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Epstein-Barr virus (EBV) reactivation in COVID-19 patients has been reported, but studies on its clinical significance are lacking. We herein report the occurrence of infectious mononucleosis (IM) due to EBV reactivation in a 60-year-old man with rheumatoid arthritis being treated with methotrexate and tocilizumab. The patient presented with a fever and tested positive for COVID-19. Laboratory findings revealed an increased atypical lymphocyte count, decreased platelet count, and elevated liver enzyme levels. Flow cytometry showed predominant expansion of reactive T cells. EBV reactivation was confirmed using real-time polymerase chain reaction. The patient was treated with remdesivir, and clinical improvement was observed after 10 days of treatment. Follow-up showed a gradual decrease in the EBV-DNA load with no recurrence of atypical lymphocytes. These findings suggest that COVID-19 in immunocompromised patients may lead to unexpected EBV reactivation and IM, even for patients outside the age at which IM is likely to occur.
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COVID-19 , Herpesvirus Humano 4 , Hospedeiro Imunocomprometido , Mononucleose Infecciosa , SARS-CoV-2 , Ativação Viral , Humanos , Masculino , Pessoa de Meia-Idade , COVID-19/imunologia , COVID-19/complicações , COVID-19/virologia , COVID-19/diagnóstico , Mononucleose Infecciosa/complicações , Mononucleose Infecciosa/imunologia , Mononucleose Infecciosa/virologia , Mononucleose Infecciosa/tratamento farmacológico , Ativação Viral/efeitos dos fármacos , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/complicações , Artrite Reumatoide/imunologia , Antivirais/uso terapêutico , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Alanina/análogos & derivados , Alanina/uso terapêutico , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/imunologia , Infecções por Vírus Epstein-Barr/virologia , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Metotrexato/uso terapêutico , Carga Viral , Anticorpos Monoclonais HumanizadosRESUMO
The use of anti-SARS-CoV-2 antibody products like tixagevimab/cilgavimab represents an important strategy to protect immunocompromised patients with haematological malignancies from COVID-19. Although patients who receive these agents should still be vaccinated, the use of tixagevimab/cilgavimab can mask the production of anti-spike antibody after vaccination, making it hard to assess vaccine response. We have newly established a quantification method to assess the response to SARS-CoV-2 vaccination at the mRNA level using B-cell receptor (BCR) repertoire assay and the Coronavirus Antibody Database (CoV-AbDab). Repeated blood samples before and after vaccination were analysed for the BCR repertoire, and BCR sequences were searched in the database. We analysed the number and percentage frequency of matched sequences. We found that the number of matched sequences increased 2 weeks after the first vaccination and quickly decreased. Meanwhile, the number of matched sequences more rapidly increased after the second vaccination. These results show that the postvaccine immune response can be assessed at the mRNA level by analysing the fluctuation in matching sequences. Finally, BCR repertoire analysis with CoV-AbDab clearly demonstrated the response to mRNA SARS-CoV-2 vaccination even after tixagevimab/cilgavimab administration in haematological malignancy patients who underwent allogeneic haematopoietic stem cell transplantation.
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COVID-19 , Neoplasias Hematológicas , Humanos , COVID-19/prevenção & controle , Vacinas contra COVID-19 , SARS-CoV-2 , Vacinação , Anticorpos Antivirais , Neoplasias Hematológicas/tratamento farmacológico , RNA Mensageiro , Receptores de Antígenos de Linfócitos B/genéticaRESUMO
PURPOSE: Many effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed, but a weaker response in individuals undergoing anticancer treatment has been reported. This study evaluates the immunogenic status and safety of SARS-CoV-2 vaccines for patients with non-small-cell lung cancer (NSCLC), receiving tegafur-uracil (UFT) as postoperative adjuvant chemotherapy. METHODS: The subjects of this prospective study were 40 patients who underwent surgery for NSCLC and received SARS-CoV-2 vaccines postoperatively. We compared the antibody titers of SARS-CoV-2 vaccines and the adverse events between patients who received adjuvant UFT and patients who did not. RESULTS: The mean anti-S1 IgG titers were not significantly different between the UFT and without-UFT groups (mean optimal density, 0.194 vs. 0.205; P = 0.76). Multivariate analysis identified the period after the second vaccination as an independent predictor of anti-S1 IgG titer (P = 0.049), but not the UFT status (with or without-UFT treatment; P = 0.47). The prevalence of adverse events did not differ significantly between the groups, and no severe adverse events occurred. CONCLUSIONS: The efficacy and safety of the SARS-CoV-2 vaccines for NSCLC patients who received postoperative adjuvant UFT chemotherapy were comparable to those for NSCLC patients who did not receive postoperative adjuvant UFT chemotherapy. CLINICAL TRIAL REGISTRATION: This study was registered with the University Hospital Medical Information Network (UMIN) in Japan (UMIN000047380).
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COVID-19 , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Quimioterapia Adjuvante , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Imunoglobulina G/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/cirurgia , Estadiamento de Neoplasias , Estudos Prospectivos , SARS-CoV-2 , Tegafur , UracilaRESUMO
BACKGROUND: Cutibacterium modestum was named in 2020. C. modestum was previously called Propionibacterium humerusii. Several implant-associated infections caused by Cutibacterium species have been previously reported, but native vertebral osteomyelitis due to these bacteria has rarely been reported. CASE PRESENTATION: A 72-year-old man, who had previously received several nerve block injections for low back pain, was referred to our hospital for deterioration in back pain in the last 1 month. MRI findings were suggestive of L5-S1 vertebral osteomyelitis. Blood cultures and bone biopsy culture revealed the presence of Gram-positive bacilli. The isolate was identified as C. modestum by 16SrRNA gene sequencing. A diagnosis of vertebral osteomyelitis caused by C. modestum was made. Minocycline followed by oral amoxicillin was administered for 3 months. His symptom improved and did not recur after treatment completion. CONCLUSION: A case of vertebral osteomyelitis caused by C. modestum was encountered. Although C. modestum is very similar to C. acnes, it could be accurately identified by 16SrRNA gene sequencing. This case represents the first documented C. modestum infection in humans.
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Osteomielite , Idoso , Dor nas Costas , Osso e Ossos , Humanos , Imageamento por Ressonância Magnética , Masculino , Osteomielite/diagnóstico , Osteomielite/tratamento farmacológico , Osteomielite/microbiologiaRESUMO
BACKGROUND: Although COVID-19 severity in cancer patients is high, the safety and immunogenicity of the BNT162b2 mRNA COVID-19 vaccine in patients undergoing chemotherapy for solid cancers in Japan have not been reported. METHODS: We investigated the safety and immunogenicity of BNT162b2 in 41 patients undergoing chemotherapy for solid cancers and in healthy volunteers who received 2 doses of BNT162b2. We evaluated serum IgG antibody titers for S1 protein by ELISA at pre-vaccination, prior to the second dose and 14 days after the second vaccination in 24 cancer patients undergoing cytotoxic chemotherapy (CC group), 17 cancer patients undergoing immune checkpoint inhibitor therapy (ICI group) and 12 age-matched healthy volunteers (HV group). Additionally, inflammatory cytokine levels were compared between the HV and ICI groups at pre and the next day of each vaccination. RESULTS: Anti-S1 antibody levels were significantly lower in the ICI and CC groups than in the HV group after the second dose (median optimal density: 0.241 [0.063-1.205] and 0.161 [0.07-0.857] vs 0.644 [0.259-1.498], p = 0.0024 and p < 0.0001, respectively). Adverse effect profile did not differ among the three groups, and no serious adverse event occurred. There were no differences in vaccine-induced inflammatory cytokines between the HV and ICI groups. CONCLUSION: Although there were no significant differences in adverse events in three groups, antibody titers were significantly lower in the ICI and CC groups than in the HV group. Further protection strategies should be considered in cancer patients undergoing CC or ICI.
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COVID-19 , Neoplasias , Anticorpos Antivirais , Vacina BNT162 , Vacinas contra COVID-19/efeitos adversos , Humanos , Imunogenicidade da Vacina , Neoplasias/tratamento farmacológico , Estudos Prospectivos , SARS-CoV-2RESUMO
Congenital syphilis may lead to severe sequelae in affected infants. The prevalence of syphilis in women of childbearing age has increased worldwide. From 2015 to 2018, we encountered eight pregnant women with syphilis including six with late latent and two with early latent syphilis. Seven pregnant women with syphilis received antibiotic therapies of oral amoxicillin, intravenous penicillin G, or the both. The syphilotherapies in four cases were considered effective, because rapid plasma reagin titers decreased. None of the seven pregnant women who received syphilotherapies had congenital syphilis. The remaining one woman who did not undergo a maternity checkup or syphilotherapy delivered a stillbirth with congenital syphilis at 29 gestational weeks.
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Complicações Infecciosas na Gravidez , Sífilis , Adulto , Antibacterianos/uso terapêutico , Feminino , Humanos , Lactente , Recém-Nascido , Gravidez , Sífilis Congênita , Adulto JovemRESUMO
PURPOSE: This study aimed to evaluate the efficacy of an educational intervention on reducing the inappropriate use of oral third-generation cephalosporins, the prevalence of resistant bacteria, and clinical outcomes. METHODS: A before-after study was conducted to compare the data for 1 year before and after intervention at a Japanese university hospital. Educational intervention included lectures for all medical staff on oral antibiotics and educational meetings with each medical department. The primary outcome was the use of oral third-generation cephalosporins in inpatients as measured by the monthly median days of therapy (DOTs) per 1000 patient days. Secondary outcomes included the use of each oral antibiotic in inpatients and outpatients, proportion of ß-lactamase-nonproducing ampicillin-resistant Haemophilus influenzae (BLNAR), penicillin-resistant Streptococcus pneumoniae (PRSP) and extended-spectrum ß-lactamase producing Escherichia coli (ESBLEC), the incidence of hospital-acquired Clostridioides difficile infection (HA-CDI), and hospital mortality. RESULTS: The use of oral third-generation cephalosporins in inpatients was significantly decreased after intervention [DOTs (interquartile range): 24.2 (23.5-25.1) vs. 3.7 (0.0-7.1), P < 0.001], and the value in outpatients was also decreased significantly. The use of fluoroquinolones and macrolides did not increase after intervention. The proportion of BLNAR, PRSP and ESBLEC did not change significantly during the study period. The incidence of HA-CDI was significantly decreased, and hospital mortality did not change after intervention. CONCLUSION: Educational intervention was effective in reducing the use of oral third-generation cephalosporins without increasing the use of broad-spectrum antibiotics and worsening clinical outcome. The prevalence of resistant bacteria did not change during the study period.
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Antibacterianos/uso terapêutico , Cefalosporinas/uso terapêutico , Farmacorresistência Bacteriana , Hospitais Universitários/estatística & dados numéricos , Prescrição Inadequada/prevenção & controle , JapãoRESUMO
BACKGROUND: There are many side effects of antituberculous drugs, however, renal failure is relatively rare. Therefore, this side effect is thought to be unrecognized by most physicians. We experienced one case of acute renal failure caused by antituberculous therapy (rifampicin). CASE REPORT: A 64-year-old Japanese male developed tuberculous pleuritis. Six weeks after starting isoniazid (INH), rifampicin (RFP), and ethambutol (EB), his renal function worsened. We temporarily stopped antituberculous therapy, but the patient's renal failure did not improve, and he was admitted to our hospital for renal biopsy. Renal pathology indicated a diagnosis of acute interstitial nephritis. After starting prednisolone, his renal function slowly improved while INH was continued. A drug-induced lymphocyte stimulation test (DLST) of the antituberculous drugs did not reveal the causative agent. However, we consider RFP to be the most likely culprit. CONCLUSION: In recent reports, renal failure is not a rare complication during antituberculous treatment in the elderly population. Physicians who are involved with the administration of antituberculous therapy have to be aware of this side effect. DLST is not useful for identifying the causative agent of antituberculous drug side effects. Leukocyte migration test may be more useful than DLST for this purpose, but further clinical studies are necessary to verify effectiveness.â©.
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Antituberculosos/efeitos adversos , Nefrite Intersticial/induzido quimicamente , Rifampina/efeitos adversos , Etambutol , Humanos , Isoniazida , Masculino , Pessoa de Meia-Idade , Tuberculose Pleural/tratamento farmacológicoRESUMO
OBJECTIVE: To evaluate the long-term effects of comprehensive antibiotic stewardship programs (ASPs) on antibiotic use, antimicrobial-resistant bacteria, and clinical outcomes. DESIGN: Before-after study. SETTING: National university hospital with 934 beds. INTERVENTION: Implementation in March 2010 of a comprehensive ASPs including, among other strategies, weekly prospective audit and feedback with multidisciplinary collaboration. METHODS: The primary outcome was the use of antipseudomonal antibiotics as measured by the monthly mean days of therapy per 1000 patient days each year. Secondary outcomes included overall antibiotic use and that of each antibiotic class, susceptibility of Pseudomonas aeruginosa, the proportion of patients isolated methicillin-resistant Staphylococcus aureus (MRSA) among all patients isolated S. aureus, the incidence of MRSA, and the 30-day mortality attributable to bacteremia. RESULTS: The mean monthly use of antipseudomonal antibiotics significantly decreased in 2011 and after as compared with 2009. Susceptibility to levofloxacin was significantly increased from 2009 to 2016 (P = 0.01 for trend). Its susceptibility to other antibiotics remained over 84% and did not change significantly during the study period. The proportion of patients isolated MRSA and the incidence of MRSA decreased significantly from 2009 to 2016 (P < 0.001 and = 0.02 for trend, respectively). There were no significant changes in the 30-day mortality attributable to bacteremia during the study period (P = 0.57 for trend). CONCLUSION: The comprehensive ASPs had long-term efficacy for reducing the use of the targeted broad-spectrum antibiotics, maintaining the antibiotic susceptibility of P. aeruginosa, and decreasing the prevalence of MRSA, without adversely affecting clinical outcome.
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Gestão de Antimicrobianos , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/epidemiologia , Clostridiales , Comissão Para Atividades Profissionais e Hospitalares , Estudos Controlados Antes e Depois , Retroalimentação , Humanos , Comunicação Interdisciplinar , Japão/epidemiologia , Staphylococcus aureus Resistente à Meticilina , Pseudomonas aeruginosa , Resultado do TratamentoRESUMO
BACKGROUND: Mycotic aneurysm is an uncommon disease which could be fatal without appropriate treatment. Although standard therapy for mycotic aneurysms consists of resection of the infected aorta and in situ graft replacement, some treat with endovascular stent-grafting because patients may not tolerate graft replacement due to underlying diseases. There are 6 more reported cases of mycotic aneurysm caused by Edwardsiella tarda. With the exception of our case, all underwent resection and debridement of the infected aorta or vascular prosthesis. Herein we report the first case ever of mycotic aneurysm caused by E. tarda, successfully treated with stenting and suppressive antibiotic therapy without resection of the infected aorta. CASE PRESENTATION: A 65-year-old Japanese woman with cirrhosis and hepatocellular carcinoma complained of fatigue. Her work up revealed a ruptured aneurysm of the descending aorta. She went through endovascular stent-graft placement. Edwardsiella tarda grew from blood cultures, which led to the diagnosis of mycotic aneurysm. Edwardsiella tarda is a Gram negative bacillus which rarely causes infections in humans. In the case of bacteremia, its mortality is reported to be very high and all reported cases with mycotic aneurysm caused by E. tarda ended up with resection of the infected aorta. CONCLUSION: Our case shows that in the case of mycotic aneurysm caused by E. tarda, endovascular stent-graft placement could be an alternative to in situ graft replacement.
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Aneurisma Infectado/tratamento farmacológico , Aneurisma Infectado/cirurgia , Antibacterianos/uso terapêutico , Aorta/cirurgia , Implante de Prótese Vascular/métodos , Infecções por Enterobacteriaceae/tratamento farmacológico , Idoso , Aneurisma Infectado/microbiologia , Prótese Vascular , Edwardsiella tarda/isolamento & purificação , Infecções por Enterobacteriaceae/microbiologia , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: ESBL (Extended spectrum beta-lactamase) producing enterobacteriaceae are challenging organisms with little treatment options. Carbapenems are frequently used, but the emergence of carbapenem resistant enterobacteriaceae is a concerning issue, which may hinder the use of carbapenems. Although cephamycins such as cefoxitin, cefmetazole or cefotetan are effective against ESBL-producers in vitro, there are few clinical data demonstrating effects against bacteremia caused by these organisms. METHODS: We performed a retrospective observational study on cases of bacteremia caused by ESBL-producers to investigate the efficacy of cefmetazole compared with carbapenems. We also evaluated whether the trend of antibiotic choice changed over years. RESULTS: Sixty-nine patients (male 34, age 69.2 ± 14.4), including two relapse cases, were reviewed for this analysis. The most common causative organisms were Escherichia coli (64, 93 %), followed by Klebsiella pneumoniae and K. oxytoca (2 each, 4 %). The group that received carbapenem therapy (43, 62 %) had increased severity in the Pittsburgh Bacteremic score than the group that received cefmetazole therapy, (1.5 ± 1.5 vs 2.5 ± 2.1, p = 0.048), while analysis of other factors didn't reveal any statistical differences. Five patients in the carbapenem group and one patient in the cefmetazole group died during the observation period (p = 0.24). CTX-M-9 were predominant in this series (59 %). Infectious disease physicians initially recommended carbapenems at the beginning of the current research period, which gradually changed over time favoring the use of cefmetazole instead (p = 0.002). CONCLUSION: Cefmetazole may be safely given to patients with bacteremia caused by ESBL-producers as a definitive therapy, if one can select out relatively stable patients.
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Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Carbapenêmicos/uso terapêutico , Cefmetazol/uso terapêutico , Enterobacteriaceae/enzimologia , beta-Lactamases/metabolismo , Idoso , Bacteriemia/microbiologia , Farmacorresistência Bacteriana , Escherichia coli/isolamento & purificação , Feminino , Humanos , Klebsiella oxytoca/isolamento & purificação , Klebsiella pneumoniae/isolamento & purificação , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/microbiologiaRESUMO
We report herein on a case of community-acquired necrotizing soft tissue infection caused by Serratia marcescens. The patient had been treated with prednisolone, tocilizumab and tacrolimus for rheumatoid arthritis. Since Gram staining of the tissue revealed Gram negative rod bacteria, ceftriaxone and clindamycin were administered as empiric therapy. Tissue culture revealed S. marcescens. Ceftriaxone was continued according to the antibiotic sensitivity. She underwent debridement of necrotic tissue and continued ceftriaxone for 17 days. She recovered and was discharged after skin grafting.
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Antibacterianos/uso terapêutico , Ceftriaxona/uso terapêutico , Clindamicina/uso terapêutico , Serratia marcescens , Infecções dos Tecidos Moles/tratamento farmacológico , Infecções dos Tecidos Moles/microbiologia , Feminino , Humanos , Pessoa de Meia-Idade , Infecções dos Tecidos Moles/diagnóstico , Resultado do TratamentoRESUMO
BACKGROUND: Recently, necrotizing fasciitis has been reported in patients treated with bevacizumab, usually secondary to wound healing complications, gastrointestinal perforations, or fistula formation. The risk of invasive Haemophilus influenzae type b infection is significantly increased in immunocompromised hosts. However, necrotizing fasciitis due to Haemophilus influenzae type b in a patient treated with combined bevacizumab and chemotherapy has not been previously reported. CASE PRESENTATION: A 59-year-old woman was admitted to the intensive care unit after sudden onset of fever, chills, and right thigh pain. She received chemotherapy with fluorouracil, irinotecan, and bevacizumab for colon cancer 10 days prior to admission. The advancing erythematous margin and her worsening clinical condition prompted us to suspect necrotizing fasciitis and consult the orthopedics department for a fascia biopsy and debridement. Surgical exploration revealed a murky dishwater-colored pus exudate from the incision site and the lack of a shiny appearance of the fascia that also suggested necrotizing fasciitis. After 2 days, the final results of the blood and exudate cultures confirmed the presence of Haemophilus influenzae type b. A diagnosis of necrotizing fasciitis due to Haemophilus influenzae type b was made. The patient required recurrent surgical debridement and drainage, but she recovered from the septic shock. CONCLUSIONS: We report a case of necrotizing fasciitis due to Haemophilus influenzae type b in a patient without injury and with rectal cancer treated with combined bevacizumab and chemotherapy. Physicians should consider invasive Haemophilus influenzae type b disease in the presence of necrotizing fasciitis in patients treated with this combined treatment modality.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fasciite Necrosante/virologia , Infecções por Haemophilus/virologia , Haemophilus influenzae tipo b/isolamento & purificação , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/virologia , Anticorpos Monoclonais Humanizados/administração & dosagem , Bevacizumab , Feminino , Humanos , Pessoa de Meia-Idade , Choque Séptico/virologiaRESUMO
BACKGROUND: Although it has received a degree of notoriety as a cause for antibiotic-associated enterocolitis (AAE), the role of methicillin resistant Staphylococcus aureus (MRSA) in the pathogenesis of this disease remains enigmatic despite a multitude of efforts, and previous studies have failed to conclude whether MRSA can cause AAE. Numerous cases of AAE caused by MRSA have been reported from Japan; however, due to the fact that these reports were written in the Japanese language and a good portion lacked scientific rigor, many of these reports went unnoticed. METHODS: We conducted a systematic review of pertinent literatures to verify the existence of AAE caused by MRSA. We modified and applied methods in common use today and used a total of 9 criteria to prove the existence of AAE caused by Klebsiella oxytoca. MEDLINE/Pubmed, Excerpta Medica Database (EMBASE), the Cochrane Database of Systematic Reviews, and the Japan Medical Abstract Society database were searched for studies published prior to March 2013. RESULTS: A total of 1,999 articles were retrieved for evaluation. Forty-five case reports/series and 9 basic studies were reviewed in detail. We successfully identified articles reporting AAE with pathological and microscopic findings supporting MRSA as the etiological agent. We also found comparative studies involving the use of healthy subjects, and studies detecting probable toxins. In addition, we found animal models in which enteritis was induced by introducing MRSA from patients. Although we were unable to identify a single study that encompasses all of the defined criteria, we were able to fulfill all 9 elements of the criteria by collectively analyzing multiple studies. CONCLUSIONS: AAE caused by MRSA-although likely to be rarer than previous Japanese literatures have suggested-most likely does exist.
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Antibacterianos/efeitos adversos , Enterocolite Pseudomembranosa/microbiologia , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas/microbiologia , Animais , Enterocolite Pseudomembranosa/induzido quimicamente , Humanos , Meticilina , Resistência a Meticilina , Infecções Estafilocócicas/induzido quimicamenteRESUMO
This report highlights two cases of surgical site infections (SSIs) caused by Mycobacterium fortuitum (Mf) following abdominal mesh implantation. The first case involved an 83-year-old male experiencing non-healing erythema and wounds post-operation, which persisted despite multiple treatments, until effective management was achieved with targeted antibiotics after Mf identification. The second case concerned a female patient with a gynecological postoperative hernia, where Mf was quickly detected following SSI onset three weeks after surgery. Prompt mesh removal and appropriate antibiotic treatment led to a rapid and full recovery. These cases emphasize the importance of early detection and intervention in managing Mf infections effectively, illustrating how the timing of diagnosis can significantly influence treatment outcomes.
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We retrospectively reviewed patients with Corynebacterium striatum bacteremia treated with daptomycin. All 11 isolates were initially susceptible to daptomycin, but the emergence of daptomycin nonsusceptibility during treatment and clinical failure occurred in 36% and 45% of patients, respectively.
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PURPOSE: While nirmatrelvir/ritonavir (NMV-r) has been positioned as a first-line treatment for mild to moderate COVID-19, it has multiple and significant drug-drug interactions (DDIs). The use of NMV-r in Japan has been limited compared to the United States. This study aimed to describe the distribution of DDIs with NMV-r and their management in patients with COVID-19 under the control of a management system for the appropriate use of NMV-r. METHODS: A retrospective observational study was conducted at a Japanese university hospital. The management system included a flowchart for selecting antivirals and a list for reviewing DDI management, based on the National Institutes of Health guidelines and the guidance of the Japanese Society of Pharmaceutical Health Care and Sciences. Patients with mild to moderate COVID-19 and prescribed NMV-r or molnupiravir (MOV) were included. The primary outcome was DDI management practices, including the selected COVID-19 medications. The secondary outcome included the distribution of DDI classification and the 30-day all-cause mortality. RESULTS: This study included 241 patients (median age of 60 years, 112 [46.5%] females), of whom 126 and 115 received NMV-r and MOV, respectively. Of the 241 patients, 145 (60.2%) received concomitant medications that have DDIs with NMV-r. All 30 patients with severe renal impairment or insufficient details on concomitant medications received MOV. Forty-nine patients with concomitant medications required alternative COVID-19 therapy consideration due to DDIs, of whom 42 (85.7%) patients received MOV. Eighty-one patients had concomitant medications requiring temporary adjustment, of whom 44 (54.3%) patients received NMV-r, and 42 of these patients temporarily adjusted these concomitant medications. Five patients with concomitant medications that can continued by monitoring the effects/adverse effects, of whom 4 (80.0%) patients received NMV-r. Seventy-six patients without concomitant medications requiring DDI management, of whom 71 (93.4%) patients received NMV-r. The 30-day all-cause mortality for eligible patients was 0.9% [95% confidence interval, 0.1-3.1]. CONCLUSIONS: Most patients received appropriate antivirals according to the classification of DDIs, and most patients with concomitant medications requiring temporary adjustment received the recommended DDI management. Our management system is effective in promoting the use of NMV-r in the appropriate patients and managing problematic DDIs.
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A monovalent Omicron XBB.1.5 mRNA RBD analogue vaccine, MAFB-7256a (DS-5670d), was newly developed and approved in Japan in the Spring of 2024 for the prevention of COVID-19. However, clinical efficacy data for this vaccine are currently lacking. We previously established the Quantification of Antigen-specific Antibody Sequence (QASAS) method to assess the response to SARS-CoV-2 vaccination at the mRNA level using B-cell receptor (BCR) repertoire assays and the Coronavirus Antibody Database (CoV-AbDab). Here, we used this method to evaluate the immunogenicity of MAFB-7256a. We analyzed repeated blood samples using the QASAS method from three healthy volunteers before and after MAFB-7256a vaccination. BCR response increased rapidly one week post-vaccination and then decreased, as with conventional vaccine. Notably, the matched sequences after MAFB-7256a vaccination specifically bound to the receptor-binding domain (RBD), with no sequences binding to other epitopes. These results validate that MAFB-7256a is an effective vaccine that exclusively induces antibodies specific for the RBD, demonstrating its targeted immunogenic effect.
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Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , Receptores de Antígenos de Linfócitos B , SARS-CoV-2 , Humanos , SARS-CoV-2/imunologia , Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , COVID-19/imunologia , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/sangue , Receptores de Antígenos de Linfócitos B/imunologia , Receptores de Antígenos de Linfócitos B/genética , Imunogenicidade da Vacina , Vacinas de mRNA/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/genética , Masculino , Adulto , Vacinas Sintéticas/imunologia , Feminino , Vacinação , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/sangueRESUMO
Monovalent Omicron XBB.1.5 mRNA vaccines were newly developed and approved by the FDA in Autumn 2023 for preventing COVID-19. However, clinical efficacy for these vaccines is currently lacking. We previously established the quantification of antigen-specific antibody sequence (QASAS) method to assess the response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination at the mRNA level using B-cell receptor (BCR) repertoire assay and the coronavirus antibody database (CoV-AbDab). Here, we used this method to evaluate the immunogenicity of monovalent XBB.1.5 vaccines. We analyzed repeated blood samples of healthy volunteers before and after monovalent XBB.1.5 vaccination (BNT162b2 XBB.1.5 or mRNA-1273.815) for the BCR repertoire to assess BCR/antibody sequences that matched SARS-CoV-2-specific sequences in the database. The number of matched unique sequences and their total reads quickly increased 1 week after vaccination. Matched sequences included those bound to the Omicron strain and Omicron XBB sublineage. The antibody sequences that can bind to the Omicron strain and XBB sublineage revealed that the monovalent XBB.1.5 vaccines showed a stronger response than previous vaccines or SARS-CoV-2 infection before the emergence of XBB sublineage. The QASAS method was able to demonstrate the immunogenic effect of monovalent XBB.1.5 vaccines for the 2023-2024 COVID-19 vaccination campaign.
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We report a case of biliary tract infection caused by a strain of Burkholderia contaminans, a member of the Burkholderia cepacia complex. The patient developed sepsis after endoscopic retrograde cholangiopancreatography (ERCP). Gram-negative bacilli were isolated from blood and bile cultures. Automated bacterial identification systems identified the organism as Burkholderia cepacia, whereas DNA sequence analysis revealed that the recA gene isolate was identical to that of B. contaminans. The patient responded to therapy with the antibiotics trimethoprim/sulfamethoxazole and biliary tract decompression. This case suggests that B. contaminans can be a causative agent of healthcare-associated biliary tract infections such as ERCP-related cholangitis.