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1.
Ther Apher Dial ; 28(4): 599-607, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38504452

RESUMEN

INTRODUCTION: Vaccination is the effective strategy for coronavirus disease 2019 (COVID-19). However, few studies have investigated the association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin (Ig)G and vitamin D. METHODS: This study aimed to investigate the association between SARS-CoV-2 IgG and active vitamin D analogs in hemodialysis patients. Blood samples were collected four times: before vaccination and 30, 60, and 90 days after vaccination, BNT162b2 (Pfizer©). RESULTS: A total of 418 patients were enrolled. The mean age was 71.1 ± 12 years. Almost two thirds of the patients were prescribed active vitamin D analogs. The distribution of SARS-CoV-2 IgG before vaccination was 235 (93-454) AU/mL. After multiple regression analyses, active vitamin D analog use was found to be associated with higher SARS-CoV-2 IgG levels from prevaccination to 90 days postvaccination. CONCLUSION: This study demonstrated an association between higher SARS-CoV-2 IgG and active vitamin D analog use in hemodialysis patients. CLINICAL TRIAL REGISTRATION: The study information was registered in the UMIN-CTR (UMIN 000046906).


Asunto(s)
Anticuerpos Antivirales , Vacuna BNT162 , COVID-19 , Inmunoglobulina G , Diálisis Renal , Vitamina D , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Anticuerpos Antivirales/sangre , COVID-19/prevención & control , COVID-19/inmunología , Inmunoglobulina G/sangre , SARS-CoV-2/inmunología , Vacunación , Vitamina D/análogos & derivados , Vitamina D/sangre
2.
Sci Rep ; 13(1): 9976, 2023 06 20.
Artículo en Inglés | MEDLINE | ID: mdl-37340001

RESUMEN

The humoral response of kidney transplant recipients (KTR) to the mRNA vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is generally poor. We evaluated the booster effect of the third dose (D3) of two SARS-CoV-2 mRNA vaccines 6 months after the second dose (D2) in Japanese KTR. The anti-spike (anti-S) antibody titer 1 and 3 months after the D3 was evaluated in 82 Japanese KTR. The primary endpoint was the seropositivity rate, and factors associated with the lack of a response were evaluated in a logistic regression model. Overall, the anti-S antibody seropositivity rate 1 and 3 months after the D3 was 74.7% and 76.0%. The anti-S antibody titers after the first and second doses were higher in patients vaccinated with the mRNA-1273 than with the BNT162b2 vaccine. Among the 38 KTR who were seronegative 5 months after the D2, 18 (47.4%) became seropositive following the D3. Factors associated with a non-response were mycophenolic acid dose, post-transplant duration, hemoglobin, and lymphocyte count. A humoral response 1 and 3 months after the D3 was obtained in ~ 75% of KTR, but 20% were non-responders. Additional studies are needed to clarify the factors hindering a vaccine response.


Asunto(s)
Vacuna BNT162 , COVID-19 , Inmunización Secundaria , Trasplante de Riñón , Humanos , Anticuerpos Antivirales , Vacuna BNT162/administración & dosificación , COVID-19/prevención & control , Pueblos del Este de Asia , Receptores de Trasplantes
3.
Intern Med ; 62(12): 1795-1800, 2023 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-36351581

RESUMEN

Tuberculosis is a common etiology of granulomatous interstitial nephritis (GIN). However, the absence of evidence of lung involvement and lack of mycobacterial isolation in cultures make the etiological diagnosis and treatment decision challenging. We herein report a 46-year-old man with severe renal failure, a persistent fever, and a history of lymphoma. A renal biopsy exhibited GIN. Despite no evidence of tuberculosis except for a positive interferon-gamma release assay (IGRA), the patient was successfully treated with anti-tuberculosis drugs. Our case suggests that anti-tuberculosis therapy should be considered for patients with IGRA-positive GIN after excluding other etiologies.


Asunto(s)
Linfoma de Células B Grandes Difuso , Nefritis Intersticial , Insuficiencia Renal , Tuberculosis , Masculino , Humanos , Persona de Mediana Edad , Ensayos de Liberación de Interferón gamma , Nefritis Intersticial/complicaciones , Nefritis Intersticial/diagnóstico , Granuloma/etiología , Granuloma/complicaciones , Insuficiencia Renal/complicaciones , Linfoma de Células B Grandes Difuso/complicaciones , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico
4.
J Infect Chemother ; 28(10): 1439-1444, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35717438

RESUMEN

INTRODUCTION: In Japan, patients with coronavirus disease 2019 (COVID-19) who do not require medical intervention are provided care in recovery accommodation facilities (RAFs). However, some patients may require hospitalization if their symptoms become more severe during their stay. We conducted an observational study using epidemiological data of patients with COVID-19 admitted to RAFs in Tokyo. METHODS: This was an observational cohort study using data from COVID-19 patients admitted to one of the RAFs in Tokyo from December 2020 to November 2021. Admissions to the facilities were limited to patients with asymptomatic or mild COVID-19 with no underlying disease or at least stable underlying disease at the time of admission. Patients were hospitalized when they required oxygen administration or when they had, or persistent fever, or severe respiratory symptoms. We evaluated the association between hospitalization and the risk factors for hospitalization using a Cox regression model. RESULTS: The number of patients with COVID-19 admitted to the RAF was 6176. The number of hospitalized patients was 393 (6.4%), and the median length of stay was 5.50 days (IQR: 4.50, 6.50). In the Cox regression analysis, the hazard ratio increased with age and was significantly higher among patients aged >60 years (HR = 10.23, 95% CI: 6.72-15.57) than those in other age groups. This trend is similar to that observed in the sensitivity analysis. CONCLUSION: Patients with diabetes, the elderly, obesity, and medications for gout and psychiatric diseases may be at a high risk of hospitalization. In particular, an age over 60 years was strongly associated with hospitalization.


Asunto(s)
COVID-19 , Anciano , COVID-19/epidemiología , COVID-19/terapia , Hospitalización , Humanos , Estudios Retrospectivos , Factores de Riesgo , SARS-CoV-2 , Tokio/epidemiología
5.
Front Microbiol ; 13: 922042, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35756063

RESUMEN

Background: The mortality rate due to COVID-19 in kidney transplant recipients (KTRs) is 16.8 to 32%. Vaccination against COVID-19 is expected to contribute to the prevention of infection, severe disease, and mortality; however, it has been reported that the humoral response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine in KTRs is poor. Vaccination strategies against COVID-19 vary from country to country, and in Japan, the third dose is given 6 months after the second dose. Few studies have evaluated long-term humoral responses after the second dose of SARS-CoV-2 mRNA vaccine. In addition, the superiority of BNT162b2 vaccine and mRNA-1,273 vaccine in KTRs regarding humoral response is controversial. Methods: Ninety-four KTRs were administered a second dose of the BNT162b2 or mRNA-1,273 vaccines, and anti-spike (anti-S) and anti-nucleocapsid (anti-N) SARS-CoV-2 antibody levels were measured 5 months (149.2 ± 45.5 days) later. The cutoff value of anti-S antibodies was defined ≥50 AU/ml and 1.4 Index for anti-N antibodies. The primary outcome was the rate of seropositivity, and factors associated with an appropriate humoral response were assessed by univariate and multivariate analysis. Results: Of 94 KTRs, only 45 (47.9%) patients were positive for anti-S antibodies. The median anti-S SARS-CoV-2 IgG antibody titers was 35.3 (Interquartile range 3.8 to 159.7). Anti-N SARS-CoV-2 IgG antibodies in all patients were < 1.4 Index. Response to SARS-CoV-2 mRNA vaccines were 43.2 and 65% for BNT162b2 and mRNA-1,273, respectively (p = 0.152). In comparison with high-dose, low-dose of mycophenolic acid was a robust factor associated with an adequate humoral response. Conclusion: The long-term humoral response after a second dose of SARS-CoV-2 mRNA vaccine in Japanese KTRs was poor. In comparison with high-dose, low-dose mycophenolic acid was related to an appropriate humoral response. Five months is too long to wait for a 3rd dose after 2nd dose of SARS-CoV-2 vaccine in KTRs. In this cohort, there was no statistical difference in humoral response to the BNT162b2 and mRNA-1,273 vaccines. Additional large observational studies and meta-analyses are needed to clarify the factors related to an appropriate humoral immune response to COVID-19 vaccination.

6.
J Extracell Vesicles ; 10(8): e12092, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-34122778

RESUMEN

The clinical manifestations of COVID-19 vary broadly, ranging from asymptomatic infection to acute respiratory failure and death. But the predictive biomarkers for characterizing the variability are still lacking. Since emerging evidence indicates that extracellular vesicles (EVs) and extracellular RNAs (exRNAs) are functionally involved in a number of pathological processes, we hypothesize that these extracellular components may be key determinants and/or predictors of COVID-19 severity. To test our hypothesis, we collected serum samples from 31 patients with mild COVID-19 symptoms at the time of their admission for discovery cohort. After symptomatic treatment without corticosteroids, 9 of the 31 patients developed severe/critical COVID-19 symptoms. We analyzed EV protein and exRNA profiles to look for correlations between these profiles and COVID-19 severity. Strikingly, we identified three distinct groups of markers (antiviral response-related EV proteins, coagulation-related markers, and liver damage-related exRNAs) with the potential to serve as early predictive biomarkers for COVID-19 severity. As the best predictive marker, EV COPB2 protein, a subunit of the Golgi coatomer complex, exhibited significantly higher abundance in patients remained mild than developed severe/critical COVID-19 and healthy controls in discovery cohort (AUC 1.00 (95% CI: 1.00-1.00)). The validation set included 40 COVID-19 patients and 39 healthy controls, and showed exactly the same trend between the three groups with excellent predictive value (AUC 0.85 (95% CI: 0.73-0.97)). These findings highlight the potential of EV COPB2 expression for patient stratification and for making early clinical decisions about strategies for COVID-19 therapy.


Asunto(s)
COVID-19/sangre , COVID-19/fisiopatología , Ácidos Nucleicos Libres de Células/sangre , Proteína Coatómero/sangre , Vesículas Extracelulares/química , Biomarcadores/sangre , COVID-19/inmunología , Humanos , Estudios Retrospectivos , SARS-CoV-2/fisiología , Índice de Severidad de la Enfermedad
7.
Biol Pharm Bull ; 43(7): 1081-1087, 2020 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-32295975

RESUMEN

Vancomycin (VAN) is an anti-microbial agent used to treat a number of bacterial infections, which has a high incidence of nephrotoxicity. We examined the pharmacokinetics of VAN retrospectively based on trough concentrations at large scale and identified pharmacokinetic differences between Japanese patients having solid malignancy and non-malignancy patients. Data were analyzed from 162 solid malignancy patients and 261 non-malignancy patients, including the patient's background, VAN dose, and pharmacokinetics of VAN. We failed to detect differences in values for VAN clearance or shorter elimination half-lives between these two groups. In contrast, multiple regression analysis under adjusting for confounding factors by propensity score, showed that VAN clearance significantly increased in relation to solid malignancies in each stage. We conclude that VAN clearance in solid malignancy patients is increased and that the blood concentration of VAN becomes lower than expected. These results suggest that early monitoring of VAN levels in solid malignancy patients might be essential for maintaining desired effects without side-effects.


Asunto(s)
Antibacterianos/sangre , Monitoreo de Drogas/métodos , Neoplasias/sangre , Vancomicina/sangre , Anciano , Anciano de 80 o más Años , Antibacterianos/uso terapéutico , Femenino , Humanos , Masculino , Tasa de Depuración Metabólica/efectos de los fármacos , Tasa de Depuración Metabólica/fisiología , Persona de Mediana Edad , Neoplasias/tratamiento farmacológico , Estudios Retrospectivos , Vancomicina/uso terapéutico
8.
J Infect Chemother ; 26(1): 33-37, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31350182

RESUMEN

HIV infection, in particular in patients with developing AIDS, carries a risk of causing toxoplasmosis with encephalitis, which is mostly caused by a form (bradyzoite) of the protozoan parasite Toxoplasma gondii. HIV/AIDS in Japan has been recognized as a serious health issue in recent years. In this study, to elucidate T. gondii seroprevalence in HIV-positive patients in Japan and associated characteristics with Toxoplasma parasite infection, the titer of T. gondii IgG (Tg-IgG) was measured in 399 HIV-positive patients who visited a hospital in Tokyo, Japan, between 2015 and 2017. A questionnaire survey was also conducted to investigate associations between lifestyle and customs. As a result, the overall prevalence of Tg-IgG-positive serum was 8.27% (33 cases of 399). All the cases positive for Tg-IgG were confirmed using the Sabin-Feldman dye test; the titers between each examination correlated robustly (p < 0.001, r = 0.6). A correlation between Toxoplasma infection rate and age was determined (p < 0.001), whereas there was no significant correlation with lifestyle customs such as consuming undercooked meat or owning a cat. An association between Toxoplasma infection and experience of dwelling in the Hokkaido area, the northern part of Japan, was observed (p = 0.001). These results suggested that the proportion of those who were previously exposed to Toxoplasma parasites in the HIV-positive population has been maintained at a similar level as that of the HIV-negative population in Japan, providing clear information about the potential risk of toxoplasmic encephalitis.


Asunto(s)
Infecciones por VIH , Toxoplasmosis , Adulto , Anciano , Anticuerpos Antiprotozoarios/sangre , Estudios Transversales , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Estudios Seroepidemiológicos , Tokio/epidemiología , Toxoplasma/inmunología , Toxoplasmosis/complicaciones , Toxoplasmosis/epidemiología , Toxoplasmosis/inmunología , Adulto Joven
9.
J Infect Chemother ; 26(2): 162-169, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31676266

RESUMEN

Staphylococcus aureus causes various infections, including skin and soft tissue infections and pneumonia via both, community-associated and nosocomial infection. These infectious diseases can lead to bacteremia, and may subsequently result in metastatic infections in several cases. Metastatic infections are critical complications in patients with S. aureus bacteremia, since the optimal duration of the antimicrobial treatment differs in patients with and without metastatic infection. Notably, two weeks of antimicrobial treatment is recommended in case of uncomplicated S. aureus bacteremia, whereas in patients with S. aureus bacteremia-associated endocarditis or vertebral osteomyelitis, six weeks of antimicrobial administration is vital. In addition, misdiagnosis or insufficient treatment in metastatic infection is associated with poor prognosis, functional disability, and relapse. Although echocardiography is recommended to examine endocarditis in the patients with S. aureus bacteremia, it remains unclear which patients should undergo additional examinations, such as CT and MRI, to detect the presence of other metastatic infections. Clinical studies have revealed that permanent foreign body and persistent bacteremia are predictive factors for metastatic infections, and experimental studies have demonstrated that the virulence factors of S. aureus, such as fnbA and clfA, are associated with endocarditis; however, these factors are not proven to increase the risk of metastatic infections. In this review, we assessed the incidence, predictive factors, diagnosis, and treatment for metastatic infections during S. aureus bacteremia.


Asunto(s)
Bacteriemia/microbiología , Infecciones Estafilocócicas/epidemiología , Infecciones Estafilocócicas/microbiología , Staphylococcus aureus/patogenicidad , Antibacterianos/uso terapéutico , Bacteriemia/tratamiento farmacológico , Bacteriemia/epidemiología , Endocarditis Bacteriana/diagnóstico , Endocarditis Bacteriana/tratamiento farmacológico , Endocarditis Bacteriana/epidemiología , Endocarditis Bacteriana/microbiología , Humanos , Incidencia , Osteomielitis/diagnóstico , Osteomielitis/tratamiento farmacológico , Osteomielitis/epidemiología , Osteomielitis/microbiología , Pronóstico , Factores de Riesgo , Infecciones Estafilocócicas/diagnóstico , Infecciones Estafilocócicas/tratamiento farmacológico , Staphylococcus aureus/aislamiento & purificación , Factores de Virulencia
10.
Biol Pharm Bull ; 42(12): 2089-2094, 2019 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-31534058

RESUMEN

The pharmacokinetics of vancomycin (VAN) was retrospectively examined based on trough concentrations at large scale to identify pharmacokinetic differences between Japanese hematologic malignancy and non-malignancy patients. Data from 261 hematologic malignancy patients and 261 non-malignancy patients, including the patient's background, VAN dose, and pharmacokinetics of VAN estimated by an empirical Bayesian method, were collected and analyzed. Our results showed significantly higher values for VAN clearance and shorter elimination half-lives in patients with hematologic malignancies than non-malignancy patients. In addition, multiple regression analysis under adjusting for confounding factors by propensity score, showed that VAN clearance significantly increased in relation to hematologic malignancies. In conclusion, since in hematologic cancer patients VAN clearance is increased, the blood concentration of VAN becomes lower than expected and this may contribute to the survival of resistant bacteria when VAN is administered at low doses. These results suggest that early monitoring of VAN levels in hematologic cancer patients might be recommended to maintain desired effects without side-effects.


Asunto(s)
Antibacterianos/farmacocinética , Neoplasias Hematológicas/tratamiento farmacológico , Vancomicina/farmacocinética , Adulto , Anciano , Anciano de 80 o más Años , Monitoreo de Drogas , Femenino , Humanos , Japón , Masculino , Tasa de Depuración Metabólica , Persona de Mediana Edad , Estudios Retrospectivos , Vancomicina/administración & dosificación , Vancomicina/sangre
11.
Intern Med ; 56(16): 2229-2232, 2017 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-28781310

RESUMEN

A 56-year-old Japanese man diagnosed with acquired immunodeficiency syndrome, Pneumocystis jirovecii pneumonia and cytomegalovirus infection presented with thrombocytopenia after starting antiretroviral therapy, which included dolutegravir (DTG). Although good control of the human immunodeficiency virus and cytomegalovirus infections was achieved, the patient's thrombocytopenia persisted. The patient's platelet count decreased to ≤50,000/µL even after the cessation of valganciclovir, which can cause bone marrow suppression. At five months after starting antiretroviral therapy, DTG was replaced by ritonavir-boosted darunavir. Soon after, his platelet count improved and was maintained at a level of >100,000/µL. This is the first reported case of severe thrombocytopenia during DTG-containing antiretroviral therapy.


Asunto(s)
Inhibidores de Integrasa VIH/efectos adversos , Compuestos Heterocíclicos con 3 Anillos/efectos adversos , Trombocitopenia/inducido químicamente , Terapia Antirretroviral Altamente Activa/efectos adversos , Infecciones por VIH/tratamiento farmacológico , Inhibidores de Integrasa VIH/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Oxazinas , Piperazinas , Recuento de Plaquetas , Piridonas , Trombocitopenia/sangre
12.
Clinics (Sao Paulo) ; 71(2): 73-7, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26934235

RESUMEN

OBJECTIVES: This study was conducted to clarify the rate of late diagnosis of HIV infection and to identify relationships between the reasons for HIV testing and a late diagnosis. METHODS: This retrospective cohort study was conducted among HIV-positive patients at the Jikei University Hospital between 2001 and 2014. Patient characteristics from medical records, including age, sex, sexuality, the reason for HIV testing and the number of CD4-positive lymphocytes at HIV diagnosis, were assessed. RESULTS: A total of 459 patients (men, n=437; 95.2%) were included in this study and the median age at HIV diagnosis was 36 years (range, 18-71 years). Late (CD4 cell count <350/mm3) and very late (CD4 cell count <200/mm3) diagnoses were observed in 61.4% (282/459) and 36.6% (168/459) of patients, respectively. The most common reason for HIV diagnosis was voluntary testing (38.6%, 177/459 patients), followed by AIDS-defining illness (18.3%, 84/459 patients). Multivariate analysis revealed a significant association of voluntary HIV testing with non-late and non-very-late diagnoses and there was a high proportion of AIDS-defining illness in the late and very late diagnosis groups compared with other groups. Men who have sex with men was a relative factor for non-late diagnosis, whereas nonspecific abnormal blood test results, such as hypergammaglobulinemia and thrombocytopenia, were risk factors for very late diagnosis. CONCLUSIONS: Voluntary HIV testing should be encouraged and physicians should screen all patients who have symptoms or signs and particularly hypergammaglobulinemia and thrombocytopenia, that may nonspecifically indicate HIV infection.


Asunto(s)
Diagnóstico Tardío , Infecciones por VIH/diagnóstico , Conductas Relacionadas con la Salud , Hipergammaglobulinemia/sangre , Adolescente , Adulto , Anciano , Recuento de Linfocito CD4 , Estudios de Cohortes , Femenino , Infecciones por VIH/complicaciones , Hospitales Universitarios , Humanos , Japón , Masculino , Tamizaje Masivo/normas , Persona de Mediana Edad , Neumonía por Pneumocystis/complicaciones , Estudios Retrospectivos , Trombocitopenia/sangre , Adulto Joven
13.
Clinics ; 71(2): 73-77, Feb. 2016. tab, graf
Artículo en Inglés | LILACS | ID: lil-774530

RESUMEN

OBJECTIVES: This study was conducted to clarify the rate of late diagnosis of HIV infection and to identify relationships between the reasons for HIV testing and a late diagnosis. METHODS: This retrospective cohort study was conducted among HIV-positive patients at the Jikei University Hospital between 2001 and 2014. Patient characteristics from medical records, including age, sex, sexuality, the reason for HIV testing and the number of CD4-positive lymphocytes at HIV diagnosis, were assessed. RESULTS: A total of 459 patients (men, n=437; 95.2%) were included in this study and the median age at HIV diagnosis was 36 years (range, 18-71 years). Late (CD4 cell count <350/mm3) and very late (CD4 cell count <200/mm3) diagnoses were observed in 61.4% (282/459) and 36.6% (168/459) of patients, respectively. The most common reason for HIV diagnosis was voluntary testing (38.6%, 177/459 patients), followed by AIDS-defining illness (18.3%, 84/459 patients). Multivariate analysis revealed a significant association of voluntary HIV testing with non-late and non-very-late diagnoses and there was a high proportion of AIDS-defining illness in the late and very late diagnosis groups compared with other groups. Men who have sex with men was a relative factor for non-late diagnosis, whereas nonspecific abnormal blood test results, such as hypergammaglobulinemia and thrombocytopenia, were risk factors for very late diagnosis. CONCLUSIONS: Voluntary HIV testing should be encouraged and physicians should screen all patients who have symptoms or signs and particularly hypergammaglobulinemia and thrombocytopenia, that may nonspecifically indicate HIV infection.


Asunto(s)
Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Diagnóstico Tardío , Conductas Relacionadas con la Salud , Infecciones por VIH/diagnóstico , Hipergammaglobulinemia/sangre , Estudios de Cohortes , Infecciones por VIH/complicaciones , Hospitales Universitarios , Japón , Tamizaje Masivo/normas , Neumonía por Pneumocystis/complicaciones , Estudios Retrospectivos , Trombocitopenia/sangre
14.
Clin Pharmacol ; 7: 79-82, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26056496

RESUMEN

BACKGROUND: Daptomycin is recommended for complicated skin and skin-structure infections. However, information on the penetration of daptomycin into skin is limited. Therefore, the aim of this in vivo investigation was to determine the pharmacokinetics and skin penetration of daptomycin in rats. MATERIALS AND METHODS: Concentrations of daptomycin were determined by high-performance liquid chromatography. A noncompartmental pharmacokinetic analysis was conducted to estimate the rate and extent of daptomycin penetration from the systemic circulation into skin tissue. Since protein binding of daptomycin in rat serum was 89.3%, the free maximum concentration (Cmax) and free area under the curve from time 0 to infinity (AUC0-∞) for plasma were calculated as follows: fCmax, plasma = (1 - 0.893) × Cmax, plasma, fAUC0-∞, plasma = (1 - 0.893) × AUC0-∞, plasma. RESULTS: The following values (mean ± standard deviation) were obtained: 0.06±0 L/h/kg for total clearance (CLtotal), 0.44±0.06 hours for elimination-rate constant, 1.58±0.23 hours for half-life, 0.14±0.02 L/kg for steady-state volume distribution, and 2.28±0.33 hours for mean residence time. Time to Cmax was 3.0 hours for plasma and skin tissue. Cmax and AUC0-∞ for plasma were 175.8±5.1 µg/mL and 811.8±31.9 µg × h/mL, respectively. Cmax and AUC0-∞ for skin tissue were 19.1±1.7 µg/mL and 113.9±21.8 µg × h/mL, respectively. Furthermore, fCmax and fAUC0-∞ for plasma were 18.8 µg/mL and 86.9 µg × h/mL, respectively. The degrees of skin-tissue penetration, defined as the Cmax, skin tissue/fCmax, plasma ratio and AUC0-∞, skin tissue/fAUC0-∞, plasma ratio, were 1.0 and 1.3, respectively. CONCLUSION: Daptomycin exhibited good penetration into skin tissue, supporting its use for the treatment of complicated skin and skin-structure infections. However, further studies are needed in infected patients in order to investigate the relationship between the antimicrobial efficacy of daptomycin and its drug concentrations in skin tissues.

15.
J Infect Chemother ; 21(6): 476-8, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25869915

RESUMEN

The pharmacokinetics of meropenem have not yet been examined in Japanese patients receiving Continuous venovenous hemodialysis (CVVHD). The aim of this clinical investigation was to determine the pharmacokinetic parameters of meropenem in critically ill patients receiving CVVHD in order to estimate dosing regimens for the patient population in Japan. The values of pharmacokinetic parameters were 17.5 ± 5.6 l for V1, 1.27 ± 0.38 h(-1) for K12, 0.71 ± 0.40 h(-1) for K21 and 0.17 ± 0.02 h(-1) for K10. Based on these mean parameters (V1, K12, K21 and K10), time above MIC (T > MIC) values were estimated at different MICs using various meropenem regimens. For bacteria with a meropenem MIC of ≤ 2 µg/ml, a dosing regimen of 0.25 g every 24 h achieved more than 40% T > MIC. For a MIC of 4 µg/ml, all the regimens tested, except for 0.25 g every 24 h, achieved more than 40% T > MIC. For a MIC of 16 µg/ml, dosing regimens of 0.5 g every 8 h, 1 g every 12 h, and 1 g every 8 h achieved 40% T > MIC, reaching the pharmacokinetic-pharmacodynamic target range. This is the first study to examine the pharmacokinetics of meropenem under a CVVHD setting in Japan. The pharmacokinetic-pharmacodynamic profile of dosing regimens tested in this study will assist in selecting the appropriate meropenem regimens for patients receiving CVVHD.


Asunto(s)
Antibacterianos/administración & dosificación , Antibacterianos/farmacocinética , Tienamicinas/administración & dosificación , Tienamicinas/farmacocinética , Adulto , Anciano , Pueblo Asiatico , Enfermedad Crítica , Femenino , Humanos , Masculino , Meropenem , Persona de Mediana Edad , Diálisis Renal/métodos
16.
Am J Med Sci ; 349(1): 24-8, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25250988

RESUMEN

BACKGROUND: Metastatic infections such as infective endocarditis and psoas abscess are serious complications of Staphylococcus aureus bacteremia because failure to identify these infections may result in bacteremia relapse or poor prognosis. In the present study, we determined the predictive factors for metastatic infection due to methicillin-sensitive S. aureus bacteremia. METHODS: A retrospective cohort study was conducted among patients with methicillin-sensitive S. aureus bacteremia at the Jikei University Hospital between January 2008 and December 2012. Factors analyzed included the underlying disease, initial antimicrobial treatment and primary site of infection. RESULTS: During the 5-year study period, 73 patients met the inclusion criteria and were assessed. The most common primary site of bacteremia was catheter-related bloodstream infection (25/73 [34.2%]). Metastatic infection occurred in 14 of 73 patients (19.2%) (infective endocarditis [3], septic pulmonary abscess [3], spondylitis [4], psoas abscess [4], epidural abscess [3] and septic arthritis [1]). Six patients had multiple metastatic infections. Multivariate analysis revealed that the predictive factors associated with the development of metastatic infection were a delay in appropriate antimicrobial treatment of >48 hours, persistent fever for >72 hours after starting antibiotic treatment and lowest C-reactive protein levels of >3 mg/dL during 2 weeks after the onset of bacteremia. CONCLUSIONS: This study demonstrated that additional diagnostic tests should be conducted to identify metastatic infection, particularly in patients with delayed antimicrobial treatment, persistent fever and persistently high C-reactive protein levels.


Asunto(s)
Bacteriemia/epidemiología , Infecciones Estafilocócicas/epidemiología , Staphylococcus aureus , Anciano , Antibacterianos/uso terapéutico , Bacteriemia/sangre , Bacteriemia/tratamiento farmacológico , Bacteriemia/microbiología , Proteína C-Reactiva/análisis , Infecciones Relacionadas con Catéteres/sangre , Infecciones Relacionadas con Catéteres/tratamiento farmacológico , Infecciones Relacionadas con Catéteres/epidemiología , Infecciones Relacionadas con Catéteres/microbiología , Femenino , Fiebre/sangre , Fiebre/tratamiento farmacológico , Fiebre/epidemiología , Fiebre/microbiología , Humanos , Japón/epidemiología , Masculino , Meticilina/uso terapéutico , Estudios Retrospectivos , Infecciones Estafilocócicas/sangre , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología
17.
Kansenshogaku Zasshi ; 88(6): 866-70, 2014 Nov.
Artículo en Japonés | MEDLINE | ID: mdl-25764810

RESUMEN

We report two cases of Paragonimus westermani infection in a Chinese family in Japan. A 41-year-old husband and his 40-year-old wife were infected with P. westermani after consuming a homemade Chinese traditional "Drunken Crab." They were a family with two children who had lived in Japan for 19 years. The crabs were Eriocheir japonica sent from the Kyusyu area that they had pickled at home with soy sauce and Chinese liquor for 5 days. Their children did not eat any of the crabs. One month after consuming the crabs, the husband came to our outpatient clinic with fever and chest pain and his wife also presented with a persistent cough. Both patients had a high peripheral blood eosinophil count (husband:18,900/µL, wife:10,600/µL) with pulmonary effusion, nodular shadow, and pneumothorax in chest X-ray findings. Paragonimiasis was suspected from the episode of consuming the crabs. No parasite eggs were seen in their sputum and stool samples. A multiple-dot ELISA was performed with the sera to screen for parasitic infections, but the result was only weakly positive for P. westermani antigen in the husband and a slightly positive reaction in the wife. The diagnosis of P. westermani was achieved with the double diffusion Ouchterlony method using P. westermani antigen and P. miyazakii antigen. Praziquantel administration for three days improved the symptoms in both patients. The Ouchterlony method proved useful in diagnosing paragonimiasis in these cases.


Asunto(s)
Inmunodifusión , Paragonimiasis/diagnóstico , Adulto , China/etnología , Familia , Femenino , Humanos , Japón , Masculino
18.
J Infect Chemother ; 19(2): 330-2, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22965842

RESUMEN

A 52-year-old male Japanese businessman with massive cerebral bleeding was transferred from India to Japan and was admitted to our hospital. Multidrug-resistant Acinetobacter baumannii was isolated from his sputum. The minimum inhibitory concentrations for this strain were as follows: imipenem, 64 µg/ml; meropenem, 32 µg/ml; ciprofloxacin, 16 µg/ml; amikacin, 16 µg/ml; aztreonam, 16 µg/ml; colistin, <1 µg/ml. This A. baumannii strain had both bla NDM-1 and bla OXA-23 by polymerase chain reaction analysis. In Japan, NDM-1-producing bacteria are extremely rare in clinical specimens. To date, three NDM-1-positive cases have been detected in Japan, and this is the first case of A. baumannii-producing NDM-1 in Japan. Our case suggests that NDM-1-producing bacteria could be introduced into our country easily. There is concern that various resistant bacteria may be transferred from epidemic countries as a result of international medical care.


Asunto(s)
Infecciones por Acinetobacter/microbiología , Acinetobacter baumannii/enzimología , Acinetobacter baumannii/aislamiento & purificación , beta-Lactamasas/biosíntesis , Acinetobacter baumannii/genética , Antibacterianos , Proteínas Bacterianas/biosíntesis , Proteínas Bacterianas/genética , Humanos , India , Japón , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Tipificación Molecular , Reacción en Cadena de la Polimerasa , Vigilancia en Salud Pública , beta-Lactamasas/genética
19.
J Infect Chemother ; 18(5): 704-8, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22437886

RESUMEN

We gathered data regarding age, sex, and positivity rates for human immunodeficiency virus (HIV), syphilis, gonococcus, and chlamydia from individuals who underwent free and anonymous sexually transmitted infection (STI) testing conducted at the Jikei University School of Medicine Hospital (our hospital). These data were compared to results of subjects who underwent similar testing at the Minato Health Center and several private facilities of urologists and gynecologists belonging to the Minato Ward Medical Association. The positivity rate of chlamydia was found to be high in female subjects, particularly at the Minato Health Center, with 15 of 194 subjects (7.73 %) testing positive. In our hospital, we only detected 3 of 133 subjects (2.26 %) who were gonococcus positive. On the other hand, at the doctor's facilities, 10 of 188 male subjects (5.32 %) were syphilis positive, and 8 of 185 male subjects (4.32 %) were chlamydia positive, thus showing high positivity rates for both infections. At our hospital, 1 of 231 subjects was positive for gonococcus and 4 of 230 subjects (1.74 %) were positive for chlamydia, thus showing lower positivity rates for both infections. HIV-positive subjects were, however, only confirmed at our hospital, with 2 of 243 subjects (0.82 %) being positive. We were able to diagnose infected patients using free and anonymous STI testing at hospitals, and the same as at doctors' facilities. This result suggests that the hospitals that have many opportunities to diagnose HIV patients may become potential candidates for the development of new consultation facilities, establishment of testing facilities, and enhancement of consultation processes that include STI prevention.


Asunto(s)
Pruebas Anónimas/estadística & datos numéricos , Infecciones por VIH/diagnóstico , Hospitales Universitarios/estadística & datos numéricos , Enfermedades de Transmisión Sexual/diagnóstico , Adolescente , Adulto , Anciano , Niño , Femenino , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control , Humanos , Masculino , Persona de Mediana Edad , Enfermedades de Transmisión Sexual/epidemiología , Enfermedades de Transmisión Sexual/prevención & control , Tokio/epidemiología
20.
Intern Med ; 51(1): 59-64, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22214624

RESUMEN

OBJECTIVE: The mortality rates for bacteremia due to Pseudomonas aeruginosa remain high. In our hospital, we performed retrospective analyses to determine risk factors for mortality among patients with bacteremia caused by P. aeruginosa. MATERIALS AND METHODS: This retrospective cohort study was conducted among adult patients with bacteremia due to P. aeruginosa at Jikei University Hospital. We analyzed factors, such as age, gender, underlying disease, initial antimicrobial treatment, and primary site of infection to determine which of these were predictive of mortality in patients with P. aeruginosa bacteremia. RESULTS: One hundred and thirty-four patients with P. aeruginosa bacteremia were identified between April 2003 and March 2010. The 30-day mortality rate among all patients with P. aeruginosa bacteremia was 20.9%. The most common underlying disease was leukemia (20.9%), and the most common primary site of infection was the urinary tract (24.6%). Seventy-one patients (65.7%) were treated with an appropriate initial antimicrobial regimen for P. aeruginosa bacteremia. However, these patients had similar 30-day mortality to that observed in patients not administered appropriate antibiotics. This study revealed that risk factors for the 30-day mortality were thrombocytopenia and polymicrobial P. aeruginosa bacteremia (p<0.01). CONCLUSION: Thrombocytopenia and polymicrobial bacteremia were associated with a greater incidence of 30-day mortality among patients with P. aeruginosa bacteremia. On the other hand, age, underlying disease, and inappropriate initial empirical antimicrobial treatment did not affect mortality.


Asunto(s)
Bacteriemia/mortalidad , Infecciones por Pseudomonas/mortalidad , Anciano , Antibacterianos/uso terapéutico , Bacteriemia/tratamiento farmacológico , Bacteriemia/etiología , Estudios de Cohortes , Femenino , Humanos , Japón/epidemiología , Leucemia/complicaciones , Modelos Logísticos , Masculino , Persona de Mediana Edad , Pronóstico , Infecciones por Pseudomonas/tratamiento farmacológico , Infecciones por Pseudomonas/etiología , Estudios Retrospectivos , Factores de Riesgo , Trombocitopenia/complicaciones , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/etiología , Infecciones Urinarias/mortalidad
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