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1.
J Infect Chemother ; 2022 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-35016830

RESUMO

BACKGROUND/PURPOSE: Rapid detection of ß-lactamases is important in a recent situation where resistant bacteria are increasing. By using the drug susceptibility testing microfluidic device (DSTM), rapid screening of extended spectrum ß-lactamases (ESBLs) and metallo-ß-lactamases (MBLs) has become possible. METHODS: ß-lactams and ß-lactamase inhibitors were pre-fixed in the DSTM for use. A bacterial suspension in Mueller-Hinton broth (McF 0.25) was introduced into the device, and the effects of ß-lactamase inhibitor on morphological changes caused by ß-lactam were evaluated after 3 h incubation. RESULTS: Clinical isolates genetically confirmed to produce ß-lactamase were used. Of the 84 ESBL-producing strains, 80 strains (95%) turned to be ESBL positive, and five strains (6%) of them MBL were positive as well as ESBL. Four strains (5%) were negative for both ESBL and MBL. Of the 24 MBL-producing strains, 23 strains (96%) were positive for MBL. All the 43 AmpC-producing strains were negative for both ESBL and MBL. Of the 156 ESBL- and MBL-nonproducing strains, 155 strains (99%) were negative for both ESBL and MBL, and one strain was positive for ESBL. With this method, the detection sensitivity was 95% and the specificity was 100% for ESBL, whereas the detection sensitivity was 96% and the specificity was 98% for MBL. These results were not significantly different from the results of the disc diffusion method. CONCLUSION: The DSTM method allows rapid detection of ß-lactamases in 3 h and may be a useful replacement for the disc diffusion method.

2.
J Infect Chemother ; 2022 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-35031202

RESUMO

INTRODUCTION: Despite the advance in antibiotics and widespread chest tube drainage, acute empyema still shows a high mortality rate, accounting for 10-25%. We experienced a case of acute empyema caused by A. hydrophila, which is extremely uncommon, and reviewed all previously published articles. CASE PRESENTATION: A 76-year older man with a medical history of liver cirrhosis (LC) due to chronic hepatitis C and hepatic cell carcinoma was admitted to our institute. Elevated inflammatory reaction and effusions on chest CT were seen, and he was suspected of having acute empyema. Although an empiric antibiotic therapy of meropenem with chest tube drainage was performed as an initial treatment, he died within 8 hours of admission. Postmortem, both blood and left pleural fluid cultures yielded Aeromonas hydrophila. The final diagnosis was acute empyema caused by A. hydrophila. We reviewed previously reported empyema caused by Aeromonas species cases (4 A. hydrophila, and 1 A. veronii) in 4 previous reports written in English, including ours. Of 5, all were male, and the mean age was 52 years (range 27-76 years). All patients had LC due to alcohol or viral infections. As for antibiotics initially prescribed, third-generation cephalosporins were most frequently used in 3/5 (60%). Thoracentesis was performed in all patients (100%). As for prognosis, 2 (40%) survived, and 3 (60%) died. CONCLUSION: Physicians should be aware of the possibility of acute empyema caused by A. hydrophila among patients with chronic hepatic disease.

3.
J Infect Chemother ; 28(1): 120-123, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34580006

RESUMO

INTRODUCTION: The pandemic of a novel coronavirus disease 2019 (COVID-19) caused by a severe acute respiratory coronavirus 2 (SARS-CoV-2) infection has been problematic worldwide. A new SARS-CoV-2 diagnostic test (SmartAmp) was licensed in Japan in July 2021. This method, which enables us to diagnose COVID-19 as well as a gene mutation on the virus, is promising to reduce medical costs and staff labor. PATIENTS AND METHODS: To analyze the diagnostic accuracy of the SmartAmp assay for diagnosing COVID-19, we performed this retrospective study at our institute during April and May 2021. We compared the results of the SmartAmp assay and real-time reverse transcription-polymerase chain reaction (rRT-PCR) using a saliva sample from individuals suspected as having COVID-19. RESULTS: Out of 70 samples tested, the SmartAmp assay had 50 (71%) positive and 20 (29%) negative results. Using rRT-PCR as a reference, the diagnostic accuracy displayed a sensitivity of 84%, a specificity of 95%, a positive predictive value of 97.7%, and a negative predictive value of 70.4%. On the other hand, false-negative cases were found in 7 (10%), and there was no significant difference of Ct-value between true positive and false negative cases (Mean Ct-value 25.2 vs. 27.5 cycles, p = 0.226 by Mann-Whitney U test). CONCLUSION: The SmartAmp assay is a valuable method to diagnose COVID-19 rapidly. However, the negative predictive value is not high enough to diagnose the disease, so that negative results should be considered for rRT-PCR testing if patients are suspected of having COVID-19.


Assuntos
COVID-19 , Saliva , Humanos , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transcrição Reversa , SARS-CoV-2 , Sensibilidade e Especificidade
4.
J Infect Chemother ; 28(1): 24-28, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34580007

RESUMO

INTRODUCTION: Patients with nursing and healthcare-associated pneumonia (NHCAP) commonly receive empiric antibiotic therapy according to the guideline's recommendation corresponding to the patient's deteriorated conditions. However, it is unclear whether guideline-concordant treatment (GCT) could be effective or not. PATIENTS AND METHODS: To evaluate the efficacy and validity of GCT according to the current guideline for pneumonia, we conducted this retrospective study. NHCAP patients who were admitted to our institute between 2014 and 2017 were enrolled. Based on the initial antibiotic treatment, these patients were divided into two groups, the GCT group (n = 83) and the non-GCT group (n = 146). Propensity score matching (PSM) was used to balance the baseline characteristics and potential confounders between the two groups. After PSM, patients' characteristics, microbial profiles, and clinical outcomes were evaluated. RESULTS: Both groups were well-balanced after PSM, and 78 patients were selected from each group. There were no differences in patients' characteristics or microbial profiles between the two groups. As for outcomes, there were no differences in 30-day, in-hospital mortality rate, duration of antibiotic treatment, or admission. The severity of pneumonia was more severe in patients with the GCT group than those with the non-GCT group. Anti-pseudomonal agents as initial treatment were more frequently seen in patients with the GCT group than those in the non-GCT group. CONCLUSION: Unlike previous studies, GCT's recommendation for management of pneumonia by the JRS in 2017 would appear to be valid and does not increase the mortality rate.


Assuntos
Infecções Comunitárias Adquiridas , Pneumonia Associada a Assistência à Saúde , Pneumonia , Adulto , Antibacterianos/uso terapêutico , Infecções Comunitárias Adquiridas/tratamento farmacológico , Pneumonia Associada a Assistência à Saúde/tratamento farmacológico , Humanos , Pneumonia/tratamento farmacológico , Pontuação de Propensão , Estudos Retrospectivos
5.
Hum Vaccin Immunother ; : 1-10, 2021 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-34919493

RESUMO

The prognosis of patients with advanced pancreatic cancer is poor despite the recent introduction of immune checkpoint inhibitors. Therefore, the development of new therapeutic approaches is urgently required. In the present phase I/II study, we have evaluated the safety, the efficacy and the prognostic factors of Wilms' tumor 1 (WT1) and/or mucin 1 (MUC1) peptide-loaded dendritic cell (DC) vaccination in combination with a chemotherapy employing gemcitabine plus nab-paclitaxel or a combination chemotherapy regimen consisting of oxaliplatin, irinotecan, fluorouracil and leucovorin (FOLFIRINOX) in patients with advanced or relapsed pancreatic ductal adenocarcinoma (PDAC). Forty-eight eligible patients were enrolled and received the vaccinations approximately every 2-4 weeks at least seven times. No severe adverse events related to the vaccinations were observed. Median progression free survival and overall survival were 8.1 months and 15.1 months, respectively. DC vaccinations augmented tumor specific immunity which might be related to clinical outcome. The multivariate analyses demonstrated that WT1 or MUC1-specific interferonɤ enzyme-linked immunospot number prior to DC vaccination was an independent prognostic factor related to overall survival. These results indicate that DC-based immunotherapy combined with a conventional chemotherapy is safe and has clinical benefits for patients in advanced stage of PDAC. The precise evaluation of the baseline antitumor specific immunity is critical to predict clinical outcome.

6.
Anaerobe ; 73: 102478, 2021 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-34808391

RESUMO

The current guidelines suggest that hospital rooms previously occupied with Clostridioides difficile infection (CDI) patients should be decontaminated with recommended decontamination methods because C. difficile can persist on surfaces despite adherence to the recommended procedures. Recently, ultraviolet (UV) light and hydrogen peroxide have increasingly been used as innovative decontamination methods. Hence, we conducted a systematic review and meta-analysis to investigate which decontamination methods are effective in reducing environmental C. difficile contamination. We systematically searched the EMBASE, PubMed, CINAHL, Scopus, and Ichushi until March 11, 2021. We evaluated the efficacy of decontamination methods in terms of the frequency of C. difficile contamination on high-touch surfaces in hospital rooms and the incidence of hospital-acquired C. difficile infection. Among the 15 studies retrieved in our meta-analysis, eight evaluated decontamination methods with the frequency of C. difficile detection among samples after disinfection procedures, and eight reported the number of hospital-acquired CDI cases. Pooled analysis indicated that hydrogen peroxide significantly reduced the frequency of environmental C. difficile contamination, compared with hypochlorite (odds ratios [OR]: 0.12; 95% confidence interval [CI]: 0.07-0.23). Additionally, hydrogen peroxide reduced the incidence of hospital-acquired CDI compared to other methods (OR: 0.52; 95% CI: 0.28-0.96). Decontamination with UV significantly reduced the incidence of hospital-acquired CDI compared to hypochlorite (OR 0.52, 95% CI 0.28-0.96). The use of hydrogen peroxide and UV can help prevent environmental C. difficile contamination and transmission in healthcare facilities.

7.
Mycoses ; 64(12): 1498-1507, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34655487

RESUMO

BACKGROUND: Several severity indexes have been reported for critically ill patients. The Pitt bacteremia score (PBS) is commonly used to predict the risk of mortality in patients with bacteraemia. OBJECTIVES: To develop a scoring system for predicting mortality in candidaemia patients. METHODS: Medical records at five Japanese tertiary hospitals were reviewed. Factors associated with mortality were analysed using logistic regression modelling. The discriminatory power of scoring models was evaluated by assessing the area under the receiver operating characteristic curve (AUC), net reclassification improvement (NRI) and integrated discrimination improvement (IDI). RESULTS: In total, 422 candidaemia patients were included. Higher PBS, dialysis and retainment of central venous catheter were independent risk factors for all-cause 30-day mortality. However, among the five PBS components, fever was not associated with mortality; therefore, we developed a modified version of the PBS (mPBS) by replacing fever with dialysis. AUC for PBS and mPBS were 0.74 (95% confidence interval [CI]: 0.68-0.80) and 0.76 (95% CI: 0.71-0.82), respectively. The increase in predictive ability of mPBS for 30-day mortality was statistically significant as assessed by NRI (0.24, 95% CI: 0.01-0.46, p = .04) and IRI (0.04, 95% CI: 0.02-0.06, p = .0008). When patients were stratified by mPBS into low (scores 0-3), moderate (4-7) and high risk (≥8), there were significant differences among the survival curves (p < .0001, log-rank test), and 30-day mortality rates were 13.8% (40/290), 36.8% (28/76) and 69.4% (34/49), respectively. CONCLUSIONS: mPBS can be a useful tool for predicting mortality in candidaemia patients.

8.
Antibiotics (Basel) ; 10(10)2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34680760

RESUMO

Carbapenem-resistant Enterobacterales (CRE) and carbapenemase-producing Enterobacterales (CPE) have become global threats. CRE- and CPE- derived infections have been associated with high mortality due to limited treatment options. Nacubactam is a ß-lactamase inhibitor and belongs to the new class of diazabicyclooctane. The agent has an in vitro antimicrobial activity against several classes of ß-lactamase-producing Enterobacterales. This study evaluated antimicrobial activity of combination therapies including ß-lactams (aztreonam, cefepime, and meropenem) and nacubactam against four Enterobacter cloacae and six Klebsiella pneumoniae isolates with murine pneumonia model. Based on changes in bacterial quantity, antimicrobial activities of some regimens were assessed. Combination therapies including ß-lactams (aztreonam, cefepime, and meropenem) with nacubactam showed enhanced antimicrobial activity against CRE E. cloacae (-3.70 to -2.08 Δlog10 CFU/lungs) and K. pneumoniae (-4.24 to 1.47 Δlog10 CFU/lungs) with IMP-1, IMP-6, or KPC genes, compared with aztreonam, cefepime, meropenem, and nacubactam monotherapies. Most combination therapies showed bacteriostatic (-3.0 to 0 Δlog10 CFU/lungs) to bactericidal (<-3.0 Δlog10 CFU/lungs) activities against CRE isolates. This study revealed that combination regimens with ß-lactams (aztreonam, cefepime, and meropenem) and nacubactam are preferable candidates to treat pneumonia due to CRE and CPE.

9.
Biomedicines ; 9(8)2021 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-34440269

RESUMO

The gut microbiome is closely related to gut metabolic functions, and the gut microbiome and host metabolic functions affect each other. Clostridium butyricum MIYAIRI 588 (CBM 588) upregulates protectin D1 production in host colon tissue following G protein-coupled receptor (GPR) 120 activation to protect gut epithelial cells under antibiotic-induced dysbiosis. However, how CBM 588 enhances polyunsaturated fatty acid (PUFA) metabolites remains unclear. Therefore, we focused on the metabolic function alterations of the gut microbiome after CBM 588 and protectin D1 administration to reveal the interaction between the host and gut microbiome through lipid metabolism during antibiotic-induced dysbiosis. Consequently, CBM 588 modified gut microbiome and increased the butyric acid and oleic acid content. These lipid metabolic modifications induced GPR activation, which is a trigger of ERK 1/2 signaling and directed differentiation of downstream immune cells in the host colon tissue. Moreover, endogenous protectin D1 modified the gut microbiome, similar to CBM 588. This is the first study to report that CBM 588 influences the interrelationship between colon tissue and the gut microbiome through lipid metabolism. These findings provide insights into the mechanisms of prevention and recovery from inflammation and the improvement of host metabolism by CBM 588.

10.
Sci Rep ; 11(1): 15007, 2021 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-34294848

RESUMO

Clostridioides difficile infection (CDI) represents the leading cause of nosocomial diarrhea worldwide and is associated with gut dysbiosis and intestinal damage. Clostridium butyricum MIYAIRI 588 (CBM 588) contributes significantly to reduce epithelial damage. However, the impacts of CBM 588 on antibacterial therapy for CDI are not clear. Here we show that CBM 588 enhanced the antibacterial activity of fidaxomicin against C. difficile and negatively modulated gut succinate levels to prevent C. difficile proliferation and downregulate tumor necrosis factor-α (TNF-α) producing macrophages in the colon lumina propria (cLP), resulting in a significant decrease in colon epithelial damage. Additionally, CBM 588 upregulated T cell-dependent pathogen specific immunoglobulin A (IgA) via interleukin (IL)-17A producing CD4+ cells and plasma B cells in the cLP, and Th17 cells in the cLP enhanced the gut epithelial barrier function. IL-17A and succinic acid modulations with CBM 588 enhance gut colonization resistance to C. difficile and protect the colon tissue from CDI.


Assuntos
Antibiose , Clostridioides difficile/fisiologia , Infecções por Clostridium/microbiologia , Clostridium butyricum/fisiologia , Metabolismo Energético , Imunomodulação , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Infecções por Clostridium/tratamento farmacológico , Infecções por Clostridium/metabolismo , Modelos Animais de Doenças , Suscetibilidade a Doenças , Feminino , Microbioma Gastrointestinal , Imunoglobulina A/imunologia , Interleucina-17/biossíntese , Camundongos , Modelos Biológicos , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo
11.
J Infect Chemother ; 27(11): 1562-1570, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34217605

RESUMO

BACKGROUND: Current guidelines recommend echinocandins for the initial treatment of candidemia. However, polyenes are often chosen in clinical settings because of their fungicidal and anti-biofilm effects. Therefore, we performed a systematic review and meta-analysis to evaluate whether echinocandins are superior to polyenes in terms of mortality for the initial treatment of candidemia. METHODS: We systematically searched the Scopus, EMBASE, Cochrane Central Register of Controlled Trials, PubMed, and CINAHL databases until July 1, 2020. We compared the mortality rates of patients who received echinocandins and polyenes. As a subgroup analysis, we compared the mortality rates following the use of echinocandins versus liposomal amphotericin B. RESULTS: Fifteen studies involving 854 patients were included. Various Candida species were detected, and the rates of resistance of echinocandins and polyenes against the overall detected isolates were 1.0% and 0%, respectively. The overall mortality recorded in 15 studies was 41.0%, and the mortality was significantly higher for polyenes than echinocandins (odd ratios [OR] 1.68, 95% confidential interval [CI] 1.17-2.42). Furthermore, liposomal amphotericin B showed higher mortality in the initial treatment than echinocandins (OR 1.42; 95% CI 0.84-2.39). CONCLUSIONS: We revealed an association between echinocandin treatment and reduced mortality in the initial treatment of candidemia when causative fungi were not considered. Our findings partially support current guidelines recommending echinocandins for the treatment of candidemia.


Assuntos
Candidemia , Equinocandinas , Antifúngicos/uso terapêutico , Candidemia/tratamento farmacológico , Equinocandinas/uso terapêutico , Fluconazol , Humanos , Polienos/uso terapêutico
12.
Int J Antimicrob Agents ; 58(2): 106393, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34174409

RESUMO

The aim of this study was to investigate the association between vancomycin trough level and clinical outcomes (mortality and nephrotoxicity) among infected paediatric patients with Gram-positive pathogens. We systematically searched the Scopus, EMBASE, Cochrane Central Register of Controlled Trials, PubMed and CINAHL databases up to March 2020. A total of seven retrospective cohort or case-control studies were included to compare clinical effects and safety: three studies set the threshold of vancomycin trough level at 10 mg/L and the others set it at 15 mg/L. Our analysis showed that vancomycin trough level of 10-15 mg/L was associated with significantly lower mortality [<10 mg/L vs. ≥10 mg/L, odds ratio (OR) = 3.21, 95% confidence interval (CI) 1.74-5.91; and <15 mg/L vs. ≥15 mg/L, OR = 0.31, 95% CI 0.10-0.95). The high vancomycin trough group (≥10 mg/L or ≥15 mg/L) showed a higher incidence of nephrotoxicity (<10 mg/L vs. ≥10 mg/L, OR = 0.06, 95% CI 0.03-0.12; and <15 mg/L vs. ≥15 mg/L, OR = 0.28, 95% CI 0.12-0.65). This is the first meta-analysis to reveal the optimal therapeutic range of vancomycin trough level in children. Our findings strongly suggest a superior benefit of vancomycin trough of 10-15 mg/L for paediatric patients.


Assuntos
Antibacterianos/uso terapêutico , Relação Dose-Resposta a Droga , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/mortalidade , Insuficiência Renal/induzido quimicamente , Vancomicina/efeitos adversos , Vancomicina/uso terapêutico , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino
13.
J Infect Chemother ; 27(10): 1465-1470, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34158237

RESUMO

INTRODUCTION: Aspiration pneumonia (AP) accounts for 5.0-53.2% of hospitalized pneumonia and the treatment commonly used is by broad-spectrum antibiotics to cover anaerobes. Since ceftriaxone (CTRX) could generally cover oral streptococcus and anaerobes implicated in AP, it could be a useful option in the treatment of AP, instead of piperacillin-tazobactam/(PIPC/TAZ) or Carbapenems. PATIENTS AND METHODS: For the purpose of examining whether CTRX is as effective as broad-spectrum antibiotics for the treatment of AP, this retrospective study included consecutive community-onset patients who were admitted to our institute between 2014 and 2017. These patients were divided into two groups, a CTRX group (n = 25) and a PIPC/TAZ or carbapenems group (n = 97) based on the initial antibiotic treatment. Propensity score matching (PSM) was used to balance the potential confounders, and 23 patients were selected from each group. Patients among CTXR group received CTRX, while those among PIPC/TAZ or carbapenems group received PIPC/TAZ, or carbapenems and/or other agents. RESULTS: Both groups were well-balanced after PSM. There were no differences in 30-day mortality, duration of hospital stay or antibiotic treatments in the between them. The medical costs were much more expensive in the PIPC/TAZ or carbapenems group than in the CTR group (35,582 v. s. 8678 Japanese yen, p < 0.001). CONCLUSION: CTRX is one of the most useful antibiotic treatment for AP, which is not inferior to broad-spectrum antibiotic treatment. In addition, usage of CTRX in the treatment of AP is more economical than broad-spectrum antibiotic treatment, and could contribute to reduction of medical costs.


Assuntos
Ceftriaxona , Pneumonia Aspirativa , Antibacterianos/uso terapêutico , Carbapenêmicos/uso terapêutico , Ceftriaxona/uso terapêutico , Humanos , Ácido Penicilânico/uso terapêutico , Piperacilina/uso terapêutico , Combinação Piperacilina e Tazobactam/uso terapêutico , Pneumonia Aspirativa/tratamento farmacológico , Pontuação de Propensão , Estudos Retrospectivos
14.
Ther Apher Dial ; 25(4): 415-424, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33886156

RESUMO

The prognosis of patients with advanced pancreatic cancer is poor. In the present phase I/II study, we have evaluated the safety and the feasibility of Wilms' tumor 1 (WT1) and/or mucin1 (MUC1) peptide-pulsed dendritic cell (DC) vaccination in combination with chemotherapy in patients with advanced or relapsed pancreatic ductal adenocarcinoma (PDAC). Sixty-five eligible patients were enrolled. No severe adverse events related to the vaccinations were observed. Objective response rate and disease control rate was 12.3% and 50.8%, respectively. Median progression-free survival and overall survival were 4.9 and 9.6 months, respectively. DC vaccinations augmented WT1- and MUC1-specific immunity which might be related to clinical outcome. These results indicate that DC-based immunotherapy combined with a conventional chemotherapy is safe and feasible for patients in advanced stage of PDAC.

15.
J Infect Chemother ; 27(7): 1039-1042, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33840598

RESUMO

INTRODUCTION: The pandemic of a novel coronavirus disease 2019 (COVID-19) caused by a severe acute respiratory coronavirus 2 (SARS-CoV-2) infection has been problematic worldwide. A new SARS-CoV-2 antigen test (LUMIPULSEⓇ) was licensed and widely used in Japan since May 2020. We conducted this study intending to whether the automated quantitative CLEIA antigen test using a saliva sample is effective and valid for the diagnosis of COVID-19. PATIENTS AND METHODS: We analyzed and compared the diagnostic accuracy of both the automated quantitative CLEIA antigen test and real-time RT-PCR (rRT-PCR) using a saliva sample from individuals suspected as having COVID-19. RESULTS: A total of 305 samples were collected and tested in Aichi Medical University Hospital and affiliated facilities from December 2020 until January 2021 at our institute. Using reverse-transcription PCR as a reference, the AUROC of the automated quantitative CLEIA antigen test was 0.903 (95% confidential interval 0.845-0.962, p < 0.001). The appropriate cut-off antigen level was 4.0 pg/mL and had a sensitivity of 77.8%, a specificity of 99.6%, a positive predictive value of 98%, and a negative predictive value of 94.5%. On the other hand, the diagnostic accuracy of the antigen test decreased among patients among patients with COVID-19 with threshold cycle (Ct-value)≥27, which shows the AUROC was 0.795 (95%CI 0.687-0.907, p < 0.001). CONCLUSION: While the automated quantitative CLEIA antigen test from saliva specimen could be one of the most useful diagnostic tests for the diagnosis of COVID-19 in general practice, clinicians should know the limitations of the antigen test.


Assuntos
COVID-19 , Saliva , Humanos , Técnicas Imunoenzimáticas , Japão , SARS-CoV-2 , Sensibilidade e Especificidade
16.
Front Immunol ; 12: 624802, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33912155

RESUMO

Kawasaki disease (KD) is a febrile disease of childhood characterized by systemic vasculitis that can lead to coronary artery lesions (CAL). This was a prospective cohort study to determine the levels of the pentraxin 3 (PTX3), soluble CD24-Subtype (Presepsin) and N-terminal pro-brain natriuretic peptide (NT-pro BNP) in consecutive KD patients. From January 2013 to March 2015, all patients with KD admitted to Aichi Medical University Hospital who provided consent had their plasma saved before IVIG administration. In total, 97 cases were registered. 22 cases of incomplete KD were excluded from the outcome analysis. The total 75 cases were used for statistical analyses. A PTX3 threshold of >7.92 ng/ml provided a specificity of 88.5 %, a sensitivity of 94.4 %, and a likelihood ratio as high as 15.92 for the diagnosis of KD compared with febrile non-KD controls. Although an echocardiographic diagnosis of CAL in the early course of the disease was confirmed in 24 cases, it was not in the remaining 51 cases. Neither NT-proBNP nor Presepsin had statistical significance for the prediction of the echocardiographic CAL diagnosis. Only PTX3 was significantly predictive of the echocardiographic CAL diagnosis (p=0.01). The PTX3 level was significantly higher in the intravenous immunoglobulin (IVIG) non-responders (45.9±7.45) than in the IVIG responders (17.0 ± 1.46 ng/ml) (p< 0.001). The PTX3 level also correlated with the number of IVIG treatment courses needed to resolve fever (R² =0.64). Persistent CAL (pCAL) formation was observed in three cases; one of aneurysm only and two aneurysms with dilatations. The patients with pCAL had significantly higher PTX3 levels (85 ± 8.4 ng/ml) than patients without pCAL (22 ± 2.2 ng/ml) (p< 0.0001). In terms of pCAL prediction, the area under the curve (AUC) of receiver operating characteristic ROC curve of PTX3 was 0.99, and it was significantly greater than that of Presepsin (0.67) or NT-proBNP (0.75). PTX3 is a soluble pattern recognition molecule that acts as a main component of the innate immune system. These data suggest that PTX3 can be utilized as a definitive biomarker for the prediction of IVIG resistance and subsequent CAL formation in patients with KD.


Assuntos
Proteína C-Reativa/análise , Aneurisma Coronário/sangue , Síndrome de Linfonodos Mucocutâneos/sangue , Componente Amiloide P Sérico/análise , Biomarcadores/sangue , Estudos de Casos e Controles , Criança , Pré-Escolar , Aneurisma Coronário/diagnóstico por imagem , Aneurisma Coronário/etiologia , Aneurisma Coronário/prevenção & controle , Ecocardiografia , Feminino , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Lactente , Receptores de Lipopolissacarídeos/sangue , Masculino , Síndrome de Linfonodos Mucocutâneos/complicações , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Valor Preditivo dos Testes , Estudos Prospectivos , Reprodutibilidade dos Testes , Resultado do Tratamento , Regulação para Cima
17.
J Infect Chemother ; 27(6): 919-923, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33678549

RESUMO

INTRODUCTION: While necrotizing fasciitis (NF) is a rare but rapidly progressive devastating soft tissue infectious disease showing a high in-hospital mortality rate of 20-30%, there are no evidence-based predictive tools. PATIENTS AND METHODS: For the purpose of examining which predictive tools could correctly reflect the severity and prognosis of NF, we retrospectively reviewed all patients who were diagnosed with NF at our institute. The disease severity was evaluated by quick SOFA (qSOFA), SOFA score, SIRS score, APACHE II score, LRINEC score and the combined score of qSOFA and CCI. RESULTS: A total of 27 patients were enrolled in this study. The median age was 68 years (range 39-96 years). With respect to the predictive values for in-hospital mortality among NF patients, the area under the ROC curve for qSOFA, SOFA score, APACHE II score, the combined score of qSOFA and CCI were 0.653 (p = 0.192), 0.588 (p = 0.12), 0.709 (p = 0.075) and 0.782 (p = 0.016) respectively. A univariate analysis showed that the combined score of qSOFA and CCI≥5 and the initial treatment failure were poor prognostic indicators for the in-hospital death among NF patients. The appropriate cut-offs of qSOFA and CCI were based on the Youden Index. CONCLUSION: We concluded that the combined score of qSOFA and CCI could reflect the severity and prognosis of NF for in-hospital death.


Assuntos
Fasciite Necrosante , Sepse , Adulto , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Fasciite Necrosante/diagnóstico , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva , Pessoa de Meia-Idade , Escores de Disfunção Orgânica , Prognóstico , Curva ROC , Estudos Retrospectivos
18.
J Infect Chemother ; 27(8): 1143-1150, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33727025

RESUMO

BACKGROUND: The incidence of linezolid-induced myelosuppression in pediatric patients was reported at large difference among prospective studies, with a range of 0-24%. Additionally, there is little study which evaluated the impact of linezolid administration period on myelosuppression in pediatric patients, while it is one of the most frequent reason that linezolid therapy has to be discontinued in adult patients. Here, we performed a systematic review and meta-analysis to reveal the incidence of linezolid-induced thrombocytopenia and anemia, and impact of the administration period of linezolid on myelosuppression based on individual data analysis of pediatric patients. METHODS: We systematically searched the Scopus, EMBASE, Cochrane Central Register of Controlled Trials, PubMed, and CINAHL until April 2020. We investigated the incidence of linezolid-induced thrombocytopenia and anemia using pooled analysis, and evaluated the impact of linezolid administration period on myelosuppression using meta-analysis. RESULTS: Thirteen studies with 969 pediatric patients were identified. The pooled incidences of thrombocytopenia and anemia were 9% (95% confidence interval (CI), 3-18%) and 4% (95% CI, 0-12%), respectively. Our meta-analysis showed the extension of linezolid administration period (more than 14 days) resulted in higher incidence of thrombocytopenia (OR 4.86, 95% CI 1.10-21.55) and anemia (OR 4.57, 95% CI 0.13-160.49). CONCLUSIONS: The incidence of linezolid-induced myelosuppression in pediatric patients was less than 10%. However, our meta-analysis revealed linezolid administration period for more than 14 days was one of risk factors associated with linezolid-induced myelosuppression. Therefore, especially for pediatric patients treated with linezolid for more than 14 days, careful monitoring of myelosuppression is required.


Assuntos
Infecções por Bactérias Gram-Positivas , Leucopenia , Trombocitopenia , Adulto , Criança , Humanos , Linezolida/efeitos adversos , Estudos Prospectivos , Trombocitopenia/induzido quimicamente , Trombocitopenia/epidemiologia
19.
Int J Antimicrob Agents ; 57(5): 106330, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33789129

RESUMO

BACKGROUND: Carbapenem-resistant Enterobacterales (CRE) and carbapenemase-producing Enterobacterales (CPE) are difficult to treat and are a serious public health threat. Nacubactam (NAC) is a novel non-ß-lactam diazabicyclooctane ß-lactamase inhibitor with in vitro activity against some Enterobacterales expressing classes of ß-lactamases. METHODS: The antimicrobial efficacy of meropenem (MEM), cefepime (FEP), and aztreonam (ATM), each in combination with NAC, were assessed in vitro and in vivo against Klebsiella pneumoniae and Escherichia coli. Ten isolates, including CRE and/or CPE with ß-lactamase genes, were used in this study. The relationship between phenotype and in vivo efficacy was assessed in a murine neutropenic thigh-infection model. Efficacy was determined by the change in bacterial quantity. RESULTS: The results of the in vitro study showed the minimum inhibitory concentrations of the combination of NAC with either MEM, FEP, or ATM in a 1:1 ratio were 2 to >128-fold lower than those of MEM, FEP, or ATM alone against CRE+ isolates. In addition, combinations of ß-lactams and NAC administered in the murine thigh-infection model showed greater efficacy against CRE+/CPE+, CRE+/CPE-, and CRE-/CPE+ isolates harboring various ß-lactamase genes (IMP-1, IMP-6, KPC, DHA-1, or OXA-48) compared with MEM, FEP, ATM, and NAC alone. CONCLUSION: MEM, FEP, or ATM in combination with NAC showed potent in vivo antimicrobial activity in a murine thigh-infection model caused by K. pneumoniae and E. coli, including CRE and/or CPE isolates. These findings indicate that these combinations of ß-lactams and NAC are potential candidates for the treatment of CRE and/or CPE infections.


Assuntos
Compostos Azabicíclicos/farmacologia , Aztreonam/farmacologia , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Cefepima/farmacologia , Quimioterapia Combinada , Infecções por Enterobacteriaceae/tratamento farmacológico , Lactamas/farmacologia , Meropeném/farmacologia , Animais , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Relação Dose-Resposta a Droga , Farmacorresistência Bacteriana , Infecções por Enterobacteriaceae/microbiologia , Escherichia coli/efeitos dos fármacos , Humanos , Klebsiella pneumoniae/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos ICR , Testes de Sensibilidade Microbiana , Modelos Animais , Organismos Livres de Patógenos Específicos , beta-Lactamases/genética , beta-Lactamases/metabolismo
20.
Anaerobe ; 69: 102346, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33600958

RESUMO

This study aimed to evaluate the antimicrobial activity of a new quinolone, lascufloxacin, for the treatment of complicated pneumonia caused by Streptococcus pneumoniae and Prevotella intermedia using a neutropenic mice pneumonia mixed-infection model. In this study, one S. pneumoniae and four P. intermedia isolates were utilized. Antimicrobial efficacy was calculated for each isolate as the reduction of the bacterial count comparatively to the non-treated mice (log10 colony forming units (cfu)/mL) obtained in the lungs of the treated mice after 24 h. Consequently, the bacterial densities of S. pneumoniae (KY-9) and P. intermedia (335) in the lungs of control animals were 8.20 ± 0.19 log10 cfu/mL and 5.26 ± 1.50 log10 cfu/mL, respectively. At human-simulated doses, lascufloxacin and levofloxacin showed high antimicrobial activities against not only S. pneumoniae (lascufloxacin: 1.88 ± 0.43 log10 cfu/mL, p < 0.001; levofloxacin 4.30 ± 0.75 log10 cfu/mL, p < 0.001), but also P. intermedia (lascufloxacin: 1.54 ± 0.57 log10 cfu/mL, p < 0.001; levofloxacin: 2.79 ± 0.55 log10 cfu/mL, p = 0.0102). Additionally, levofloxacin demonstrated attenuated antimicrobial efficacies against S. pneumoniae in the mixed-infection model compared with that in the single infection model. In contrast, lascufloxacin showed enhanced antimicrobial activities against S. pneumoniae and P. intermedia in the mixed-infection model. In conclusion, lascufloxacin resulted in enhanced efficacies against S. pneumoniae and P. intermedia, in both the single and mixed-infection models used. These data support the clinical utility of lascufloxacin for use against S. pneumoniae and P. intermedia in the treatment of pneumonia.


Assuntos
Antibacterianos/farmacologia , Infecções por Bacteroidaceae/tratamento farmacológico , Fluoroquinolonas/farmacologia , Levofloxacino/farmacologia , Infecções Pneumocócicas/tratamento farmacológico , Pneumonia/tratamento farmacológico , Prevotella intermedia/efeitos dos fármacos , Streptococcus pneumoniae/efeitos dos fármacos , Animais , Coinfecção/tratamento farmacológico , Modelos Animais de Doenças , Humanos , Camundongos , Testes de Sensibilidade Microbiana , Pneumonia/fisiopatologia
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