Clinical Infectious Diseases最新文献

{"title":"Refractory and Resistant Herpes Simplex Virus Mucocutaneous Infections in Immunocompromised Patients: Literature Review and Proposed Definitions for Use in Clinical Trials","authors":"Roy F Chemaly, Tali Shafat, Anna Wald, Camille N Kotton, Genovefa Papanicolaou, Michelle K Yong, Veronica Miller, Takashi E Komatsu, Charu Mullick, Aimee C Hodowanec, Gabriel Westman, Fareed Khawaja, Alexander Birkmann, Per Ljungman","doi":"10.1093/cid/ciae638","DOIUrl":"https://doi.org/10.1093/cid/ciae638","url":null,"abstract":"Herpes simplex virus (HSV) infection is one of the most prevalent viral infections worldwide. In general, host immunity is sufficient to clear viral shedding and recurrences, although it is insufficient to prevent subsequent virologic reactivations. In immunocompromised patients, prolonged and difficult-to-treat HSV infections may develop. The diagnosis of refractory HSV infection is based on the lack of clinical response to nucleoside analogs. Antiviral resistance is confirmed via genotypic and/or phenotypic testing. To provide consensus definitions of refractory and/or resistant (R/R) HSV mucocutaneous infections for clinical trial use, the HSV Resistance Working Group of the Transplant Associated Viral Infections Forum, which includes international clinicians, scientists, industry representatives, and regulatory officials, conducted a literature review of previously published data related to R/R HSV infections in immunocompromised patients. We propose definitions of R/R HSV mucocutaneous infections, which will be subject to re-evaluation and revision based on forthcoming data and future studies.","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":"26 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056617","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":"Thigh Injections of Cabotegravir + Rilpivirine in Virally Suppressed Adults With Human Immunodeficiency Virus Type 1: A Substudy of the Phase 3b ATLAS-2M Study.","authors":"Susan L Ford,Franco Felizarta,Kelong Han,Kehui Wang,Herta Crauwels,Anna Dari,Mar Masia,Miguel Garcia Deltoro,Olaf Degen,Jonathan B Angel,Chiu-Bin Hsiao,Carolina Acuipil,Irina Kolobova,Conn Harrington,Kelly Rimler,William Spreen,Ronald D'Amico","doi":"10.1093/cid/ciae620","DOIUrl":"https://doi.org/10.1093/cid/ciae620","url":null,"abstract":"BACKGROUNDCabotegravir + rilpivirine (CAB + RPV) administered via intramuscular gluteal injections is the first complete long-acting regimen for maintaining human immunodeficiency virus type 1 (HIV-1) virologic suppression. We present substudy results on short-term repeat intramuscular CAB + RPV long-acting thigh injections in participants with ≥3 years of experience with gluteal administration during the ATLAS-2M study.METHODSSubstudy phases included screening, thigh injection (day 1-week 16), and return to gluteal injection (week 16-week 24). The injection schedule was unchanged from the main study. Outcomes included pharmacokinetics, safety, tolerability, efficacy, and patient-reported outcomes. Pharmacokinetic parameters were determined using noncompartmental analysis and mixed-effects modeling. Population pharmacokinetic simulations were performed.RESULTSThere were 118 participants. In the arm that received injections every 2 months (Q2M), first CAB thigh injection including area under the concentration-time curve and maximum observed concentration (Cmax) and first RPV thigh injection Cmax and all last RPV thigh injection parameters were statistically higher vs gluteal injections (paired comparison). No significant differences occurred with once-monthly (QM) dosing. No participants had HIV-1 RNA ≥50 copies/mL after thigh injections. Overall, 4%-7% of injection site reactions (ISRs) were grade 3. Five participants withdrew due to an ISR or injection intolerability. Overall, 30% preferred thigh vs gluteal injections. Simulations demonstrated the potential for chronic/continuous QM or ≤2 consecutive Q2M thigh injections.CONCLUSIONSThese data demonstrate the potential use of chronic/continuous QM and rotational/short-term QM or Q2M (≤4 months of continuous dosing), CAB + RPV long-acting intramuscular thigh administration for HIV-1 treatment.","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":"74 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057059","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":"A New Choice for Doxycycline Prophylaxis.","authors":"Jeffrey D Klausner","doi":"10.1093/cid/ciaf044","DOIUrl":"https://doi.org/10.1093/cid/ciaf044","url":null,"abstract":"","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":"60 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062056","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":"Comparative Outcomes of Babesiosis in Immunocompromised and Non-Immunocompromised Hosts: A Multicenter Cohort Study.","authors":"Loukas Kakoullis, Carolyn D Alonso, Rebecca Burns, Muneerah M Aleissa, Esther Arbona Haddad, Andy J Kim, Rebecca Rooks, Bridget Yates, Urwah Kanwal, Nicholas P Morreale, Alexandra Morgan, Ramy Arnaout, Alexandra Tong, Natalie E Izaguirre, Jessica S Little, Sarah P Hammond, Mary W Montgomery, Amy C Sherman, James H Maguire, Ann E Woolley, Lindsey R Baden, Nicolas C Issa, Courtney E Harris","doi":"10.1093/cid/ciaf034","DOIUrl":"https://doi.org/10.1093/cid/ciaf034","url":null,"abstract":"<p><strong>Background: </strong>Babesiosis poses significant risks of adverse outcomes in individuals with immunocompromising conditions (IC) and asplenia/hyposplenia (AH). This study compares clinical outcomes between these vulnerable groups and immunocompetent patients.</p><p><strong>Methods: </strong>A multicenter retrospective cohort study included adult patients with laboratory-confirmed babesiosis from 2009 to 2023. Complications, management, and outcomes were compared between patients with IC/AH (ICAH) and without ICAH (immune intact cohort).</p><p><strong>Results: </strong>Of 225 patients (mean age 66 years, 36% female), 112 were ICAH. ICAH patients had higher median peak parasitemia (2.8% vs. 0.9%, p<0.0001) and higher rates of complications, including acute kidney injury (24% vs. 11%, p=0.016), acute respiratory distress syndrome (11% vs. 4%, p=0.041), and were more likely to undergo packed red blood cell transfusion (31% vs. 17%, p=0.023) and exchange transfusion (18% vs. 6%, p=0.008). Treatment duration was longer in the ICAH cohort (median 27 vs. 10 days, p<0.001), particularly in those with both IC and AH (median 43 days, p=0.003). ICAH patients had higher 12-month all-cause mortality (7% vs. 1%, p=0.019) and recurrence rates (8% vs. 0%, p=0.001). Hematologic malignancy (OR=7.0, p=0.023) and B-cell-depleting therapies (OR=9.4, p=0.015) were significant predictors of recurrence. Despite most patients undergoing follow-up testing with blood smears and PCR, these did not reliably predict recurrence.</p><p><strong>Conclusion: </strong>Patients with ICAH with babesiosis experience more severe disease and higher complication rates. Follow-up testing, including blood smear and PCR, did not reliably predict recurrence, highlighting the need for more effective monitoring strategies in these high-risk populations.</p>","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051922","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":"Policy Recommendations to Support Equitable Access to Long-Acting Injectables for Human Immunodeficiency Virus Prevention and Treatment: A Policy Paper of the Infectious Diseases Society of America and the HIV Medicine Association.","authors":"Julia L Marcus, Andrea Weddle, Colleen F Kelley, Allison Agwu, Sheila Montalvo, Elizabeth Sherman, Tara Vijayan, Jose Gutierrez, Matthew D Hickey, Samantha E Dilworth, Douglas Krakower, Teaniese L Davis, Lauren F Collins, Moira C McNulty, Jonathan A Colasanti, Katerina A Christopoulos","doi":"10.1093/cid/ciae648","DOIUrl":"10.1093/cid/ciae648","url":null,"abstract":"<p><p>Long-acting injectables (LAIs) for HIV prevention and treatment could dramatically improve health outcomes and health equity for people with HIV and those who could benefit from pre-exposure prophylaxis. Despite widespread acceptability and demand by providers and potential users of LAIs, implementation has been extremely limited since the introduction of cabotegravir/rilpivirine, the first LAI for HIV treatment, in January 2021, and long-acting cabotegravir, the first LAI for HIV prevention, in December 2021. We report results of a provider survey, conducted by the HIV Medicine Association, which identified LAI implementation barriers related to health insurance processes, staffing and administrative support, drug costs and acquisition, and access for individuals who are uninsured. We provide policy recommendations to address those barriers and facilitate broad and equitable access to LAIs for HIV prevention and treatment, which will be necessary to achieve the goals of the US Ending the HIV Epidemic initiative.</p>","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051924","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":"Association between Delayed Broad-Spectrum Gram-negative Antibiotics and Clinical Outcomes: How Much Does Getting It Right with Empiric Antibiotics Matter?","authors":"Jonathan D Baghdadi, Katherine E Goodman, Laurence S Magder, Kimberly C Claeys, Mark E Sutherland, Anthony D Harris","doi":"10.1093/cid/ciaf039","DOIUrl":"https://doi.org/10.1093/cid/ciaf039","url":null,"abstract":"Background Clinicians often start unnecessarily broad-spectrum empiric Gram-negative antibiotics out of the concern that delaying effective therapy could lead to a worse clinical outcome. This study examined the consequences of delayed initiation of broad-spectrum Gram-negative antibiotics. Methods In a retrospective cohort of adult inpatients from 928 US hospitals, we compared clinical outcomes after (1) empiric narrow-spectrum antibiotics escalated to broad-spectrum antibiotics (delayed broad-spectrum therapy, DBT) and (2) empiric broad-spectrum antibiotics continued for at least 5 days (early broad-spectrum therapy, EBT) using Win Ratios. DBT and EBT patients were matched on hospital, admitting diagnosis, and propensity scores incorporating 28 clinical variables. The outcome of interest was a ranked composite of mortality, readmission, and adverse drug events. Results Out of 746,880 inpatients, 82,276 (11%) received DBT and 664,604 (89.0%) received EBT. Among the 67,046 with DBT who were matched to 67,046 with EBT, mortality was 8.7% after DBT and 9.5% after EBT (p=0.022), readmission was 10.5% after DBT and 11.8% after EBT (p&amp;lt;0.0001), and the rate of adverse drug events was 8.4% after DBT and 7.2% after EBT (p&amp;lt;0.0001). Among matched patients, clinical outcomes were superior after DBT than after EBT (win-ratio 1.06; p &amp;lt; 0.0001). Conclusions On average, among a large sample of adult inpatients who ultimately received broad-spectrum antibiotic therapy, delaying initiation of a broad-spectrum antibiotic was not associated with worse outcomes. Though broad-spectrum empiric therapy is undoubtedly sometimes warranted, this finding challenges the common belief that is it safer to err towards overly broad-spectrum empiric antibiotic therapy.","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":"15 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143055004","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":"Population-Based Analysis of the Risk of Mycobacterial Infections Associated With Immune Checkpoint Inhibitors.","authors":"Marie Yan, Alejandro Hernandez, Kelvin K Chan, Matthew B Stanbrook, Phillip S Blanchette, James C Johnston, Samantha M Lee, Liane Macdonald, Melissa Richard-Greenblatt, Theodore K Marras, Sarah K Brode","doi":"10.1093/cid/ciae626","DOIUrl":"https://doi.org/10.1093/cid/ciae626","url":null,"abstract":"<p><p>In this population-based study, we examined the risk of nontuberculous mycobacterial disease associated with immune checkpoint inhibitors among people with cancer. Using a nested case-control design, we identified 184 cases and 714 matched controls; there was no significant association on conditional logistic regression (adjusted odds ratio, 0.51 [95% confidence interval, .17-1.50]; P = .22).</p>","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051927","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":"Translating PK-PD principles into improved methodology for clinical trials which compare intermittent with prolonged infusion of beta-lactam antibiotics","authors":"Alwin M Tilanus, Ryan K Shields, Thomas P Lodise, George L Drusano","doi":"10.1093/cid/ciaf038","DOIUrl":"https://doi.org/10.1093/cid/ciaf038","url":null,"abstract":"Based on the fact that beta-lactam antibiotics demonstrate time-dependent killing, different dosing strategies have been implemented to increase the time that free (f) (unbound) antibiotic concentrations remain above the Minimal Inhibitory Concentration (MIC), including prolonged and continuous infusion. Multiple studies have been performed that compared continuous with traditional intermittent infusion to improve outcomes in patients with severe sepsis and/or septic shock. These studies have yielded inconsistent results for patients as measured by clinical response to treatment and mortality due to heterogeneity of included patients, pathogens, dosing strategies and the absence of Therapeutic Drug Monitoring (TDM). The MERCY and BLING III studies failed to show a difference in mortality between patients randomized to receive continuous and intermittent infusion of beta-lactam antibiotics.&amp;#x2028; A deeper understanding of pharmacokinetic (PK) and pharmacodynamic (PD) mechanisms that occur in critically ill patients should guide us in dose optimization and improvement in methodology for future clinical trials.","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":"39 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143049812","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":"Estimating the economic consequences of leveraging the novel cobas® HIV-1/HIV-2 Qualitative NAT Test in routine HIV testing","authors":"S Pinar Bilir, Pallavi Krishnamurthy, James K Karichu, Sara J Blosser, Debbie Hernandez, Tamar Tchelidze, Kwaku Tawiah, Cheryl P Ferrufino","doi":"10.1093/cid/ciaf025","DOIUrl":"https://doi.org/10.1093/cid/ciaf025","url":null,"abstract":"Background Efficient and cost-effective testing strategies are needed to reduce HIV transmission. The aim of this study was to compare the costs of using the current CDC 3-step HIV algorithm - antigen/antibody screening, differentiation immunoassay (Geenius) and NAT against an alternative algorithm using a cobas® HIV-1/HIV-2 qualitative NAT. Methods A one-year cost calculator was developed from a US payer perspective using a decision-tree approach to simulate testing in a population of 1 million individuals. An estimated 2.44% of individuals were tested for HIV with an antigen/antibody immunoassay test, of which 0.72% were reactive. Based on real-world evidence, it was estimated that 8.78% and 1.95% of those tested with Geenius and cobas, respectively, were retested after indeterminate/invalid results. HIV-1/HIV-2 prevalence was applied along with test performance and retest rates to estimate the total number of tests required and the overall costs per algorithm. Results Among 175 patients, overall payer costs with the current and alternative algorithm were $5,299.37 and $6,870.24 respectively, yielding $8.95 additional cost per patient. The total number of tests performed decreased by 21.29% using the alternative algorithm (191.8 vs 243.7). The total number of retests were 20.7 and 4.5 with the current and alternative algorithm, respectively. Conclusion The study demonstrates a significant reduction in the number of cumulative tests needed to diagnose HIV accurately while remaining cost neutral to payers using the alternative algorithm. These findings suggest that the proposed alternative algorithm can streamline HIV testing, without a substantial increase in healthcare costs and minimize adverse patient outcomes.","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":"40 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056620","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 on outcomes of patients with primary pulmonary coccidioidomycosis: a commercial health insurance claims-based, propensity score matched analysis.","authors":"Kaitlin Benedict, Ian Hennessee, Dallas J Smith, Mitsuru Toda, George R Thompson","doi":"10.1093/cid/ciaf036","DOIUrl":"https://doi.org/10.1093/cid/ciaf036","url":null,"abstract":"<p><strong>Background: </strong>Patients with pulmonary coccidioidomycosis often experience prolonged symptoms lasting weeks to months. Limited data exist regarding whether fluconazole prevents development of disseminated disease or shortens symptom duration. We describe factors associated with fluconazole receipt and assess its effect on outcomes among patients with pulmonary coccidioidomycosis.</p><p><strong>Methods: </strong>Using the MerativeTM MarketScan® Commercial Database, we identified immunocompetent patients ages 18-64 with incident pulmonary coccidioidomycosis during 2017-2023 and continuous enrollment in the 180 days before and after diagnosis. We examined demographic and clinical differences between patients treated vs. not treated with fluconazole and performed 1:1 greedy nearest neighbor propensity score matching to control for these differences. We performed bivariate analyses on the matched subset to evaluate patient outcomes by fluconazole receipt.</p><p><strong>Results: </strong>Among 1,448 patients with pulmonary coccidioidomycosis, 659 (46%) received fluconazole. Patients who received fluconazole more frequently had pre-diagnosis symptoms (95% vs. 72%, p<0.001) and antibiotic prescriptions (68% vs. 32%, p<0.001) than those who did not. Among the propensity score matched subset (n=696), hospitalization (4% vs. 1%, p=0.004) and disseminated coccidioidomycosis (3% vs. 0%, p=0.006) were more frequent among patients who received fluconazole. The median number of days from diagnosis to last visit for chest pain (50.0 vs. 46.5), cough (64.0 vs. 39.0), fatigue (63.0 vs. 65.5), myalgia (98.0 vs. 74.0), and joint pain (93.5 vs. 107.5) was not significantly different between treatment groups.</p><p><strong>Conclusions: </strong>Our results support existing guidelines that fluconazole may not be associated with improved outcomes for certain immunocompetent patients with pulmonary coccidioidomycosis.</p>","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021642","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}