Search

Jun Hirai,1,2 Nobuaki Mori,1,2 Daisuke Sakanashi,2 Yuichi Shibata,2 Nobuhiro Asai,1,2 Mao Hagihara,3 Hiroshige Mikamo1,2 1Department of Clinical Infectious Diseases, Aichi Medical University Hospital, Nagakute, Aichi, Japan; 2Department of Infection Control and Prevention, Aichi Medical University Hospital, Nagakute, Aichi, Japan; 3Department of Molecular Epidemiology and Biomedical Sciences, Aichi Medical University, Nagakute, Aichi, JapanCorrespondence: Jun Hirai, Department of Clinical Infectious Diseases, Aichi Medical University Hospital, 1-1, Yazako-karimata, Nagakute, Aichi, 480-1195, Japan, Tel +81-561-62-3311, Fax +81-561-76-2673, Email hiraichimed@gmail.comAbstract: Stenotrophomonas maltophilia (S. maltophilia) is increasingly recognized as a pathogen responsible for nosocomial infections, particularly in immunocompromised patients. The most common types of S. maltophilia infections are pneumonia and catheter-related bloodstream infection, and clinical cases of intra-abdominal abscesses due to S. maltophilia are rare. We present a rare case of intra-abdominal abscess and bacteremia as a surgical site infection (SSI) caused by S. maltophilia in a patient following total gastrectomy. We also reviewed previous literature to elucidate the clinical characteristics of intra-abdominal abscess due to S. maltophilia. The patient, a 75-year-old man with diabetes and polymyositis (treated with prednisolone), developed a fever 17 days after undergoing a total gastrectomy for gastric cancer. Abdominal computed tomography revealed a hypodense solid mass at the esophagojejunostomy site, which appeared to be an intra-abdominal abscess. The culture of both blood and drained abscess pus confirmed only S. maltophilia. Treatment with intravenous trimethoprim-sulfamethoxazole and abscess drainage led to complete resolution. The patient recovered and was discharged and did not experience a recurrence. We reviewed the English literature and found only two additional case reports of intra-abdominal abscesses caused by S. maltophilia. As in our case, the intra-abdominal abscess occurred after abdominal surgery and the source was suspected to be deep SSI. This case highlights the importance of considering S. maltophilia as a potential pathogen in patients with atypical post-surgical abdominal infections. Physicians should be aware that S. maltophilia has the potential to cause intra-abdominal abscesses secondary to SSI, in addition to Enterobacteriaceae, a major causative pathogen of SSI. Further studies are required to elucidate the etiology, epidemiology, and risk factors for SSI caused by S. maltophilia.Keywords: Stenotrophomonas maltophilia, abdominal abscess, surgical site infection

Jun Sada,1 Jun Hirai,2,3 Koki Ota,1 Shingo Numoto,1 Hitoshi Honma,1 Nobuaki Mori,2,3 Daisuke Sakanashi,3 Hiroshige Mikamo,2,3 Akihisa Okumura1 1Department of Pediatrics, Aichi Medical University Hospital, Nagakute, Aichi, Japan; 2Department of Clinical Infectious Diseases, Aichi Medical University Hospital, Nagakute, Aichi, Japan; 3Department of Infection Control and Prevention, Aichi Medical University Hospital, Nagakute, Aichi, JapanCorrespondence: Jun Sada, Department of Pediatrics, Aichi Medical University Hospital, 1-1, Yazako-karimata, Nagakute, Aichi, 480-1195, Japan, Tel +81-561-62-3311, Fax +81-561-76-2673, Email sada.jun.043@mail.aichi-med-u.ac.jpAbstract: Kalamiella piersonii is rare pathogen, and its pathogenicity to humans has been unknown. We describe an infant with bacteremia caused by Kalamiella piersonii. The patient was a 2-month-old girl presented with diarrhea, poor oral intake, and vomiting. The patient was tentatively diagnosed with acute enterocolitis. After admission, the patient developed a fever and blood culture yielded Gram-negative cocci, first determined to be Pantoea septica by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. However, genetic analysis of 16S rRNA allowed its identification as Kalamiella piersonii (GenBank accession number is OQ547240). Other housekeeping genes such as gyrB, rpoB, and atpD also identified the isolated strain as Kalamiella piersonii. The patient was successfully treated with cefotaxime without sequelae. Later, the patient was diagnosed as non-IgE-mediated gastrointestinal food allergy. Our experience indicated that Kalamiella piersonii is a potential human pathogen that can cause invasive infections even in infants and children. Identification of Kalamiella piersonii is difficult with routine conventional tests, and detailed studies including genetic analyses are necessary to clarify the pathogenicity of Kalamiella piersonii in humans.Keywords: Kalamiella piersonii, 16S rRNA, non-IgE-mediated gastrointestinal food allergy, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry

Jun Hirai,1,2 Hiroyuki Suzuki,3 Daisuke Sakanashi,2 Yuji Kuge,4 Takaaki Kishino,4 Nobuhiro Asai,1,2 Mao Hagihara,5 Hiroshige Mikamo1,2 1Department of Clinical Infectious Diseases, Aichi Medical University Hospital, Nagakute, Aichi, Japan; 2Department of Infection Control and Prevention, Aichi Medical University Hospital, Nagakute, Aichi, Japan; 3Department of Neurology, Aichi Medical University, Nagakute, Aichi, Japan; 4Department of Emergency and Critical Care Medicine, Aichi Medical University Hospital, Nagakute, Aichi, Japan; 5Department of Molecular Epidemiology and Biomedical Sciences, Aichi Medical University, Nagakute, Aichi, JapanCorrespondence: Jun Hirai, Department of Clinical Infectious Diseases, Aichi Medical University Hospital, 1-1, Yazako-karimata, Nagakute, Aichi, 480-1195, Japan, Tel +81-561-62-3311, Fax +81-561-76-2673, Email hiraichimed@gmail.comAbstract: Staphylococcus argenteus is a new species classified as part of the Staphylococcus aureus-related complex in 2015 and has been recognized to be as pathogenic as S. aureus. We describe the first case of endocarditis caused by S. argenteus. A 51-year-old man presented with chief complaints of fever and headaches. On admission, he showed a slight decrease in consciousness level (Glasgow Coma Scale, E4V4M6). Careful physical examination and imaging revealed a systolic heart murmur, Janeway lesions, and complicating convexity subarachnoid hemorrhage (cSAH) of the left frontal lobe. Ceftriaxone 4 g/day was administered immediately after blood cultures were obtained. The next day, all blood cultures grew Gram-positive cocci, identified as Staphylococcus aureus or Staphylococcus argenteus by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). However, the version of MALDI-TOF MS used could not distinguish these bacteria. Although we could not find valvular vegetation, he was clinically diagnosed with infective endocarditis according to the modified Duke’s criteria. Meropenem 6 g/day and linezolid 1.2 g/day were started to cover S. aureus and methicillin-resistant S. aureus. Finally, ampicillin was selected based on drug susceptibility, and the patient was treated for 8 weeks and recovered without permanent damage. The isolated strain formed white colonies on blood agar plates, characteristic of S. argenteus, and differs from golden colony-forming S. aureus. Genetic analysis revealed the isolated strain as S. argenteus (sequence type 1223). Although distinguishing S. argenteus from S. aureus using routine conventional laboratory tests is difficult, the updated library version of MALDI-TOF MS is useful in identifying S. argenteus. Interestingly, all published cases of infection caused by ST1223 have been reported in Japan. Therefore, the trend of infections from the ST1223 strain should be carefully monitored, particularly in Japan. Further investigation is needed to clarify the epidemiology and clinical characteristics of S. argenteus infection, as there are few studies regarding this pathogen.Keywords: Staphylococcus argenteus, sequence type 1223, infective endocarditis, convexity subarachnoid hemorrhage, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, Japan

Jun Hirai,1,2 Tessei Kuruma,3 Daisuke Sakanashi,2 Yuji Kuge,4 Takaaki Kishino,4 Yuuichi Shibata,5 Nobuhiro Asai,1,2 Mao Hagihara,6 Hiroshige Mikamo1,2 1Department of Clinical Infectious Diseases, Aichi Medical University Hospital, Nagakute, Aichi, 480-1195, Japan; 2Department of Infection Control and Prevention, Aichi Medical University Hospital, Nagakute, Aichi, 480-1195, Japan; 3Department of Otolaryngology, Aichi Medical University Hospital, Nagakute, Aichi, 480-1195, Japan; 4Department of Emergency and Critical Care Medicine, Aichi Medical University Hospital, Nagakute, Aichi, 480-1195, Japan; 5Department of Pharmacy, Aichi Medical University Hospital, Nagakute, Aichi, 480-1195, Japan; 6Department of Molecular Epidemiology and Biomedical Sciences, Aichi Medical University, Nagakute, Aichi, 480-1195, JapanCorrespondence: Jun Hirai, Department of Clinical Infectious Diseases, Aichi Medical University Hospital, Nagakute, Aichi, 480-1195, Japan, Tel +81-561-62-3311, Fax +81-561-76-2673, Email hiraichimed@gmail.comAbstract: Although Dialister pneumosintes is a commensal microorganism of the oral cavity, it may sometimes cause severe systemic infections. We report a case of Lemierre syndrome (LS), which developed after D. pneumosintes infection, in a 73-year-old Japanese woman who was admitted to the hospital for throat pain, neck swelling, and fever for 3 days. She had a 3-month history of neglected dental caries, gingivitis, and periodontitis. Physical examination revealed right tonsillar erythema and swelling, and computed tomography (CT) showed peritonsillar and retropharyngeal abscesses. Ampicillin/sulbactam was promptly administered after collecting two sets of blood cultures. Surgical drainage for peritonsillar and retropharyngeal abscesses was also conducted on the second hospital day. Although only commensal oral microflora grew in the culture from the drained pus, Gram-negative bacilli were confirmed in the anaerobic blood cultures. Metronidazole was administered intravenously; however, the fever and neck swelling persisted. Repeat CT performed on the fifth hospital day revealed right internal jugular vein thrombosis, a known complication of tonsillitis and pharyngitis once the infection extends beyond the oropharynx. We diagnosed she had coexisting LS, and anticoagulant therapy was added to her treatment regimen. Her condition improved, and she was discharged after completing 3 weeks of antibiotics. Conventional methods failed to identify the isolated bacterium, and 16S rRNA sequencing ultimately identified it as D. pneumosintes. In a literature review of bacteremia due to D. pneumosintes, poor oral hygiene was considered a probable risk factor for invasive D. pneumosintes infection. We consider this to be the case in our patient who presented with dental caries, gingivitis, and periodontitis. In addition, all cases revealed that the 16S rRNA gene sequencing is useful for identifying this species. Although the diagnosis of LS by physical examination is difficult, physicians should always consider it as a potential complication of infections in the pharyngeal area.Keywords: Dialister pneumosintes, Lemierre syndrome, tonsillar abscess, retropharyngeal abscess, oral hygiene, anticoagulation

Jun Hirai,1 Daisuke Sakanashi,2 Takeshi Kinjo,1 Shusaku Haranaga,3 Jiro Fujita2 1Department of Infectious, Respiratory and Digestive Medicine, Graduate School of Medicine, University of the Ryukyus, Okinawa 903-0215, Japan; 2Department of Infection Control and Prevention, Aichi Medical University Hospital, Aichi 480-1195, Japan; 3Comprehensive Health Professions Education Center, University of the Ryukyus Hospital, Okinawa 903-0215, JapanCorrespondence: Jun Hirai Email j.eichi419@gmail.comAbstract: Hypervirulent Klebsiella pneumoniae (HV-KP) typically causes pyogenic liver abscess and bacteremia with metastatic infections. Community-acquired pneumonia (CAP) due to HV-KP is uncommon and details of its clinical and microbiological features are limited. We report the first case of CAP due to capsular genotype K2-ST86 HV-KP in Okinawa, Japan and review infections caused by the K2-ST86 strain. A 79-year-old woman presenting with fever and productive cough persisting for the past three days was admitted to hospital. Her vital signs indicated septic shock. Lung examination by auscultation revealed holo-crackle and lobar pneumonia in chest radiography, and Streptococcus pneumoniae was suspected. However, sputum and blood cultures revealed Gram-negative coccus identified as K. pneumoniae. Genetic analysis identified the isolated strain as the K2 serotype harboring rmpA, iutA, entB, and mrkD. Therefore, we identified the isolated strain as hypervirulent. The isolate belonged to ST86 as determined by multilocus sequence typing. The case was not complicated by predisposing factors such as diabetes mellitus and malignancy related to HV-KP infection; thus, this CAP-causing HV-KP strain may differ from the typical HV-KP strain that induces liver abscess. A literature review identified only nine cases with CAP due to HV-KP. In all cases, the disease mainly occurred in older males with diabetes mellitus, which makes the present case unusual, and had high rates of septic shock and death. No case, including ours, was complicated by metastatic infection, suggesting that CAP due to HV-KP poses little distant metastasis risk, even in patients with bloodstream infection. In our review, consistent with our case, K2-ST86 was the most common strain of HV-KP in patients with CAP. Therefore, studies are needed to elucidate the clinical and microbiological features of HV-KP CAP, with a focus on the K2-ST86 strain. Physicians should always consider K. pneumoniae in cases of sepsis CAP with lobar pneumonia.Keywords: hypervirulent Klebsiella pneumoniae, community-acquired pneumonia, serotype K2, sequence type 86, lobar pneumonia, Streptococcus pneumoniae

Jun Hirai,1,2 Daisuke Sakanashi,3 Masashi Momose,1 Tomomi Koga,4 Takeshi Kinjo,2 Shusaku Haranaga,5 Eiji Motonaga,6 Jiro Fujita2 1Department of Internal Medicine, Okinawa Miyako Hospital, Okinawa 906-0012, Japan; 2Department of Infectious, Respiratory and Digestive Medicine, Graduate School of Medicine, University of the Ryukyus, Okinawa 903-0215, Japan; 3Department of Infection Control and Prevention, Aichi Medical University Hospital, Aichi 480-1195, Japan; 4Department of Radiology, Graduate School of Medicine, University of the Ryukyus, Okinawa 903-0215, Japan; 5Comprehensive Health Professions Education Center, University of the Ryukyus Hospital, Okinawa 903-0215, Japan; 6Department of General Medicine, Okinawa Miyako Hospital, Okinawa 906-0012, JapanCorrespondence: Jun Hirai Email j.eichi419@gmail.comAbstract: Hypervirulent Klebsiella pneumoniae (HV-KP) is typically associated with community-acquired liver abscess and bacteremia with metastatic infection; however, primary lung abscess (PLA) caused by HV-KP is rare, with only one such case report to date. A 69-year-old man with a history of diabetes mellitus (DM) was admitted to hospital complaining of slight bloody sputum. Chest imaging showed multiple consolidations with cavities in both lung fields. A culture of bronchoalveolar lavage fluid confirmed the presence of K. pneumoniae. Genetic analyses identified the isolate as serotype K2 and sequence type 375 (K2-ST375), and that it harbored the rmpA gene. The patient was an Asian middle-aged male with DM, all of which are risk factors for HV-KP infection. Although complicating DM and the presence of the rmpA gene are more likely to induce disseminated infection, metastatic infections were not found in this patient. The clinical and microbiological characteristics of our patient were different from those of a previous reported case, although in both cases the patient was from Asia and had DM. Therefore, DM appears to be one of the predisposing factors for HV-KP lung abscesses and physicians should pay attention to emerging HV-KP lung abscess infection, particularly in Asian countries. Previous studies have also revealed that K2-ST375 is one of the major clones causing HV-KP infection, and that it is mainly isolated from patients with liver abscess. Interestingly, including the present case, most of the infectious cases caused by K2-ST375 have been reported from Okinawa Prefecture in Japan. Therefore, the trend of the K2-ST375 strain should be carefully monitored, particularly in Okinawa, Japan. The serotype of HV-KP that causes PLA is still unknown and further study is needed to elucidate the etiology of PLA due to HV-KP and the relationship between the strain K2-ST375 and PLA.Keywords: hypervirulent Klebsiella pneumoniae, primary lung abscess, serotype K2, sequence type 375, Okinawa, Japan

Introduction: Despite the advancements in diagnostic methods and antibiotic treatment, empyema is a critical respiratory infection, showing a high mortality rate of 10-25%. Patients and Methods: To evaluate the bacterial etiology and prognostic factors of acute empyema, we conducted this long-term retrospective cohort study at our institute between 2008 and 2022. Results: A total of 80 patients were enrolled in this cohort. The median age was 72 years (range 19 to 93 years), and 61 (76%) were male. The most common underlying disease was malignancy, seen in 28 (35%). The mean Charlson comorbidity index (CCI) was 2.7 (±2.4). The 30-day and in-hospital mortality were 9 (11%) and 15 (19%), respectively. Univariate analysis revealed that healthcare-associated infection, inappropriate treatment, high CCI score, performance status (PS) of 2-4, and isolation of potentially drug-resistant (PDR) pathogens were poor prognostic factors. Finally, multivariate analysis showed that high CCI score ( p = 0.009) and isolation of PDR pathogens ( p = 0.011) were independent poor prognostic factors for in-hospital death in acute empyema. Conclusions: We found that higher CCI scores and isolation of PDR pathogens were independent poor prognostic factors for in-hospital mortality among empyema patients.

Diagnosing the cause of death can be challenging, particularly for patients with no prior history of visits to the treating hospital. We encountered a case involving a 76-year-old male who was discovered in a state of cardiopulmonary arrest at his home and subsequently declared deceased in our hospital due to severe pneumonia. He had exhibited symptoms of fever over 37°C and severe coughing for several days. Despite consulting a primary care physician one day prior, his symptoms worsened. Autopsy findings revealed an increase in lung weight and diffuse changes in parenchyma. Histological analysis showed numerous inflammatory cells and exudate within the alveoli. Gram and Periodic acid-Schiff staining were negative, but slight staining was observed in the cytoplasm of macrophages by Warthin-starry and Gimenez stains. Tests using a pan bacterial/viral detection kit and qualitative polymerase chain reaction (PCR) for Legionella pneumophila were negative. However, using deoxyribonucleic acid extracted from formalin-fixed paraffin-embedded lung tissue, PCR amplification of the ssrA gene of congeneric Legionella species yielded positive results. The results suggest that the cause of death was likely due to bacterial pneumonia caused by Legionella species., (© 2024 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.)

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.)

In the diagnosis of coronavirus disease 2019 (COVID-19), several types of instruments and reagents for SARS-CoV-2 nucleic acid testing have been introduced to meet clinical needs. We evaluated the clinical performances of ID NOW™ COVID-19 2.0 (ID NOW™ 2.0), which is capable of detecting SARS-CoV-2 within 12 min as part of point-of-care testing (POCT). Patients who displayed COVID-19 related symptoms, and who were tested for screening purposes, were recruited to this study. Two nasopharyngeal swabs were collected and tested using the ID NOW™ 2.0 test. Reference testing was performed using the cobas 8800 or 6800 (reagents: cobas SARS-CoV-2 and Flu A/B). A total of 38 samples and 46 samples were tested positive and negative, respectively, by the reference test. The ID NOW™ 2.0 showed a sensitivity of 94.7% (95% CI: 82.3-99.4) and a specificity of 100% (95% CI: 92.3-100). Samples that were positive by reference testing had cycle threshold (Ct) values ranging from 11.90 to 35.41. Among these reference positive samples, two samples were negative by ID NOW™ 2.0 with Ct values of 35.25 and 35.41. For samples with Ct values < 35, the sensitivity of ID NOW™ 2.0 was 100%. In Japan, the restrictions related to COVID-19 have been relaxed, however the COVID-19 epidemic still continues. ID NOW™ 2.0 is expected to be used as a rapid and reliable alternative to laboratory-based RT-PCR methods., Competing Interests: Declaration of competing interest This study was sponsored by Abbott Diagnostics Medical Co., Ltd (Tokyo, Japan)., (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.)

Purpose: Anaerobic bacteria, existing on human skin and mucous membranes, can cause severe infections with complications or mortality. We examined the clinical characteristics of patients infected with Fusobacterium spp. and assessed their antibiotic susceptibility., Methods: Clinical data were collated from patients diagnosed with Fusobacterium infections in a Japanese university hospital between 2014 and 2023. Antibiotic susceptibility tests were conducted following the Clinical and Laboratory Standards Institute guidelines., Results: We identified 299 Fusobacterium isolates. The median age was 61 years (range, 14-95 years), with females constituting 43.1% of the patients. Most infections were community-acquired (84.6%, 253/299). Multiple bacterial strains were isolated simultaneously in 74.6% of cases. One-fourth of the patients had solid organ malignancies (25.4%, 76/299), and 14.5% (11/76) of those had colorectal cancer. The 30-day mortality rate was 1.3%. Fusobacterium species were isolated from blood cultures in 6% (18/299) of the patients. Patients, aged 75 years or older, with cerebrovascular disease or hematologic malignancy exhibited significantly higher prevalence of blood culture isolates in univariate analysis. Each Fusobacterium species had its characteristic infection site. Approximately 5% F. nucleatum and F. necrophorum isolates showed penicillin G resistance. Moxifloxacin resistance was observed in varying degrees across strains, ranging from 4.6 to 100% of isolates. All isolates were sensitive to β-lactam/β-lactamase inhibitors, carbapenems, and metronidazole., Conclusion: We show a link between Fusobacterium species and solid organ malignancies. We observed resistance to penicillin, cefmetazole, clindamycin, and moxifloxacin, warranting caution in their clinical use. This study offers valuable insights for managing Fusobacterium infections and guiding empirical treatments., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Tuberculous otitis media (TOM) is a rare manifestation caused by Mycobacterium tuberculosis with low incidence rates among extrapulmonary tuberculosis cases. Diagnosis is often delayed because of the presence of several clinical manifestations and the high prevalence of secondary bacterial infections. Few reports have attributed secondary bacterial infections in patients with TOM to commensal Neisseria . Thus, understanding the pathogenic mechanisms and clinical features of commensal Neisseria is important, considering its recent presentation as an infection-causing pathogen. Neisseria mucosa is a commensal inhabitant in humans and is generally considered non-pathogenic but can cause infection in rare cases. Here, we report an atypical secondary infection caused by Neisseria mucosa in an 81-year-old woman with TOM being treated for pulmonary tuberculosis. Direct purulent otorrhea smear microscopy revealed no acid-fast bacilli using Ziehl-Neelsen staining, whereas the phagocytosis of gram-negative cocci by white blood cells was confirmed using Gram staining. Otorrhea culture revealed the growth of N. mucosa . Subsequently, M. tuberculosis infection in the otorrhea was identified using a culture-based method. Vigilance is critical for the early detection of TOM to prevent further complications. This report raises awareness regarding TOM and provides insight into the pathogenicity of N. mucosa in otitis media., (© [copyright 2023] PLA General Hospital Department of Otolaryngology Head and Neck Surgery. Production and hosting by Elsevier (Singapore) Pte Ltd.)

Yersinia enterocolitica is a causative agent of food poisoning and has been isolated from pork and stream water, causing Yersinia enterocolitica in humans. The bacterium is divided into multiple serotypes and biotypes, among which serotypes O3 and O8 and biotypes 1B, 3, and 4 are frequently isolated in Japan. Biotype 3 can be classified as [VP+, Suc+], [VP-, Suc+], [VP-, Suc-] based on the biochemical properties. Among them, [O3, 3, VP-, Suc-] has been reported to be identified as Yersinia kristensenii in a simple identification kit. An increasing number of facilities in the field of microbiological testing are currently using mass spectrometers to identify species of microorganisms. However, there are many facilities where mass spectrometers have not yet been installed and microbial identification and susceptibility testing devices are used to identify bacterial species. No reports have described how the [O3, 3, VP-, Suc-] type, which is identified as Y. kristensenii in the simple identification kit, is identified by the microbial identification and susceptibility testing devices. In this study, 15 strains of Y. enterocolitica , which were previously isolated, serotyped, and biotyped from fecal culture tests at our hospital, were analyzed to see how these strains were identified in RAISUS S4, Microscan WalkAway, VITEK2 Blue, and BD Phoenix. [O3, 3, VP-, Suc-] was identified as Y. kristensenii in RAISUS S4, Microscan WalkAway, and VITEK2 Blue and as Y. enterocolitica in BD Phoenix. [O3, 3, VP-, Suc+], [O3, 4] and [O8, 1B] were identified as Y. enterocolitica . Therefore, when a sample was identified as Y. kristensenii by RAISUS S4, Microscan WalkAway, or VITEK2 Blue, the possibility that it was actually [O3, 3, VP-, Suc-] could not be ruled out. The possibility of Y. enterocolitica should be informed to attending physicians.

The coronavirus disease (COVID-19) pandemic continues to threaten global public health. Remdesivir and monoclonal antibodies have shown promise for COVID-19 treatment of patients who are immunocompromised, including those with cancer, transplant recipients, and those with autoimmune disorder. However, the effectiveness and safety of this combination therapy for patients who are immunosuppressed remain unclear. We compared the efficacy and safety of combination therapy and remdesivir monotherapy for patients with mild-to-moderate COVID-19 who were immunosuppressed. Eighty-six patients treated in July 2021-March 2023 were analyzed. The combination therapy group (CTG) showed a statistically significant reduction in viral load compared with the monotherapy group (MTG) ( p < 0.01). Patients in the CTG also experienced earlier resolution of fever than those in the MTG ( p = 0.02), although this difference was not significant in the multivariate analysis ( p = 0.21). Additionally, the CTG had significantly higher discharge rates on days 7, 14, and 28 than the MTG ( p < 0.01, p < 0.01, and p = 0.04, respectively). No serious adverse events were observed with combination therapy. These findings suggest that combination therapy may improve the clinical outcomes of immunosuppressed COVID-19 patients by reducing the viral load and hastening recovery. Further studies are required to fully understand the benefits of this combination therapy for immunocompromised COVID-19 patients.

As bone and joint infections (BJIs) require long-term treatment, identifying their causative pathogens is vital. However, the detection rate of conventional culturing remains inadequate. This study aimed to evaluate the usefulness of the FilmArray blood culture identification (BCID) panel for identifying causative pathogens in patients with BJIs. We tested a BCID panel using collected samples, in addition to conventional cultures. The primary outcome was to evaluate the diagnostic performance of the BCID panel, calculated using conventional culturing methods. A total of 44 patients who underwent BJI-related specimen collection were enrolled. Of the 44 patients, 22 were diagnosed with a BJI. Conventional culture identified 15 of 22 organisms (68.2%), whereas the BCID panel identified 14 of 22 organisms (63.4%). The overall sensitivity and specificity of the BCID panel were 73.3% and 57.1%, respectively, compared to those of the conventional culture. However, the sensitivity reached 100% when only pathogens included in the BCID panel were considered. In seven culture-negative cases, the BCID panel identified three organisms (42.9%). The BCID panel also indicated the appropriate therapy against a BJI caused by methicillin-resistant Staphylococcus aureus by detecting the mecA gene. This study demonstrated that the BCID panel has the potential for early and accurate diagnosis of the causative organism of BJI using specimens such as joint fluid and bone tissue. Our results suggest that BCID panels, in addition to routine culture, may improve our ability to diagnose the causative microorganisms of BJI in clinical practice, thereby contributing to the selection of appropriate antimicrobial agents., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (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.)

Background: Proteus spp. are widespread in the environment and comprise a part of the normal flora of the human gastrointestinal tract. Only six species in this genus, including Proteus mirabilis, Proteus vulgaris, Proteus terrae, Proteus penneri, Proteus hauseri, and Proteus faecis, have been isolated from human clinical specimens. However, there are no reports of Proteus alimentorum isolated from humans, and the clinical characteristics of P. alimentorum infection are unknown., Case Presentation: An 85-year-old female patient with peritoneal cancer was hospitalized for complicated pyelonephritis and bacteremia caused by P. alimentorum. The patient received antimicrobial therapy and was discharged on day 7 of hospitalization. No recurrence was observed 14 days after the treatment. Various methods were used to identify the Proteus sp. Furthermore, the VITEK-2 GN ID card resulted in low discrimination between P. hauseri and P. penneri. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry showed P. hauseri with a spectral score of 2.22 as the best match. Nevertheless, the pathogen was identified as P. alimentorum based on genetic investigation using 16 S rRNA gene sequencing and biochemical tests., Conclusion: Proteus alimentorum is a human pathogen, and its infection has an excellent therapeutic response to antimicrobials based on antimicrobial susceptibility. Genomic methods may be helpful for the precise identification of P. alimentorum., (© 2023. The Author(s).)

Fungemia is a fatal systemic infection that can occur in immunocompromised patients. Despite that, antifungal stewardship is spreading widely, but the mortality rate is extremely high, showing 40-60%. Loderomyces elongiporus is a newly morphologically detected pathogen, first described in 1994, followed by isolation in humans in 2008. It has been misrecognized as Candida parapsilosis . Recently, fever attributable to L. elongisporus fungemia cases has been reported, and the etiology and clinical features are still unknown. Here, we present three successfully treated L. elongisporus fungemia cases by echinocandin. In total, 11 cases were reviewed, including ours. Six of the eleven cases (55%) had external devices. All cases had some immunocompromised conditions or underlying diseases, such as diabetes mellitus, lung cancer, etc. Six patients survived, and the remaining five died. Seven patients who had received echinocandin initially survived. Risk factors for L. elongiporus fungemia overlap with those of candidemia. Even though there is no breakpoint for L. elongiporus , echinocandin can be a helpful treatment regimen for L. elongiporus fungemia.

Introduction: A randomized control trial (RCT) is considered to be the highest level in the Evidence-Based Medicine (EBM) pyramid. While EBM is essential to make a practical tool such as a prognostic guideline, it has been unclear how many patients in the real world can be eligible for a randomized control trial (RCT). Patients and method: This study was performed to clarify if there is a difference in patients' profiles and clinical outcomes between the patients eligible and not eligible for any RCT. We reviewed all IE patients at our institute between 2007 and 2019. The patients were divided into two groups: those eligible for RCTs (RCT appropriate group) and those who were not (RCT inappropriate group). Exclusion criteria for clinical trials were set based on previous clinical trials. Results: A total of 66 patients were enrolled in the study. The median age was 70 years (range 18 to 87 years), and 46 (70%) were male. Seventeen (26%) of the patients were eligible for RCTs. Comparing the two groups, patients in the RCT appropriate group were younger and had fewer comorbidities. The disease severity was milder in the RCT appropriate groups than in the RCT inappropriate groups. Patients in the RCT appropriate group showed significantly longer overall survival times than those in the RCT inappropriate group (Log-Rank test, p < 0.001). Conclusions: We found a significant gap in patients' characteristics and clinical outcomes between the groups. Physicians should be aware that RCT can never reflect the real-world population.

Competing Interests: We declare that all authors have no Conflict of Interest (COI).

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.)

Cefazolin (CFZ) is the first-line treatment for beta-lactamase-producing methicillin-sensitive Staphylococcus aureus (BP-MSSA) infection. In 2019, Japan experienced a CFZ shortage because of foreign object inclusion in a batch. Ampicillin/sulbactam (SAM) was preferred in many cases as definitive therapy for the treatment of BP-MSSA bacteremia to preserve broad-spectrum antibiotic stock. However, there are no previous studies reporting the clinical efficacy of SAM for BP-MSSA bacteremia. We aimed to compare the clinical efficacy and adverse effects of SAM versus CFZ in patients with BP-MSSA bacteremia. In total, 41 and 30 patients treated with SAM and CFZ, respectively, were identified. The baseline characteristics were similar in both groups. No significant differences were observed in length of hospital stay and all 30-day mortality between the two groups ( p = 0.270 and 0.643, respectively). Moreover, no intergroup difference in 90-day mortality was found (hazard ratio 1.02, 95% confidential interval 0.227-4.53). Adverse effects, such as liver dysfunction, were less in the CFZ group than in the SAM group ( p = 0.030). Therefore, in cases of poor CFZ supply or in patients allergic to CFZ and penicillinase-stable penicillins, SAM can be an effective therapeutic option for bacteremia due to BP-MSSA with attention of adverse effects, such as liver dysfunction., Competing Interests: The authors declare no conflicts of interest.

Objectives: Clostridioides difficile infection (CDI) often recurs. Approximately 25% of patients have recurrences after the initial treatment, and patients who have relapsed once are more likely to relapse. We aimed to identify the risk factors for initial CDI recurrence., Methods: We performed a retrospective survey of patient backgrounds and treatment-related factors. Risk factors were analyzed using single and multiple logistic regression analyses., Results: A total of 134 patients were included in the study. Prophylactic probiotic use and nasogastric tube feeding were independent risk factors for the initial recurrence of CDI. Patients using prophylactic probiotics had significantly higher recurrence rates than those not using prophylactic probiotics., Conclusion: Prophylactic probiotic use and nasogastric tube placement may be risk factors for the initial recurrence of CDI. It is noteworthy that CDI that occurs during the use of prophylactic probiotics may be prone to recurrence., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 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: Evidenced based medicine (EBM) is necessary to standardize or treatment for infection since EBM is established based on the results of clinical trials. Entry criteria for clinical trials are very strict, and many patients have difficulties in being enrolled in any clinical trials regarding candidemia. It is questionable if the results of clinical trials reflect the real world of general medicine in this case., Patients and Methods: For the purpose of examining how many patients could join any randomized clinical trials for the treatment of candidemia, we reviewed all the candidemia patients in our institute during 2014-2018. The patients were divided into two groups: patients who were eligible for clinical trials (participation possible group), and those who were not (participation impossible group). Exclusion criteria for clinical trials were set based on previous clinical trials., Results: A total of 70 patients was enrolled in this study. The median age was 73 years (range 36-93 years). Of these, 41 patients (59%) were male. As for site of infections, catheter related blood stream infection was most frequently seen in 37 (53%). Seventeen patients (24%) were classified as participation possible group and 53 patients (76%) were participation impossible group. Comparing the two groups, participation possible group patients have much better performance status, have less comorbidities and have longer overall survival times than participation impossible group patients., Conclusion: Only 24% of candidemia patients were eligible for the clinical trials. Thus, we can see that clinical trials might not correctly reflect the real world among candidemia patients., (Copyright © 2020. Published by Elsevier B.V.)

(1) Introduction: Evidence-based medicine (EBM) is necessary to standardize treatments for infections because EBM has been established based on the results of clinical trials. Since entry criteria for clinical trials are very strict, it may cause skepticism or questions on whether the results of clinical trials reflect the real world of medical practice. (2) Methods: To examine how many patients could join any randomized clinical trials for the treatment of community-acquired pneumonia (CAP) and healthcare-associated pneumonia (HCAP). We reviewed all the pneumonia patients in our institute during 2014-2017. The patients were divided into two groups: patients who were eligible for clinical trials (participation-possible group), and those who were not (participation-impossible group). Exclusion criteria for clinical trials were set based on previous clinical trials. (3) Results: A total of 406 patients were enrolled in the present study. Fifty-seven (14%) patients were categorized into the participation-possible group, while 86% of patients belonged to the participation-impossible group. Patients in the participation-possible group had less comorbidities and more favorable outcomes than those with the participation-impossible group. As for the outcomes, there were significant differences in the 30-day and in-hospital mortality rates between the two groups. In addition, the participation-possible group showed a longer overall survival time than the participation-impossible group ( p < 0.001 by Log-Rank test). (4) Conclusion: There is a difference in patients' profile and outcomes between clinical trials and the real world. Though EBM is essential to advance medicine, we should acknowledge the facts and the limits of the clinical trials.

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., (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.)

Objectives: Procalcitonin (PCT) is an early diagnosis marker of sepsis/bacteremia. However, some reports refer to its lower responsiveness to gram-positive bacteremia. We retrospectively evaluated the PCT values at the onset of bacteremia in relation to severity index., Methods: Patients with bacteremia caused by two gram-negative bacteria (46 E. coli and 50 Klebsiella pneumoniae) and three gram-positive bacteria (45 S. aureus, 56 S. epidermidis, and 10 S. mitis) were studied. The plasma PCT and C-reactive protein (CRP) levels were compared between species and different Sequential Organ Failure Assessment (SOFA) score groups., Results: The median PCT level was higher in gram-negative than in gram-positive bacteremia in overall (13.09 vs. 0.50 ng/mL, p < 0.0001), in SOFA score≥4 group (28.85 vs.1.72 ng/mL, p < 0.0001) and in SOFA<4 group (2.64 vs. 0.42 ng/mL, p < 0.0001). Only 46%, and 11% of patients showed PCT ≥0.5 ng/mL in S. epidermidis, and S. mitis bacteremia, respectively. PCT was significantly better than CRP in discriminating gram-negative from gram-positive bacteremia (AUCROC; 0.828 and 0.634, p < 0.001), but it was low in Staphylococcus epidermidis bacteremia regardless of SOFA scores., Conclusions: PCT levels are lower in gram-positive bacteremia regardless of SOFA scores or the presence of shock. The conventional sepsis cutoff of 0.5 ng/mL may overlook certain proportions of gram-positive bacteremia., Competing Interests: Declaration of competing interest None of the authors have financial relationships with any commercial entity with an interest in the subject of this manuscript., (Copyright © 2020. Published by Elsevier B.V.)

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.)

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 β-lactamase inhibitor and belongs to the new class of diazabicyclooctane. The agent has an in vitro antimicrobial activity against several classes of β-lactamase-producing Enterobacterales. This study evaluated antimicrobial activity of combination therapies including β-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 β-lactams (aztreonam, cefepime, and meropenem) with nacubactam showed enhanced antimicrobial activity against CRE E. cloacae (-3.70 to -2.08 Δlog 10 CFU/lungs) and K. pneumoniae (-4.24 to 1.47 Δlog 10 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 Δlog 10 CFU/lungs) to bactericidal (<-3.0 Δlog 10 CFU/lungs) activities against CRE isolates. This study revealed that combination regimens with β-lactams (aztreonam, cefepime, and meropenem) and nacubactam are preferable candidates to treat pneumonia due to CRE and CPE.

Introduction: Staphylococci is the most commonly isolated bacteria in blood cultures (BC), and is mostly regarded as contamination. However, the clinical relevance and characteristics of CNS other than Staphylococcus epidermidis (Non-SE-CNS) is still unknown., Methods: For the purpose of clarifying the epidemiology and clinical significance of Non-Se-CNS infections, we retrospectively evaluated BC isolates of Non-Se-CNS at our institute from May 2013 to March 2017. Infections were defined as true bacteremia if (1) two or more positive BCs of the same species were present (or detection of the same species in another clinically relevant sample), (2) the patient had clinical symptoms as outlined in the Centers for Disease Control and Prevention's definition of primary blood stream infection 8 and the symptoms or markers of inflammation (e.g., fever, symptoms, white cell counts, C-reactive protein, or procalcitonin) were improved after pathogen-directed therapy (e.g. either antibiotic therapy and/or removal of the foreign body in the case of catheter-related blood stream infections suspected) and (3) without any other infection., Results: During the period, 279 patients with BC positive for Non Se-CNS were identified. 44 patients were excluded, either due to missing data or multiple pathogens in the same BC. Among the remaining 235 patients, 67 (29%) were categorized as true bacteremia (n = 43) or possible infections (n = 24). Resistance rate to methicillin among Non-SE-CNS is about 60%, which is lower than those among S. epidermidis of 78%., Conclusion: About 30% of Non-Se-CNS isolates were clinically relevant in our study. Antibiotic susceptibility of Non-SE-CNS is quite different than those of S. epidermidis., (Copyright © 2020. Published by Elsevier B.V.)

Introduction: The novel coronavirus disease (COVID-19) could cause a severe acute respiratory infectious disease, showing a high mortality rate of 12-45% among cases who required intensive care unit admission. COVID-19 pneumonia PATIENTS AND METHODS: For the purpose of identifying clinical manifestations and radiological findings of COVID-19 pneumonia, we reviewed all cases of COVID-19 pneumonia which were published by the homepage of the Japanese Association for Infectious Diseases from Feb 5 2020 until April 30 2020, including our cases. All patients were diagnosed based on positive results of the novel coronavirus-real-time RT-PCR with chest computed tomography (CT) findings., Results: A total of 92 patients were enrolled in this study. The median age was 66 years (range 16-92 years). For all, 50 (54%) were males. The most common underlying disease was hypertension in 32 (36%). Any comorbidity was seen in 60 (67%). The mortality rate was 4 (6%). In terms of clinical symptoms on an initial visit, fever and cough were confirmed in 66 (72%) and 37 (40%). Forty-three (47%) had no respiratory symptoms. As for radiological findings by chest CT scan, ground-glass opacities (GGO)s, peripheral distribution, bilateral lung involvements were seen in 88 (96%), 76 (83%) and 78 (85%), respectively., Conclusion: It is difficult to diagnose as COVID-19 pneumonia due to poor respiratory symptoms. Chest CT findings typically show GGO, peripheral and bilateral shadows. Patients should have chest CT performed if suspected for early diagnosis and therapeutic intervention, resulting in a favorable outcome and prevention of secondary nosocomial transmitted infection., Competing Interests: Declaration of competing interest All co-authors have none declared., (Copyright © 2020. Published by Elsevier B.V.)

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.)

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 (log 10 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 log 10  cfu/mL and 5.26 ± 1.50 log 10  cfu/mL, respectively. At human-simulated doses, lascufloxacin and levofloxacin showed high antimicrobial activities against not only S. pneumoniae (lascufloxacin: 1.88 ± 0.43 log 10  cfu/mL, p < 0.001; levofloxacin 4.30 ± 0.75 log 10  cfu/mL, p < 0.001), but also P. intermedia (lascufloxacin: 1.54 ± 0.57 log 10  cfu/mL, p < 0.001; levofloxacin: 2.79 ± 0.55 log 10  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., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: HM 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., and 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., and MIYARISAN Pharmaceutical Co., Ltd., (Copyright © 2021 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.)

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-β-lactam diazabicyclooctane β-lactamase inhibitor with in vitro activity against some Enterobacterales expressing classes of β-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 β-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 β-lactams and NAC administered in the murine thigh-infection model showed greater efficacy against CRE+/CPE+, CRE+/CPE-, and CRE-/CPE+ isolates harboring various β-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 β-lactams and NAC are potential candidates for the treatment of CRE and/or CPE infections., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

We report a case of prosthetic arthritis caused by Cardiobacterium valvarum, which has been exclusively reported to cause intravascular infections. A 81-year-old Japanese female complained prosthetic knee joint pain. Arthrocentesis cultured no pathogen, and surgical replacement of the implant surface was performed. Modified Levinthal medium culture and 16S rRNA sequencing has finally led to diagnosis of C. valvarum prosthetic knee arthritis without cardiac lesions. Fastidious bacteria such as C. valvarum can be candidate pathogens of orthopedic infections whose causative agents are sometimes unidentified. Further development of molecular diagnostics is expected, but also the importance of conventional methods should be noted., Competing Interests: Declaration of competing interest None of the authors have financial relationships with any commercial entity with an interest in the subject of this manuscript., (Copyright © 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Candidemia has emerged as an important nosocomial infection, with a mortality rate of 30-50%. It is the fourth most common nosocomial bloodstream infection (BSI) in the United States and the seventh most common nosocomial BSI in Europe and Japan. The aim of this study was to assess the performance of the Sequential Organ Failure Assessment (SOFA) score for determining the severity and prognosis of candidemia., Methods: We performed a retrospective study of patients admitted to hospital with candidemia between September 2014 and May 2018. The severity of candidemia was evaluated using the SOFA score and the Acute Physiology, Age, Chronic Health Evaluation II (APACHE II) score. Patients' underlying diseases were assessed by the Charlson Comorbidity Index (CCI)., Results: Of 70 patients enrolled, 41 (59%) were males, and 29 (41%) were females. Their median age was 73 years (range: 36-93 years). The most common infection site was catheter-related bloodstream infection (n=36, 51%).The 30-day, and in-hospital mortality rates were 36 and 43%, respectively. Univariate analysis showed that SOFA score ≥5, APACHE II score ≥13, initial antifungal treatment with echinocandin, albumin < 2.3, C-reactive protein > 6, disturbance of consciousness, and CCI ≥3 were related with 30-day mortality. Of these 7, multivariate analysis showed that the combination of SOFA score ≥5 and CCI ≥3 was the best independent prognostic indicator for 30-day and in-hospital mortality., Conclusions: The combined SOFA score and CCI was a better predictor of the 30-day mortality and in-hospital mortality than the APACHE II score alone.

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.)

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/μL (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., Competing Interests: Declaration of competing interest Mikamo H received Research funding from Sumitomo Dainippon Pharma Co., Ltd., ASAHIKASEI Pharma Co. Ltd., Astellas Pharma, MSD K·K., Shionogi & Co., Ltd., Taisho Toyama Pharmaceutical Co., Ltd., Daiichi-Sankyo, FUJIFILM Toyama Chemical Co., Ltd., Pfizer, MIYARISAN Pharmaceutical Co., Ltd., and Meiji Seika Pharma; Consulting fee/honorarium from MSD K·K., FUJIFILM Toyama Chemical Co., Ltd., Astellas Pharma, Daiichi-Sankyo, MSD K·K., MIYARISAN Pharmaceutical Co., Ltd., and Shionogi & Co., Ltd. None declared for other authors., (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: Presepsin (soluble CD14 subtype) is a novel biomarker of sepsis used for early diagnosis. Originally, CD14 is known as the pattern recognition receptor for the lipopolysaccharide (LPS)/LBP complexes, and the diagnostic value of this molecule for gram-positive bacteria, which contain less amount of LPS, is uncertain. To confirm its effectiveness in the diagnosis of bacteremia caused by gram positive bacteria, and to evaluate the interspecies difference of presepsin production against various bacterial strains, we conducted an in vitro assay to evaluate presepsin levels in response to five Gram negative and four Gram positive bacteria., Results: Whole blood was yielded from five healthy volunteers and co-cultured with bacterial strains at 37 °C for 4 h. Twenty seven clinical isolates of nine species (E. coli, K. pneumoniae, E. cloacae, P. aeruginosa, S. maltophilia, S. aureus, S. pyogenes, B. cereus, and C. striatum) derived from blood cultures of non-neutropenic bacteremia patients were used. Culture supernatants were harvested and presepsin levels were measured. The presepsin level in the gram-negative bacteria 273 (218-352) pg/mL was significantly higher than in the gram-positive bacteria 200 (143-275) pg/mL (p = 0.0002). The presepsin levels were significantly lower in C. striatum, in comparison to other bacteria, and S. pyogenes showed similar results. And the presepsin levels in P. aeruginosa were significantly lower compared to E. cloacae, K. pneumoniae, and S. aureus., Conclusions: Presepsin production can also be evoked by gram-positive bacteria, and interspecies differences of presepsin response may exist, which should be considered in the diagnosis of sepsis, especially in certain gram-positive bacteremia such as S. pyogenes or C. striatum.

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.)

Streptococcus pneumoniae is one of the major bacterial pathogens of community-acquired pneumonia. Immunochromatographic assay tests are used to detect pneumococcal capsular antigen. In many cases, They can be read visually. The Alere™ reader (Reader), which was developed in October 2018 by Alere Medical Co., Ltd. (currently, Abbott Diagnostics Medical Co., Ltd.) for interpreting BinaxNOW™ Streptococcus pneumoniae test (BinaxNOW™), quickly displays the results of the immunochromatographic tests, objectively and accurately, as it was launched for the purpose of streamlining laboratory workflow. The performance of the reader was evaluated by using urine samples from 100 patients, who were ordered pneumococcal urine antigen test from September 2018 to February 2019 at our hospital. Of the 100 samples, 14 were visually positive and 19 were reader positive. All visually positive samples generated reader positive result. Because 1 of the 5 cases which indicated a negative visual determination and positive reader determination was a sample with strong viscosity and turbidity, it was retested after centrifugation at 3,000×g for 10 min, resulting in negative reader determination. In 2 cases, S. pneumoniae were detected in sputum gram stains and culture tests. 5 discrepant samples were all visually and reader positive after concentration by centrifugal ultrafiltration. A questionnaire about visual interpretation was conducted among 31 individuals, by using urine from day 0 to day 4 collected from the patients whose test result was visually negative, reader positive and sputum culture positive at day 0. As a result, the number of operators who determined visually positive was 0 on day 0 (0%), 16 on day 1 (51.6%), 13 on day 2 (41.9%), 2 on day 3 (6.5%), and 0 on day 4 (0%). There were individual differences in ability to interpret low level positive result visually. On the other hand, reader can remove individual differences among operators from the interpretation of BinaxNOW™ and interpret positive result earlier than visual interpretation. Therefore reader was considered to be useful tool in clinical settings.

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/purpose: Acinetobacter is an aerobic, gram-negative coccobacillus, which causes nosocomial infections including bacteremia. Recent development of molecular techniques has made classification of the Acinetobacter genomospecies possible, but there are still only a few studies comparing clinical features of the subspecies. We investigated bacteremia caused by Acinetobacter, isolated subspecies, and compared clinical features for each group., Methods: A retrospective analysis of Acinetobacter bacteremia cases was made in a 900-bed hospital in Japan. In addition to conventional procedures, subspecies identification based on rpoB sequence was made, and comparison of clinical characteristics between each subspecies were analyzed., Results: We collected 35 cases (Acinetobacter baumannii 14, A. nosocomialis 12, Acinetobacter ursingii 6, and A. seifertii 3). All of the A. seifertii bacteremia cases were blood stream infection occurring in cerebrovascular disease patients, showing particularly higher incidence of shock (100%) and high Pitt bacteremia score (PBS) (6.33 ± 2.52) in comparison to A. baumannii (43% and 2.86 ± 2.25, respectively). Sequential Organ Failure Assessment (SOFA) score and the PBS were slightly higher in A. nosocomialis in comparison to A. baumannii, and the 7 day mortality rate was higher in A. nosocomialis (25%) than in A. baumannii (7%), though this difference was not found to be significant., Conclusions: A.seifertii, the recently defined novel species, showed distinctive clinical features of bacteremia. And, in contrast to previous studies, the severity of A. nosocomialis infection was not lower than that of A. baumannii, which might suggest the influence of local epidemiology. Further characterization of these subspecies should be continued., (Copyright © 2019. Published by Elsevier B.V.)

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.)