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Introduction: While respiratory syncytial virus (RSV) is one of the most common pathogens in adults admitted to the ICU due to respiratory diseases, no reports regarding the occurrence rate of RSV infections in adults in Japan during the COVID-19 pandemic exist., Patients and Methods: We conducted this retrospective study to examine the exact occurrence rate of RSV infections in adults. We reviewed all patients (≥18 years) with any respiratory symptoms who received quantitative polymerase chain reaction (PCR) using nasopharyngeal samples for respiratory viruses by GeneLEAD at the Aichi Medical University Hospital between November 2022 and November 2023., Results: A total of 541 adult patients who underwent PCR test were enrolled in this study. RSV was identified in 18 cases (3.3 %); 8 (1.5 %) upper and 10 (1.8 %) lower respiratory tract infections. Influenza A and SARS-CoV-2 were found in 10 (1.8 %) and 61 (11.3 %), respectively. Patients with RSV infections and COVID-19 had more comorbidities than those with Influenza virus infections. As for RSV-associated with lower respiratory tract infection cases, 10 developed acute respiratory failure, resulting in 1 fatal case due to pneumonia and 1 died of septic shock due to ileus. The 30-, 90-day mortality rates were 1 (6 %) and 2 (11 %) respectively., Conclusion: About 3 % of adults had RSV infections during the COVID-19 pandemic. The outcomes of RSV infections in adults were similar to those by COVID-19. Those with comorbidities should have a preventive method against RSV infections, the same as for COVID-19., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

The trends and prevalence of antimicrobial susceptibility of pathogens vary by country, region, and time. Long-term regular surveillance is required to investigate trends in the antimicrobial resistance of various isolated bacterial pathogens. We report the results of a nationwide surveillance on the antimicrobial susceptibility of bacterial respiratory pathogens in Japan conducted by the Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology. The isolates were collected from clinical specimens obtained from adult patients who visited a collaborating medical facility between June 2019 and December 2020 and were diagnosed with respiratory tract infections by a physician. Antimicrobial susceptibility testing was performed in a centralized laboratory according to the methods recommended by the Clinical and Laboratory Standards Institute. Susceptibility testing was performed for 932 strains (201 Staphylococcus aureus, 158 Streptococcus pneumoniae, 6 S. pyogenes, 136 Haemophilus influenzae, 127 Moraxella catarrhalis, 141 Klebsiella pneumoniae, and 163 Pseudomonas aeruginosa) collected from 32 facilities in Japan. The proportions of methicillin-resistant S. aureus and penicillin-resistant S. pneumoniae were 35.3% and 0%, respectively. In H. influenzae, 16.2% and 16.9% were β-lactamase-producing ampicillin resistant and β-lactamase-negative ampicillin resistant, respectively. Extended-spectrum β-lactamase-producing K. pneumoniae accounted for 5.0% of all K. pneumoniae infections. Carbapenemase-producing K. pneumoniae and multi-drug-resistant P. aeruginosa with metallo-β-lactamase were not detected in this study. This surveillance will be a useful reference for treating respiratory infections in Japan and will provide evidence to enhance the appropriate use of antimicrobial agents., Competing Interests: Declaration of competing interest Issei Tokimatsu received research funding from Asahi Kasei Pharma Corporation, and scholarship donations from Shionogi & Co., Ltd., and Daiichi Sankyo Co., Ltd. Tetsuya Matsumoto received speaker honoraria from MSD K.K., and Pfizer Japan Inc. Makoto Miki hold shares in Daiichi Sankyo Co., Ltd., and received speaker honoraria from Kyorin Pharmaceutical Co., Ltd. Tomotaro Wakamura is an employee of Sumitomo Pharma Co., Ltd. Daisuke Kurai received research funding from Daiichi Sankyo Co., Ltd., and scholarship donations from Shionogi & Co., Ltd. Hiroki Tsukada received speaker honoraria from Kyorin Pharmaceutical Co., Ltd. Nobuki Aoki received speaker honoraria from Kyorin Pharmaceutical Co., Ltd. Hiroshige Mikamo received speaker honoraria from Nippon Becton Dickinson Company, Ltd., Astellas Pharma Inc., Sumitomo Pharma Co., Ltd. (formerly Sumitomo Dainippon Pharma Co., Ltd.), Pfizer Japan Inc., MSD K.K., Daiichi Sankyo Co., Ltd., Fujifilm Toyama Chemical Co., Ltd., Miyarisan Pharmaceutical Co. Ltd., Kyorin Pharmaceutical Co., Ltd., Gilead Sciences K.K., Saraya Co., Ltd., Tsumura & Co., Meiji Seika Pharma Co., Ltd., Sanofi K.K., Shionogi & Co., Ltd., Fukoku Co., Ltd., GlaxoSmithKline K.K., Kowa Company, Ltd., research funding from Fukoku Co., Ltd., Sekisui Medical Co., Ltd., Meiji Seika Pharma Co., Ltd., Pfizer Japan Inc., Saraya Co., Ltd., Miyarisan Pharmaceutical Co. Ltd., Roche Diagnostics K.K., ASKA Pharmaceutical Co., Ltd., Tosoh Corporation, Bruker Japan K.K., Abbott Diagnostics Medical Co., Ltd., Ortho Clinical Diagnostics K.K., Kyorin Pharmaceutical Co., Ltd., and scholarship donations from Asahi Kasei Pharma Co., Shionogi & Co., Ltd., Daiichi Sankyo Co., Ltd., Fujifilm Toyama Chemical Co., Ltd., Sumitomo Pharma Co., Ltd. (formerly Sumitomo Dainippon Pharma Co., Ltd.), Fukoku Co., Ltd., and Morii Co., Ltd. Atsushi Nakamura received speaker honoraria from Kyorin Pharmaceutical Co., Ltd., MSD K.K., Astellas Pharma Inc. Akira Ukimura received scholarship donations from Shionogi & Co., Ltd. Hiroshi Kakeya received speaker honoraria from MSD K.K., Sumitomo Pharma Co., Ltd. (formerly Sumitomo Dainippon Pharma Co., Ltd.), Shionogi & Co., Ltd., Asahi Kasei Pharma Corporation., Astellas Pharma Inc., and Pfizer Japan Inc. Katsunori Yanagihara received speaker honoraria from Daiichi Sankyo Co., Ltd., MSD K.K., Astellas Pharma Inc., and Taisho Pharma Co., Ltd. (formerly Taisho Toyama Pharmaceutical Co., Ltd.), research funding from Fujifilm Toyama Chemical Co., Ltd., Meiji Seika Pharma Co., Ltd., Kyorin Pharmaceutical Co., Ltd., and Shionogi & Co., Ltd., and scholarship donations from Sumitomo Pharma Co., Ltd. (formerly Sumitomo Dainippon Pharma Co., Ltd.), Fujifilm Toyama Chemical Co., Ltd., Taiho Pharmaceutical Co., Ltd., and Kyorin Pharmaceutical Co., Ltd., (Copyright © 2023 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

While acute empyema is a critical infectious disease showing a high mortality rate, there are no prognostic tools to evaluate the disease severity and prognosis for patients. We conducted a retrospective cohort to determine whether quick Sequential Organ Failure Assessment (qSOFA) and SOFA score can predict the disease severity and prognosis of acute empyema. A total of 53 patients were enrolled in the study. The mean age was 69 years and 41 patients (77%) were male. Twenty-two patients (42%) had multiple underlying diseases with the Charlson comorbidity index ≥3. The-30 days, and in-hospital deaths were 7 (13%) and 10 (19%), respectively. The area under the ROC curve of SOFA score and CCI for 30-day and in-hospital deaths were 0.814 (p = 0.073) and 0.752 (p = 0.082), 0.848 (p = 0.07) and 0.762 (p = 0.011), respectively. Univariate analysis showed that qSOFA ≥2 and SOFA score ≥2, isolation of potentially drug-resistant (PDR) pathogen, high CCI (≥3), performance status of 2-4, surgical intervention, and anaerobic bacteria involvement were prognostic factors. Of these, multivariate logistic regression analysis showed that qSOFA ≥2 and SOFA score ≥2 (p = 0.011), isolation of PDR pathogen (p = 0.005), and high CCI (≥3) (p = 0.015) were independently poor prognostic factors. We concluded that qSOFA and SOFA scores could predict the disease severity and prognosis in acute empyema. Additionally, isolation of PDR pathogens and high CCI could be poor prognostic factors for patients., Competing Interests: Declaration of competing interest All co-authors have none declared., (Copyright © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

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., (Copyright © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background/purpose: Rapid detection of β-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 β-lactamases (ESBLs) and metallo-β-lactamases (MBLs) has become possible., Methods: β-lactams and β-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 β-lactamase inhibitor on morphological changes caused by β-lactam were evaluated after 3 h incubation., Results: Clinical isolates genetically confirmed to produce β-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 β-lactamases in 3 h and may be a useful replacement for the disc diffusion method., (Copyright © 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

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., (Copyright © 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

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., (Copyright © 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

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., (Copyright © 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

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., Competing Interests: Declaration of competing interest All co-authors have none declared., (Copyright © 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Introduction: While the early diagnosis of necrotizing fasciitis (NF) is crucial and could lead to a favorable outcome, it is difficult to differentiate NF from cellulitis, resulting in delay for the appropriate treatment., Patients and Methods: For the purpose of examining which diagnostic tools could correctly differentiate NF from cellulitis, we conducted this case-control study. We retrospectively reviewed all patients who were diagnosed with NF at our institute during 2014-2019. The patients who were diagnosed with cellulitis were randomly selected during the study period as the control group. The severity of NF is evaluated by serum-procalcitonin (PCT), LRINEC score, NTSI assessment and SIARI score., Results: A total of 25 NF patients were enrolled in this study. The median age was 68 years (range 39-79) and 18 (72%) were male. Comparing NF and cellulitis groups, NF group showed a higher LRINEC score and serum PCT than cellulitis group did, even though there was no statistical significance in serum PCT. With respect to the diagnostic value for differentiating NF from cellulitis, the area under the ROC curve for of serum PCT and LRINEC scores were 0.928 [95% confidential interval (CI) 0.864-0.992, p < 0.001] and 0.846 (95% CI 0.757-0.936, p < 0.001). The appropriate serum-PCT cutoff value was 1.0 and had a sensitivity of 88%, a specificity of 89%, a positive predictive value of 81%, and a negative predictive value of 93%., Conclusion: Serum-PCT could be a useful diagnostic marker for differentiating diagnosis of NF from cellulitis., Competing Interests: Declaration of competing interest All co-authors have none declared., (Copyright © 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Considering the issues of shortage of medical resources and the invasiveness and infection risk involved in the collection of nasopharyngeal swab specimens, there is a need for an effective alternative test specimen for SARS-CoV-2 RNA detection. Here, we investigated suitability of saliva as a non-invasively obtained specimen for molecular detection of SARS-CoV-2 RNA in Japanese patients with COVID-19. In total, 28 paired clinical specimens of saliva and nasopharyngeal swabs were collected from 12 patients at various time points after symptom onset. Each specimen was assayed using reverse transcription real-time polymerase chain reaction (rRT-PCR) on the BD MAX open system using primers and probes targeting the N-gene. The saliva and nasopharyngeal swab specimens showed 19 and 15 positive results, respectively. No invalid (PCR inhibition) result was observed for any specimen. The qualitative results of each specimen obtained in the period immediately after symptom onset were similar. Three convalescent patients presented saliva-positive results, whereas their nasopharyngeal swabs were negative at four different time points, suggesting that saliva may be superior to nasopharyngeal swabs in terms of obtaining stable assay result of SARS-CoV-2. In conclusion, our results suggest that saliva can potentially serve as an alternative to nasopharyngeal swabs as a specimen for SARS-CoV-2 rRT-PCR. As saliva can be collected by patients themselves, it may be an effective way to overcome the shortage of personal protective equipment and specimen sampling tools., Competing Interests: Declaration of competing interest H. Mikamo has received grant support from Asahi Kasei Pharma Corporation, Shionogi & Co. Ltd., Daiichi Sankyo Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Pfizer Japan Inc. and FUJIFILM Toyama Chemical Co., Ltd., payment for lectures from Astellas Pharma Inc., MSD K.K., Daiichi Sankyo Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., MIYARISAN Pharmaceutical Co., Ltd. Becton, Dickinson and Company Japan, and FUJIFILM Toyama Chemical Co. Ltd. The other authors declare that they have no conflicts of interest., (Copyright © 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

The novel coronavirus disease 2019 (COVID-19) is diagnosed by positive result of reverse transcription polymerase chain reaction (RT-PCR) for the novel coronavirus. We concluded that cycle threshold value (Ct-value) of real-time RT-PCR (rRT-PCR) assay could decrease as patients recover. Results of rRT-PCR assay could remain positive among asymptomatic patients for longer than 2 weeks. The discharge criteria of COVID-19 patients using a negative result of rRT-PCR should be reconsidered., Competing Interests: Declaration of competing interest All co-authors have none declared., (Copyright © 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

While community-onset pneumonia patients such as community-acquired pneumonia (CAP) and healthcare-associated pneumonia (HCAP) have several risk factors of Clostridium difficile infection (CDI), prognostic guidelines for pneumonia never mention the occurrence of CDI following treatment for pneumonia. For the purpose of examining the occurrence and prevalence of CDI, we reviewed all community-onset pneumonia patients who were admitted to our institute during the study period. A total of 406 patients were enrolled in this study. Among them, 257 patients (63%) were male, and the median age was 79 years (range 19-103 years). Surprisingly, 155 CAP (88%) and all HCAP (100%) patients had one or more risk factors for CDI. Furthermore, 70 CAP (40%) and 157 HCAP (69%) patients had more than 3 risk factors for CDI. Despite these facts, probiotic medication for prevention of CDI were prescribed for 12 (7%) CAP and 15 (7%) HCAP patients as the initial treatment. Finally, 3% and 9% of CAP and HCAP patients had CDI after completing the treatment for pneumonia. Regarding the duration of antibiotic therapy, 146 CAP (82%) and 176 HCAP (77%) patients received it for longer than 8 days, even though bacteremia was not confirmed in those patients. In addition, 27 CAP (15%) and 26 HCAP (11%) patients received a combination antibiotic therapy as an initial treatment. They seemed to be unnecessary. Physicians should acknowledge community-onset pneumonia has several risk factors for CDI, and should avoid a longer than necessary antibiotic therapy and unnecessary combination antibiotic therapy for pneumonia patients with risk factors for CDI., Competing Interests: Declaration of Competing Interest Mikamo H received Research funding from Sumitomo Dainippon Pharma Co., Ltd., Taisho Toyama Pharmaceutical Co. Ltd., Daiichi Sankyo Co., Ltd., Pfizer Co. Ltd., Astellas Pharma Inc., MSD K.K., Toyama Chemical Co. Ltd., MIYARISAN Pharmaceutical Co., Ltd., Shionogi & Co. Ltd.; Consulting fee/honorarium from Sumitomo Dainippon Pharma Co., Ltd., Taisho Toyama Pharmaceutical Co. Ltd., Daiichi Sankyo Co., Ltd., Pfizer Co. Ltd., MSD K.K., Astellas Pharma Inc., MIYARISAN Pharmaceutical Co., Ltd., (Copyright © 2020. Published by Elsevier Ltd.)

Background: Carbapenem-resistant Enterobacteriaceae (CRE), especially for carbapenemase-producing Enterobacteriaceae (CPE), is an emerging cause that pose a significant threat to public health. However, efficient therapy has not been established. We assessed the antimicrobial efficacy of meropenem (MEPM) and amikacin (AMK) combination therapy., Material and Methods: Total eight isolates of Escherichia coli or Klebsiella pneumoniae, including CRE and/or CPE have carbapenemase genes were used. The relationship between phenotype and in vivo efficacy was assessed in neutropenic murine thigh infection model. Efficacy was determined using the change in bacterial density and survival rate., Results: The combination therapy showed enhanced antimicrobial activities against CRE+/CPE+ and CRE+/CPE-K. pneumoniae isolates than MEPM monotherapy (0.63 ± 0.04 vs. 2.56 ± 0.24 ⊿log 10  cfu/mL, p < 0.05; -1.05 ± 0.15 vs. -0.48 ± 0.30 ⊿log 10  cfu/mL, p < 0.05). Likewise, the combination therapy showed enhanced antimicrobial activities against CRE+/CPE+ and CRE+/CPE-E. coli isolates than MEPM monotherapy (0.90 ± 0.68 vs. 1.86 ± 0.23 ⊿log 10  cfu/mL, p < 0.05; -1.81 ± 0.06 vs. -0.88 ± 0.23 ⊿log 10  cfu/mL, p < 0.05). Also, combination therapy group showed similar to higher survival rates in CRE + E. coli infection mice, compared to MEPM monotherapy group., Conclusion: Our results are the first supportive data to threat CRE infections with combination therapy of MEPM and AMK with in vivo model. The current results verify the promising utility of the combination therapy with MEPM and AMK against CRE isolates with a wide range of MEPM MICs., (Copyright © 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Linezolid has been the common antimicrobial treatment for Gram-positive infection even in neonates and infants. Major adverse events associated with linezolid treatment is cytopenia. However, there were few reports about the relationship between cytopenia and gestational age. Primary objective of this study was to compare the relationship between cytopenia in infants and neonates treated with linezolid therapy and gestational age., Methods: In total, 44 patients were divided into two groups depend on their gestational age [<180 days; low gestational age group (20 patients); >180 days group; high gestational age group (24 patients)]. All patients treated with linezolid from April 2014 to March 2018 at NICU or GCU of Aichi Medical University Hospital. Investigation items were as follows; sex, age, weight, duration of treatment, Apgar score, laboratory data, rate of patients with blood transfusion, concomitant medications, hematologic abnormalities during linezolid treatment., Results: The incidence of overall cytopenia in low gestational age group was significantly higher than high gestational age group (65.0 % vs. 25.0 %; p < 0.05). Of note, the incidence of thrombocytopenia in low gestational age group showed significantly higher than high gestational age group (45.0% vs. 8.3%, p < 0.05). Then, the proportion of patients occurred thrombocytopenia who received linezolid 10 mg/kg every 8 h were higher than 10 mg/kg every 12 h in both groups., Conclusion: In cases linezolid is administered three times a day should be more carefully of thrombocytopenia in patients with gestational days less than 180 days., (Copyright © 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Introduction: Although infectious endocarditis (IE) is a potentially severe infectious disease, there are no prognostic tools for in-hospital mortality for IE patients. This is the first report documenting that the Sequential Organ Failure Assessment (SOFA) score could evaluate the severity and outcome among IE patients., Patients and Methods: From 2007 to 2018, we reviewed all patients who were diagnosed as having IE at our institue. Patients diagnosed as definite IE according to the modified Duke criteria or by surgical procedure were included in this study., Results: A total of 66 IE patients were enrolled in this study. They were 45 males (68%) and the median age was 70 years. As for prognostic factors for in-hospital death among IE patients, SOFA score ≥6, CCI ≥3, surgical procedure, heart failure, immunological phenomena and detection of S. aureus as a causative pathogen were identified as prognostic factors by univariate analysis. Of these 6 factors, SOFA score ≥6 (OR 7.6, 95%CI 1.3-46.6, p = 0.029), heart failure (OR 9.7, 95%CI 1.1-86.1, p = 0.042), surgery (OR 0.1, 95%CI 0-0.8, p = 0.037) and immunological phenomena (OR 0.1, 95%CI 0-0.9, p = 0.042) were independent prognostic factors for in-hospital mortality among IE by logistic regression analysis., Conclusion: The SOFA score could be a good prognostic tool to use for IE patients. Also, SOFA score ≥6, surgery, immunological phenomena and heart failure were independent prognostic factors for in-hospital mortality among IE patients., (Copyright © 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: While it has been increasing cases of C. hominis endocarditis in the past decades due to advances of diagnostic methods, the epidemiology and clinical manifestations of IE caused by C. hominis is still unknown., Case Presentation: A 62-year old man was admitted to our institute with fever, anorexia and general fatigue for the preceding one month. He had a past medical history of both aortic and mitral valves replacement due to cardiac diseases. He was diagnosed as IE caused by C. hominis according to the modified duke criteria. The patient received 2 weeks of combination therapy of intravenous ceftriaxone (CTRX) 2g and gentamycin 180mg daily followed by 4 weeks CTRX 2g daily alone. Oral moxifloxacin 400mg once daily was given for an additional 4 weeks. After the antibiotic therapy was discontinued, disease recurrence was not observed. We reviewed previously reported C. hominis IE cases in 60 publications including ours. Of 73 patients enrolled, 53 were male, the mean age was 52 years. The most common risk factor of IE was past history of cardiac diseases in 44/73 (60%). As for antibiotics initially prescribed, third-generation cephalosporins was most frequently used in 28/69 (41%). While the cure rate was 67/73 (93%), 31/73 patients (43%) received a surgical intervention. Embolic lesions to the central nervous system and vertebrae were seen in 16/72 (22%) and 5/72 (7%)., Conclusion: IE caused by C. hominis has a favorable prognosis, showing the cure rate of 93%. Physicians should recognize the possible occurrence of emboli among IE patients., (Copyright © 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

To clarify the etiology, patients' characteristics and risk factors for community-onset AP (Acinetobacter species pneumonia), we conducted this case-control study. We reviewed all patients with community-onset AP at our institute from 2010 until 2018. We defined non-AP group as a control. The patients with non-Acinetobacter spp. pneumonia (non-AP) were randomly selected during the study period without clinical information based on medical records' list among patients with community-onset pneumonia. The age (±2 years) and sex were matched to the patients with community-onset AP, and the ratio was AP:non-AP group = 1:3. Patients' characteristics, clinical outcomes, pathogens isolated and drug susceptibility were evaluated by comparing AP and non-AP group. The mean age of community-onset AP group was 79 years. They were 8 males and 5 females. The 30-day and in-hospital mortality rates of community-onset AP were 23% (v.s. 3%, p = 0.049) and 31% (v.s. 5%, p = 0.029) respectively, which are higher than the control group. Heavy alcohol consumption (23% v.v. 0%, p = 0.023), higher Charlson Comorbidity index (3.2 v.s. 2.0, p = 0.046) and lobar pneumonia by chest radiology (50% v.s. 23%, p = 0.071) were seen more frequently in community-onset AP than in the control group. In conclusion, community-onset AP shows poor outcomes despite the appropriate antibiotic therapy. Heavy alcohol history might be a risk factor of AP. Patients with community-onset AP could have more comorbidity and poor general conditions than the control group., (Copyright © 2019. Published by Elsevier Ltd.)

A 76-year-old Japanese woman was admitted due to uncontrolled cellulitis of the right lower leg. She had deep vein thrombosis on the right limb. Moreover, she had a long history of rheumatoid arthritis treated with corticosteroids. Skin biopsy and lumbar puncture were performed to diagnose disseminated cryptococcosis. She was administered antifungal agents (liposomal amphotericin B and 5-fluorocytosine). On treatment day 14, debridement was performed, and cryptococcosis was controlled. However, she developed toxic megacolon due to Clostridioides difficile infection (CDI). On day 32, she was transferred to the intensive care unit due to severe acidosis and acute kidney injury secondary to CDI-related toxic megacolon. Vancomycin, metronidazole, and tigecycline were administered for treatment of CDI. After several weeks of intensive care, toxic megacolon was improved, but renal replacement therapy was discontinued according to the patient's will. On day 73, she died of renal failure. We experienced a complex of rare diseases, Cryptococcus neoformans cellulitis and Clostridioides difficile-related toxic megacolon. Both diseases were presumed to be the result of corticosteroid and methotrexate use. Hence, careful monitoring is required when treating immunocompromised hosts to reduce the risk of developing complications., (Copyright © 2018 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objective: Current phenotypic methods for extended-spectrum β-lactamase (ESBL), AmpC β-lactamase (AmpC), and carbapenemases fail to detect isolates that co-produce other classes of β-lactamases. In this study, we have developed a novel assay (Applied Multiplex Disk Method: AMU-DM) for the phenotypic detection and identification of β-lactamases produced by Enterobacteriaceae., Methods: We evaluated the performance of the method by comparison with PCR results for 78 Enterobacteriaceae clinical isolates that were positive by the ESBL screening test and negative by the ESBL confirmation test. Additionally, one NCTC strain and four ATCC strains were also included in the test population for the study as reference., Results: For 79/83 (95%) isolates tested, the AMU-DM results matched those obtained by PCR. The concordance rates were 31/31 (100%), 11/11 (100%), 3/3 (100%), 0/1 (0%), 15/15 (100%), 16/19 (84%), and 3/3 (100%) for AmpC, ESBL and AmpC co-production, Klebsiella pneumoniae carbapenemase (KPC), KPC and ESBL co-production, metallo β-lactamase (MBL), MBL and ESBL co-production, and MBL and AmpC co-production, respectively., Conclusion: The AMU-DM is convenient to perform, economical, and highly sensitive in identifying ESBLs, AmpCs, and carbapenemases. Our method may be useful in clinical settings for the implementation of relevant infection control measures and for surveillance purposes., (Copyright © 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Introduction: Solithromycin is a novel fluoroketolide developed to treat pneumonia. But, few studies evaluating its antimicrobial activity against S. pneumoniae in a mixed-infection model with anaerobes are available, while community-acquired pneumonia can involve mixed-infection of Streptococcus pneumoniae and anaerobic bacteria. This study evaluated the antimicrobial activity of solithromycin against macrolide-resistant S. pneumoniae and anaerobic bacteria with a murine pneumonia mixed-infection model., Material and Methods: We evaluated antimicrobial activity of solithromycin (10 and 20 mg/kg) and levofloxacin (126 mg/kg) against S. pneumoniae with a three-point mutation in penicillin-binding protein and an ermB gene, and Parvimonas micra. Antimicrobial efficacy was calculated for each isolate as the change in bacterial count (Δlog 10  CFU/mL) obtained in the treated mice after 24 h compared with the count in the starting control animals., Results: The solithromycin and levofloxacin minimum inhibitory concentrations (MICs) for S. pneumoniae were 0.03 and 0.5 μg/mL, respectively. The solithromycin and levofloxacin MICs for P. micra were 0.015 and 0.12 μg/mL, respectively. In a mixed-infection model, solithromycin showed significantly higher antimicrobial activity against S. pneumoniae than levofloxacin (solithromycin 20 mg/kg; -2.87 ± 1.33 log 10  CFU/mL vs. levofloxacin; -1.35 ± 0.37 log 10  CFU/mL, p = 0.0397). Similarly, solithromycin showed significantly higher antimicrobial activity against P. micra than levofloxacin (solithromycin 20 mg/kg; -2.78 ± 0.98 log 10  CFU/mL vs. levofloxacin; -1.57 ± 0.47 log 10  CFU/mL, p = 0.0400)., Discussion: Solithromycin showed higher antimicrobial activities against macrolide-resistant S. pneumoniae and P. micra than levofloxacin, even though they were coexisted in murine lung tissue. Our results suggest that solithromycin could be effective for pneumonia patients due to S. pneumoniae to reduce bacterial density in lung tissue., (Copyright © 2018 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

We compared the susceptibility of six commercially available antifungal agents (fluconazole, itraconazole, voriconazole, caspofungin, micafungin, and amphotericin B) against 133 Candida bloodstream isolates between 2008 and 2013 at Aichi Medical University Hospital. C. albicans was the most common isolate, followed by C. parapsilosis, C. glabrata, and C. tropicalis. MIC 90 s of voriconazole against C. albicans, C. parapsilosis, and C. tropicalis were the lowest and that of micafungin against C. glabrata was the lowest among the agents tested. Of the 133 isolates, two strains were identified as drug-resistant. One was a fluconazole-resistant C. glabrata strain, in which the ATP-binding cassette (ABC) transporter gene expression was upregulated. The other was a micafungin-resistant C. glabrata strain, that had 13 amino acid substitutions in FKS1 and FKS2, including a novel substitution V1342I in FKS1 hotspot 2. We also evaluated the susceptibility of T-2307, a novel class of antifungal agents used in clinical trials, against the fluconazole- and micafungin-resistant C. glabrata strain; the MICs of T-2307 were 0.0039 and 0.0078 μg/mL, respectively. In conclusion, the incidence of bloodstream infection caused by drug-resistant Candida spp. was rare from 2008 to 2013 at our hospital. Of 133 isolates, only two strains of C. glabrata were resistant to azoles or echinocandins, that upregulated the ABC transporter genes or had novel FKS mutations, respectively., (Copyright © 2018 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

We determined the optimal antimicrobial in the sodium mercaptoacetic acid double disk synergy test (SMA-DDST) for the detection of IMP-1-producing Pseudomonas aeruginosa isolates in Japan and evaluated the performance of the test. Fifty-four P. aeruginosa clinical isolates were tested, including 39 IMP-1 producers and 15 non-metallo-β-lactamase (MBL)-producing carbapenem- and ceftazidime (CAZ)-resistant isolates. The SMA-DDST was performed with CAZ, cefepime (CFPM), imipenem (IPM), meropenem (MEPM), doripenem (DRPM), or biapenem (BIPM)-containing disks. The sensitivity of the SMA-DDST with CAZ, CFPM, IPM, MEPM, DRPM, and BIPM was 39/39 (100%), 36/39 (92%), 18/39 (46%), 8/39 (21%), 19/39 (49%), and 36/39 (92%), respectively. The specificity was 15/15 (100%) for all SMA-DDSTs. This suggests that the isolates may have a resistance mechanism other than MBL production for IPM, MEPM, or DRPM. Since the CAZ resistance mechanism in P. aeruginosa is the same as that of CFPM, but differs from that of carbapenems, we conclude that combining CAZ with BIPM SMA-DDSTs can prevent any failure in the detection of IMP-1-producing P. aeruginosa., (Copyright © 2018 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Vancomycin has been the common antimicrobial treatment for Gram-positive infection even in neonates and infants, while it is difficult to adjust blood concentration. Linezolid is also effective for Gram-positive infection, and is not necessary to monitor drug blood concentration. Primary objective of this study was to compare the safety of linezolid and vancomycin in infants and neonates for resistant Gram-positive infections., Methods: In total, 68 patients [linezolid group (32 patients); vancomycin group (36 patients)] treated with antimicrobials at Aichi Medical University Hospital between April 2014 and March 2017. Investigation items were as follows; sex, age, gestational age, birth weight, body weight, duration of treatment, Apgar score, laboratory data, rate of patients with blood transfusion, serum levels of vancomycin, disease type, concomitant medications, clinical isolates, adverse effects during antimicrobial treatment, antimicrobial susceptibility of isolated Gram-positive bacteria., Results: Any substantially abnormal laboratory values were admitted in linezolid 40.6% (13/32) and vancomycin 41.7% (15/36) groups, respectively (p = 0.93). Platelet count was significantly decreased in only linezolid group (p = 0.03). Any adverse events during antimicrobial treatment were admitted in linezolid 46.9% (15/32) and vancomycin 58.3% (21/36) groups, respectively (p = 0.34)., Conclusion: There were no notable differences in safety of linezolid and vancomycin groups even in neonates and infants. However, platelet count was significantly decreased in only linezolid group. The careful monitoring of platelet count would be required for infants and neonates receiving linezolid treatment., (Copyright © 2018 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Introduction: While the emergence and spread of carbapenem-resistant enterobacteriaceae (CRE) carriage and infections are serious threats to public health worldwide, its prevalence and epidemiology are still unknown., Methods and Patients: For the purpose of examining the prevalence, patients' background and risk factors for CRE carriage and infections, we conducted this case-control study. We retrospectively reviewed all patients isolating CRE at Aichi Medical University hospital from January 2010 until March 2017. The patients isolated with carbapenem-susceptible enterobacteriaceae (CSE) were randomly selected during the study period., Results: A total of 26 patients, isolating 28 CRE infections were enrolled in this study. The detection rate of CRE carriage and infection was 0.22% (28/12,600). Compared to the CSE group, the CRE group had poorer PS and higher CCI scores. The CRE group tended to stay longer in hospital (121 v.s. 63 days, p = 0.052) and admission fee was much more expensive than CSE group (220,710 v.s. 69,904 JPY, p < 0.001). PS 2-4 (ECOG) and CCI≧3 (p = 0.002), prior hospitalization within 90 days (p = 0.006) and prior antibiotics use within 90 days (p = 0.005) were risk factors for acquisition of CRE by univariate analysis. The combination of PS 2-4 and CCI≧3 was an independent risk factor for CRE carriage and infection by multivariate logistic regression analysis., Conclusion: The combination of PS 2-4 (ECOG) and CCI score≧3 was an independent risk factor of CRE carriage and infections. The CRE group tended to stay longer in hospital, and the medical expense was much more expensive than those in the CSE group., (Copyright © 2018 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Frequency of Treponema pallidum invasion into cerebrospinal fluid (CSF) has not been clear at this present. Since it is impossible to culture T. pallidum in vitro at this present, we need molecular based-approach to detect it in CSF. Additionally, neurosyphilis is usually a late sequela, however it might result in asymptomatic neurosyphilis even at primary or secondary syphilis. This study was to reveal the frequency of T. pallidum invasion into CSF especially at primary or secondary syphilis with polymerase chain reaction (PCR) test. All patients were visited the Aichi Medical University Hospital or Izumi ladies' clinic between 2016 and 2017. Clinical CSF samples were collected from patients with early and late stages of syphilis. The PCR was done using primers targeting the tpN47gene. CSF samples were collected from 9 patients (4 patients with primary syphilis, 3 with secondary syphilis, and 1 early latent syphilis and 1 with late latent syphilis). PCR showed positive reaction in 2 of 7 (28.6%) primary and secondary syphilis patients, in 1 of 1 (100%) early latent syphilis patients, and in 1 of 1 (100%) late latent syphilis patients. Despite its lack of sensitivity for use alone as a diagnostic test, this PCR test should be preferred for the diagnosis of neurosyphilis. Because, T. pallidum was detected in the 28.6% CSF of patients at primary and secondary syphilis, which indicated that they invade the central nervous system from the early stages of infection. However, studies in a larger population are required to confirm these preliminary results., (Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

The Japanese Respiratory Society newly updated the prognostic guidelines for pneumonia in 2017. Quick Sequential Organ Failure Assessment (qSOFA) and Sequential Organ Failure Assessment (SOFA) score are used to evaluate the severity of pneumonia and to select the therapy for pneumonia. This is a retrospective study at Aichi Medical University hospital from January to December of 2016 to investigate the accuracy and usefulness of qSOFA and SOFA score in evaluating the severity and prognosis of healthcare-associated pneumonia (HCAP). A total of 81 HCAP patients were enrolled in this study. Both the 30-day and in-hospital mortality were 7.5% (6/81). qSOFA≧2 was in 33/78 patients (42%) and <2 in 45/78 patients (58%), showing a 30-day mortality of 9.1% (3/33) and 6.7% (3/45) (p = 0.45), respectively. Comparing with qSOFA≧2 and < 2 group, HCAP patients with qSOFA≧2 had much higher A-DROP (31. v.s. 2.2, p < 0.001), CURB-65 (2.7 v.s. 1.9, p < 0.001), PSI (133 v.s. 114, p = 0.014), I-ROAD (2.7 v.s. 1.9, p < 0.001) and SOFA scores (3.8 v.s. 2.8, p < 0.001). With respect to the diagnostic value of predictive values for 30-day mortality among HCAP patients, the area under the receiver-operating characteristic curve for SOFA score was 0.930 with a statistical significance (p < 0.001). The SOFA score cutoff value was 4 and had a sensitivity of 20%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 68%. In conclusion, SOFA core could be one of the most useful tools in evaluating the severity of HCAP., (Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is pathogenic to healthy individuals and a significant issue throughout the world. Panton-Valentine leukocidin gene (pvl)-positive sequence type (ST) 8-staphylococcal cassette chromosome (SCC) mec type IV (ST8-IV) as represented by the USA300 clone, is the most prevalent CA-MRSA in many countries. However, the prevalence of pvl-positive CA-MRSA was limited in Japan. Here, we report the incidence of pvl-positive community-onset MRSA (CO-MRSA) isolated from 10 patients seen between 2009 and 2014 at a Japanese university hospital. All patients were Japanese and eight cases involved severe skin infections. Antimicrobial susceptibility patterns of the pvl-positive isolates were consistent with those of a typical CA-MRSA clone. Detailed molecular epidemiological analyses showed that three isolates were ST8-IV USA300 clones, whereas the other seven were ST30-IV (three isolates), ST30-I (one isolate), ST59-V (two isolates), and ST1-V (one isolate) clones. No clear difference of infection severity was found between the patients associated with the USA300 clone and those with the other clones. Our findings show that, not only the USA300 clone, but also diverse pvl-positive CO-MRSA clones exist in the community and cause severe skin infections in Japan., (Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

We evaluated the susceptibility of 100 Japanese Clostridium difficile isolates to fidaxomicin, a new macrocyclic antibiotic. The minimum inhibitory concentration (MIC) range of fidaxomicin was 0.03-0.5 μg/mL, with a MIC for inhibition of 50% (MIC 50 ) of 0.12 μg/mL, and for inhibition of 90% (MIC 90 ) of 0.25 μg/mL. We also evaluated the susceptibilities of the same 100 C. difficile isolates to vancomycin, metronidazole, moxifloxacin, clindamycin, meropenem, and ampicillin. Of all the antibiotics tested, fidaxomicin showed the most potent antimicrobial activity against this group of C. difficile isolates. MIC levels against C. difficile isolates, including those producing binary toxin, did not substantially differ from those previously reported in Europe, North America and Taiwan., (Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objects: Changes in patients' background and life environment could contribute to increase healthcare-associated (HCA) empyema. There are no guidelines and statements for HCA empyema., Methods: We retrospectively reviewed all patients with empyema who were admitted to the Aichi Medical University Hospital, Japan between 2008 and 2015. We evaluated patients' characteristics, microbial profiles, treatment and outcomes, and analyzed prognostic factors for 90-day mortality., Results: A total of 48 patients were enrolled in this study. They were categorized into community-acquired (CA) empyema (16 patients) and healthcare-associated (HCA) empyema (32 patients). HCA empyema patients had higher Charlson comorbidity index (CCI) scores, and poorer performance status (PS) than CA empyema patients. Potentially-drug resistant (PDR) pathogens were seen more frequently in HCA empyema than in CA empyema. Compared with survival and death groups, the death group showed higher CCI scores and poorer PSs than the survival group. The death group had more malignancy than the survival group. PDR pathogens were detected more frequently in the death group than in the survival group. Multivariate analysis showed that emergence of PDR pathogens and malignancies were independent poor prognostic factors for 90-days mortality among empyema., Conclusion: The etiology and bacteriology of HCA empyema are quite different from those of CA empyema. Especially, the mortality of HCA empyema was higher than the one of CA empyema. Emergence of PDR pathogens in the pleural fluid detected by culture, pulmonary disease and malignancies were independent poor prognostic factors among CA and HCA empyema by multivariate logistic regression analysis., (Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objectives: This study was designed to evaluate the sodium mercaptoacetic acid double disk synergy test (SMA-DDST), the Etest metallo-β-lactamase (MBL) MP/MPI (Etest MP/MPI), and the Mastdiscs ID Carbapenemase Detection Disc Set (MAST-CDS) for the detection of MBL-producing Enterobacteriaceae isolates in Japan., Methods: Fifty-one clinical isolates and four reference strains were tested. These isolates included 40, 4, and 11 IMP-, New Delhi MBL (NDM)-, and non-MBL-producers, respectively. SMA-DDST was performed with meropenem (MEPM)-containing disks., Results: Sensitivities were 38/44 (86%), 40/44 (91%), and 15/44 (34%), and the cost ratio was 1:9.4:3.8 for MEPM-SMA-DDST:Etest MP/MPI:MAST-CDS, respectively. The specificity was 11/11 (100%) for all assays. MEPM-SMA-DDST detected IMP-producing isolates with high sensitivity (38/40; 95%), but the assay was inadequate for NDM-producing isolates (0/4; 0%). The Etest MP/MPI detected both IMP- (36/40; 90%) and NDM-producing isolates (4/4; 100%), but was the most expensive. MAST-CDS detected IMP-producing isolates with low sensitivity (11/40; 28%), but the assay worked well for NDM-producing isolates (4/4; 100%)., Conclusions: Our results indicated that MEPM-SMA-DDST was the most cost-effective assay for the detection of IMP-producing isolates. Therefore, we conclude that MEPM-SMA-DDST is the optimal available assay for clinical first-line screening in IMP-endemic areas such as Japan. However, this assay could not detect NDM-producing isolates, whereas the Etest MP/MPI and MAST-CDS could. When MEPM-SMA-DDST is negative, the Etest MP/MPI and MAST-CDS could be used to obtain supportive data and prevent detection failure for NDM-producing isolates., (Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objective: The purpose of this study is to compare the antimicrobial activity of human simulated exposures of tedizolid 200 mg daily, and linezolid 600 mg every 12 h for the treatment of complicated skin and skin structure infection (cSSSI) caused by MRSA and Peptostreptococcus anaerobius in both the neutropenic mice thigh mixed-infection models., Material and Method: Tedizolid phosphate and linezolid were used for all in vivo testing. A total of one MRSA and two P. anaerobius isolates were utilized. Antimicrobial efficacy was calculated for each isolate as the change in bacterial numbers (Δlog 10 CFU/ml) obtained in the treated mice after 24 h compared with the numbers in the starting control animals (0 h)., Results: The tedizolid and linezolid MICs for MRSA was 0.25 and 2 μg/ml. Tedizolid MIC for P. anaerobius was 0.12 μg/ml, and linezolid MICs for two P. anaerobius isolates were 0.5 and 1 μg/ml. In mixed infection model, tedizolid therapy showed similar antimicrobial activities for one MRSA and two P. anaerobius isolates evaluated, compared with linezolid therapy. Additionally, when comparing the activity of tedizolid and linezolid monotherapy between single infection and mixed infection model, antimicrobial activities of both antimicrobials were attenuated when mixed infection model was used., Conclusion: In the neutropenic murine thigh infection model, human simulated exposures of tedizolid and linezolid resulted in similar efficacies against MRSA, even though single and mixed infection models were used. These data support the clinical utility of tedizolid for use against MRSA and P. anaerobius in the treatment of cSSSI., (Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

This is the first report to test the loading dosage of colistin against Pseudomonas aeruginosa, including MDRP. Using in vivo murine thigh infection model, in the loading dosage regimen (Day 1:50 mg/kg q12 h, Day 2-3: 25 mg/kg q12 h) group, 5 to 6 log10 CFU/ml reduction compared with control were observed for both strains of P. aeruginosa with colistin MIC 0.5 and 1 μg/mL at 72 h. But, similar reduction was observed for the strains with colistin MIC 0.5 μg/mL only in normal dosage regimen (Day 1-3: 25 mg/kg q12 h) group. For P. aeruginosa with colistin MIC 1 μg/mL, colistin loading dosage regimens showed greater antimicrobial activity than that of without loading dosage group (p < 0.05). These data suggest that the colistin loading regimen would be one of the useful options for P. aeruginosa with antimicrobial resistance infection treatment., (Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background and Objective: In recent years, Streptococcus anginosus group (SAG) bacteria are becoming increasingly recognized as important pneumonia-causing pathogens. Although several small studies have been reported, the features of SAG pneumonia remain unclear, because the identification of SAG from sputum cultures is not routinely performed in most microbiology laboratories. The aim of this study was to elucidate the clinical characteristics of SAG pneumonia., Patient and Methods: This was a retrospective case-control study utilizing data obtained in our hospital between September 2009 and June 2016. We investigated 31 patients with SAG pneumonia (PWP), and also assessed the difference between the 31 PWP and 37 patients without pneumonia (PWOP) in whose sputum SAG was detected., Results: Seventy-one percent of the patients were men and the median age was 78 years in the PWP. Univariate analysis indicated that the PWP were significantly more often a bed-ridden (p < 0.01) with comorbid aspiration than were the PWOP (p < 0.05). Among the PWP, nursing and healthcare-associated pneumonia (NHCAP) was the more common type of pneumonia (54.8%). S. anginosus was detected significantly more frequently in sputum cultures of PWP than PWOP (p < 0.01), and multiple pathogens were detected more frequently in PWP (p < 0.01). Streptococcus constellatus was the most frequently detected pathogen in patients with a single bacterial infection. Empyema was observed only in patients with multiple bacteria., Conclusions: SAG should be recognized as important causative pathogens of pneumonia, particularly among elderly patients with underlying disease associated with aspiration. NHCAP was the more common type of SAG pneumonia in this study., (Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Gene sequence analysis methods, including 16S rRNA identification, allows accurate identification of Streptococcus species, which include phenotypically closely related species that are difficult to differentiate using conventional chemical methods. We report a case of bacteremia due to Streptococcus tigurinus, identified by 16S rRNA, in a 72-year-old woman with gastrointestinal cancer and ascites. She was hospitalized to undergo elective tumor-related surgery. Five days prior to undergoing surgery, she developed a fever with no obvious source of infection. Blood cultures identified gram-positive cocci. The patient's bacteremia was initially thought to be caused by an Enterococcus species, given her underlying gastrointestinal disease. However, alpha-hemolytic, mucoid, circular colonies were observed on sheep blood agar the following day. Although matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and biochemical testing suggested Streptococcus pneumoniae, we conducted further investigation to identify the bacterium, as the patient had no symptoms of infections usually related with S. pneumoniae such as pneumonia, meningitis, or sinusitis, and the bacteremia occurred 30 days after hospitalization. Finally, the gram-positive cocci were identified as S. tigurinus, assigned to the Streptococcus mitis group in 2012. Although the origin of infection was unclear, it was suspected that peritonitis or bacterial translocation from the gastrointestinal tract caused the bacteremia. This novel species was recently reported as being extremely pathogenic and different from other Streptococcus species. It has been reported to occur in cases of infectious endocarditis and bacteremia. In this article, we reviewed previous reports of S. tigurinus infection and summarized the clinical and pathogenetic features., (Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Uterine cervical cancer is a treatable and preventable cancer. Medical efforts to reduce rates of cervical cancer focus on the promotion of human papillomavirus (HPV) vaccination and the promotion of routine cervical cancer screening done by cervical cytology and cervical HPV testing. Urine-based HPV testing would be simple and noninvasive approach to screen for cervical cancer., Methods: Two biospecimens (clinician-taken sample from cervix and initial stream urine sample) were provided from a total of 240 healthy women attending for cancer screening provided for HPV testing. We have assessed the HPV detection rates among cervical samples and pellet fraction of urine samples using HPV test (Anyplex™ II HPV28 Detection kit, Seegene, Korea)., Results: Among 240 samples screened, HPV prevalence was 42.9% in pellet fractions of urine samples. The agreement between the two kinds of samples was 98.4%, k = 0.792. Discordant results were observed in 27 cases; 5 were positive only by urine samples and 22 were positive only by smear samples. Sensitivity and specificity for all HPV DNA in pellet fractions of urine using cervical samples as reference was 68.4% and 99.9%., Conclusions: Comparing methodologies of collection of samples for HPV detection, they showed the higher agreements for almost genotypes between cervical samples and pellet fractions of urine samples. These results suggest that urine could be a good noninvasive tool to monitor HPV infection in women. Additional research in a larger and general screening population would be needed., (Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

The efficacy of arbekacin in patients with MRSA infections is influenced by the peak concentration (Cpeak)/MIC ratio (≧8). A daily arbekacin dose of 4-6 mg/kg is primarily used for the treatment of MRSA infection. However, clinical pharmacokinetic studies of arbekacin that evaluate changes in patients with different infectious diseases have been limited. This study was to evaluate the pharmacokinetics of arbekacin in different infectious diseases and to evaluate its dosing regimens. This work describes a single-centre, retrospective study. The pharmacokinetic parameters of arbekacin were calculated from individual serum-concentration data using WinNonlin ver. 6.3. A total of 331 serum samples were obtained from 170 patients. Our drug concentration-time data were well described by a two-compartment open model. The final model showed that drug clearance was related to creatinine clearance and that the total distribution volume (Vd) was related to actual body weight and the presence of bacteremia. The individual Vd in bacteremia patients was significantly higher than those of other patients (bacteremia: 29.7 ± 0.5 L, pneumonia: 20.8 ± 0.4 L, other infections: 21.4 ± 0.4 L; p < 0.05). Additionally, Monte Carlo simulation showed that target (Cpeak/MIC ≧ 8) attainment was only 10.1%, even at a dose of 6 mg/kg, especially for MRSA bacteremia patients with an arbekacin MIC = 2 μg/mL. In conclusion, our study revealed that the Vd may be higher in bacteremia patients than in patients with other infectious diseases. Therefore, an increase in the daily dose of arbekacin should be considered for bacteremia patients., (Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Previously, Veillonella species had been considered as nonpathogenic and rarely caused serious infections. We report a case of 25-year-old man with osteomyelitis caused by Veillonella species. He was admitted to the hospital due to an open fracture to the left radial bone caused by industrial washing machine accident, and emergency surgery was performed. However, wound infections occurred one week after the operation. Although Acinetobacter baumannii and Serratia marcescens were cultured from the pus, obligate anaerobic bacteria were not detected at that point. Debridement was repeated and antibiotics were changed according to the result of bacterial culture and drug sensitivity. Despite this, the infection was poorly controlled. On the 5th debridement, granulomatous bone tissues on pseudarthrosis were found for the first time at the infection site. Although no bacteria was detected with aerobic culture, anaerobic incubation revealed Gram-negative cocci which was later identified as Veillonella species by 16S rRNA gene sequence analysis. His condition improved without any additional debridement after adding effective antibiotics against Veillonella species. It is well known that prolonged infection with aerobes consumes oxygen in the infection site and leads the environment to more favorable conditions for anaerobic bacteria, thus we speculated that prolonged infection with bacteria such as S. marcescens induced the favorable environment for Veillonella species. Physicians should realize the importance of anaerobic culture method in routine practice, especially in complicated cases such as the present case. In this article, we reviewed case reports of Veillonella infection and summarized the clinical features of this organism., (Copyright © 2016. Published by Elsevier Ltd.)

Background: The purpose of this study was to examine the pharmacokinetics/pharmacodynamics of rifampicin against methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA), and vancomycin-intermediate S. aureus (VISA) in a neutropenic murine thigh infection model., Methods: Three S. aureus isolates (MSSA [ATCC 25923], MRSA and VISA [Mu50]) with rifampicin MIC 0.06 to >256 μg/mL were tested. The efficacy was calculated as the change in bacterial density. A maximum effect model was used to determine the PK/PD index that best described the dose-response data., Results: The area under the curve (AUC)/MIC and maximum concentration of drug in serum (Cmax/MIC) were the best correlated with in vivo efficacy (AUC/MIC, R(2) = 0.96; Cmax/MIC, R(2) = 0.97) for S. aureus ATCC 25923 strain, and the dose fractionation-response study did not show significantly different antimicrobial activity (p = 0.10). The AUC/MIC values associated with stasis and 1-log kill for the S. aureus ATCC 25923 strain were 386 and 952, respectively. On the other hand, no antimicrobial efficacy was observed against two strains (MRSA and VISA) with MIC of 128 μg/mL or more., Conclusion: Rifampicin demonstrated concentration-dependent killing. The AUC/MIC was a predictive PK/PD index., (Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objective: To study the clinical characteristics and associated risk factors of infections caused by extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae., Methods: A case-control study at a large university hospital in Japan, comparing patients who were infected or colonized with ESBL-producing Enterobacteriaceae (n = 212) and non-ESBL-producing Enterobacteriaceae (n = 2089) in 2010-2013. Data were collected from medical charts, retrospectively. Multivariate logistic regression analysis was used to explore risk factors of ESBL-producing Enterobacteriaceae (Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Proteus mirabilis) infection or colonization for each pathogen, respectively., Results: ESBL-producing Enterobacteriaceae [E. coli (n = 113), K. oxytoca (n = 46), K. pneumoniae (n = 41), P. mirabilis (n = 12)] were taken from patients were identified in 1409 outpatient and 892 inpatients. Infection or colonization caused by ESBL-producing Enterobacteriaceae was considered to be hospital-acquired, healthcare-associated and community-acquired in 60.4%, 17.9% and 21.7% patients, respectively. Independent risk factors for ESBL-producing Enterobacteriaceae infection or colonization were male sex, cerebrovascular disease, intubation/tracheostomy, major surgery within 60 days (p < 0.001). Moreover, antimicrobial usage (more than 4 days) during preceding 60 days, especially aminoglycoside, oxazolidinone, tetracycline, fluoroquinolone, trimethoprim/sulfamethoxazole, and second- and fourth-generation cephalosporin were risk factors (p < 0.001). However, acquisition location of infection (hospital-acquired and community-onset) was not a risk factor (p > 0.05)., Conclusion: The problem of ESBL production is no longer limited to hospital-acquired infections. The presence of chronic illness, such as cerebrovascular disease, and recent antimicrobial use were independent risk factors for ESBL-producing Enterobacteriaceae infection or colonization., (Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

We report findings for a 74-year-old woman with Candida tropicalis endophthalmitis for whom an increase in b-D-glucan level and worsening of endophthalmitis were observed after intravenous injection of micafungin, an echinocandin antifungal agent. Endogenous endophthalmitis caused by C. tropicalis developed in both eyes. On the basis of her surgical history, laboratory data,and lesions, tentative diagnosis of fungal endophthalmitis was made. She was then treated with fluconazole and itraconazole, but the b-D-glucan level did not decrease, and there was no improvement of the endophthalmitis. The fluconazole was discontinued and replaced by micafungin.Unexpectedly, the level of b-D-glucan increased and endophthalmitis did not improve. The micafungin was immediately stopped and replaced by intravenous fluconazole with amphotericin B syrup, but the itraconazole was continued. Marked resolution of the vitreous inflammation was observed in both eyes, and the serum b-D-glucan level was reduced. Because active macular infiltrates were observed in the right eye, vitrectomy was performed. The micafungin minimum inhibitory concentration against the C. tropicalis strain isolated from our patient was 0.03 lg/ml. This paradoxical effect of micafungin should be remembered, and b-D-glucan level should be frequently monitored after intravenous injection of micafungin.