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1.
Antimicrob Agents Chemother ; : AAC0199121, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35007139

RESUMO

There is an urgent global need for new strategies and drugs to control and treat multi-drug resistant bacterial infections. In 2017, the World Health Organization (WHO) released a list of 12 antibiotic-resistant priority pathogens and began to critically analyze the antibacterial clinical pipeline. This review analyzes 'traditional' and 'non-traditional' antibacterial agents and modulators in clinical development current on 30 June 2021 with activity against the WHO priority pathogens, mycobacteria and Clostridioides difficile. Since 2017, 12 new antibacterial drugs have been approved globally, but only vaborbactam belongs to a new antibacterial class. Also innovative is the cephalosporin derivative cefiderocol, which incorporates an iron-chelating siderophore that facilitates Gram-negative bacteria cell entry. Overall, there were 76 antibacterial agents in clinical development (45 traditional and 31 non-traditional) with 28 in Phase 1, 32 in Phase 2, 12 in Phase 3 and four under regulatory evaluation. Forty-one out of 76 (54%) targeted WHO priority pathogens, 16 (21%) against mycobacteria, 15 (20%) against C. difficile and 4 (5%) are non-traditional agents with broad spectrum effects. Nineteen of the 76 antibacterial agents have new pharmacophores and four of these have new modes of actions not previously exploited by marketed antibacterial drugs. Despite there being 76 antibacterial clinical candidates, this analysis indicated that there were still relatively few clinically differentiated antibacterial agents in late-stage clinical development, especially against critical Priority Pathogens. We believe that future antibacterial R&D should focus on the development of innovative and clinically differentiated candidates that have clear and feasible progression pathways to the market.

2.
Gerontology ; : 1-11, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34999588

RESUMO

INTRODUCTION: Old age is an independent risk factor (RF) for severe COVID-19; evidence for clinico-epidemiological characteristics among elderly COVID-19 patients is scarce. We aimed to analyze clinical and epidemiological characteristics and comorbidities associated with COVID-19 inpatients in age-stratified populations of an elderly COVID-19 cohort. METHODS: We conducted a retrospective cohort study, using nationwide registry data of COVID-19 patients hospitalized before October 31, 2020 (major information entered in the registry as of December 28, 2020). Participants were divided by age according to the Japan Geriatrics Society and the Japan Gerontological Society: pre-old (65-74 years), old (75-89 years), and super-old (≥90 years). Multivariable logistic regression (MLR) analyses were conducted to identify stratified risk and relationships with comorbidities associated with worse outcomes in different age-groups of elderly patients. Demographics and supportive care were evaluated by category. RESULTS: Data of 4,701 patients from 444 hospitals were included. Most patients (79.3%) had at least one comorbidity; the proportion of patients with hypertension was high in all categories. The proportion of patients with dementia, cardiovascular disease, and cerebrovascular disease increased with age. The percentage of patients who underwent invasive mechanical ventilation/extracorporeal membrane oxygenation was lower in the super-old group. In total, 11.5% of patients died (5.3%, pre-old; 15.2%, old; and 22.4%, super-old). MLR showed that the risk of critical illness differed among age-groups. Male sex was a significant RF in all ages. Collagen disease, moderate to severe renal disorder, and dialysis were significant RFs in older patients, while hematological malignancies and metastatic tumors were more important RFs for severe disease in relatively younger patients. Most of the RFs for critical illnesses were associated with death. CONCLUSION: Differences in the epidemiological and clinical characteristics among the different age-groups were found.

3.
Clin Infect Dis ; 2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-34979547

RESUMO

In November 2021, the World Health Organization designated a new SARS-CoV-2 variant of concern, Omicron (PANGO lineage B.1.1.529). We report on first two cases of breakthrough COVID-19 caused by Omicron in Japan among international travelers returning from the country with undetected infection. The spread of infection by Omicron were considered.

4.
J Infect Chemother ; 2022 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-35016822

RESUMO

We report the case of a 67-year-old woman with disseminated Streptococcus anginosus invasive infection. Even under a maximal dose of susceptible antibiotics, her condition was complicated by pulmonary septic emboli and intracranial subdural abscess. Effective antibiotics and emergent surgical drainage were performed, but the sequelae of aphasia and hemiplegia remained. Underlying immunocompromised conditions of diabetes mellitus and monoclonal gammopathy of unknown significance might partially affect the clinical course of invasive S. anginosus infection. Once the infection becomes invasive, it can be refractory and difficult to treat. Clinicians should acknowledge the characteristics of invasive S. anginosus infection.

5.
Clin Nutr Open Sci ; 2022 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-35039809

RESUMO

Background & Aim: This study examined the association between green tea consumption and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among Japanese. Methods: Participants were staff of a large referral hospital in Tokyo. Green tea consumption was ascertained via a questionnaire. SARS-CoV-2 infection was identified through in-house records of PCR-confirmed COVID-19 cases or antibody tests. Multiple logistic regression was used to estimate the odds ratio of SARS-CoV-2 infection according to green tea consumption. Results: Of 2640 participants (767 men and 1873 women; aged 21-75 years), 74 (2.8%) were confirmed or suspected to have been infected with SARS-CoV-2 during the epidemic. Overall, SARS-CoV-2 infection was not significantly associated with green tea consumption. There was a suggestion of a decrease in the odds of this infection associated with green tea consumption of ≥4 cups/day (odds ratio 0.51, 95% confidence interval 0.20-1.31). Conclusions: Green tea consumption was not appreciably associated with the risk of SARS-CoV-2 infection. A lower odds of infection among those who consumed high green tea consumption deserves further investigation.

6.
Clin Infect Dis ; 2022 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-35037051

RESUMO

BACKGROUND: Several studies have investigated whether pregnancy is a risk factor for developing severe COVID-19; however, the results remain controversial. In addition, the information regarding risk factors for developing severe COVID-19 in pregnant women is limited. METHODS: A retrospective cohort study analyzing the data from the nationwide COVID-19 registry in Japan was conducted. Propensity score matched analysis was performed to compare COVID-19 severity between pregnant and nonpregnant women. Multivariate analysis was also conducted to evaluate risk factors for developing moderate-to-severe COVID-19 in pregnant women. RESULTS: During the study period, 254 pregnant and 3752 nonpregnant women of reproductive age were identified. After propensity score matching, 187 pregnant women and 935 nonpregnant women were selected. A composite outcome of moderate-to-severe COVID-19 was more frequently observed in pregnant women than that of nonpregnant women (n=18, 9.6% vs. n=46, 4.9%; P=0.0155). In multivariate analysis, the presence of underlying diseases and being in the second-to-third trimester of pregnancy were recognized as risk factors for moderate-to-severe COVID-19 in pregnant women (odds ratio [95% confidence interval]: 5.295 [1.21-23.069] and 3.871 [1.201-12.477], respectively). CONCLUSIONS: Pregnancy could be a risk factor for moderate-to-severe COVID-19 for women in Japan. In addition to the presence of comorbidities, advanced pregnancy stages may contribute to greater risks for developing moderate-to-severe COVID-19 in pregnant women.

7.
J Infect Chemother ; 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-35034854

RESUMO

The main objective of the study is to assess the impact of regional heterogeneity on the severity of COVID-19 in Japan. We included 27,865 cases registered between January 2020 and February 2021 in the COVID-19 Registry of Japan, to examine the relationship between the National Early Warning Score (NEWS) of COVID-19 patients on the day of admission and the prefecture where the patients live. A hierarchical Bayesian model was used to examine the random effect of each prefecture in addition to the patients' backgrounds. Additionally, we compared the results of two models; one model included the number of beds secured for COVID-19 patients in each prefecture as one of the fixed effects, and the other model did not. The results indicated that the prefecture had a substantial impact on the severity of COVID-19 on admission, even when considering the effect of the number of beds separately. Our analysis revealed a possible association between regional heterogeneity and increased/decreased risk of severe COVID-19 infection on admission. This heterogeneity was derived not only from the number of beds secured in each prefecture but also from other factors.

8.
J Infect Chemother ; 28(2): 356-358, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34916136

RESUMO

INTRODUCTION: We previously showed the trend of antimicrobial use (AMU) for Clostridioides (Clostridium) difficile infection (CDI) using sales data. However, the details of the prescribing medical institutions and regional characteristics are unknown. Therefore, the purpose of this study was to clarify the details of the medical institutions where antibiotics for CDI were prescribed, and evaluate the AMU for CDI and the regional characteristics. METHODS: Antibiotics for CDI, including oral vancomycin (VCM), oral metronidazole (MNZ), and intravenous (IV) MNZ, were collected from the National Database of Health Insurance Claims and Specific Health Checkups (NDB) between 2013 and 2016. The PID (patients/1000 inhabitants/day) was used as an evaluation index for AMU. The PID was calculated using the claim types: inpatient, outpatient, dental, and pharmacy. The PID of each prefecture was calculated for inpatient claims in 2016. RESULTS: The AMU of oral VCM and IV MNZ were observed mainly in the inpatient claims. For oral MNZ, the total AMU in the outpatient and pharmacy claims accounted for approximately 80% per year throughout the study period. For inpatient claims of each prefecture in 2016, the PID of the antibiotics used for CDIs was approximately 3.5 times the difference between the highest and lowest prefectures. CONCLUSIONS: The AMU for CDI that takes into account the purpose of use was clarified by using the information of the prescribed medical institutions that were included in the NDB. Oral MNZ was used frequently in outpatients, and attention should be paid to the acquisition of resistance.


Assuntos
Antibacterianos , Infecções por Clostridium , Antibacterianos/uso terapêutico , Clostridioides , Clostridium , Infecções por Clostridium/tratamento farmacológico , Infecções por Clostridium/epidemiologia , Humanos , Seguro Saúde , Japão/epidemiologia , Estudos Retrospectivos
9.
J Infect Chemother ; 28(1): 41-46, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34635449

RESUMO

INTRODUCTION: In response to global outbreaks of infectious diseases, the need for support from organizations such as the World Health Organization Global Outbreak Alert and Response Network (GOARN) is increasing. Identifying the obstacles and support needs for applicants could increase GOARN deployments from Japan. METHODS: This cross-sectional study involved a web-based, self-administered questionnaire survey targeting Japanese participants in the GOARN Tier 1.5 training workshop, held in Tokyo in December 2019. RESULTS: All 47 Japanese participants in the workshop responded to the survey. Most responders were male and in their 30s and 40s. Participants specialized in case management (42.6%), infection prevention and control (25.6%), epidemiology and surveillance (19.1%). Only two participants (4.6%) had experienced a GOARN deployment. Their motivations for joining the GOARN training workshop were "Desire to be part of an international emerging infectious disease response team" (44.6%), "Interest in making an international contribution" (19.1%), and "Interest in working for the Japanese government in the field of international infectious diseases" (14.9%). Obstacles to GOARN deployments were "Making time for deployments" (45.7%) and "Lack of required professional skills and knowledge" (40.4%). The support needs for GOARN deployments constituted "Periodic simulation training" (51.1%), "Financial support during deployments" (44.7%), and "Technical support for deployments" (40.4%). CONCLUSIONS: Our study revealed the obstacles and support needs of Japanese candidates for GOARN deployment. Making time and upskilling for GOARN deployment were the main obstacles. More practical training (like GOARN Tier 2.0) with other supports are needed. The national framework is desirable to realize these supports.


Assuntos
Doenças Transmissíveis Emergentes , Estudos Transversais , Surtos de Doenças , Saúde Global , Humanos , Japão/epidemiologia , Masculino , Recursos Humanos
10.
Int J Epidemiol ; 2021 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-34894230

RESUMO

BACKGROUND: The aim of this study was to identify associations between smoking status and the severity of COVID-19, using a large-scale data registry of hospitalized COVID-19 patients in Japan (COVIREGI-JP), and to explore the reasons for the inconsistent results previously reported on this subject. METHODS: The analysis included 17 666 COVID-19 inpatients aged 20-89 years (10 250 men and 7416 women). We graded the severity of COVID-19 (grades 0 to 5) according to the most intensive treatment required during hospitalization. The smoking status of severe grades 3/4/5 (invasive mechanical ventilation/extracorporeal membrane oxygenation/death) and separately of grade 5 (death) were compared with that of grade 0 (no oxygen, reference group) using multiple logistic regression. Results were expressed as odds ratios (OR) and 95% confidence intervals (CI) adjusted for age and other factors considering the potential intermediate effects of comorbidities. RESULTS: Among men, former smoking significantly increased the risk of grade 3/4/5 and grade 5, using grade 0 as a reference group, with age- and admission-date-adjusted ORs (95% CI) of 1.51 (1.18-1.93) and 1.65 (1.22-2.24), respectively. An additional adjustment for comorbidities weakened the ORs. Similar results were seen for women. Current smoking did not significantly increase the risk of grade 3/4/5 and grade 5 in either sex. CONCLUSIONS: The severity of COVID-19 was not associated with current or former smoking per se but with the comorbidities caused by smoking. Thus, smoking cessation is likely to be a key factor for preventing smoking-related disease and hence for reducing the risk of severe COVID-19.

11.
Respir Investig ; 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34872886

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2, has been a significant concern worldwide since its outbreak in December 2019. Various treatments are being researched and developed, and there are reports that dexamethasone has reduced the mortality rate and improved the clinical course of critically ill patients with COVID-19. In this study, we examined the clinical efficacy of corticosteroid therapy for patients with COVID-19 in our hospital during the first wave of infections. METHODS: We retrospectively reviewed the medical records of patients with COVID-19 who were treated with or without corticosteroid therapy at the National Center for Global Health and Medicine in Japan between February and April 2020. The primary outcome was improvement in the patients' clinical course using a seven-category ordinal scale. We collected data on patient characteristics, treatment, and clinical course, and compared them between two groups: the steroid-using group and the non-steroid-using group. RESULTS: Between February and April 2020, 110 patients were diagnosed with COVID-19. Despite poor conditions during admission into the steroid group, there were no statistical differences in clinical course between both groups, as measured using the scale. There were no statistical differences between the two groups in the number of days to fever resolution or negative polymerase chain reaction results. CONCLUSIONS: There was no difference in the clinical course between both groups. Because of the difference in background, corticosteroids may potentially make the clinical course of severely ill patients similar to that of mildly ill patients.

12.
Clin Infect Dis ; 2021 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-34950947

RESUMO

BACKGROUND: While increasing coverage of effective vaccines against coronavirus disease 2019 (COVID-19), emergent variants raise concerns about breakthrough infection. Data are limited, however, whether breakthrough infection during the epidemic of the variant is ascribed to insufficient vaccine-induced immunogenicity. METHODS: We described incident COVID-19 in relation to the vaccination program among workers of a referral hospital in Tokyo. During the predominantly Delta epidemic, we followed 2,415 fully vaccinated staff (BNT162b2) for breakthrough infection and selected three matched controls. We measured post-vaccination neutralizing antibodies against the wild-type, Alpha (B.1.1.7), and Delta (B.1.617.2) strains using live viruses and anti-spike antibodies using quantitative assays, and compared them using the generalized estimating equation model between the two groups. RESULTS: No COVID-19 cases occurred 1-2 months after the vaccination program during the fourth epidemic wave in Japan, dominated by the Alpha variant, while 22 cases emerged 2-4 months after the vaccination program during the fifth wave, dominated by the Delta variant. In the vaccinated cohort, all 17 cases of breakthrough infection were mild or asymptomatic and had returned to work early. There was no measurable difference between cases and controls in post-vaccination neutralizing antibody titers against the wild-type, Alpha, and Delta, and anti-spike antibody titers, while neutralizing titers against the variants were considerably lower than those against the wild-type. CONCLUSIONS: Post-vaccination neutralizing antibody titers were not decreased among patients with breakthrough infection relative to their controls under the Delta variant rampage. The result points to the importance of infection control measures in the post-vaccination era, irrespective of immunogenicity profile.

13.
Ann Intensive Care ; 11(1): 171, 2021 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-34897587

RESUMO

BACKGROUND: Only a few studies have reported the association between age and mortality in COVID-19 patients who require invasive mechanical ventilation (IMV). We aimed to evaluate the effect of age on COVID-19-related mortality among patients undergoing IMV therapy. METHODS: This cohort study was conducted using the COVID-19 Registry Japan database, a nationwide multi-centre study of hospitalized patients with laboratory-confirmed COVID-19. Of all 33,808 cases registered between 1 January 2020 to 28 February 2021, we analysed 1555 patients who had undergone IMV. We evaluated mortality rates between age groups using multivariable regression analysis after adjusting for known potential components, such as within-hospital clustering, comorbidities, steroid use, medication for COVID-19, and vital signs on admission, using generalized estimation equation. RESULTS: By age group, the mortality rates in the IMV group were 8.6%, 20.7%, 34.9%, 49.7% and 83.3% for patients in their 50s, 60s, 70s, 80s, and 90s, respectively. Multivariable analysis showed that compared with those for patients aged < 60 years, the odds ratios (95% confidence interval) of death were 2.6 (1.6-4.1), 6.9 (4.2-11.3), 13.2 (7.2-24.1), 92.6 (16.7-515.0) for patients in their 60s, 70s, 80s, and 90s, respectively. CONCLUSIONS: In this cohort study, age had a great effect on mortality in COVID-19 patients undergoing IMV, after adjusting for variables independently associated with mortality. This study suggested that age was associated with higher mortality and that preventing progression to severe COVID-19 in elderly patients may be a great public health issue.

14.
Antibiotics (Basel) ; 10(11)2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34827231

RESUMO

The threat from antimicrobial resistance (AMR) continues to grow. Japan's National Action Plan on Antimicrobial Resistance, which was formulated in 2016 and targets six areas, has already had a major impact on the countermeasures implemented against AMR. Particular advances have been made in AMR-related surveillance, and we now know the situation regarding antimicrobial use and antimicrobial-resistant bacteria in the country. Educational and awareness-raising activities for medical professionals and the general public have been actively implemented and seem to have contributed to a gradual move toward an appropriate use of antimicrobials. However, there is still insufficient understanding of the issue among the general public. Determining how to use surveillance results and implementing further awareness-raising activities are crucial to address this. Tasks for the future include both raising awareness and the promotion of AMR research and development and international cooperation. The government's next Action Plan, which will detail future countermeasures against AMR based on the outcomes of and tasks identified in the current Action Plan, has been delayed due to the COVID-19 pandemic and is urgently awaited.

15.
Int J Antimicrob Agents ; : 106480, 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34801675

RESUMO

BACKGROUND: The plasmid-mediated bacterial colistin-resistant gene, mcr, is of global concern in clinical health care. However, there are few reports of surveillance for mcr in Japan. This study aimed to study the prevalence of colistin resistance by identifying nine mcr genes in ESBL-producing Enterobacteriaceae and CRE isolates in Japan. METHODS: We collected 273 ESBL and CRE clinical isolates from the patients in five tertiary hospitals between August 2016 to March 2017. MIC of colistin was measured using the microdilution method. PCR was performed to detect mcr-1 to mcr-9 genes in all strains. Additionally, if we identified a mcr-gene that had not been reported from patients in Japan, we performed a WGS analysis. RESULTS: The rate of colistin resistance was 7.7% in all strains. The rate of colistin resistance in the CRE strains was higher than that in the ESBL-producing strains (20.4% versus 1.1%). The mcr-5 and mcr-9 gene were detected in one ESBL-producing E. coli strain (1/273, 0.37%) and three CRE strains (3/273, 1.1%), respectively. Since the ESBL-producing E. coli strain was the first clinical strain with mcr-5 in Japan, whole-genome sequencing analysis was performed for the strain. The sequence type of the mcr-5 positive strain was ST1642 and it carried two distinct plasmids, ESBL gene-carrying pN-ES-6-1, and mcr-5.1-carrying pN-ES-6-2. CONCLUSIONS: We showed that the frequency of colistin resistance and mcr-positive strains is not high in Japan. Since the MIC for colistin was low in the mcr-5.1 and mcr-9 gene-positive strain, continuous monitoring of mcr genes is necessary.

16.
J Infect Chemother ; 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34802889

RESUMO

Tsukamurella spp. causes mainly bacteremia and central venous catheter-related bloodstream infections. To the best of our knowledge, there is no documented evidence that Tsukamurella ocularis causes catheter-related bloodstream infections like other species of Tsukamurella. We present a novel case of T. ocularis bacteremia in a 69-year-old woman with malignant cancer, wherein the patient was successfully treated with a peripherally inserted central venous catheter. We administered combination antimicrobial therapy to the patient, which was terminated only after confirming the absence of infection. We identified T. ocularis by sequencing three housekeeping genes that could not be identified using conventional mass spectrometry and 16S rRNA gene analysis.

17.
J Infect Chemother ; 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34756573

RESUMO

INTRODUCTION: The ability to predict which patients with a history of coronavirus disease (COVID-19) will exhibit a high antibody titer is necessary for more efficient screening of potential convalescent plasma donors. We aimed to identify factors associated with a high immunoglobulin G (IgG) titer in Japanese convalescent plasma donors after COVID-19. METHODS: This cross-sectional study included volunteers undergoing screening for convalescent plasma donation after COVID-19. Serum anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) S-protein IgG antibodies were measured using a high-sensitivity chemiluminescence enzyme immunoassay. RESULTS: IgG antibodies were measured in 581 patients, 534 of whom had full information of selected independent variables. Multiple linear regression analysis revealed that increasing age (1.037 [1,025, 1.048]), days from symptom onset to sampling (0.997 [0.995, 0.998]), fever (1.664 [1.226, 2.259]), systemic corticosteroid use during SARS-CoV-2 infection (2.382 [1.576, 3.601]), and blood type AB (1.478 [1.032, 2.117]) predict antibody titer. CONCLUSION: Older participants, those who experienced fever during infection, those treated with systemic corticosteroids during infection, those from whom samples were obtained earlier after symptom onset, and those with blood type AB are the best candidates for convalescent plasma donation. Therefore, these factors should be incorporated into the screening criteria for convalescent plasma donation after SARS-CoV-2 infection.

18.
J Infect Chemother ; 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34756574

RESUMO

OBJECTIVES: To alleviate the overflow of coronavirus disease 2019 (COVID-19) patients in hospitals, less invasive and simple criteria are required to triage the patients. We evaluated the relationship between COVID-19 severity and fatty liver on plain computed tomography (CT) scan performed on admission. METHODS: In this retrospective cohort study, we considered all COVID-19 patients at a large tertiary care hospital between January 31 and August 31, 2020. COVID-19 severity was categorized into severe (moderate and severe) and non-severe (asymptomatic and mild) groups, based on the Japanese National COVID-19 guidelines. Fatty liver was detected on plain CT scan. Multivariate logistic regression analysis was performed to evaluate factors associated with severe COVID-19. RESULTS: Of 222 patients (median age: 52 years), 3.2%, 58.1%, 20.7%, and 18.0% presented with asymptomatic, mild, moderate, and severe COVID-19, respectively. Although 59.9% had no fatty liver on plain CT, mild, moderate, and severe fatty liver occurred in 13.1%, 18.9%, and 8.1%, respectively. Age and presence of fatty liver were significantly associated with severe COVID-19. CONCLUSION: Our study showed that fatty liver on plain CT scan on admission can become a risk factor for severe COVID-19. This finding may help clinicians to easily triage COVID-19 patients.

19.
J Infect Chemother ; 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34776348

RESUMO

INTRODUCTION: We aimed to analyze the clinical characteristics and outcomes of immunosuppressed inpatients with coronavirus disease 2019 (COVID-19). METHODS: In this observational study, we utilized a large nationwide registry of hospitalized patients with COVID-19 in Japan. Patients' baseline characteristics and outcomes were compared according to the immunosuppressed states of the patients. The impact of different therapeutic agents on the clinical courses of the patients was evaluated. RESULTS: Data of 14,760 patients were included, and 887 (5.9%) were immunosuppressed. The immunosuppressed state of the patient resulted from solid tumor (43.3%, n = 384), chemotherapy within 3 months (15.6%, n = 138), collagen disease (16.9%, n = 150), use of immunosuppressive agents (16.0%, n = 142), and metastatic solid tumor (13.5%, n = 120). Immunosuppressed patients were older and had a higher severity of illness at admission and during hospitalization than non-immunosuppressed patients. The mortality rates for major diseases causing immunosuppression were as follows: solid tumor, 12.5% (48/384; P < 0.001; relative risk [RR], 3.41); metastatic solid tumor, 31.7% (38/120; P < 0.001; RR, 8.43); leukemia, 23.1% (9/39; P < 0.001; RR, 5.87); lymphoma, 33.3% (20/60; P < 0.001; RR, 8.63); and collagen disease, 15.3% (23/150; P < 0.001; RR 3.97). Underlying diseases with high mortality rates were not necessarily associated with high rates of invasive supportive care. CONCLUSIONS: The prognosis of immunosuppressed COVID-19 inpatients varied according to the different immunosuppressed states. Multiple factors, including the severity of the underlying diseases, might have affected their invasive supportive care indications.

20.
IDCases ; 26: e01343, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34804800

RESUMO

Remdesivir is an antiviral drug that results in clinical improvement after five days of treatment and accelerates recovery by 31%. No studies have discussed the pharmacokinetic analysis of remdesivir in patients with severe COVID-19 requiring extracorporeal membrane oxygenation (ECMO). A 63-year-old American man who underwent mechanical ventilation and ECMO for severe COVID-19 was administered remdesivir for ten days. The loading dosage was 200 mg at 7 PM on day 12 and 100 mg daily at 0:00 PM from day 13-21, administered within 1 h. The pharmacokinetic analysis was performed. The serum creatinine concentration was within the normal range of 0.5-0.7 mg/dL during treatment. According to the pharmacokinetic analysis, the plasma concentrations of remdesivir and GS-441524 4 h after administration (C4) were 662 ng/mL and 58 ng/mL, respectively, and the concentrations 18 h after administration (C18) were 32 ng/mL and 44 ng/mL, respectively. Therefore, the half-life of remdesivir and GS-441524 was 3.2 and 35.1 h, respectively. Monitoring the plasma concentrations of remdesivir and GS-441524 in patients undergoing ECMO may be necessary.

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