查看更多>>摘要：Background: The emergence and spread of carbapenem-resistant Enterobacteriaceae (CRE) is a global health problem due to its high mortality and limited treatment options. Combination antimicrobial therapy is reported to be effective against CRE in vitro; however, its efficacy in vivo has not been thoroughly evaluated. Thus, this study assessed the efficacy of combination therapy of meropenem (MEPM) and amikacin (AMK) in a carbapenem-resistant Klebsiella pneumoniae (CR-Kp) mouse model of pneumonia. Materials and methods: Agar-based bacterial suspension of CR-Kp clinical isolates was inoculated into the trachea of BALB/c mice. Treatment was initiated 6 h post infection, with 100 mg/kg MEPM every 6 h, 100 mg/kg AMK every 12 h, or in combination; survival was evaluated for 7 days. The number of viable bacteria in the lungs, lung histopathology, and neutrophil counts in broncho-alveolar lavage fluid (BALF) were evaluated 42 h after infection. Results: All mice in the untreated control group died in 48 h, while all the mice in treatment groups survived past 7 days following infection. The bacterial count in the lungs (log(10) CFU/mL, mean +/- SEM) in the combination group (2.00 +/- 0.00) decreased significantly compared to that in control (10.19 +/- 0.11, p < 0.0001), MEPM (6.38 +/- 0.17, p < 0.0001), and AMK (6.17 +/- 0.16, p < 0.0001) groups. BALF neutrophil count reduced only in the combination therapy group. Combination therapy prevented the progression of lung inflammation, including alveolar neutrophil infiltration and hemorrhage. Conclusions: This study demonstrates in vivo efficacy of MEPM and AMK combination therapy against CR-Kp pneumonia. (C) 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
查看更多>>摘要：Objective: The aim of this study was to clarify the role of Methicillin-resistant Staphylococcus aureus (MRSA) carriers in the development of surgical site infection (SSI) after colorectal surgery. Summary background data: MRSA is commonly implicated in hospital-acquired infections. Active surveillance culture (ASC) using the nasal swab test is useful to detect MRSA in surgical patients. We hypothesized that MRSA carriers would be more susceptible to SSI after colorectal surgery Methods: Patients who underwent ASC between 2010 and 2013 were included in this study. The incidence of SSI was compared between MRSA carriers and non-carriers using the chi-square test. The odds ratio for SSI was computed using logistic regression analyses. Results: Among 355 patients, 12 (3.4%) were identified as MRSA carriers and 343 as non-carriers. Of all the patients, 65 patients (18.3%) developed an SSI. Of these, 6 cases were in MRSA carriers and 59 cases were in non-carriers (p < 0.01). This meant that half of the 12 MRSA carriers developed an SSI, compared with only 17.2% of non-carriers (59 cases out of 343 patients). Therefore, MRSA carriers had a significantly higher risk of SSI (adjusted odds ratio = 4.77 [1.37 to 16.6], p = 0.01). Conclusions: Detection of MRSA via ASC is significantly associated with the development of SSI after colorectal surgery. These findings indicate that ASC for MRSA is useful to predict an SSI. (C) 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
查看更多>>摘要：Introduction: Dengue fever, Chikungunya fever, and Zika virus infection have similar symptoms and overlapping areas of endemicity and so cannot be distinguished clinically. Rapid diagnosis tests are available for each infection but each test covers only single target. There are PCR-based methods available that test for all three infections simultaneously, not applicable for in-vitro diagnostic use. The aim of this study was to evaluate the diagnostic accuracy of a new point-of-care testing (LAMP POCT) based on loop-mediated isothermal amplification method that tests for all three viruses simultaneously, using serum or urine samples, and takes about 45 min. Methods: LAMP POCT was evaluated as the comparator on 67 individuals, of whom 56 had dengue, three had Chikungunya, two had Zika virus infection and six did not have any kind of these infections confirmed by RT-PCR. Results: Among individuals with dengue, the sensitivity of LAMP POCT was 100% in samples collected in the first 3 days after illness onset, all three patients with Chikungunya were LAMP POCT positive, and both patients with Zika virus infection were LAMP POCT negative. There were no false-positive test results. Conclusions: LAMP POCT has potential utility as a point-of-care combination test for dengue and Chikungunya viruses, but further prospective studies are needed among individuals with Chikungunya virus and Zika virus infection, using serum and urine samples. (C) 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
查看更多>>摘要：Background: In patients infected with human immunodeficiency virus (HIV)-1 at our hospital, we observed increases in skin and soft-tissue infections (SSTIs) by community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA). Therefore, we analyzed factors related to CA-MRSA infection and performed a molecular epidemiological investigation. Methods: HIV-1-infected patients were diagnosed with SSTIs related to S. aureus between 2007 and 2017, and MRSA was classified into community and hospital-acquired types according to published criteria. Information was collected retrospectively from clinical records, and multivariate analysis by logistic regression was performed concerning factors related to CA-MRSA infection. We evaluated the staphylococcal cassette chromosome mec (SCCmec) type, multilocus sequence type, and the presence of genes encoding Panton-Valentine leucocidin (PVL) in 27 MRSA samples isolated during and after 2015. Results: We found 218 episodes of SSTIs in 169 patients, and among initial episodes of SSTIs, the MRSA ratio was higher from 2015 to 2017 relative to that from 2007 to 2014 (88% vs. 44%; p < 0.0001). Multivariate analysis showed that in men having sex with men [MSM; odds ratio (OR): 13] and exhibiting onset during and after 2015 (OR: 5.4), CD4(+) cell count >= 200 cells/mu L (OR: 5.6) and the presence of lesions in the lower abdomen or buttocks (OR: 9.5) were independent factors related to CA-MRSA infection. Additionally, PVL+/ST8/SCCmec type IV MRSA was the predominant pathogen (22 cases; 81%). Conclusions: These data describe an increased prevalence of SSTIs due to PVL-positive ST8-MRSA-IV, not previously considered epidemic in Japan, in MSM infected with HIV-1 in Osaka, Japan. (C) 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
查看更多>>摘要：Objectives: The objective of this study was to describe the recent epidemiology of Pneumocystis pneumonia (PCP) in Japan using a nationwide database. Methods: We extracted data of inpatients with PCP from the Diagnostic Procedure Combination database, a national inpatient database in Japan, from January 2010 to December 2016. Results: During the study period, 4293 PCP patients were identified, including 4073 adults and 220 children. In adults, the most common comorbidity was hematologic malignancy (31%), followed by diabetes mellitus (30%), rheumatic/collagen diseases (26%), and solid organ tumors (18%). In children, there were few patients with rheumatic diseases (5%) or diabetes mellitus (2%), but immunodeficiency (without human immunodeficiency virus) was more common (28%). Few biological products were used for adult and pediatric patients; CD20 inhibitors, TNF-alpha inhibitors, interleukin receptor inhibitors, and CTLA-4 inhibitor were used for 8.6% and 2.4%, 1.3% and 0%, 1.2% and 4.7%, and 0.2% and 0% of adult and pediatric patients, respectively. Based on data stratified by bed count, the annual numbers of PCP patients in Japan were estimated as 2221 adults and 123 pediatric patients. The mortality was higher in adults (27%) than in pediatric patients (21%) (P = 0.041). Conclusions: The underlying disease and mortality were apparently different between adult and pediatric PCP patients. (C) 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
查看更多>>摘要：Background: Recent studies report incongruent finds regarding the addition of pegylated interferon -alpha (Peg- IFN alpha) to nucleos(t)ide analogues. This study was designed to compare the efficacy of Peg-IFN alpha and tenofovir disoproxil fumarate (TDF) combination therapy with each of the treatments separately. Methods: In this open-label, randomized clinical trial, treatment-naive hepatitis B e antigen (HBeAg)-negative patients were randomly assigned to three treatment groups: Group A: Peg- IFN alpha (180 mcg/week) with TDF (300 mg/day); Group B: TDF (300 mg/day); and Group C: Peg- IFN alpha (180 mcg/week). The intervention spanned 48 weeks and patients were followed up every 12 weeks. The primary end-point was HBV DNA load <20 IU/mL. Results: Groups A, B and C each comprised of 22, 23 and 22 patients, respectively. The number of patients with HBV DNA suppression in group A was significantly higher compared to groups B and C (P = 0.034). No significant difference was observed in the normalization trends of serum ALT levels between the three groups (P = 0.082). At week 48, combination therapy was significantly more effective in suppressing HBV DNA concentration to below the level of detection than TDF monotherapy (OR = 2.1, 95%CI: 1.18-4.15; P = 0.034). Furthermore, a comparison between monotherapy arms revealed that both interventions had similar effects on the overall outcome (OR = 1.24, 95%CI: 1.02-5.8; P = 0.062). Conclusion: A Peg- IFN alpha and TDF combination therapy resulted in improved virologic response and was safe in HBeAg negative patients. Monotherapy with Peg-IFN alpha or TDF procured limited benefits in comparison. (C) 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
查看更多>>摘要：Introduction: Eradication of asymptomatic bacteriuria (ASB) before urological procedures is important to reduce the risk for infectious complications after surgery. However, the appropriate regimen for antimicrobial treatment has not been fully determined. We experienced continuous (over 10 months) isolation of extended spectrum beta-lactamase (ESBL)-producing fluoroquinolone-resistant Escherichia coli from urine of an asymptomatic patient. The four isolates obtained (SMESC1 to 4) were international high-risk clones of O25b:H4-ST131-H30R, and originated from one strain, as revealed by the whole genome sequences. Although the patient received meropenem (MEPM) and fosfomycin (FOM), to which the strains were susceptible before the urological procedures, they could not be eradicated. Methods: To explore the reason for the continuous isolation even after MEPM and FOM administration, antimicrobial killing of adherent and/or intracellular bacterial communities (IBC) formed by coculture of the E. coli cells and T24 bladder epithelial cells were examined. Results: FOM and levofloxacin did not decrease viable E. coli cells compared with gentamicin. MEPM partly decreased them, and sitafloxacin (STFX) decreased them most potently. These observations indicate that E. coli can survive in the urinary tract under antimicrobial administration, and some antimicrobials such as FOM and MEPM cannot eradicate E. coli in uroepithelial cells. Adhesion on urinary epithelial cells and/or IBC formation might result in continuous isolation from the urinary tract and recurrence of ASB and urinary tract infections. Conclusions: The present study suggests that STFX is a promising optional agent for the eradication of ESBL-producing fluoroquinolone-resistant E. coli in the urinary tract before urological procedures. (C) 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
查看更多>>摘要：Background: There is clinical and epidemiological evidence indicating that cigarette smoke exposure can significantly increase the usage of antibiotics by smokers to treat pulmonary infections, suggesting an increased risk of bacterial drug resistance. Pseudomonas aeruginosa is commonly found in infectious diseases closely related to cigarette smoke exposure and frequently acquires drug resistance. Recently, a study has demonstrated that cigarette smoke extract may induce Pseudomonas aeruginosa antibiotic resistance but the mechanism remain unknown. Objectives: To explore the effect of cigarette smoke exposure on drug resistance in P. aeruginosa and the underlying mechanism using an in vitro model of cigarette smoke extract (CSE) exposure. Methods: P. aeruginosa strains PAO1, PA103 and ATCC27853 were used in this study. Changes in drug resistance in P. aeruginosa after CSE exposure were evaluated by antimicrobial susceptibility tests. Additionally, differentially expressed genes related to drug resistance were detected by transcriptome sequencing and qRT-PCR. Results: CSE increased both the MIC and MBC of levofloxacin and imipenem (MIC was not changed in ATCC 27853) against P. aeruginosa. However, CSE could only increase the minimum inhibitory concentration of tigecycline and minocycline against P. aeruginosa. Transcriptome sequencing and qRT-PCR indicated that MvaT and OprD levels decreased and MexEF-OprN levels increased. Conclusions: Overall, our results showed that CSE may induce antibiotic resistance in P. aeruginosa. The results of antimicrobial susceptibility tests, transcriptome sequencing and qRT-PCR showed that CSE induced P. aeruginosa to the nfxC drug-resistant phenotype. (C) 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
查看更多>>摘要：Introduction: Antibody tests for detecting varicella-zoster virus include the fluorescent-antibody-to-membrane-antigen (FAMA) assay, immune adherence hemagglutination assay (IAHA), enzyme immunoassay (EIA), and the glycoprotein-based enzyme-linked immunosorbent assay (gpELISA). Although FAMA and gpELISA are highly sensitive, FAMA is not available commercially. Therefore, this study was performed to compare potential high-sensitivity tests with commercially available tests. Methods: Four antibody tests, FAMA, gpELISA, EIA, and IAHA, were performed using sera collected from 32 children aged 7 months-10 years. Using FAMA as a reference, the sensitivity and specificity of gpELISA, EIA, and IAHA were assessed. Subsequently, using gpELISA as a reference, the positive agreement rate of EIA and IAHA was assessed. Results: On a reference scale with FAMA set at 100%, the sensitivity and specificity of the antibody tests were as follows: gpELISA, 67% and 100%; EIA, 67% and 100%; and IAHA, 47% and 100%, respectively. The positive agreement rates of EIA and IAHA relative to gpELISA were 86% and 64%, respectively. Conclusions: gpELISA had a lower positive rate than did FAMA, and showed comparable sensitivity to that of EIA. (C) 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
查看更多>>摘要：Objective: Terminally ill patients with hematological malignancy tend to be treated aggressively. We aimed to clarify the status and costs of antimicrobial treatment of patients dying with hematological malignancies. Methods: This retrospective study was conducted in a Japanese acute hospital between September 2010 and August 2015. A total of 141 patients who stayed for 14 days or longer and died in the hospital were investigated. Results: The median patient age was 67 years (range, 22-93). Most patients were treated with antibacterial, antifungal, and antiviral agents (98%, 75%, and 27% of the patients, respectively) in the last 14 days of their lives. The frequency of antibiotics used in the last 7 days did not differ from that of the week before. The median cost of antimicrobials was 245,000 JPY (2227 USD), which reflected 16% of the total medical costs spent over the last 14 days. A subgroup analysis of the patients according to care policy (aggressive care policy (A) and palliative care policy (P), respectively) showed that the total medical cost in group P in the last 7 days decreased from that of the preceding week; however, the cost of antimicrobials did not lessen even in the last 7 days. Conclusions: Most patients dying with hematological malignancy were treated with a broad spectrum of antimicrobials. It appeared to be difficult to reduce, let alone discontinue antimicrobial treatment even in patients treated according to the palliative care policy. The optimal use of antibiotics for hematological patients in their end-of-life should be discussed. (C) 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
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