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Yoshiro Hadano,1 Kenta Ito,1 Jun Suzuki,1 Ichiro Kawamura,1 Hanako Kurai,1 Kiyofumi Ohkusu21Division of Infectious Diseases, Shizuoka Cancer Center, Shizuoka; 2Department of Microbiology, Graduate Medical School of Medicine, Gifu University, Gifu, JapanAbstract: Moraxella osloensis is a rare causative organism of infections in humans, with most cases reported in cancer patients. We report the case of a 67-year-old Japanese man with advanced cancer of the pancreatic head and multiple liver metastases who developed fever with chills. Blood culture was found to be positive for Gram-negative bacilli that were aerobic, oxidase-positive, and catalase-positive. M. osloensis was identified by 16 rRNA gene sequencing. Prompt control of the infection was achieved by treatment with cefepime for 14 days, without the need for removal of the central venous catheter.Keywords: Moraxella osloensis, central venous catheter, infection, cancer

Background: Prolonged installation of a nephrostomy tube causes colonization of various microorganisms within the lumen of the tube, leading to the development of nephrostomy tube-associated pyelonephritis (NTAP). Patients with malignancy, often necessitating long-term installation of a nephrostomy tube, are susceptible to NTAP. However, information regarding the characteristics of NTAP in this population is limited., Methods: We reviewed 43 NTAP cases of patients with malignancy in a cancer center and examined causative and non-causative microorganisms among those detected in urine culture. Causative microorganisms were defined as (1) those detected simultaneously in urine and blood cultures or (2) those detected in monomicrobial urine culture and to which physicians administered active antimicrobials for ≥5 days. Non-causative microorganisms were defined as those to which active antimicrobials were given for a total of <5 days., Results: Patients in 42 of the 43 NTAP cases recovered with antimicrobial therapy for ≥7 days. Causative microorganisms were identified in 25 cases, where Escherichia coli and Klebsiella pneumoniae were most frequent. All enterococci other than Enterococcus faecalis, Corynebacterium species, and Candida species other than Candida albicans and most of Stenotrophomonas maltophilia detected in urine culture were considered non-causative of NTAP., Conclusion: E. coli was a common organism causing NTAP of this population. Several microorganisms resistant to cephalosporin were non-causative of NTAP, for which administration of antimicrobials may be unnecessary even if detected in urine culture., Competing Interests: Declaration of competing interest None., (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.)

We report a case where the patient may have developed Graves' disease after COVID-19 infection, and where the COVID-19 vaccination may have exacerbated the condition, inducing the onset of a thyroid storm. Although any association between the vaccine and the onset of thyroid disease is impossible to demonstrate through a single case, the antecedent COVID-19 infection and COVID-19 messenger ribonucleic acid vaccination may have synergistically contributed to the development of Graves' disease followed by thyroid storm., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction Postoperative cholangitis (POC) after pancreaticoduodenectomy is a serious complication. However, the prognostic factors are unclear. We aimed to investigate the relationships between biliary lesions and prognosis in patients with cholangitis after pancreaticoduodenectomy. Methods We conducted a single-centered retrospective cohort study. The unit of analysis was hospital admissions. We extracted patients who underwent pancreaticoduodenectomy from 2010 to 2018, and have a record of hospitalization of cholangitis from January 2010 to October 2019. We defined the bile duct lesions as the presence of one of the following: biliary stent, intrahepatic bile duct dilatation, intrahepatic bile duct stones, or common bile duct stones on imaging studies. The primary outcome was the treatment failure of POC. We defined the failure as a composite outcome of death within 30 days of initiation of treatment, relapse during treatment, or recurrence of cholangitis. We used logistic regression analysis to examine the association between the presence of bile duct lesions and the occurrence of outcomes. Results Of 154 admissions included in the present study, 120 cases (77.9%) were with bile duct lesions. Bile duct lesions were associated with the treatment failure (crude odds ratio [OR] 2.56, 95% confidence intervals [CI] 1.08 to 6.32; adjusted OR 2.81, 95%CI 1.08 to 7.34). Conclusions Clinicians should follow the patient of POC with bile duct lesions on imaging carefully because of the high risk of treatment failure, especially for recurrence. Further studies are warranted to confirm our results., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Yamamoto et al.)

The clinical significance of enterococci in intra-abdominal infections, particularly those caused by multiple organisms, remains unclear. There are no definitive guidelines regarding the use of empiric therapy with antimicrobial agents targeting enterococci. In this study, we evaluated the impact of the initial antimicrobial therapy administration of anti-enterococcal agents on the treatment of intra-abdominal infections in patients with cancer in whom enterococci were isolated from ascitic fluid cultures. This retrospective study was conducted at Shizuoka Cancer Center between January 1, 2014, and December 31, 2020, on all adult patients with cancer with enterococci in their ascitic fluid cultures. The primary outcome was all-cause mortality, and the secondary outcomes were composite outcomes consisting of three components (mortality, recurrence, and treatment failure) and the risk factors associated with all-cause mortality and composite outcomes. In total, 103 patients were included: 61 received treatment covering enterococci, and 42 did not. The mortality rates did not differ significantly between the treated and untreated groups (treated: 8/61 [13.1%]; untreated: 5/42 [11.9%]; p = 1.00). Additionally, no significant difference was observed between the groups in terms of composite outcomes (treated group: 11/61 [18.0%]; untreated group: 9/42 [21.4%]; p = 0.80). Multivariate analysis showed that performance status (PS2-4; p < 0.0001) was an independent risk factor for mortality. The composite outcome was also significantly higher for PS2-4 (p = 0.007). Anti-enterococcal treatment was not associated with mortality or the composite outcome. In patients with cancer and intra-abdominal infections caused by enterococci, anti-enterococcal therapy was not associated with prognosis, whereas PS2 or higher was associated with prognosis. The results of this study suggest that the initial routine administration of anti-enterococcal agents for intra-abdominal infections may not be essential for all patients with cancer. To substantiate these findings, validation by a prospective randomized trial is warranted., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Akazawa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In vitro excystation of cysts of microscopically identified Chilomastix mesnili and Retortamonas sp. isolated from Japanese macaques and Retortamonas sp. isolated from small Indian mongooses could be induced using an established protocol for Giardia intestinalis and subsequently by culturing with H2S-rich Robinson's medium supplemented with Desulfovibrio desulfuricans. Excystation usually began 2 h after incubation in Robinson's medium. DNA was isolated from excysted flagellates after 4 h of incubation or from cultured excysted flagellates. Phylogenetic analysis based on their 18S rRNA genes revealed that two isolates of C. mesnili from Japanese macaques belonged to the same cluster as a C. mesnili isolate from humans, whereas a mammalian Retortamonas sp. isolate from a small Indian mongoose belonged to the same cluster as that of an amphibian Retortamonas spp. isolate from a 'poison arrow frog' [sequence identity to AF439347 (94.9%)]. These results suggest that the sequence homology of the 18S rRNA gene of the two C. mesnili isolates from Japanese macaques was similar to that of humans, in addition to the morphological similarity, and Retortamonas sp. infection of the amphibian type in the small Indian mongoose highlighted the possibility of the effect of host feeding habitats.

There is no clear consensus regarding the optimal isolation duration for immunocompromised patients with coronavirus disease 2019 (COVID-19). Therefore, we conducted a questionnaire survey at eight Japanese cancer centers to investigate the practices of infectious disease specialists regarding the duration of isolation for COVID-19 inpatients with cancer. For asymptomatic to severely ill COVID-19 inpatients without severe immunodeficiency, four centers reported at least 10 days of isolation without testing, and two reported at least 20 days. Two centers incorporated polymerase chain reaction (PCR) as a criterion for terminating the isolation of inpatients without severe immunodeficiency. For severely immunocompromised COVID-19 inpatients, at least 20 days of isolation were required in seven facilities, regardless of illness severity. Additionally, seven centers had implemented Ct or antigen quantification test values as criteria for de-isolating severely immunocompromised inpatients. No cases caused nosocomial outbreaks after isolation was terminated based on each facility's criteria for isolation termination. Thus, cancer patients required longer isolation periods than the general population in most facilities, and for those with severe immunodeficiency, the isolation periods were longer and more tightly controlled with tests., Competing Interests: Declaration of competing interest None., (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: The optimal perioperative antimicrobial agent for preventing surgical site infection (SSI) in pancreatoduodenectomy (PD) with preoperative biliary drainage (PBD) remains unclear., Methods: We retrospectively reviewed 288 patients who underwent PD after PBD between 2010 and 2020 at our institution. Patients were classified into two groups according to the perioperative antimicrobial agent used (cefazoline [CEZ] group [n = 108] and ceftriaxone [CTRX] group [n = 180]). The incidence of SSI, type of bacteria in intraoperative bile culture (IBC), and antimicrobial susceptibility to prophylactic antimicrobial agents were analyzed., Results: The incidence of incisional SSI was significantly lower in the CTRX group than in the CEZ group (18% vs. 31%, P = 0.021), whereas the incidence of organ/space SSI in the two groups did not differ to a statistically significant extent (35% vs. 44%, P = 0.133). Gram-negative rod (GNR) bacteria in the IBC showed better antimicrobial susceptibility in the CTRX group than in the CEZ group. In multivariate analysis, antimicrobial resistance due to GNR was a significant risk factor for incisional SSI (odds ratio, 3.50; P < 0.001)., Conclusions: CTRX had better antimicrobial coverage than CEZ for GNR cultured from intraoperative bile samples. In addition, CTRX provides better antimicrobial prophylaxis than CEZ against superficial SSI in patients with PD after PBD., Trial Registration Number: This study was not a clinical trial and had no registration numbers., (© 2023. The Author(s) under exclusive licence to Société Internationale de Chirurgie.)

Background: Clostridium perfringens sepsis has been reported to have a rapid onset and severe clinical outcome. We herein report a case of C. perfringens sepsis associated with massive intravascular hemolysis after left hepatic trisectionectomy for perihilar cholangiocarcinoma., Case Presentation: A 72-year-old woman underwent left hepatic trisectionectomy for perihilar cholangiocarcinoma. Her postoperative course was uneventful except for bile leakage. She was discharged on postoperative day (POD) 35. On POD 54, she was readmitted because of abdominal pain with a high fever. Although her vital signs were stable on arrival at the hospital, a laboratory examination showed a severe inflammatory reaction and hemolysis, and she had developed disseminated intravascular coagulation. Abdominal contrast-enhanced computed tomography showed a 70-mm irregular shape and low-density containing air in liver segment 6, which suggested a liver abscess. The abscess was immediately drained of pus containing air. The pus showed multiple Gram-positive bacilli, and two blood cultures showed Gram-positive bacilli and hemolysis. Empirical antibiotic therapy with vancomycin and meropenem was started because C. perfringens was detected from the preoperative bile culture. Four hours after arrival, tachypnea and decreased oxygen saturation were observed. Her general condition deteriorated rapidly with significant hypoglycemia, progressive acidosis, anemia, and thrombocytopenia. Despite rapid drainage and empiric therapy, she died six hours after her arrival. At autopsy, the abscess consisted of coagulation necrosis of liver cells with inflammatory cell infiltration, and clusters of Gram-positive large bacilli were observed in the necrotic debris. C. perfringens was detected in the drainage fluid and blood culture. She was diagnosed with a liver abscess and severe sepsis caused by C. perfringens and treated promptly, but the disease progressed rapidly and led to her death., Conclusions: Sepsis caused by C. perfringens can progress rapidly and lead to death in a few hours, so prompt treatment is needed. When patients who have undergone highly invasive hepatobiliary-pancreatic surgery show hemolysis and hepatic abscesses with gas, C. perfringens should be considered the most likely bacterium., (© 2023. The Author(s).)

Objective: We investigated longitudinal changes in circulating CD4 + and CD8 + T cells positive for programed cell death protein-1 (PD-1) and in other subsets of CD4 + T cells in untreated hyperthyroid patients with Graves' disease after treatment with methimazole (MMI)., Design and Patients: The study included 18 untreated hyperthyroid patients with Graves' disease and 18 age-matched controls. Before and after 12-week treatment with MMI, we used flow cytometry to measure circulating PD-1 +  D4 + and PD-1 + CD8+ T cells and subsets of CD4 + T cells in peripheral blood, as well as serum levels of chemokines related to T-helper type 1 (Th-1) and Th-2 cells., Results: At baseline, the percentage of CD4 + and CD8 + T cells expressing PD-1 was significantly higher in patients than in age-matched controls. Serum levels of chemokines related to Th-1 and Th-2 also were higher in patients. Twelve weeks after initiation of MMI, the percentage of CD4 + T cells expressing PD-1 was significantly lower than at baseline, but no such change was seen in CD8 + T cells. Furthermore, the percentage of Th-1 cells among CD4 + T cells and the serum levels of soluble CD26/dipeptidyl peptidase-4, a surface marker of Th-1 cells, also were significantly lower than at baseline., Conclusions: The expression of PD-1 on circulating CD4 + and CD8 + T cells is increased in hyperthyroid patients with active Graves' disease. MMI significantly decreases levels of circulating PD-1 +  CD4 + T cells, suggesting that PD-1 + T lymphocytes may be associated with the pathogenesis of Graves' disease., (© 2022 John Wiley & Sons Ltd.)

Antimicrobial resistance (AMR) is a threat to patient health. However, data to optimize antimicrobial use are limited. Furthermore, reducing antibiotic use raises concerns regarding patient safety. The effectiveness of antibiotics in reducing the prevalence of AMR is controversial. Researchers at the Japanese Red Cross Ishinomaki Hospital (JRCIH), the only tertiary care hospital in the medical zone, along with local medical and pharmacy associations and public health centers have been leading the AMR control program since 2018. The program involves lectures aimed at optimizing antimicrobial use, regular publication of surveillance data of drug-resistant strains at the JRCIH, and presentation of first-line treatments for community-acquired infections. The delivery of oral antimicrobial agents across the region in 2020 was 28.7% lower than that in 2013, with delivery of cephalosporins, quinolones, and macrolides decreasing by 34.8%, 46.8%, and 56.0%, respectively. Despite these reductions, there has been no associated increase in the number of patients with severe infectious diseases admitted to the JRCIH. The rates of representative drug-resistant bacterial strains, such as extended-spectrum beta-lactamase-producing Escherichia coli and methicillin-resistant Staphylococcus aureus, decreased by half. Herein, we demonstrated the potential of collaborative efforts to optimize antimicrobial agent use and reduce the AMR prevalence without compromising patient safety.

Aims: To investigate synergistic effects of liver fibrosis evaluated by FibroScan and sarcopenia on endothelial function and arterial stiffness in patients with type 2 diabetes., Methods: This cross-sectional study evaluated liver fibrosis (LF) and sarcopenia in 115 patients with type 2 diabetes. LF was assessed as the liver stiffness measurement (LSM) in transient elastography (FibroScan) and was defined as an LSM greater than or equal to 8.0 kPa. Sarcopenia was defined as a ratio of appendicula skeletal muscle mass to body mass index of<0.789 in men and<0.512 in women. Endothelial function was measured by reactive hyperemia index (RHI) with tonometry, and arterial stiffness was evaluated by the cardio-ankle vascular index (CAVI). Endothelial dysfunction was defined an RHI value below 1.67, while arterial stiffness was defined a CAVI value above 9.0. Patients were divided into four groups: no LF and no sarcopenia; LF but no sarcopenia; no LF but sarcopenia; and LF and sarcopenia. The composite of endothelial dysfunction of arterial stiffness was defined as an outcome., Results: In patients with LF, RHI was significantly lower and CAVI was significantly higher than in patients without LF. Furthermore, RHI was significantly lower in patients with sarcopenia than in those without it. Patients with both LF and sarcopenia had the lowest RHI and the highest CAVI and urinary albumin levels. Sarcopenia and HDL cholesterol were independent factor the composite of endothelial dysfunction and arterial stiffness., Conclusion: LF and sarcopenia are independently associated with endothelial dysfunction and arterial stiffness in patients with type 2 diabetes. Coexistence of LF and sarcopenia may synergistically lead to vascular damage and thus contribute to the high risk of cardiovascular disease in people with type 2 diabetes., Competing Interests: 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., (© 2022 The Author(s).)

Aim: To investigate acute effects of add-on therapy with the sodium glucose co-transporter 2 inhibitor tofogliflozin to dipeptidyl peptidase (DPP)-4 inhibitors on 24-hours glucose profile and glycaemic variability evaluated by continuous glucose monitoring (CGM) in patients with type 2 diabetes., Patients and Methods: We studied 17 patients with type 2 diabetes who were hospitalised for glycaemic control. CGM was performed for 7 consecutive days in the last week of hospitalization. Tofogliflozin 20 mg/d was started on day 4 after initiating CGM and was administered to 10 patients receiving DPP-4 inhibitors and 7 patients not receiving DPP-4 inhibitors. We compared several CGM parameters between day 2-3 (ie, before treatment with tofogliflozin) and day 5-6 (ie, after starting treatment with tofogliflozin)., Results: After starting treatment with tofogliflozin, mean 24-hours glucose and postprandial glucose after each meal were significantly decreased in both groups of patients. Time in range (ie, at a glucose level of 70-180 mg/dL) was significantly increased in both groups. The standard deviation of 24-hours glucose and mean amplitude of glycaemic excursions (MAGE), 2 indexes of glycaemic variability, were significantly decreased in patients receiving DPP-4 inhibitors but were unchanged in those not receiving these drugs., Conclusions: Add-on therapy with tofogliflozin to DPP-4 inhibitors acutely reduces 24-hours glucose levels and improves glycaemic variability in patients with type 2 diabetes., (© 2021 John Wiley & Sons Ltd.)

This is a case of pseudoaneurysm associated with lung abscess caused by Streptococcus intermedius . This infection can be fatal, as these bacteria can invade the vascular wall and induce lethal hemorrhage., Competing Interests: The authors have stated explicitly that there are no conflicts of interest in connection with this article., (© 2021 The Authors. Journal of General and Family Medicine published by John Wiley & Sons Australia, Ltd on behalf of Japan Primary Care Association.)

Background: Neisseria macacae was discovered in the oral cavity of monkeys in 1983. In humans, it has been isolated from the upper respiratory tract of neutropenic patients. However, only two cases of N. macacae bacteremia have been reported in a 65-year-old man with infective endocarditis and a 5-month-old child with fever and petechiae. There are no reports of infections in cancer patients. Here, we present two cases of N. macacae bacteremia in cancer patients., Case Presentation: In the first case, a 42-year-old woman who underwent ovarian cancer surgery presented with duodenal invasion associated with multiple lymph node metastasis. N. macacae was isolated from her blood culture and identified using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS). In the second case, a 69-year-old woman with a long-standing history of esophagogastric junction cancer presented with fever. She had stage IVB cancer with lung, bone, and multiple lymph node metastasis. The last chemotherapy was administered 5 weeks before N. macacae was detected using MALDI-TOF MS and nitrate test negative. In both cases, transthoracic echography showed no vegetation. Antibiotics were administered for 14 and 13 days in the first and second cases, respectively. In both cases, fever alleviated on day 4 of antibiotic administration. Both patients were discharged after their conditions improved., Conclusions: This, to our knowledge, is the first report of N. macacae bacteremia in cancer patients. Both patients, mucosal damage was observed in the upper gastrointestinal tract. Therefore, exclusion diagnosis suggested that bacteremia invasion was caused by mucosal rupture in both cases. Both cases responded well to treatment with β-lactam antibiotics and improved after 2 weeks. Modifying the treatment based on the source of the infection may shorten the treatment period. Therefore, further research on N. macacae bacteremia is necessary. Immunocompromised patients such as those with cancer are susceptible to mucosal damage by unusual bacterial species such as N. macacae despite not having contact with monkeys.

Background: Little is known about the impact of infectious disease (ID) consultations on the management of patients with cancer. This study aimed to describe the consultation services provided by ID specialists to all departments in a comprehensive cancer center in Japan., Methods: We conducted a retrospective review of ID consultations with adult patients at a comprehensive cancer center in Japan from April 2017 to March 2018., Results: During the study period, 776 patients with cancer had an ID consultation. Of these, 414 (53.4%) were hospital inpatients. Reasons for the ID consultation comprised clinical management (n = 481, 62.0%), immunization (n = 272, 35.1%), and infection control (n = 23, 3.0%). Of the 474 ID consultations for diagnostic purposes, the most frequent condition was fever or elevated inflammatory markers of unknown origin (n = 125, 26.4%). The most frequent diagnoses after the diagnostic ID consultation were hepatobiliary infections (n = 97, 22.4%), respiratory infections (n = 89, 20.618.8%), and intra-abdominal infections (n = 71, 16.4%). The commonest reasons for immunization consultations were to prevent seasonal influenza (n = 193, 71.0%) and post-splenectomy vaccination (n = 58, 21.3%). The commonest reasons for infection control consultations were suspected tuberculosis or contact with tuberculosis (n = 11, 47.8%) and herpes zoster infection (shingles) (n = 7, 30.4%)., Conclusions: ID specialists play an important role in the clinical management of patients with cancer. ID physicians who work in cancer centers need to be specialized in treating IDs, diagnosing the causes of fevers of unknown origin, and controlling infection.

In cancer patients, fungal diseases are rare but remains an important complication. Chemotherapy or surgery procedures are often delayed or postponed in patients with fungal disease which might lead to impaired overall survival. Candida, Aspergillus, Cryptococcus and Pneumocystis jirovecii have accounted for most of yeast and mold infections reported in cancer patients. We have to know each risk factor and clinical picture. Early diagnosis strategies improve cancer outcomes. Recently immune checkpoint inhibitors(ICIs)-anti-PD-1(nivolumab, pembrolizumab), anti-PD-L1(atezolizumab, avelumab), anti- CTLA-4(ipilimumab)-have improved outcomes for several malignancies. Use of these drugs is associated with immunerelated adverse effects, requirement for immunosuppressive therapy. Prolonged immunosuppressive therapies may increase fungal diseases.

Background: Recently, the spread of multidrug-resistant bacteria has become a global problem. Extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae (enterobacteria) is one example. The incidence of urinary tract infections caused by ESBL-producing enterobacteria has been increasing in some Japanese community settings. Currently, there is insufficient evidence on the effectiveness of oral antibiotics used for the treatment of pyelonephritis caused by ESBL-producing enterobacteria. We investigated the effectiveness of oral antibacterial agents against pyelonephritis caused by ESBL-producing Enterobacteriaceae ., Methods: The records of patients who had been treated for pyelonephritis caused by ESBL-producing enterobacteria with oral antibiotics between April 1, 2014, and March 31, 2019, were reviewed retrospectively to assess the effectiveness of oral antibiotic treatment., Results: A total of seven cases were identified, including 1 patient with a positive blood culture and one patient with a Pitt bacteremia score of four points, indicating that the infections were severe. The antibiotics used to treat pyelonephritis were amoxicillin-clavulanic acid (n = 3), minocycline (n = 1), levofloxacin (n = 3), and sulfamethoxazole-trimethoprim with amoxicillin-clavulanic acid (n = 1). None of the patients had recurrence of pyelonephritis in the 60 days following oral antibiotic treatment, and there were no deaths during the 60-day follow-up period., Conclusions: These antibiotics should be considered for oral treatment of pyelonephritis caused by ESBL-producing enterobacteria. However, as there is insufficient evidence available on the effectiveness of these antibiotics for the management of ESBL-producing enterobacterial infections, further large-scale prospective studies are needed., Competing Interests: The authors have stated explicitly that there are no conflicts of interest in connection with this article., (© 2020 The Authors. Journal of General and Family Medicine published by John Wiley & Sons Australia, Ltd on behalf of Japan Primary Care Association.)

Background: Carbapenem-resistant Enterobacteriaceae (CRE) are classified as carbapenemase-producing Enterobacteriaceae (CPE) and non-CPE; the majority of CPE in Japan produce IMP carbapenemase., Objectives: We evaluated the clinico-epidemiological and microbiological information and effects of IMP-type carbapenemase production in CRE., Methods: Patients with isolations of CRE (MICs of meropenem ≥2 mg/L, imipenem ≥2 mg/L or cefmetazole ≥64 mg/L) from August 2016 to March 2018 were included. Microbiological analyses and WGS were conducted and clinical parameters were compared between groups. Independent predictors for the isolation of CPE from patients were identified by logistic regression. For comparing clinical outcomes, a stabilized inverse probability weighting method was used to conduct propensity score-adjusted analysis., Results: Ninety isolates (27 CPE and 63 non-CPE) were collected from 88 patients (25 CPE and 63 non-CPE). All CPE tested positive for IMP carbapenemase. Antibiotic resistance (and the presence of resistance genes) was more frequent in the CPE group than in the non-CPE group. Independent predictors for CPE isolation were residence in a nursing home or long-term care facility, longer prior length of hospital stay (LOS), use of a urinary catheter and/or nasogastric tube, dependent functional status and exposure to carbapenem. Although in-hospital and 30 day mortality rates were similar between the two groups, LOS after CRE isolation was longer in the CPE group., Conclusions: IMP-CPE were associated with prolonged hospital stays and had different clinical and microbiological characteristics compared with non-CPE. Tailored approaches are necessary for the investigational and public health reporting, and clinical and infection prevention perspectives for IMP-CPE and non-CPE., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

An 81-year-old man with lung cancer with bone metastases, interstitial pneumonia, and emphysema, was hospitalized for pain control. He developed fever and chills during hospitalization. Physical examination revealed a fever of 39.1 °C, but there were no findings on history or physical examination to suggest the source of the infection. Gram-negative cocci were detected in the blood culture (Fig. 1) and in a Gram stained sputum smear (Figs. 3 and 4). Neisseria meningitis and Neisseria gonorrhoeae were ruled out based on history and an absence of suggestive symptoms. The cause of his fever was diagnosed as Moraxella catarrhalis bacteremic pneumonia based on the blood culture and the sputum smear results, and he was treated with intravenous ceftriaxone. This case illustrates the importance of Gram staining of sputum and blood culture. Moraxella catarrhalis should be considered in the differential diagnosis when gram-negative cocci are detected in the blood and the sputum., Competing Interests: None., (© 2020 The Authors.)

In Japan, hospitals' pharmaceutical affairs committees freely select the drugs to be purchased depending on the regulations of each hospital. This system poses a risk of the absence of essential drugs or an excess of similar drugs, and may promote inappropriate use of third-generation cephalosporins (3GCs) and quinolones. Against this backdrop, we researched availability of antibacterial agents in Japanese hospitals. We conducted a questionnaire-based study in eastern Shizuoka Prefecture, Japan. Questionnaires were sent to 33 hospitals that had established an interactive regional partnership on infection control. We analyzed the number of available oral cephalosporins, macrolides, and quinolones in each hospital, and the correlation between the number of total available antibacterial agents and the hospital scale and cephalexin availability. Thirty-one hospitals participated in this study. First-generation cephalosporin (1 GC) was available in only 22.5% of them. In all participating hospitals, 3GCs were available, with more than one 3 GC available in 74.2%. Quinolones were available in all hospitals, and more than one quinolone in 67.7%. The numbers of hospital beds and total available antibacterial agents were positively correlated and hospitals that owned cephalexin available also significantly more often owned other available antibacterial agents. 1 GC were available in only a few hospitals, while multiple 3GCs and quinolones were available in most. This situation may lead to excess use of 3GCs or quinolones in Japan. A low number of available drugs was associated with cephalexin unavailability. Outpatient antimicrobial stewardship may focus not only on the quality of medicine, but also on the prescribing environment., (Copyright © 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Clostridium bacteremia is a well-known cause of infection in patients with gastrointestinal lesions. However, the clinical characteristics of this infection in cancer patients are unclear. We retrospectively reviewed cases of blood cultures positive for Clostridium species between March 1, 2004 and May 30, 2018 at the Shizuoka Cancer Center Hospital. Medical records of 40 patients who met the study criteria were reviewed for age, gender, underlying disease, history of disease, blood culture results, laboratory test results, and radiographic data. The common sources of Clostridium species in these patients were hepatobiliary tract infection and liver abscess (13/40; 32.5%) and bacteremia/enteritis due to gastrointestinal tumor (13/40; 32.5%). All patients had malignancies, with the most common being colorectal cancer (n = 9) followed by pancreatic cancer (n = 8) and gastric cancer (n = 6). The most common species isolated was C. perfringens followed by C. ramnosum. Twenty-five patients (62.5%) had polymicrobial bacteremia with the following organisms isolated from concurrent blood cultures: Escherichia coli (n = 8) and Klebsiella spp. (n = 7). Of these bacteremia cases, 37 had digestive organ lesions such as gastrointestinal malignancy, peritoneal dissemination, or intestinal infiltration. Seventeen patients died, resulting in an overall mortality rate of 42.5% at 30 days. Common cases of Clostridium bacteremia were derived from gastrointestinal lesions, and because Clostridium bacteremia is observed regardless of species, it should be considered necessary to examine gastrointestinal lesions., (Copyright © 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Although hypervirulent Klebsiella pneumoniae (hvKp) has been associated with severe community-acquired infections that occur among relatively healthy individuals, information about hvKp infections in health care settings remains limited. Here, we systematically analyzed the clinical and molecular characteristics of K. pneumoniae isolates causing bloodstream infections in a cross-sectional study. Clinical characteristics of K. pneumoniae bloodstream infections from hospitals across Japan were analyzed by a review of the medical records. Whole-genome sequencing of the causative isolates was performed. Bacterial species were confirmed and hvKp were identified using whole-genome sequencing data. Clinical characteristics of hvKp infections were compared with those of non-hvKp infections by bivariate analyses. Of 140 cases of K. pneumoniae bloodstream infections, 26 cases (18.6%) were caused by various clones of hvKp defined by the carriage of cardinal virulence genes. Molecular identification revealed that 24 (17.1%) and 14 (10%) cases were caused by Klebsiella variicola and Klebsiella quasipneumoniae , respectively. Patients with hvKp infections had higher proportions of diabetes mellitus (risk ratio [RR], 1.75; 95% confidence interval [CI], 1.05 to 2.94), and their infections had significantly higher propensity to involve pneumonia (RR, 5.85; 95% CI, 1.39 to 24.6), liver abscess (RR, 5.85; 95% CI, 1.39 to 24.6), and disseminated infections (RR, 6.58; 95% CI, 1.16 to 37.4) than infections by other isolates. More than one-half of hvKp infections were health care associated or hospital acquired, and a probable event of health care-associated transmission of hvKp was documented. hvKp isolates, which are significantly associated with severe and disseminated infections, are frequently involved in health care-associated and hospital-acquired infections in Japan., (Copyright © 2019 American Society for Microbiology.)

Background: The aim of the present study was to investigate whether the incidence of surgical site infection after pancreatoduodenectomy decreased after changing the prophylactic antibiotic to a third-generation cephalosporin in patients with unknown preoperative bile culture results after biliary drainage., Methods: In a retrospective study of 138 pancreatoduodenectomy patients who underwent endoscopic biliary stenting and for whom recent preoperative bile culture results were unavailable, cefazolin sodium hydrate was administered as perioperative prophylactic antibiotic therapy from 2010 to 2014 (n = 69); whereas ceftriaxone was administered from 2014 to 2017 (n = 69) based on the results of institutional culture surveillance. The incidence of surgical site infection was compared between the two groups and the risk factor of surgical site infection was also evaluated., Results: The incidence of overall surgical site infection in the ceftriaxone group was significantly lower than that in the cefazolin sodium hydrate group for both Clavien-Dindo grade ≥II (28% versus 52%, P = .005) and Clavien-Dindo grade ≥IIIa (20% vs 41%, P = .016). A multivariate analysis revealed that the prophylactic administration of cefazolin sodium hydrate was associated with a higher incidence of overall surgical site infection in both Clavien-Dindo grade ≥II and Clavien-Dindo grade ≥IIIa (odds ratio 2.56, P = .019; odds ratio 3.03, P = .020, respectively). In the cefazolin sodium hydrate group, most of the patients with positive perioperative cultures had Enterobacteriaceae, which were intrinsically resistant to cefazolin sodium hydrate, and most were susceptible to ceftriaxone., Conclusion: The prophylactic administration of third-generation cephalosporin reduced the incidence of surgical site infection after pancreatoduodenectomy in patients who underwent preoperative endoscopic biliary stenting., (Copyright © 2018. Published by Elsevier Inc.)

The most common complication in cancer patients is catheter-related bloodstream infection (CRBSI), of which Staphylococcus aureus is a common pathogen. Although S. aureus CRBSI patients are recommended for prolonged intravenous therapy, this is often not feasible. We assessed the effectiveness of switching from intravenous to oral antimicrobial therapy in cancer patients with CRBSI due to methicillin-sensitive S. aureus (MSSA). We conducted a retrospective observational study of 60 patients at one tertiary-care cancer center between April 2005 and March 2016. Patients who received effective intravenous (IV) antibiotics for at least 10 days (IV group) were compared to the IV group of patients who had switched to effective oral (PO) antibiotics after IV treatment for at least 10 days (IV + PO group). The primary endpoint was all-cause mortality within 90 days. Univariate and propensity score-adjusted multivariate logistic regression analyses using variables likely to influence the outcomes were performed. Of the 60 patients, 32 (53.3%) and 28 (46.7%) were in the IV and IV + PO groups, respectively. The median antibiotic treatment durations in the IV and IV + PO groups were 17 (13-31) and 33 (26-52) days, respectively (p<0.001). The 90-day mortality in the IV and IV + PO groups were 53.1% (17/32) and 10.7% (3/28), respectively (p = 0.001). Univariate logistic regression model showed that the odds ratios of oral switch therapy for 90-day mortality was 0.106 (95% confidence interval [CI]: 0.027-0.423; p = 0.001). The propensity score-adjusted multivariate logistic regression model estimated the odds ratios of oral switched therapy for 90-day mortality as 0.377 (95% CI: 0.037-3.884; p = 0.413). Our results suggest that oral switch therapy was not associated with mortality in cancer patients with CRBSI due to MSSA compared with no oral switch therapy. Oral switch therapy may be a reasonable option for patients with CRBSI due to MSSA., Competing Interests: An author of this manuscript has the following competing interests: YN received support in the form of salary from Satista Co., Ltd and has performed data analysis that was supported by fees from NI. NI, YH, SS, MM, and HK declare no conflict of interest and have no affiliation with or financial involvement in any organization or entity with a direct financial interest in the subject matter or materials discussed in this manuscript. The authors have no other conflicts of interest that are directly relevant to the content of this manuscript and does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials.

Background: Coagulase-negative staphylococci (CoNS) are the most common contaminants of blood cultures, however, we sometimes have difficulties in determining their clinical significance. It is still controversial that there is a significant difference between the contamination group and the true bacteraemia group in the time to positivity (TTP) of blood cultures. We validated the relationship between a TTP and the presence of CoNS bacteraemia in cancer patients by using an objective, non-judgmental definition for CoNS contamination., Methods: We retrospectively reviewed 175 sets of blood cultures drawn from 95 patients that yielded CoNS from October 2011 to March 2013. We considered as contamination if an isolate of CoNS was identified in one out of multiple sets of blood cultures. We investigated the TTP, the threshold values and corresponding likelihood ratios to distinguish CoNS bacteraemia from contamination., Results: The median TTP in CoNS bacteraemia group was significantly shorter than that in contamination group (14 h 45 min and 20 h 31 min, respectively, p = .0157). A TTP of ≤16 h had a specificity of 83% for predicting CoNS bacteraemia, and that of >20 h had a sensitivity of 86% for predicting CoNS contamination., Conclusions: We validated that the median TTP in CoNS bacteraemia group was significantly shorter than that in their contamination group, and that a TTP of ≤16 h was associated with CoNS bacteraemia, while that of >20 h was associated with CoNS contamination, if evaluated with an objective, non-judgmental definition for CoNS contamination.

We report a case of Pasteurella multocida pneumonia. A 71-year old Japanese woman with pulmonary infiltration of the lingual division of left lung 3 years before, which was thought to be caused by non-tuberculous mycobacteriosis (NTM) was referred to our clinic on account of chronic cough, sputum, dyspnea, and left pulmonary infiltration. Although she owned over 10 cats, no bites or scratches were mentioned. Pasteurella multocida was confirmed by the culture of the patient's bronchoalveolar lavage (BAL) fluid. NTM infection was ruled out by acid-fast bacillus smears, cultures, and polymerase chain reaction of three sputum specimens and BAL fluid. The infection route in this case was considered to have resulted from inhalation of contaminated aerosols or contact with her cats. Close contact with animals should be avoided, particularly for patients with chronic pulmonary diseases, as it is a risk factor for pneumonia due to Pasteurella multocida .

Patients with malignant brain tumors are possibly at increased risk for surgical site infections (SSIs) considering the various medical situations associated with the disease. However, the actual rate of SSI after malignant brain tumor resection has not been well established, despite the potential impact of SSI on patient outcome. To investigate the incidence of SSI following malignant brain tumor surgery, we performed a retrospective study in 3 neurosurgical units. Subsequently, aiming at the reduction of incidence of SSI, we performed a prospective study using a care bundle technique in the same units. The SSI incidence in the retrospective (n = 161) and prospective studies (n = 68) were 4.3% and 4.4%, respectively, similar to the previously reports on general craniotomies. A care bundle does not appear to enhance prevention of SSI. However, future, large studies with a new care bundle should be planned based on a zero tolerance policy.

Staphylococcus lugdunensis (SL) is a bacterium with a highly pathogenicity than most other coagulase-negative Staphylococcus spp. (CoNS). In Japan, data on this pathogen are sparse, and the current prevalence of SL bacteremia is unknown. Therefore, we investigated the prevalence of SL in blood culture specimens in a prospective multicenter study across 5 facilities. A total of 3,284 patients had positive blood cultures, and 2,478 patients had bacteremia. Among the patients with bacteremia, 7 patients (0.28%) had SL bacteremia. A total of 281 patients had CoNS bacteremia, with SL accounting for 2.49% of these cases. Of the 7 patients with SL bacteremia, 1 patient (14.3%) had infective endocarditis, and 1 patient (14.3%) died within 30 days. In this study, SL resulted in the development of bacteremia in select patients. Clinicians in Japan should be aware of the prevalence of SL and the complications of SL bacteremia.

Herein, we report a case of Paragonimus westermani infection, which required differentiation from recurrent lung cancer. A 66-year old Japanese man with a history of lung cancer who had undergone a lobectomy was referred to our clinic for treatment of cough, sputum, dyspnea, and a right pulmonary nodule. He had previously eaten seafood he visited China. P. westermani infection was confirmed by the presence of antibody against P. westermani antigen in the patient's serum and eggs in his sputum. Eventually, molecular identification by PCR-restriction fragment length polymorphism analysis and sequencing confirmed that the patient was infected with triploid forms of P. westermani., (Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Although a high incidence of bacteremia after esophageal endoscopic procedures has been reported, the incidence of bacteremia associated with esophageal endoscopic submucosal dissection (ESD) remains unknown. Therefore, we investigated the incidence of bacteremia associated with esophageal ESD., Methods: From April 2013 to March 2014, patients who underwent esophageal ESD were enrolled prospectively. Two sets of blood cultures were collected from patients at the following time points: (1) immediately after ESD; (2) the next morning; and (3) when fever ≥38 °C was present after ESD., Results: A total of 424 blood culture sets were collected from 101 patients. Six patients had positive blood cultures immediately after ESD (4 %, 7/202 sets). Another patient had a positive blood culture the next morning (0.5 %, 1/202 sets). Ten patients (10 %) developed a post-ESD fever ≥38 °C, and blood cultures from these patients were all negative (0/20 sets). The seven patients with positive blood cultures had no post-ESD fever or infectious symptoms. Growth of Bacteroides thetaiotaomicron was only observed in one patient (1 %) with positive blood cultures immediately after ESD, and this patient was diagnosed with transient bacteremia. The other six patients were considered to have contaminants in their blood cultures. Thus, the incidence of bacteremia after esophageal ESD was 1 % [95 % confidence interval (CI) 0-5 %]. No patient had infectious symptoms, and none required antibiotics after ESD., Conclusions: The incidence of bacteremia after esophageal ESD was low and post-ESD fever was not associated with bacteremia. We conclude that use of routine prophylactic antibiotics to patients undergoing esophageal ESD is unnecessary., Clinical Trial Registry Number: UMIN000012908.

Although Streptococcus pneumoniae is an important pathogen of humans, pneumococcal cholangitis is rare because of the rapid autolysis of S. pneumoniae. The aim of this case series was to review patients with bile cultures positive for S. pneumoniae. This study was a single center retrospective case series review of patients with S. pneumoniae in their bile at a tertiary-care cancer center between September 2002 and August 2015. Subjects consisted of all patients in whom S. pneumoniae was isolated in their bile during the study period. Bile specimens for culture were obtained from biliary drainage procedures such as endoscopic retrograde biliary drainage, endoscopic nasobiliary drainage, and percutaneous transhepatic biliary drainage. There were 20 patients with bile cultures positive for S. pneumoniae during the study period. All patients presented with extrahepatic obstructive jaundice due to hepatopancreatobiliary tumors. Nineteen of 20 patients underwent the placement of plastic intrabiliary tubes. The mean time between the first-time drainage and the positive culture was 26 days (range 0-313 days). Although 12 of 20 patients met our definition of cholangitis, 5 were clinically treated with antibiotics based on a physician's assessment of whether there was a true infection. The present study is the largest case series of patients with S. pneumoniae in their bile. Based on our findings, the isolation of S. pneumoniae from bile may be attributed to the placement of biliary drainage devices., (Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Helicobacter fennelliae is a gram-negative, spiral bacillus that appears as thin-spread colonies on sheep blood agar and is similar to Helicobacter cinaedi. H fennelliae is diagnosed by genetic testing, which is not readily available in all laboratories. Therefore, H fennelliae bacteremia has only been reported sporadically, and little is known about its clinical characteristics.We describe 3 cases of H fennelliae bacteremia with gastrointestinal symptoms, including nausea, vomiting, and diarrhea. Isolates could be differentiated from H cinaedi by biochemical reaction testing, including nitrate reduction and alkaline phosphatase hydrolysis.We retrospectively reviewed 24 cases of H fennelliae bacteremia reported in the literature. Most of the patients had immunosuppressive backgrounds, including solid tumors, hematological malignancies, and autoimmune diseases. Although gastrointestinal symptoms were common, cellulitis was not often observed in patients with H fennelliae bacteremia.Clinicians should bear in mind that H fennelliae may be a differential diagnosis in patients with gastrointestinal manifestations and gram-negative, spiral bacilli. In addition, biochemical reactions, such as nitrate reduction and alkaline phosphatase hydrolysis, are useful in differentiating H fennelliae from H cinaedi.