing use of pivmecillinam/mecillinam as monotherapy or in combination, for treatment of uUTI or other infectious conditions. These studies revealed a benign safety and tolerability profile, awareness of which will inform treatment decisions as pivmecillinam is made available in the United States. Together with the evidence for efficacy of, and minimal resistance to, pivmecillinam, the findings of this review support the position of pivmecillinam as a first-line treatment for uUTI.","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":"46 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142991760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Linezolid Dosing and Pharmacokinetics in North American Patients with Tuberculosis","authors":"Nicole Maranchick, Charles A Peloquin, Connie A Haley","doi":"10.1093/cid/ciaf027","DOIUrl":"https://doi.org/10.1093/cid/ciaf027","url":null,"abstract":"Introduction Linezolid is recommended in treatment regimens for rifampin- or multi-drug-resistant tuberculosis. However, considerable pharmacokinetic variability exists, and long-term use is limited by adverse effects. This study evaluates the pharmacokinetics of linezolid in patients with tuberculosis from an international therapeutic drug monitoring service. Methods Linezolid trough, 2-hour, and 6-hour post-dose clinical samples from across North America were tested by the University of Florida Infectious Disease Pharmacokinetics Laboratory. Total serum concentrations were measured using liquid chromatography-tandem mass spectrometry. Therapeutic drug monitoring was performed, and measurements were compared to typical linezolid concentrations including a trough value of <2 mcg/mL and peak value between 12 and 26 mcg/mL. Results From January 2019 to December 2023, 1,604 linezolid samples from 500 patients and 817 unique TDM occasions were analyzed. Trough concentrations were measured on 670 samples (median 1.19 mcg/mL [range 0.00-20.06]), and 232 troughs (34.6%) were >2 mcg/mL. Among trough samples from linezolid dosing of 600mg daily or 5 days/weekly, 43.2% were >2 mcg/mL. Of 600 peak samples, 264 (44%) were outside the typical range, most (89%) being subtherapeutic at <12 mcg/mL. Conclusion High serum linezolid trough concentrations were measured in approximately one-third of samples and in more than 40% of those taking the recommended dose. More than 40% of peak concentrations were outside typical range, 89% of which were <12 mcg/mL. This study demonstrates that therapeutic drug monitoring can be used to identify patients with serum linezolid concentrations outside of targeted ranges, allowing clinicians to make appropriate dose adjustments to improve outcomes.","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":"32 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142991325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Natural History of Clostridioides difficile-related Disease Progression in the Two-Step Testing Era","authors":"Nicholas A Turner, Steven C Grambow, Chris Polage, David T Kuhar, Preeta K Kutty, Rebekah W Moehring, Deverick J Anderson","doi":"10.1093/cid/ciaf020","DOIUrl":"https://doi.org/10.1093/cid/ciaf020","url":null,"abstract":"Importance The natural history of C. difficile progression in nucleic acid amplification test (NAAT) positive, toxin enzyme immunoassay-negative patients remains poorly described. Better understanding risk for subsequent disease may improve prevention strategies. Objective Describe the natural history of C. difficile NAAT+/toxin- adults. Design A cohort of adults (≥18 years) tested for C. difficile within Duke University Health System between 15 March 2020 and 31 December 2023 were classified as NAAT-, NAAT+/toxin-, or NAAT+/toxin+ and followed up to 90 days. Three time-to-event analyses were conducted. Incidence of toxin+ episodes was assessed by initial test status (analysis 1). Treatment of NAAT+/toxin- adults was described using cumulative incidence curves (analysis 2). Rates of toxin+ episodes and severe disease were compared between treated and untreated NAAT+/toxin- adults (analysis 3). Results The cohort included 24,474 tests and 440 toxin+ episodes among 18,337 unique subjects followed for a median 71 days. NAAT+/toxin- status was associated with subsequent toxin positivity (adjusted hazard ratio, aHR 5.06, 95% CI 3.61-7.10) – especially after antibiotic receipt (aHR 15.71, 95% CI 9.85-25.06). Among 2,334 NAAT+/toxin- episodes, 33% received presumptive treatment. Just 5% of NAAT+/toxin- subjects progressed to toxin positivity. Presumptive treatment was associated with lower hazard of subsequent toxin positivity (aHR 0.12, 95% CI 0.05-0.29) but not fulminant disease (aHR 1.93, 95% CI 0.50-7.45). Conclusions and Relevance C. difficile NAAT+/toxin- status was associated with subsequent toxin positivity, especially after antibiotic receipt, though absolute risk was low overall. Further research is needed to determine whether and for whom presumptive treatment might be beneficial.","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":"31 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142989945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Concordance of non-invasive plasma cell-free DNA with invasive diagnostics for diagnosis of invasive fungal disease","authors":"Anthony Lieu, Alex N Zimmet, Joseph Pozdol, Lauren E Kushner, Dora Ho, Niaz Banaei","doi":"10.1093/cid/ciaf021","DOIUrl":"https://doi.org/10.1093/cid/ciaf021","url":null,"abstract":"Background Mold plasma cell-free DNA (cfDNA) PCR is a promising non-invasive diagnostic modality for early diagnosis of invasive mold disease (IMD) in immunocompromised patients. Although mold cfDNA PCR has been shown to be highly accurate, the value of invasive procedures to collect specimens for conventional fungal diagnostics following plasma cfDNA testing remains unclear. Methods This retrospective single-center cohort study included patients with mold plasma cfDNA PCR performed 7 days before or 2 days after invasive specimen collection. Mold PCR detected Aspergillus species, Mucorales agents, Fusarium species, and Scedosporium species. Invasive procedures included tissue biopsy and bronchoscopy. The primary endpoint was the concordance of mold plasma cfDNA PCR results with results of conventional fungal tests performed on tissue and bronchoalveolar lavage fluid (BAL). Results Five hundred and six patients with mold plasma cfDNA PCR resulting ahead of invasive specimen (123 tissue and 426 BAL) results were included, and 437 (86.4%) were immunocompromised. After adjudicating discordant results based on the EORTC/MSGERC definitions for IMD, mold plasma cfDNA PCR and invasive test results were 88.5% (448/506) concordant. In proven cases, 64.7% (11/17) of negative mold plasma cfDNA PCR results occurred in patients with fungal sinusitis (8) and limb infection (3). Non-hematologic malignancy and non-neutropenic states were statistically associated with negative mold plasma cfDNA PCR in patients with proven or probable IMD. Conclusions Non-invasive mold plasma cfDNA PCR results were highly concordant with invasive specimen fungal test results, thus indicating risk-prone invasive specimen collection can be safely curtailed in immunocompromised patients with suspected IMD.","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":"30 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142988929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Challenges and Opportunities in Leveraging Spectrum Scores to Assess Antibiotic De-escalation Practices and Outcomes in Sepsis.","authors":"Kai Qian Kam,Michael Klompas,Chanu Rhee","doi":"10.1093/cid/ciaf023","DOIUrl":"https://doi.org/10.1093/cid/ciaf023","url":null,"abstract":"","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":"78 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142988926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reported Neurologic Manifestations Among Persons with Syphilis by Stage of Infection—12 States, 2019 –2022","authors":"Sarah Wondmeneh, Robert McDonald, Laura A S Quilter, Kimberly Workowski, Elizabeth Torrone, David A Jackson","doi":"10.1093/cid/ciaf015","DOIUrl":"https://doi.org/10.1093/cid/ciaf015","url":null,"abstract":"National case-based surveillance data show that reported neurologic manifestations of syphilis increased during 2019–2022 among persons with early and late-stage syphilis. Neurologic manifestations occurred across demographic groups and among those with and without HIV, highlighting the importance of evaluating for neurologic signs and symptoms in all persons with syphilis.","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":"8 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142988927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epidemiology and Outcomes of Antibiotic De-escalation in Patients with Suspected Sepsis in US Hospitals.","authors":"Cody A Cunningham, Dan Ilges","doi":"10.1093/cid/ciaf022","DOIUrl":"https://doi.org/10.1093/cid/ciaf022","url":null,"abstract":"","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improving UTI Diagnostics in Oncology: Reliability of Reflex Urine Culture in Immunosuppressed Neutropenic and Non-neutropenic Cancer Patients","authors":"Justin C Laracy, June L Chan, Rich Kodama, Judy Yan, Kevin M Raible, Kent Sepkowitz, Lauren McVoy, N Esther Babady, Mini Kamboj","doi":"10.1093/cid/ciaf018","DOIUrl":"https://doi.org/10.1093/cid/ciaf018","url":null,"abstract":"Background Urinary tract infections are prone to overdiagnosis, and reflex urine culture protocols offer a valuable opportunity for diagnostic stewardship in this arena. However, there is no recommended standard testing approach. Cancer patients are often excluded from reflex urine culture protocols, especially if severely immunosuppressed or neutropenic. The aim of this study was to evaluate the performance characteristics of urine screening studies, including dipstick urinalysis for nitrite and leukocyte esterase and urine microscopy for white blood cell count, to detect significant pathogen growth. Methods A retrospective study of 58,098 urine cultures with a paired dipstick urinalysis with or without urine microscopy was performed at Memorial Sloan Kettering Cancer Center in New York City, evaluating data from January 1, 2018, to December 31, 2020. A dipstick urinalysis was considered negative only if leukocyte esterase and nitrite were undetected. Results A negative dipstick urinalysis had a negative predictive value (NPV) of 98% for clinically significant bacteriuria in voided urine, and 95% for catheterized urine. Notably, a negative urine dipstick test screen maintained a high NPV among patients with neutropenia and in those with antibiotic exposure before testing. Finally, the presence of pyuria ≥10 white blood cells per high power field on urine microscopy offered negligible incremental diagnostic benefit in samples with a negative dipstick urinalysis. Conclusions Reflex urine culture protocols contingent upon a screening dipstick urinalysis are a safe and effective platform for diagnostic stewardship in patients with cancer including those with neutropenia.","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":"74 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142981514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low CD4+ cell counts linked to mortality after sustained virological response: evaluating interaction with liver stiffness vs. FIB-4.","authors":"Anaïs Corma-Gómez, Jésica Martín-Carmona, Juan A Pineda, Juan Macías","doi":"10.1093/cid/ciaf017","DOIUrl":"https://doi.org/10.1093/cid/ciaf017","url":null,"abstract":"","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Fluconazole Resistance on the Outcomes of Patients With Candida parapsilosis Bloodstream Infections: A Retrospective Multicenter Study.","authors":"Antonio Vena, Giusy Tiseo, Marco Falcone, Claudia Bartalucci, Cristina Marelli, Mario Cesaretti, Vincenzo Di Pilato, Pilar Escribano, Arianna Forniti, Daniele Roberto Giacobbe, Jesus Guinea, Alessandro Limongelli, Antonella Lupetti, Marina Machado, Malgorzata Mikulska, Jon Salmanton-García, Ana Soriano-Martin, Lucia Taramasso, Maricela Valerio, Emilio Bouza, Patricia Muñoz, Matteo Bassetti","doi":"10.1093/cid/ciae603","DOIUrl":"https://doi.org/10.1093/cid/ciae603","url":null,"abstract":"<p><strong>Background: </strong>This study assesses the impact of fluconazole resistance on 30-day all-cause mortality and 1-year recurrence in patients with Candida parapsilosis bloodstream infections (BSI).</p><p><strong>Methods: </strong>A multicenter retrospective study was performed at 3 hospitals in Italy and Spain between 2018 and 2022. Adult patients with positive blood cultures for C. parapsilosis who received appropriate targeted therapy with either echinocandins or fluconazole were included.</p><p><strong>Results: </strong>Among 457 patients, 196 (42.9%) had fluconazole-resistant C. parapsilosis (FLZR-CP) BSI and 261 (57.1%) had fluconazole-susceptible C. parapsilosis (FLZS-CP) BSI. All FLZR-CP patients received targeted echinocandins, while FLZS-CP patients received either echinocandins (60.5%) or fluconazole (39.5%). Unadjusted 30-day all-cause mortality rates were 28.6% for FLZR-CP and 28.4% for FLZS-CP (log-rank test, P = .998). In multivariable analysis, increased mortality was associated with age (adjusted hazard ratio [aHR] 1.03 per year; 95% confidence interval [CI], 1.01-1.05; P = .0005), solid tumor (aHR 1.91; 95% CI, 1.06-3.46; P = .0302), previous antifungal treatment (aHR 1.84; 95% CI, 1.12-3.10; P = .0192), and septic shock (aHR 2.39; 95% CI, 1.42-4.06; P = .0010), but not fluconazole resistance (aHR 1.00; 95% CI, .62-1.63; P = .9864) nor the type of initial antifungal therapy (aHR 1.46; 95% CI, .69-3.06; P = .3202). Propensity score-matched analysis showed no 30-day all-cause mortality difference between echinocandin-treated FLZR-CP and fluconazole-treated FLZS-CP patients (HR 0.81; 95% CI, .37-1.75; P = .5915). However, a higher 1-year recurrence risk was observed in FLZR-CP patients (odds ratio, 7.37; 95% CI, 2.11-25.80; P = .0018).</p><p><strong>Conclusions: </strong>Our results suggest that fluconazole resistance is not associated with a higher mortality risk in patients with C. parapsilosis BSI, though 1-year recurrence rates were higher in the FLZR-CP group.</p>","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}