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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.

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

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.

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

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.

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.

Objective American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines suggest that linezolid (LZD) is preferred over vancomycin (VCM) for treating methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. We conducted a systematic review and comparative meta-analysis to compare VCM and LZD efficacy against proven MRSA pneumonia. Methods We searched EMBASE, CINAHL, Cochrane Central Register of Controlled Trials (CENTRAL), and PubMed up to November 2019. The outcomes of the meta-analysis were mortality, clinical cure, microbiological evaluation, and adverse events. Results Seven randomized controlled trials (RCTs) with a total of 1239 patients and eight retrospective cohort or case–control studies (CSs) with a total 6125 patients were identified. Clinical cure and microbiological eradication rates were significantly increased in patients treated with LZD in RCTs (clinical cure: risk ratio (RR) = 0.81, 95% confidential interval (CI) = 0.71–0.92; microbiological eradication: RR = 0.71, 95% CI = 0.62–0.81) and CSs (clinical cure: odds ratio (OR) = 0.35, 95% CI = 0.18–0.69). However, mortality was comparable between patients treated with VCM and LZD in RCTs (RR = 1.08, 95% CI = 0.88–1.32) and CSs (OR = 1.20, 95% CI = 0.94–1.53). Likewise, there was no significant difference in adverse events between VCM and LZD in CSs (thrombocytopenia: OR = 0.95, 95% CI = 0.50–1.82; nephrotoxicity: OR = 1.72, 95% CI = 0.85–3.45). Conclusions According to our meta-analysis of RCTs and CSs conducted worldwide, we found robust evidence to corroborate the IDSA guidelines for the treatment of proven MRSA pneumonia.

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 ⊿log10 cfu/mL, p 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.

Linezolid has been the common antimicrobial treatment for Gram-positive infection even in neonates and infants. Major adverse events associated with linezolid treatment is cytopenia. However, there were few reports about the relationship between cytopenia and gestational age. Primary objective of this study was to compare the relationship between cytopenia in infants and neonates treated with linezolid therapy and gestational age.In total, 44 patients were divided into two groups depend on their gestational age [180 days; low gestational age group (20 patients);180 days group; high gestational age group (24 patients)]. All patients treated with linezolid from April 2014 to March 2018 at NICU or GCU of Aichi Medical University Hospital. Investigation items were as follows; sex, age, weight, duration of treatment, Apgar score, laboratory data, rate of patients with blood transfusion, concomitant medications, hematologic abnormalities during linezolid treatment.The incidence of overall cytopenia in low gestational age group was significantly higher than high gestational age group (65.0 % vs. 25.0 %; p0.05). Of note, the incidence of thrombocytopenia in low gestational age group showed significantly higher than high gestational age group (45.0% vs. 8.3%, p 0.05). Then, the proportion of patients occurred thrombocytopenia who received linezolid 10 mg/kg every 8 h were higher than 10 mg/kg every 12 h in both groups.In cases linezolid is administered three times a day should be more carefully of thrombocytopenia in patients with gestational days less than 180 days.

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.

We herein report the findings of the Japan Postoperative Infectious Complication Survey in 2015 (JPICS'15), which evaluated the rate of post-operative infections and colonization due to antimicrobial-resistant (AMR) bacteria after digestive tract surgery. This survey by the Japan Society of Surgical Infection included patients undergoing digestive tract surgery at 28 centers between September 2015 and March 2016. Data included patient background characteristics, type of surgery, contamination status, and type of post-operative infections, including surgical site infections (SSIs), remote infections (RIs), and colonization. During the study period, 7,565 surgeries (of 896 types) were performed; among them, 905 cases demonstrated bacteria after digestive tract surgery. The survey revealed that post-operative infections or colonization by AMR bacteria occurred in 0.9% of the patient cohort, constituting 7.5% of post-operative infections, including 5.6% of SSIs and 1.8% of RIs. Extended-spectrum β-lactamase-producing Enterobacteriaceae and methicillin-resistant Staphylococcus aureus were the predominant AMR bacteria isolated from patients after digestive tract surgery. Patients infected with AMR bacteria had a poor prognosis. Our results reveal that 7.5% of the post-operative infections were due to AMR bacteria, indicating the need for antibacterial coverage against AMR bacteria in patients with critical post-operative infections.

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.

Community-acquired pneumonia (CAP) can involve mixed-species bacterial infection. However, few studies have investigated antimicrobial efficacy in the treatment of mixed species infections. This study aimed to compare the in vivo antimicrobial activity of garenoxacin (GRNX) and levofloxacin (LVFX) against Streptococcus pneumoniae and Parvimonas micra in a murine model of mixed species bacterial pneumonia. S. pneumoniae D-6888 and P. micra No. 242 were used in this study. Antimicrobial activity toward each isolate was calculated as the change in bacterial count in the lungs (Δlog10 CFU/mL) of mice after 24 h of treatment compared with the count in pretreated animals (0 h). The MICs of GRNX and LVFX against S. pneumoniae D-6888 were 0.06 and 0.5 mg/L and the MICs against P. micra No. 242 were 0.03 and 0.12 mg/L, respectively. In a murine pneumonia mixed-infection model, GRNX showed significantly higher in vivo antimicrobial activity against S. pneumoniae than LVFX (GRNX; －2.02 ± 0.99 log10 CFU/mL vs. LVFX; －0.97 ± 0.61 log10 CFU/mL, p = 0.0188). GRNX displayed about 2-fold more potent activity against P. micra than LVFX (GRNX; －1.12 ± 0.56 log10 CFU/mL vs. LVFX; －0.61 ± 0.43 log10 CFU/mL, p = 0.1029). These results suggest that GRNX is preferable for the treatment of mixed species bacterial CAP.

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

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 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.

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

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.

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.

There are limited data of amikacin pharmacokinetics (PK) in the elderly population. Hence, we aimed to describe the population PK of amikacin in elderly patients (&gt, 70 years old) and to establish optimized initial dosing regimens. We simulated individual maximum concentrations in plasma (Cmax) and minimal concentrations (Cmin) for several dosing regimens (200&ndash, 2000 mg every 24, 48, and 72 h) for patients with creatinine clearance (CCr) of 10&ndash, 90 mL/min and analyzed efficacy (Cmax/minimal inhibitory concentration (MIC) &ge, 8) for MICs of 4, 8, and 16 mg/L and safety (Cmin &lt, 4 mg/L). A one-compartment model best described the data. CCr was the only covariate associated with amikacin clearance. The population PK parameter estimates were 2.25 L/h for clearance and 18.0 L for volume of distribution. Dosing simulations recommended the dosing regimens (1800 mg) with dosing intervals ranging 48&ndash, 72 h for patients with CCr of 40&ndash, 90 mL/min based on achievement of both efficacy for the MIC of 8 mg/L and safety. None of the dosing regimens achieved the targets for an MIC of 16 mg/L. We recommend the initial dosing regimen using a nomogram based on CCr for an MIC of &le, 8 mg/L in elderly patients with CCr of 40&ndash, 90 mL/min.

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.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.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%.Serum-PCT could be a useful diagnostic marker for differentiating diagnosis of NF from cellulitis.

Metabolites are thought as the end products in cellular regulatory processes and their levels show the strongest relationships with the phenotype. Previously, we showed that the administration of Clostridium butyricum MIYAIRI 588 (CBM 588) upregulated protectin D1, an anti-inflammatory lipid metabolite, in colon tissue under antibiotic therapy. However, how CBM 588 induces protectin D1 expression and whether the metabolite has anti-inflammatory effects on antibiotic-induced inflammation are unclear. Therefore, here, we evaluated the effect of CBM 588 on lipid metabolism and protectin D1 in gut protection from antibiotic-induced intestinal disorders. In the CBM 588 treatment group, expression levels of genes encoding lipid receptors related to the conversion of DHA to protectin D1, such as polyunsaturated fatty acid (PUFA) receptors, G-protein coupled receptor 120 (GPR120), and 15-lipoxygenase (LOX), were increased in colon tissue. CD4+ cells producing interleukin (IL)-4, the main component of T helper type 2 (Th2) cells that can activate 15-LOX, also increased in CBM 588-treated groups even after clindamycin co-administration. In addition, similar to CBM 588, exogenously administered protectin D1 reduced inflammatory cytokines, while IL-10 and TGF-β1, works as anti-inflammatory cytokines, were increased. Our data revealed that CBM 588 activated 15-LOX to enhance protectin D1 production by increasing IL-4-producing CD4+ cell population in the intestinal tract. Additionally, CBM 588-induced protectin D1 clearly upregulated IL-10-producing CD4+ cells to control antibiotic-induced gut inflammation. We provide new insights into CBM 588-mediated lipid metabolism induction for the treatment of gut inflammatory diseases.

Background Only a single meta-analysis has reported the clinical benefit of fluoroquinolones (FQs) for Legionella pneumonia; however, there is no robust data available to confirm this result, based on current guidelines. Methods We performed a systematic review and meta-analysis comparing FQs with macrolides (MCs) on their efficacy and safety in Legionella pneumonia, using studies published until January 2020. The outcomes included mortality (overall; 30-day), clinical cure, time to apyrexia, length of hospital stay, and adverse events. Results Five RCTs and twelve retrospective studies were identified. Clinical cure was comparable between the treatment groups (risk rate (RR) 1.07, 95% confidential interval (CI) 0.86–1.31). Mortality was significantly higher for MCs than for FQs (overall, odd rate (OR) 0.59, 95% CI 0.35–0.98; 30-day, OR 0.41, 95% CI 0.20–0.85). FQs significantly reduced the length of hospital stay, compared to MCs (mean difference −3.58, 95% CI -5.48–1.69). Other outcomes were not significantly different between the treatment groups (time to apyrexia; mean difference −1.83, 95% CI -5.15–1.5, adverse events; OR 0.61, 95% CI 0.33–1.15). In subgroup analyses, levofloxacin significantly reduced the length of hospital stay over two specific MCs (azithromycin and clarithromycin) (mean difference −3.03, 95% CI -5.33–0.72), whereas mortality was not significantly different between the treatment groups (overall, OR 0.49, 95% CI 0.19–1.24; 30-day, OR 0.38, 95% CI 0.13–1.13). Conclusions FQs exhibited superior effects in terms of mortality and length of hospital stay in Legionella pneumonia. These results support current guidelines recommending FQs for the treatment of Legionella pneumonia.

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.

Summary Clostridium butyricum MIYAIRI 588 (CBM 588) is a probiotic bacterium that has previously been used to prevent antibiotic-associated diarrhea. However, the underlying mechanism by which CBM 588 protects the gut epithelial barrier remains unclear. Here, we show that CBM 588 increased the abundance of Bifidobacterium, Lactobacillus, and Lactococcus species in the gut microbiome and also enhanced the intestinal barrier function of mice with antibiotic-induced dysbiosis. Additionally, CBM 588 significantly promoted the expansion of IL-17A-producing γδT cells and IL-17A-producing CD4 cells in the colonic lamina propria (cLP), which was closely associated with changes in the intestinal microbial composition. Additionally, CBM 588 plays an important role in controlling antibiotic-induced gut inflammation through upregulation of anti-inflammatory lipid metabolites such as palmitoleic acid, 15d-prostaglandin J2, and protectin D1. This study reveals a previously unrecognized mechanism of CBM 588 and provides new insights into gut epithelial barrier protection with probiotics under conditions of antibiotic-induced dysbiosis., Graphical Abstract, Highlights • CBM 588 increases the abundance of Bifidobacterium, Lactobacillus, and Lactococcus • Microbiota-driven TGF-β1 controls the differentiation of lymphocytes to γδT cells • CBM 588 promotes the expansion of IL-17A-producing γδT cells and CD4 cells • CBM 588 upregulates anti-inflammatory lipid metabolites, Microbiome; Clinical Microbiology

Background Clostridium butyricum MIYAIRI 588 (CBM 588) is a probiotic bacterium that is used as an anti-diarrheal medicine in Japan. However, the impact of this probiotic on the gut microbiome has not been fully elucidated, especially, when used with antimicrobials. Material and methods In an in vivo study, CBM 588 monotherapy, clindamycin monotherapy, CBM 588 and clindamycin (combination therapy), or normal saline (control) was orally administered to mice for 4 days, and fecal samples were collected for 18 days to enumerate C. butyricum. We also extracted DNA from these fecal samples for metagenomics analysis by amplification of the V3-V4 region of the bacterial 16S rRNA gene and MiSeq Illumina sequencing. In addition, the concentrations of some short chain fatty acids were assessed in the fecal samples. A histological analysis was also conducted. Results On day 4 (the last treatment day), there was no difference in the total counts of C. butyricum between the CBM 588 monotherapy and combination therapy groups (5.21 ± 0.78 vs. 5.13 ± 0.45 log10 cfu/g, p = 0.86). Clindamycin treatment resulted in dramatic increases in the phylum Firmicutes, especially Enterobacteriaceae, Clostridiaceae, Lactobacillus, and Enterococcus, compared with the other groups during the treatment period. CBM 588 treatment modified the bacterial community composition at lower phylogenetic levels. Some bacterial taxa, such as Bifidobacterium, Coprococcus, and Bacteroides, were significantly increased in the combination therapy group when compared with the other groups. In the metabolic analysis, CBM 588 enhanced lactic acid production. It also enhanced the efficiency of lactic acid use for the production of butyric acid. Only the clindamycin monotherapy group showed abnormal colon tissue, with superficial epithelial necrosis and the presence of inflammatory cells. Conclusion CBM 588 treatment modulated the gut microbiota composition under dysbiosis due to the use of an antimicrobial with strong activity against anaerobes and significantly reduced epithelial damage.

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

The Japanese Respiratory Society newly updated the prognostic guidelines for pneumonia in 2017. Quick Sequential Organ Failure Assessment (qSOFA) and Sequential Organ Failure Assessment (SOFA) score are used to evaluate the severity of pneumonia and to select the therapy for pneumonia. This is a retrospective study at Aichi Medical University hospital from January to December of 2016 to investigate the accuracy and usefulness of qSOFA and SOFA score in evaluating the severity and prognosis of healthcare-associated pneumonia (HCAP). A total of 81 HCAP patients were enrolled in this study. Both the 30-day and in-hospital mortality were 7.5% (6/81). qSOFA≧2 was in 33/78 patients (42%) and

Objective From November 24 to December 9, 2013, an outbreak of the influenza (flu) A (H3) virus occurred in a tertiary-care university hospital (1,014 beds). We herein report the prophylactic effect of anti-flu agents for controlling the flu outbreak. Methods We administered pre- or post-exposure prophylaxis with anti-flu agents in flu outbreak. To test the effectiveness of prophylaxis in a flu outbreak, we used the posterior mean of the reproductive value during the pre- and post-intervention period. We also simulated the probability distribution of new flu cases. We performed an analysis to quantify the strength of the intervention effect. Results A total of 97 people were diagnosed with flu before the intervention, and 7 were diagnosed after the intervention. A molecular analysis of the flu virus revealed that this outbreak was due to the flu A (H3) virus. A total of 3,702 people received prophylaxis. There was a significant reduction in the reproductive value from 1.89 [95% confidence interval (CI), 1.59 to 2.24] to 0.65 (95% CI, 0.02 to 1.00) after the intervention (p

Introduction Solithromycin is a novel fluoroketolide developed to treat pneumonia. But, few studies evaluating its antimicrobial activity against S. pneumoniae in a mixed-infection model with anaerobes are available, while community-acquired pneumonia can involve mixed-infection of Streptococcus pneumoniae and anaerobic bacteria. This study evaluated the antimicrobial activity of solithromycin against macrolide-resistant S. pneumoniae and anaerobic bacteria with a murine pneumonia mixed-infection model. Material and methods We evaluated antimicrobial activity of solithromycin (10 and 20 mg/kg) and levofloxacin (126 mg/kg) against S. pneumoniae with a three-point mutation in penicillin-binding protein and an ermB gene, and Parvimonas micra. Antimicrobial efficacy was calculated for each isolate as the change in bacterial count (Δlog10 CFU/mL) obtained in the treated mice after 24 h compared with the count in the starting control animals. Results The solithromycin and levofloxacin minimum inhibitory concentrations (MICs) for S. pneumoniae were 0.03 and 0.5 μg/mL, respectively. The solithromycin and levofloxacin MICs for P. micra were 0.015 and 0.12 μg/mL, respectively. In a mixed-infection model, solithromycin showed significantly higher antimicrobial activity against S. pneumoniae than levofloxacin (solithromycin 20 mg/kg; −2.87 ± 1.33 log10 CFU/mL vs. levofloxacin; −1.35 ± 0.37 log10 CFU/mL, p = 0.0397). Similarly, solithromycin showed significantly higher antimicrobial activity against P. micra than levofloxacin (solithromycin 20 mg/kg; −2.78 ± 0.98 log10 CFU/mL vs. levofloxacin; −1.57 ± 0.47 log10 CFU/mL, p = 0.0400). Discussion Solithromycin showed higher antimicrobial activities against macrolide-resistant S. pneumoniae and P. micra than levofloxacin, even though they were coexisted in murine lung tissue. Our results suggest that solithromycin could be effective for pneumonia patients due to S. pneumoniae to reduce bacterial density in lung tissue.

The aim of this study was to investigate the association between vancomycin trough level and clinical outcomes (mortality and nephrotoxicity) among infected paediatric patients with Gram-positive pathogens. We systematically searched the Scopus, EMBASE, Cochrane Central Register of Controlled Trials, PubMed and CINAHL databases up to March 2020. A total of seven retrospective cohort or case-control studies were included to compare clinical effects and safety: three studies set the threshold of vancomycin trough level at 10 mg/L and the others set it at 15 mg/L. Our analysis showed that vancomycin trough level of 10-15 mg/L was associated with significantly lower mortality [10 mg/L vs. ≥10 mg/L, odds ratio (OR) = 3.21, 95% confidence interval (CI) 1.74-5.91; and15 mg/L vs. ≥15 mg/L, OR = 0.31, 95% CI 0.10-0.95). The high vancomycin trough group (≥10 mg/L or ≥15 mg/L) showed a higher incidence of nephrotoxicity (10 mg/L vs. ≥10 mg/L, OR = 0.06, 95% CI 0.03-0.12; and15 mg/L vs. ≥15 mg/L, OR = 0.28, 95% CI 0.12-0.65). This is the first meta-analysis to reveal the optimal therapeutic range of vancomycin trough level in children. Our findings strongly suggest a superior benefit of vancomycin trough of 10-15 mg/L for paediatric patients.

Previous clinical studies have showed the clinical benefits of the initiation of treatment with a daptomycin (DAP) loading dose, but only a few studies have evaluated its antimicrobial benefits. We evaluated the efficacy of a DAP loading dose against methicillin-resistant Staphylococcus aureus (MRSA) infections in a neutropenic murine thigh infection model. Three MRSA isolates (DAP MIC: 0.5, 1, and 2 mg/L) were tested. Four DAP regimens simulating human concentration-time profiles, i.e., (i) day 1: 8 mg/kg and day 2: 6 mg/kg, (ii) days 1 and 2: 6 mg/kg/day, (iii) day 1: 8 mg/kg and day 2: 4 mg/kg, and (iv) days 1 and 2: 4 mg/kg/day, were administered to the mice. Efficacy was calculated as the change in bacterial density. DAP loading-dose regimen iii showed greater antimicrobial activity against MRSA with MIC 1 mg/L than nonloading regimen iv (-3.10 ± 0.63 vs. -0.71 ± 0.34 log10 CFU; p < 0.01). Loading-dose regimen iii achieved greater log10 CFU changes than nonloading regimen ii, while the total DAP dose for 2 days was the same (-3.10 ± 0.63 vs. -1.46 ± 0.48 log10 CFU; p < 0.05). DAP loading-dose regimen iii showed enhanced antimicrobial activity against MRSA with DAP MIC 0.5 mg/L when compared with nonloading regimen iv. However, loading-dose regimens i and iii did not reduce bacterial density for MRSA with DAP MIC 2 mg/L. Our data suggest that a DAP loading-dose regimen would be an advantageous procedure for patients infected with MRSA with DAP MIC ≤1 mg/L.

A 67-year-old Japanese female with back pain and severe cachexia visited our hospital. The diagnosis was disseminated Mycobacterium avium complex infection (dMAC) with multiple bone involvement. Anti-mycobacterial chemotherapy was started, but fever persisted and dislocation of cervical vertebrae has made her bedridden. Because anti-interferon (IFN)-γ autoantibody was positive, four doses of rituximab 375 mg/m2, every 7 day, were administered. Soon after treatment, progression of osteolytic lesions and wasting has stopped. We proved that rituximab has recovered IFN-γ signaling as shown by IFN-γ-induced STAT1 phosphorylation. It can be a promising option for dMAC cases with anti-IFN-γ autoantibody.

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

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

Daptomycin is active against Staphylococcus aureus including methicillin-resistant S. aureus (MRSA), demonstrating efficacy in the treatment of infections in diabetic patients. However, daptomycin degrades in 5% glucose solution, and data on the efficacy of daptomycin in hyperglycemic patients are limited. Therefore, we investigated the effect of high levels of blood glucose on the efficacy and concentration of daptomycin. The efficacy of simulated human exposure to daptomycin against S. aureus was compared in a neutropenic murine thigh model, with and without hyperglycemia. A clinically isolated MRSA strain and S. aureus ATCC25923 standard strain were used. Daptomycin concentrations, in the serum and at the infected site, were preliminarily analyzed using the high-performance liquid chromatography assay. Even in hyperglycemic mice, the mean concentration of daptomycin in hyperglycemic mice was equivalent to that in untreated mice within the physiological blood glucose levels. Additionally, the efficacy of daptomycin against MRSA was equal to that observed in the untreated and hyperglycemic mice. Based on similar studies using S. aureus ATCC25923, the efficacy in hyperglycemic mice was equal to or greater than that observed in untreated mice. In conclusion, daptomycin is an alternative therapeutic option in diabetic mice with serious staphylococcal infections, regardless of blood glucose control in this animal model.

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 infection8 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.

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 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.

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.

It is important to evaluate the amount of daptomycin (DAP) distributed to skeletal muscles to elucidate the mechanisms related to penetration and side effects, such as myopathies. However, no attempt has been made to measure DAP concentrations in skeletal muscles. The study's aim to investigate the feasibility of trypsin digestion, as a muscle sample preparation technique for the determination of DAP in murine skeletal muscle, was evaluated in conjunction with a conventional HPLC-UV analysis. Compared with trypsin digestion, DAP was less recovered from spiked skeletal muscle by the conventional extraction, including homogenization, centrifugation, and filtration, because of its incorporation into the muscle protein. On the other hand, a sample preparation technique involving enzymatic digestion employing trypsin fully recovered DAP from the spiked skeletal muscle. Based on the spike recovery assay results, we proposed an efficient muscle sample preparation method involving trypsin digestion. HPLC analysis in conjunction with the sample preparation method has successfully determined DAP concentrations of skeletal muscles collected from mice administrated subcutaneously with DAP. The proposed method is suitable for application to investigations that include animal experiments on drug migration into muscle and mechanism underlying skeletal muscle injury as a side reaction, such as myopathies, of DAP therapy.

Background Brevibacteria are obligate aerobic gram-positive rods that are associated with milk products and are also found on human skin. Brevibacterium has been reported as a rare cause of catheter related blood steam infection mainly in immunocompromised hosts such as malignancies or AIDS patients. Case presentation A 94-year old woman, which had a past history of diabetes mellitus and chronic heart failure, presented with high fever associated with decreased oral intake and appetite loss and was admitted to our institute. A physical examination at the time of presentation was unremarkable. On day 2, both blood cultures collected on admission became positive with coryneform organism within 24 h without Staphylococci and Brevibacterium species were identified by Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Subsequently, genetic investigation by 16S ribosomal RNA analysis was performed in order to identify the organism. Finally, the result identified this pathogen as Brevibacterium paucivorans with 99.5% homology on the Ez taxon database. The patient was started empirically on meropenem and teicoplanin for broad-spectrum antibiotic coverage. The patient’s fever finally abated and labs were also improved. On day 14, the antibiotic therapy was discontinued. The site of infections was unknown. We hereby report a case of Brevibacterium paicivorans bacteremia in an immunocompetent patient and review cases of Brevibacterium specises bacteremia previously reported. This is the first case of B. paucivorans bacteremia as far as we could search. Conclusion Physicians and microbiologists should be aware that Brevibacteria are uncommon but important agents which could cause opportunistic infections in immunocompetent.

This retrospective study is to evaluate the efficacy and safety of daptomycin (DAP) intermittent doses and the effectiveness of DAP loading dose in renal failure patients received DAP intermittent doses. One hundred and ninety-seven patients received DAP for at least 3 days from 2014 to 2017. Clinical and microbiological outcomes and the safety were assessed. A total of 183 patients (93, 60 and 30 patients received DAP daily dose, every 48 h dose and thrice per week dose) were included. DAP intermittent doses, such as every 48 h dose (28.3%) and thrice per week dose (30.0%), showed significantly higher mortality rates than that of DAP daily dose (6.5%) (p = 0.0320). Especially for bacteremia patients, significantly higher mortality was admitted, compared with patients received DAP daily doses (p = 0.0160). Moreover, patients received DAP intermittent doses were admitted slower improvements of their inflammation after DAP therapy started, compared with patients received daily dose. Additionally, DAP loading dose for renal failure patients decreased their mortality and improved patients' inflammation early. Especially for patients received DAP thrice per week dose, they showed significantly lower mortality than patients received non-loading dose (p = 0.0306). Additionally, these clinical enhancements of DAP therapy with loading dose were admitted without any enhancements of its adverse effect risks, except alkaline phosphatase elevation, compared with non-loading dose. In conclusion, DAP intermittent doses showed poor clinical outcomes, compared with daily dose. Then, DAP loading dose would be better clinical option for patients received DAP intermittent doses.

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. Keywords: Acinetobacter seifertii, Acinetobacter nosocomialis, Acinetobacter baumanii, Bacteremia, rpoB, Genomospecies

Background Pantoea is a Gram-negative, non-encapsulated, non-spore-forming, ubiquitous straight rod which can be isolated from geographical and ecological sources such as plant surfaces, buckwheat seeds, human feces, and the environment. The genus Pantoea is a rare pathogen in a clinical setting, and is divided into 20 different species such as Pantoea agglomerans, Pantoea ananatis, Pantoea deleyi, Pantoea dispersa, Pantoea septica, Pantoea stewartii or Pantoea rwandensis. Pantoea dispersa has been reported to cause other infections, including respiratory infections, neonatal sepsis, and bloodstream infections. We report a case of Pantoea dispersa bacteremia caused by acute cholangitis. This is the first case report of Pantoea dispersa bacteremia caused by acute cholangitis as far as we had searched. Case presentation A 38-year-old Japanese woman suffered from acute cholangitis; a blood culture showed that Gram-negative rod was positive. The treatment was successful with intravenously administered meropenem, and it was switched to orally administered levofloxacin according to microbiological susceptibility. The organism was identified as Pantoea dispersa by both genetic investigation by 16S ribosomal RNA and additional biochemical tests. To the best of our knowledge, this is the first case report of Pantoea dispersa bacteremia caused by acute cholangitis. Conclusion The epidemiology and clinical features of Pantoea dispersa are still unknown. More cases of infections caused by Pantoea dispersa might be revealed with advancing technical methods, such as matrix-assisted laser desorption/ionization time-of-flight mass spectrometry or 16S ribosomal RNA analysis. Physicians must know that a variety of infections caused by Pantoea dispersa could occur in immunocompromised as well as immunocompetent patients.

Background Any immunological mechanisms induced by influenza virus could cause severe secondary bacterial superinfection such as those by Streptococcus pyogenes [group A streptococcus (GAS)], Streptococcus pneumoniae or Staphylococcus aureus. Over recent years, the frequency of pleural empyema has increased in children with influenza infection. We present a severe case of acute empyema caused by S.pyogenes after influenza A infection. Case presentation A previously healthy 39-year old woman was diagnosed as influenza A and received oral Oseltamivir 75 mg twice daily for 5 days. She had no vaccination of influenza A. Although her influenza A infection improved, she complained of fever and cough to our institute. Chest radiography showed encapsulated pleural effusion of the left lung and pleural effusion which was consistent with acute empyema. Then, she was diagnosed as having acute empyema and was admitted to our institute. Streptococcus pyogenes was identified by pleural fluid culture on day 4. thus, MNZ was changed to clindamycin (CLDM) 600 mg three times a day. While thoracic drainage with intrapleural urokinase and combination antibiotic therapy of ceftriaxone and CLDM were performed, her general condition and chest radiographic findings were not improved. She received video-assisted thoracic debridement on day 10. After the operation, the antibiotic therapy was changed to ABPC 6 g daily iv. Due to good clinical course, the antibiotic therapy was switched to oral amoxicillin 500 mg three times daily on day 28. Then, she was discharged. Conclusion Influenza A virus infection could lead to severe GAS infection, while the latter can occur in otherwise healthy individual as well. Physician must consider the possibility of severe GAS infection after influenza A infection.

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

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

Background: Reports of Pseudomonas aeruginosa with high antimicrobial resistance have steadily emerged, threatening the utility of a mainstay in antipseudomonal therapy. This study evaluated the antimicrobial activities of various combination therapies against P. aeruginosa with high antimicrobial resistance, including multidrug-resistant P. aeruginosa (MDRP) using an in vitro and in vivo study. Methods: We evaluated 24 combination therapies, including colistin, aztreonam, meropenem, ceftazidime, ciprofloxacin, amikacin, rifampicin, arbekacin and piperacillin against 15 MDRP isolates detected at Aichi Medical University Hospital with the break-point checkerboard method. Based on the results of the in vitro study, we evaluated antimicrobial activity against highly antimicrobial-resistant P. aeruginosa with an in vivo murine thigh infection model. Results: The combination regimens including colistin and aztreonam showed higher antimicrobial activity against the 15 MDRP isolates. In the in vivo study, the high-dose colistin monotherapy (16 mg/kg every 12 h) achieved greater log10 CFU changes than the normal-dose colistin regimen (8 mg/kg every 12 h) against 5 P. aeruginosa isolates, including 2 MDRP isolates (p < 0.05). Aztreonam monotherapy (400 mg every 8 h) yielded bacterial densities similar to untreated control mice for the MDRP isolate evaluated. The combination therapy with a higher dose of colistin had superior antimicrobial activity against 5 P. aeruginosa with colistin (MIC 0.5 μg/ml) and aztreonam (MIC ≥128 μg/ml) than colistin monotherapy. Conclusion: The data suggest that the combination treatment of colistin and aztreonam could be the most useful for treating highly resistant P. aeruginosa with a higher susceptibility to colistin, including MDRP infections.

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

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