Jordan Cates, Claire P. Mattison, Holly Groom, Judy L. Donald, Rebecca P Hall, Mark A Schmidt, Aron J Hall, Allison Naleway, Sara A Mirza
Background Norovirus-associated acute gastroenteritis (AGE) exacts a substantial disease burden, yet the health care utilization for and clinical management of norovirus-associated AGE are not well characterized. Methods We describe the health care encounters and therapeutics used for patients with all-cause and norovirus-associated AGE in the Kaiser Permanente Northwest health system from 1 April 2014 through 30 September 2016. Medical encounters for patients with AGE were extracted from electronic health records, and encounters within 30 days of one another were grouped into single episodes. An age-stratified random sample of patients completed surveys and provided stool samples for norovirus testing. Results In total, 40 348 individuals had 52 509 AGE episodes; 460 (14%) of 3310 participants in the substudy tested positive for norovirus. An overall 35% of all-cause AGE episodes and 29% of norovirus-associated AGE episodes had ≥2 encounters. While 80% of norovirus-associated AGE episodes had at least 1 encounter in the outpatient setting, all levels of the health care system were affected: 10%, 22%, 10%, and 2% of norovirus-associated AGE episodes had at least 1 encounter in virtual, urgent care, emergency department, and inpatient settings, respectively. Corresponding proportions of therapeutic use between norovirus-positive and norovirus-negative episodes were 13% and 10% for intravenous hydration (P = .07), 65% and 50% for oral rehydration (P < .001), 7% and 14% for empiric antibiotic therapy (P < .001), and 33% and 18% for antiemetics (P < .001). Conclusions Increased health care utilization and therapeutics are likely needed for norovirus-associated AGE episodes during peak norovirus winter seasons, and these data illustrate that effective norovirus vaccines will likely result in less health care utilization.
{"title":"Health Care Utilization and Clinical Management of All-Cause and Norovirus-Associated Acute Gastroenteritis Within a US Integrated Health Care System.","authors":"Jordan Cates, Claire P. Mattison, Holly Groom, Judy L. Donald, Rebecca P Hall, Mark A Schmidt, Aron J Hall, Allison Naleway, Sara A Mirza","doi":"10.1093/ofid/ofae151","DOIUrl":"https://doi.org/10.1093/ofid/ofae151","url":null,"abstract":"Background\u0000Norovirus-associated acute gastroenteritis (AGE) exacts a substantial disease burden, yet the health care utilization for and clinical management of norovirus-associated AGE are not well characterized.\u0000\u0000\u0000Methods\u0000We describe the health care encounters and therapeutics used for patients with all-cause and norovirus-associated AGE in the Kaiser Permanente Northwest health system from 1 April 2014 through 30 September 2016. Medical encounters for patients with AGE were extracted from electronic health records, and encounters within 30 days of one another were grouped into single episodes. An age-stratified random sample of patients completed surveys and provided stool samples for norovirus testing.\u0000\u0000\u0000Results\u0000In total, 40 348 individuals had 52 509 AGE episodes; 460 (14%) of 3310 participants in the substudy tested positive for norovirus. An overall 35% of all-cause AGE episodes and 29% of norovirus-associated AGE episodes had ≥2 encounters. While 80% of norovirus-associated AGE episodes had at least 1 encounter in the outpatient setting, all levels of the health care system were affected: 10%, 22%, 10%, and 2% of norovirus-associated AGE episodes had at least 1 encounter in virtual, urgent care, emergency department, and inpatient settings, respectively. Corresponding proportions of therapeutic use between norovirus-positive and norovirus-negative episodes were 13% and 10% for intravenous hydration (P = .07), 65% and 50% for oral rehydration (P < .001), 7% and 14% for empiric antibiotic therapy (P < .001), and 33% and 18% for antiemetics (P < .001).\u0000\u0000\u0000Conclusions\u0000Increased health care utilization and therapeutics are likely needed for norovirus-associated AGE episodes during peak norovirus winter seasons, and these data illustrate that effective norovirus vaccines will likely result in less health care utilization.","PeriodicalId":510506,"journal":{"name":"Open Forum Infectious Diseases","volume":"129 1","pages":"ofae151"},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140780376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ifeanyichukwu U Anidi, Shunsuke Sakai, Kelsie Brooks, S. Fling, Michael J Wagner, K. Lurain, C. L. Lindestam Arlehamn, Alessandro Sette, Kenneth S Knox, J. Brenchley, Thomas Uldrick, Elad Sharon, Daniel L Barber
Blockade of the co-inhibitory receptor PD-1 enhances anti-tumor responses by boosting the function of antigen-specific T cells. Although rare, PD-1 blockade in patients with cancer can lead to exacerbation of infection-associated pathology. Here we detail the case of a 38-year-old man who was enrolled in a clinical trial for assessment of the safety and activity of anti-PD-1 therapy for Kaposi sarcoma in people with HIV (PWH) well-controlled on anti-retroviral therapy (ART). Less than a week after receiving the first dose of anti-PD1 antibody (pembrolizumab), he presented with severe abdominal pain associated with sudden exacerbations of pre-existing cytomegalovirus (CMV) enteritis and nontuberculous mycobacterial mesenteric lymphadenitis. Plasma biomarkers of gastrointestinal (GI) tract damage were highly elevated compared to healthy controls, consistent with HIV associated loss of gut epithelial barrier integrity. Moreover, CMV-specific CD8 T cells expressed high levels of PD-1, and seven days following PD-1 blockade there was an increase in the frequency of activated CD38 + Ki67+ CMV-specific CD8 T cells. This case highlights the potential for PD-1 blockade to drive rapid exacerbations of inflammatory symptoms when administered to individuals harboring multiple unresolved infections.
通过增强抗原特异性 T 细胞的功能，阻断协同抑制受体 PD-1 可增强抗肿瘤反应。在癌症患者中阻断 PD-1 虽然罕见，但会导致感染相关病症的加重。我们在此详细介绍一名 38 岁男子的病例，他参加了一项临床试验，以评估抗逆转录病毒疗法（ART）控制良好的艾滋病病毒感染者（PWH）使用抗 PD-1 疗法治疗卡波西肉瘤的安全性和活性。在接受第一剂抗PD1抗体（pembrolizumab）治疗不到一周后，他出现了剧烈腹痛，并伴有原有的巨细胞病毒（CMV）肠炎和非结核分枝杆菌肠系膜淋巴结炎突然加重。与健康对照组相比，胃肠道（GI）损伤的血浆生物标志物高度升高，这与艾滋病导致的肠道上皮屏障完整性丧失一致。此外，CMV 特异性 CD8 T 细胞表达高水平的 PD-1，PD-1 阻断七天后，活化的 CD38 + Ki67+ CMV 特异性 CD8 T 细胞的频率增加。该病例突出表明，当对携带多种未解决感染的患者施用 PD-1 阻断剂时，可能会导致炎症症状迅速加重。
{"title":"Exacerbation of CMV and Nontuberculous Mycobacterial Infections Following PD-1 Blockade for HIV-Associated Kaposi Sarcoma","authors":"Ifeanyichukwu U Anidi, Shunsuke Sakai, Kelsie Brooks, S. Fling, Michael J Wagner, K. Lurain, C. L. Lindestam Arlehamn, Alessandro Sette, Kenneth S Knox, J. Brenchley, Thomas Uldrick, Elad Sharon, Daniel L Barber","doi":"10.1093/ofid/ofae183","DOIUrl":"https://doi.org/10.1093/ofid/ofae183","url":null,"abstract":"\u0000 Blockade of the co-inhibitory receptor PD-1 enhances anti-tumor responses by boosting the function of antigen-specific T cells. Although rare, PD-1 blockade in patients with cancer can lead to exacerbation of infection-associated pathology. Here we detail the case of a 38-year-old man who was enrolled in a clinical trial for assessment of the safety and activity of anti-PD-1 therapy for Kaposi sarcoma in people with HIV (PWH) well-controlled on anti-retroviral therapy (ART). Less than a week after receiving the first dose of anti-PD1 antibody (pembrolizumab), he presented with severe abdominal pain associated with sudden exacerbations of pre-existing cytomegalovirus (CMV) enteritis and nontuberculous mycobacterial mesenteric lymphadenitis. Plasma biomarkers of gastrointestinal (GI) tract damage were highly elevated compared to healthy controls, consistent with HIV associated loss of gut epithelial barrier integrity. Moreover, CMV-specific CD8 T cells expressed high levels of PD-1, and seven days following PD-1 blockade there was an increase in the frequency of activated CD38 + Ki67+ CMV-specific CD8 T cells. This case highlights the potential for PD-1 blockade to drive rapid exacerbations of inflammatory symptoms when administered to individuals harboring multiple unresolved infections.","PeriodicalId":510506,"journal":{"name":"Open Forum Infectious Diseases","volume":"14 24","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140358829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maria J Duarte, Phyllis C Tien, Ani Kardashian, Yifei Ma, Peter W Hunt, M. Kuniholm, A. Adimora, Margaret A. Fischl, Audrey L French, Elizabeth F Topper, D. Konkle-Parker, Howard Minkoff, Ighovwerha Ofotokun, Michael Plankey, Anjali Sharma, Jennifer C Price
Steatohepatitis is common in persons living with HIV (PLWH) and may be associated with gut microbial translocation (MT). However, few have evaluated the gut-liver axis in PLWH. We examined associations of HIV and circulating biomarkers linked to MT and gut-damage with the FibroScan-AST (FAST) score, a non-invasive surrogate for steatohepatitis with advanced fibrosis, in the Women’s Interagency HIV Study. Among 883 women with HIV (WWH) and 354 without HIV, we used multivariable regression to examine the associations of HIV and serum biomarkers linked to MT and gut-damage (KT ratio, I-FABP, sCD14, and sCD163) with log-transformed FAST score after adjusting for key covariates. We used a path analysis and mediation models to determine the mediating effect of each biomarker on the association of HIV with FAST. HIV infection was associated with a 49% higher FAST score. MT biomarker levels were higher in WWH than women without HIV (p<0.001 for each). MT biomarker MT mediated 13-32% of the association of HIV and FAST score. Biomarkers linked to MT and gut-damage are associated with higher FAST score and mediate the association of HIV with higher FAST. Our findings suggest that MT may be an important mechanism by which HIV increases the risk of steatohepatitis with advanced fibrosis.
脂肪性肝炎在艾滋病病毒感染者（PLWH）中很常见，可能与肠道微生物转位（MT）有关。然而，很少有人对艾滋病病毒感染者的肠道-肝脏轴进行评估。我们在妇女艾滋病病毒感染者机构间研究（Women's Interagency HIV Study）中研究了艾滋病病毒、与 MT 和肠道损伤相关的循环生物标志物与纤维扫描-AST（FAST）评分的关系。 在 883 名感染 HIV 的女性（WWH）和 354 名未感染 HIV 的女性中，我们使用多变量回归法研究了 HIV 和与 MT 和肠道损伤相关的血清生物标志物（KT 比值、I-FABP、sCD14 和 sCD163）与对数变换的 FAST 评分之间的关系。我们使用路径分析和中介模型来确定每种生物标志物对 HIV 与 FAST 相关性的中介效应。 HIV感染与49%的FAST评分相关。WWH妇女的MT生物标志物水平高于未感染HIV的妇女（P<0.001）。MT生物标志物MT介导了13-32%的HIV与FAST评分的关联。 与 MT 和肠道损伤相关的生物标志物与较高的 FAST 评分有关，并介导了 HIV 与较高 FAST 的关联。我们的研究结果表明，MT 可能是艾滋病毒增加晚期纤维化脂肪性肝炎风险的一个重要机制。
{"title":"Microbial Translocation and Gut-Damage is Associated with Elevated Fast Score in Women Living with and without HIV","authors":"Maria J Duarte, Phyllis C Tien, Ani Kardashian, Yifei Ma, Peter W Hunt, M. Kuniholm, A. Adimora, Margaret A. Fischl, Audrey L French, Elizabeth F Topper, D. Konkle-Parker, Howard Minkoff, Ighovwerha Ofotokun, Michael Plankey, Anjali Sharma, Jennifer C Price","doi":"10.1093/ofid/ofae187","DOIUrl":"https://doi.org/10.1093/ofid/ofae187","url":null,"abstract":"\u0000 \u0000 \u0000 Steatohepatitis is common in persons living with HIV (PLWH) and may be associated with gut microbial translocation (MT). However, few have evaluated the gut-liver axis in PLWH. We examined associations of HIV and circulating biomarkers linked to MT and gut-damage with the FibroScan-AST (FAST) score, a non-invasive surrogate for steatohepatitis with advanced fibrosis, in the Women’s Interagency HIV Study.\u0000 \u0000 \u0000 \u0000 Among 883 women with HIV (WWH) and 354 without HIV, we used multivariable regression to examine the associations of HIV and serum biomarkers linked to MT and gut-damage (KT ratio, I-FABP, sCD14, and sCD163) with log-transformed FAST score after adjusting for key covariates. We used a path analysis and mediation models to determine the mediating effect of each biomarker on the association of HIV with FAST.\u0000 \u0000 \u0000 \u0000 HIV infection was associated with a 49% higher FAST score. MT biomarker levels were higher in WWH than women without HIV (p<0.001 for each). MT biomarker MT mediated 13-32% of the association of HIV and FAST score.\u0000 \u0000 \u0000 \u0000 Biomarkers linked to MT and gut-damage are associated with higher FAST score and mediate the association of HIV with higher FAST. Our findings suggest that MT may be an important mechanism by which HIV increases the risk of steatohepatitis with advanced fibrosis.\u0000","PeriodicalId":510506,"journal":{"name":"Open Forum Infectious Diseases","volume":"56 44","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140362850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Ganesan, H. Hsieh, X. Chu, R. Colombo, C. Berjohn, T. Lalani, Joseph M. Yabes, Christie A. Joya, J. Blaylock, B. Agan
The consequences of low-level viremia in people living with HIV are unclear. We used data from the U.S. Military HIV Natural History Study (NHS) to examine the association of low-level viremia (LLV) and serious non-AIDS events (SNAEs). Included participants initiated antiretroviral therapy (ART) after 1996, had ≥3 viral loads (VLs) measured, using an assay with a lower limit of detection of <50 copies/mL, ≥6 months after ART initiation. VLs were categorized as lower levels of LLV (51-199 copies/mL), higher level of low-level viremia (HLLV-200-999 copies/mL), and virologic failure (VF- ≥200 copies/mL on 2 or more successive determinations or a single VL ≥1000 copies/mL), and virologic suppression (VS- i.e., VL <50 copies/mL). Viral blips [i.e., VLs between 50 and 999 copies/mL that are preceded and succeeded by VL <50 copies/mL] were analyzed in the VS category. Cox Proportional Hazards models were used to examine the association of LLV and SNAEs, adjusted hazard ratios and 95% CI are presented. A total of 439 (17.4%) SNAEs were recorded among the 2528 participants (93% male, 40% Caucasian, 43% African American) followed for a median of 11 years. In 8.5% and 4.6% of the participants, respectively, LLV and HLLV were the highest recorded viremia strata. Compared with VS, SNAEs were associated with LLV (1.3, [1.2 to 1.4]), HLLV (1.6, [1.5 to 1.7]), and VF (1.7, [1.7 to 1.8]). The results of this study suggest that LLV is associated with the occurrence of SNAEs and needs further study.
{"title":"Low level viremia is associated with Serious Non-AIDS Events in People Living with HIV","authors":"A. Ganesan, H. Hsieh, X. Chu, R. Colombo, C. Berjohn, T. Lalani, Joseph M. Yabes, Christie A. Joya, J. Blaylock, B. Agan","doi":"10.1093/ofid/ofae147","DOIUrl":"https://doi.org/10.1093/ofid/ofae147","url":null,"abstract":"\u0000 \u0000 \u0000 The consequences of low-level viremia in people living with HIV are unclear. We used data from the U.S. Military HIV Natural History Study (NHS) to examine the association of low-level viremia (LLV) and serious non-AIDS events (SNAEs).\u0000 \u0000 \u0000 \u0000 Included participants initiated antiretroviral therapy (ART) after 1996, had ≥3 viral loads (VLs) measured, using an assay with a lower limit of detection of <50 copies/mL, ≥6 months after ART initiation. VLs were categorized as lower levels of LLV (51-199 copies/mL), higher level of low-level viremia (HLLV-200-999 copies/mL), and virologic failure (VF- ≥200 copies/mL on 2 or more successive determinations or a single VL ≥1000 copies/mL), and virologic suppression (VS- i.e., VL <50 copies/mL). Viral blips [i.e., VLs between 50 and 999 copies/mL that are preceded and succeeded by VL <50 copies/mL] were analyzed in the VS category. Cox Proportional Hazards models were used to examine the association of LLV and SNAEs, adjusted hazard ratios and 95% CI are presented.\u0000 \u0000 \u0000 \u0000 A total of 439 (17.4%) SNAEs were recorded among the 2528 participants (93% male, 40% Caucasian, 43% African American) followed for a median of 11 years. In 8.5% and 4.6% of the participants, respectively, LLV and HLLV were the highest recorded viremia strata. Compared with VS, SNAEs were associated with LLV (1.3, [1.2 to 1.4]), HLLV (1.6, [1.5 to 1.7]), and VF (1.7, [1.7 to 1.8]).\u0000 \u0000 \u0000 \u0000 The results of this study suggest that LLV is associated with the occurrence of SNAEs and needs further study.\u0000","PeriodicalId":510506,"journal":{"name":"Open Forum Infectious Diseases","volume":"53 28","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140362882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Christine M Thomas, R. Raman, W. Schaffner, Tiffanie M. Markus, D. Ndi, Mary-Margaret A. Fill, John R Dunn, H. K. Talbot
Respiratory syncytial virus (RSV) can cause hospitalization in young children and older adults. With vaccines and monoclonal antibody prophylaxis increasingly available, identifying social factors associated with severe illnesses can guide mitigation efforts. Using data collected by the RSV Hospitalization Surveillance Network during 2016–2023, we identified RSV hospitalizations in Tennessee. We linked hospitalization information (e.g., patient demographic characteristics and outcome) with population-level variables (e.g., social vulnerability and healthcare insurance coverage) from publicly available datasets using census tract of residence. Hospitalization incidence was calculated and stratified by period (2016–2020 and 2020–2023). We modeled social vulnerability effect on hospitalization incidence using Poisson regression. Among 2,687 RSV hospitalizations, 677 (25.2%) included intensive care unit admission and 38 (1.4%) deaths. Highest RSV hospitalization incidences occurred among children aged <5 years and adults aged ≥65 years (272.8/100,000 person-years [95% CI: 258.6–287.0] and 60.6/100,000 person-years [95% CI: 56.0–65.2], respectively). Having public health insurance was associated with higher hospitalization incidence, compared with not having public insurance (60.5/100,000 person-years [95% CI: 57.6–63.4] vs 14.3/100,000 person-years [95% CI: 13.4–15.2]). Higher hospitalization incidence was associated with residing in a census tract in the most socially vulnerable quartile, compared with least vulnerable quartile after adjusting for age, sex, and period (IRR = 1.4 [95% CI: 1.3–1.6]). RSV hospitalization was associated with living in more socially vulnerable census tracts. Population measures of social vulnerability might help guide mitigation strategies, including vaccine and monoclonal antibody promotion and provision to reduce RSV hospitalization.
{"title":"Respiratory Syncytial Virus Hospitalizations Associated with Social Vulnerability by Census Tract: An Opportunity for Intervention?","authors":"Christine M Thomas, R. Raman, W. Schaffner, Tiffanie M. Markus, D. Ndi, Mary-Margaret A. Fill, John R Dunn, H. K. Talbot","doi":"10.1093/ofid/ofae184","DOIUrl":"https://doi.org/10.1093/ofid/ofae184","url":null,"abstract":"\u0000 \u0000 \u0000 Respiratory syncytial virus (RSV) can cause hospitalization in young children and older adults. With vaccines and monoclonal antibody prophylaxis increasingly available, identifying social factors associated with severe illnesses can guide mitigation efforts.\u0000 \u0000 \u0000 \u0000 Using data collected by the RSV Hospitalization Surveillance Network during 2016–2023, we identified RSV hospitalizations in Tennessee. We linked hospitalization information (e.g., patient demographic characteristics and outcome) with population-level variables (e.g., social vulnerability and healthcare insurance coverage) from publicly available datasets using census tract of residence. Hospitalization incidence was calculated and stratified by period (2016–2020 and 2020–2023). We modeled social vulnerability effect on hospitalization incidence using Poisson regression.\u0000 \u0000 \u0000 \u0000 Among 2,687 RSV hospitalizations, 677 (25.2%) included intensive care unit admission and 38 (1.4%) deaths. Highest RSV hospitalization incidences occurred among children aged <5 years and adults aged ≥65 years (272.8/100,000 person-years [95% CI: 258.6–287.0] and 60.6/100,000 person-years [95% CI: 56.0–65.2], respectively). Having public health insurance was associated with higher hospitalization incidence, compared with not having public insurance (60.5/100,000 person-years [95% CI: 57.6–63.4] vs 14.3/100,000 person-years [95% CI: 13.4–15.2]). Higher hospitalization incidence was associated with residing in a census tract in the most socially vulnerable quartile, compared with least vulnerable quartile after adjusting for age, sex, and period (IRR = 1.4 [95% CI: 1.3–1.6]).\u0000 \u0000 \u0000 \u0000 RSV hospitalization was associated with living in more socially vulnerable census tracts. Population measures of social vulnerability might help guide mitigation strategies, including vaccine and monoclonal antibody promotion and provision to reduce RSV hospitalization.\u0000","PeriodicalId":510506,"journal":{"name":"Open Forum Infectious Diseases","volume":"60 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140365063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Guy Handley, John Greene, Anthony P Cannella, Ana Paula Velez, Shivan Shah, Yanina Pasikhova
Posaconazole maintains broad antifungal activity and is employed for prevention and treatment of invasive fungal infections in oncology patients. Older formulations required therapeutic drug monitoring, and specific plasma drug levels have been recommended. This study evaluated factors associated with sub-therapeutic concentrations with the newer delayed-release tablet formulation. In this retrospective, single center cohort study at a national comprehensive cancer center all oncology patients receiving delayed-release posaconazole at standard dosing of 300mg orally per day from 06/2021–07/2023 with plasma drug concentration evaluation were identified. Demographic, clinical and laboratory data were evaluated to identify risk factors associated with sub-therapeutic drug legs at targets of ≥1.25 µg/mL and ≥1.8 µg/mL. Of 110 patients identified, 98 met criteria for inclusion into the study. Median time from initiation of posaconazole to drug level assessment was 13 days and median concentration was 1.29 µg/mL. Of the 22 patients receiving posaconazole for prophylaxis 5 (22.7%) failed to achieve concentrations ≥ 0.7 µg/mL and of 76 patients receiving posaconazole for treatment 38 (50%) failed to achieve concentrations of ≥1.25 µg/mL. In multi-variable analysis albumin of ≤3 g/dL and ideal body weight ≥60 kg were found to be associated with sub-therapeutic levels. For a higher target of ≥1.8 µg/mL only albumin ≤3 g/dL was associated with sub-therapeutic levels for variables evaluated. A higher initial dosing strategy and therapeutic drug monitoring for oncology patients with albumin ≤3 g/dL receiving posaconazole particularly for the treatment of invasive fungal infection could be considered.
{"title":"Real World Experience of Posaconazole Therapeutic Drug Monitoring in Oncology Patients: Clinical Implications of Hypoalbuminemia as a Predictor of Subtherapeutic Posaconazole Levels","authors":"Guy Handley, John Greene, Anthony P Cannella, Ana Paula Velez, Shivan Shah, Yanina Pasikhova","doi":"10.1093/ofid/ofae185","DOIUrl":"https://doi.org/10.1093/ofid/ofae185","url":null,"abstract":"\u0000 \u0000 \u0000 Posaconazole maintains broad antifungal activity and is employed for prevention and treatment of invasive fungal infections in oncology patients. Older formulations required therapeutic drug monitoring, and specific plasma drug levels have been recommended. This study evaluated factors associated with sub-therapeutic concentrations with the newer delayed-release tablet formulation.\u0000 \u0000 \u0000 \u0000 In this retrospective, single center cohort study at a national comprehensive cancer center all oncology patients receiving delayed-release posaconazole at standard dosing of 300mg orally per day from 06/2021–07/2023 with plasma drug concentration evaluation were identified. Demographic, clinical and laboratory data were evaluated to identify risk factors associated with sub-therapeutic drug legs at targets of ≥1.25 µg/mL and ≥1.8 µg/mL.\u0000 \u0000 \u0000 \u0000 Of 110 patients identified, 98 met criteria for inclusion into the study. Median time from initiation of posaconazole to drug level assessment was 13 days and median concentration was 1.29 µg/mL. Of the 22 patients receiving posaconazole for prophylaxis 5 (22.7%) failed to achieve concentrations ≥ 0.7 µg/mL and of 76 patients receiving posaconazole for treatment 38 (50%) failed to achieve concentrations of ≥1.25 µg/mL. In multi-variable analysis albumin of ≤3 g/dL and ideal body weight ≥60 kg were found to be associated with sub-therapeutic levels. For a higher target of ≥1.8 µg/mL only albumin ≤3 g/dL was associated with sub-therapeutic levels for variables evaluated.\u0000 \u0000 \u0000 \u0000 A higher initial dosing strategy and therapeutic drug monitoring for oncology patients with albumin ≤3 g/dL receiving posaconazole particularly for the treatment of invasive fungal infection could be considered.\u0000","PeriodicalId":510506,"journal":{"name":"Open Forum Infectious Diseases","volume":"50 18","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140365272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Takahiro Matsuo, S. Wurster, Ying Jiang, Jeffrey T. Tarrand, D. Kontoyiannis
{"title":"Adjunct terbinafine in patients with leukemia and invasive fusariosis with skin lesions: Discordance between responses of skin lesions and systemic outcomes","authors":"Takahiro Matsuo, S. Wurster, Ying Jiang, Jeffrey T. Tarrand, D. Kontoyiannis","doi":"10.1093/ofid/ofae068","DOIUrl":"https://doi.org/10.1093/ofid/ofae068","url":null,"abstract":"","PeriodicalId":510506,"journal":{"name":"Open Forum Infectious Diseases","volume":"27 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139781679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Takahiro Matsuo, S. Wurster, Ying Jiang, Jeffrey T. Tarrand, D. Kontoyiannis
{"title":"Adjunct terbinafine in patients with leukemia and invasive fusariosis with skin lesions: Discordance between responses of skin lesions and systemic outcomes","authors":"Takahiro Matsuo, S. Wurster, Ying Jiang, Jeffrey T. Tarrand, D. Kontoyiannis","doi":"10.1093/ofid/ofae068","DOIUrl":"https://doi.org/10.1093/ofid/ofae068","url":null,"abstract":"","PeriodicalId":510506,"journal":{"name":"Open Forum Infectious Diseases","volume":"158 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139841427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
T. Kramer, Álex Soriano, Sarah Tedeschi, Antonia F Chen, P. Tattevin, É. Senneville, J. Gómez-Junyent, Victoria Birlutiu, S. Petersdorf, Vicens Diaz de Brito, Ignacio Sancho Gonzalez, Katherine A. Belden, M. Wouthuyzen-Bakker, R. Birlutiu, Marc Trojanowski, Lansing Sugita, Haijun Xu, Montserrat Sanmarti Vilamala, L. Morata, Luisa Sorlí, J. Horcajada, Marie Dorel, Nicolo Rossi, Ashley Barnes, Björn Wandhoff, Vincent Derdour
{"title":"Should we use rifampicin in periprosthetic joint infections caused by staphylococci when the implant has been exchanged? A multicentre observational cohort study","authors":"T. Kramer, Álex Soriano, Sarah Tedeschi, Antonia F Chen, P. Tattevin, É. Senneville, J. Gómez-Junyent, Victoria Birlutiu, S. Petersdorf, Vicens Diaz de Brito, Ignacio Sancho Gonzalez, Katherine A. Belden, M. Wouthuyzen-Bakker, R. Birlutiu, Marc Trojanowski, Lansing Sugita, Haijun Xu, Montserrat Sanmarti Vilamala, L. Morata, Luisa Sorlí, J. Horcajada, Marie Dorel, Nicolo Rossi, Ashley Barnes, Björn Wandhoff, Vincent Derdour","doi":"10.1093/ofid/ofae075","DOIUrl":"https://doi.org/10.1093/ofid/ofae075","url":null,"abstract":"","PeriodicalId":510506,"journal":{"name":"Open Forum Infectious Diseases","volume":" 86","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139793067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Things We Do for No Reason – Ordering Streptococcus pneumoniae Urinary Antigen in Patients with Community-Acquired Pneumonia","authors":"Matthew R Davis, E. McCreary, Alex M Trzebucki","doi":"10.1093/ofid/ofae089","DOIUrl":"https://doi.org/10.1093/ofid/ofae089","url":null,"abstract":"","PeriodicalId":510506,"journal":{"name":"Open Forum Infectious Diseases","volume":"43 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139851188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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