Effectiveness and safety of the simulation-based first-dose design of voriconazole.

BACKGROUND: We investigated whether the initial voriconazole (VRCZ) dosing design, as determined using simulation software with a population pharmacokinetic model of Japanese patients, impacts the effectiveness and safety when compared with VRCZ initiation according to the package insert. METHODS: In this single-center retrospective observational study, we employed records from Tosei General Hospital (a 633-bed hospital), dated April 2017 to September 2023. Eligible patients were divided into the software-based simulation group, comprising patients administered initial VRCZ dosage adjustment by pharmacists using software-based simulation, and the standard therapy group, whose dosage was administered by a physician following the package insert recommendations without simulation. The primary objective of this study was to determine the efficacy of VRCZ first-dose design in reducing the incidence of hepatotoxicity and visual symptoms. RESULTS: The median ages of enrolled participants (n = 93) were 75 (68-79) and 72 (65-78) years in the software-based simulation and standard therapy groups, respectively. Regardless of formulation, initial trough concentrations were lower in the VRCZ software-based first dosage adjustment group and higher rate within the appropriate range (1-4 µg/mL). The incidence of all-grade hepatotoxicity or visual symptoms was significantly lower in the software-based simulation group. The log-rank test revealed a significant impact on the occurrence of ≥grade 2 hepatotoxicity in the software-based first dosage adjustment group compared to that in the standard therapy group. CONCLUSIONS: The initial VRCZ dosing design using simulation software improved the achievement of appropriate initial trough concentrations and resulted in fewer occurrences of hepatotoxicity (≥grade 2) when compared with the standard therapy.

Distribution and antimicrobial susceptibility pattern of CTX-M-type extended-spectrum ß-lactamase-producing Escherichia coli isolated in Chubu region, Japan.

The widespread prevalence of extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli limits treatment options and is a worldwide problem. The aim of this study was to investigate the antimicrobial susceptibility and ESBL-type of 204 strains of CTX-M-type ESBLs-producing E. coli isolated from 2011 to 2017 in the Chubu region of Japan. Minimal inhibitory concentrations were determined in accordance with the guidelines of the Clinical and Laboratory Standards Institute. Genes encoding CTX-M group ß-lactamases were detected by PCR amplification. The CTX-M subtypes were determined using sequence analysis. The CTX-M-9 group was the most frequently detected ESBL group, and CTX-M-27 was the most frequently detected ESBL gene. CTX-M-15-producing strains showed significantly lower rates of susceptibility to tazobactam/piperacillin (TAZ/PIPC) than those by CTX-M-14 and -27-producing strains. Additional analysis of secondary ß-lactamases revealed that most of the OXA-1-positive strains were CTX-M-15-producing strains (94.7%). These strains displayed significantly lower susceptibility rates to TAZ/PIPC (47.4%), sulbactam/ampicillin (SBT/ABPC) (0.0%), and amikacin (AMK) (73.7%) than those by OXA-1-negative strains, suggesting that the high non-susceptibility rate of the CTX-M-15-producing strain was due to the co-carriage of OXA-1. The CTX-M-15-producing strains showed reduced susceptibility to TAZ/PIPC, SBT/ABPC, and AMK, presumably due to the co-carriage of OXA-1.

Evaluating the antimicrobial efficacy of ceftriaxone regimens: 1†g twice daily versus 2†g once daily in a murine model of Streptococcus pneumoniae pneumonia.

Background: Ceftriaxone is administered in regimens of either 2 g once-daily or 1 g twice-daily for the treatment of pneumonia caused by Streptococcus pneumoniae. Previous clinical study suggests the 2 g once-daily regimen is more effective, but comparison of antimicrobial efficacy between are lacking. Objectives: To assess the antimicrobial efficacy of these two ceftriaxone regimens against S. pneumoniae using a murine model of pneumonia. Methods: The study employed three S. pneumoniae isolates with ceftriaxone MICs of 1, 2 and 4 mg/L and two human-simulated regimens based on the blood concentration of ceftriaxone (1 g twice-daily and 2 g once-daily). Antimicrobial activity was quantified based on the change in bacterial counts (Δlog10 cfu/lungs) observed in treated mice after 24 h, relative to the control mice at 0 h. Results: The human-simulated 2 g once-daily regimen of ceftriaxone exhibited significantly higher antimicrobial activity against S. pneumoniae isolates with MICs of 1 and 2 mg/L compared with the 1 g twice-daily regimen (1 mg/L, -5.14 ±â€Š0.19 Δlog10 cfu/lungs versus -3.47 ±â€Š0.17 Δlog10 cfu/lungs, P < 0.001; 2 mg/L, -3.41 ±â€Š0.31 Δ log10 cfu/lungs versus -2.71 ±â€Š0.37 Δlog10 cfu/lungs, P = 0.027). No significant difference in antimicrobial activity was observed against the S. pneumoniae isolate with a MIC of 4 mg/L between the two regimens (-0.33 ±â€Š0.18 Δlog10 cfu/lungs versus -0.42 ±â€Š0.37 Δlog10 cfu/lungs, P = 0.684). Conclusion: 2 g once-daily regimen of ceftriaxone is more effective for treating pneumonia caused by S. pneumoniae, with MICs of ≤2 mg/L.

Clinical characteristics and analysis of prognostic factors in methicillin-resistant Staphylococcus aureus endocarditis: A retrospective multicenter study in Japan.

BACKGROUND: Infective endocarditis (IE) caused by MRSA (methicillin-resistant Staphylococcus aureus) is associated with a high mortality rate. This study aimed to elucidate the characteristics of patients with MRSA-IE in Japan and identify the factors associated with prognosis. METHODS: This retrospective study included patients with a confirmed diagnosis of IE caused by MRSA, between January 2015 and April 2019. RESULTS: A total of 65 patients from 19 centers were included, with a mean age of 67 years and 26 % were female. Fifty percent of the patients with IE were had nosocomial infections and 25 % had prosthetic valve involvement. The most common comorbidities were hemodialysis (20 %) and diabetes (20 %). Congestive heart failure was present in 86 % of patients (NYHA class I, II: 48 %; III, IV: 38 %). The 30-day and in-hospital mortality rates were 29 % and 46 %, respectively. Multi-organ failure was the primary cause of death, accounting for 43 % of all causes of death. Prognostic factors for in-hospital mortality were age, disseminated intravascular coagulation, daptomycin and/or linezolid as initial antibiotic therapy, and surgery. Surgical treatment was associated with a lower mortality rate (odds ratio [OR], 0.026; 95 % confidence interval [CI], 0.002-0.382; p = 0.008 for 30-day mortality and OR, 0.130; 95 % CI; 0.029-0.584; p = 0.008 for in-hospital mortality). CONCLUSION: Mortality due to MRSA-IE remains high. Surgical treatment is a significant prognostic predictor of MRSA-IE.

Rapid screening of positive blood cultures for extended-spectrum ß-lactamases and metallo-ß-lactamases using a drug susceptibility testing microfluidic method.

OBJECTIVES: An increasing number of drug-resistant bacteria have been identified recently. In particular, drug-resistant bacteria have been linked to unfavorable prognoses in patients with bacteremia, highlighting the need for rapid testing. Our previous studies have focused on the utility of a drug susceptibility testing microfluidic (DSTM) method using microfluidic channels. A system with this DSTM method for screening for ß-lactamases can rapidly detect extended-spectrum ß-lactamases (ESBLs) and metallo-ß-lactamases (MBLs). In this study, we have evaluated the clinical utility of pre-treatment for screening positive blood cultures using the DSTM method. METHODS: A total of 178 positive blood cultures and five simulated samples of MBL-producing bacteria were prepared at Kochi University Hospital, Japan. The pretreatment consisted of a two-step centrifugation. The obtained sediments were screened with the DSTM method for the production of ß-lactamase based on morphological changes in the bacteria after 3 h of incubation. RESULTS: The pretreatment functioned properly for all samples. Of the 25 ESBL samples, 21 were positive for ESBLs. Four false-negative samples, all obtained from the same patient, contained CTX-M-2 enzyme-producing Proteus mirabilis and showed insusceptibility to an ESBL inhibitor. The simulated samples prepared for MBL screening were positive for MBLs. CONCLUSIONS: When combined with a method for rapidly identifying bacterial species, DSTM may enable patients with bloodstream infections to start receiving appropriate treatment within 4 h after positive blood cultures are screened.

Association between voriconazole-induced visual hallucination and dopamine in an analysis of the food and drug administration (FDA) adverse event reporting system database.

Voriconazole is a second-generation azole used to treat serious fungal infections. Visual hallucinations constitute a representative adverse event caused by voriconazole. However, its mechanism of action remains unclear. In patients with schizophrenia or Parkinson's disease, the frequency of visual hallucinations is associated with brain dopamine levels. This study investigated the frequency of visual hallucinations in patients treated with voriconazole alone or in combination with dopaminergic medicines or dopamine antagonists, using data collected from the Food and Drug Administration Adverse event Reporting System (FAERS). The frequency of visual hallucinations with voriconazole alone and in combination with a dopaminergic medicine (levodopa) or dopamine antagonists (risperidone and chlorpromazine) was compared using data from the FAERS between 2004 and 2023, using the reporting odds ratio (ROR) with relevant 95% confidence intervals (CI). The reference group comprised patients who had been administered voriconazole without dopaminergic medication or dopamine antagonists. Of the patients, 22,839, 90,810, 109,757, 6,435, 20, 83, and 26, respectively were treated with voriconazole, levodopa, risperidone, chlorpromazine, voriconazole plus levodopa, voriconazole plus risperidone, and voriconazole plus chlorpromazine. The occurrence of visual hallucinations increased when used in combination with levodopa (ROR = 12.302, 95% CI = 3.587-42.183). No increase in incidence was associated with the concomitant use of dopamine antagonists (risperidone, ROR = 1.721, 95% CI = 0.421-7.030; chlorpromazine, ROR = none, 95% CI = none). Dopaminergic medicine may increase the risk of visual hallucinations in patients treated with voriconazole. Whether voriconazole positively modulates dopamine production warrants further investigation using a translational research approach.

Epidemiological study of respiratory syncytial virus infection in adults during the pandemic of COVID-19.

INTRODUCTION: While respiratory syncytial virus (RSV) is one of the most common pathogens in adults admitted to the ICU due to respiratory diseases, no reports regarding the occurrence rate of RSV infections in adults in Japan during the COVID-19 pandemic exist. PATIENTS AND METHODS: We conducted this retrospective study to examine the exact occurrence rate of RSV infections in adults. We reviewed all patients (≥18 years) with any respiratory symptoms who received quantitative polymerase chain reaction (PCR) using nasopharyngeal samples for respiratory viruses by GeneLEAD at the Aichi Medical University Hospital between November 2022 and November 2023. RESULTS: A total of 541 adult patients who underwent PCR test were enrolled in this study. RSV was identified in 18 cases (3.3 %); 8 (1.5 %) upper and 10 (1.8 %) lower respiratory tract infections. Influenza A and SARS-CoV-2 were found in 10 (1.8 %) and 61 (11.3 %), respectively. Patients with RSV infections and COVID-19 had more comorbidities than those with Influenza virus infections. As for RSV-associated with lower respiratory tract infection cases, 10 developed acute respiratory failure, resulting in 1 fatal case due to pneumonia and 1 died of septic shock due to ileus. The 30-, 90-day mortality rates were 1 (6 %) and 2 (11 %) respectively. CONCLUSION: About 3 % of adults had RSV infections during the COVID-19 pandemic. The outcomes of RSV infections in adults were similar to those by COVID-19. Those with comorbidities should have a preventive method against RSV infections, the same as for COVID-19.

Retrospective study to investigate appropriate duration of antibiotic treatment for uncomplicated Staphylococcus aureus bacteremia in patients with immunodeficiency.

BACKGROUND: Since the appropriate antibiotic duration for uncomplicated Staphylococcus aureus (S. aureus) bacteremia (u-SAB) in an immunocompromised state is still unclear, physicians are likely to extend antibiotic therapy from 2 weeks to 4-6 weeks. To examine the appropriate duration of antibiotic therapy for u-SAB, we performed this study. PATIENTS AND METHODS: We reviewed all patients with u-SAB at our institute seen between January 2020 and August 2023. A total of 51 patients were enrolled, and they were divided into the following two groups by antibiotic duration: longer duration group ≥28 days after blood culture negativity, and shorter duration group. Then, the patients were matched by a propensity score using the covariates of age, sex, qSOFA, and CCI. The primary outcome was to identify the prognosis by duration of antibiotic treatment. RESULTS: After propensity score matching, all-cause 30-day mortality was 0 % in both groups. Hence, there was no significant difference in all-cause 90 days mortality (19.0% vs 9.5%, p = 0.33) or recurrence (9.5%% vs 0%, p = 0.22). Before propensity-score matching, we found that a serum level of CRP 2.0 mg/dL and greater after intravenous antibiotic treatment was one of the poor prognostic factors. The cut-off value of serum CRP level was 2.0 mg/dL with a sensitivity of 82.1% and a specificity of 75.0%. CONCLUSION: We suggested that 4-6 weeks of antibiotic treatment for immunodeficient u-SAB patients was unnecessary. Moreover, the serum level of CRP after completion of IV antibiotic treatment could be a prognostic marker for u-SAB.

Comparison of efficacy and safety between daptomycin plus ß-lactam and daptomycin monotherapy for bloodstream infections due to gram-positive cocci: A systematic review and meta-analysis.

Objectives: We performed a comprehensive systematic review and meta-analysis to evaluate the clinical or microbiological outcomes and safety of a combination of daptomycin (DAP) and ß-lactams compared to DAP monotherapy in patients with blood stream infection (BSI) due to gram-positive cocci (GPC). Methods: We searched Scopus, PubMed, EMBASE, CINAHL, and Ityuushi databases up to January 30, 2023. Outcomes included all-cause mortality, clinical failure, and creatine phosphokinase (CPK) elevation. Results: Six cohorts or case-control studies fulfilled the inclusion criteria and were included in the final meta-analysis. Combination therapy of DAP and ß-lactams significantly reduced the mortality and clinical failure rate for all BSI due to GPC compared with the DAP monotherapy (mortality, odds ratio [OR] = 0.63, 95 % confidence interval [CI] = 0.41-0.98; clinical failure, OR = 0.42, 95 % CI = 0.22-0.81). In contrast, no significant difference was noted in the incidence of CPK elevation between the two groups (OR = 0.85, 95 % CI = 0.39-1.84). Conclusion: Altogether, combination therapy of DAP and ß-lactams can improve the prognosis for patients with BSI due to GPC compared with DAP alone. Therefore, it should be considered as an option for the empirical treatment of BSI caused by GPC.

Evaluation of effectiveness, hyperkalaemia, and hepatotoxicity of trimethoprim-sulphamethoxazole prophylaxis for Pneumocystis jirovecii pneumonia in paediatric patients: A single-centre retrospective study.

BACKGROUND: American guidelines recommend trimethoprim-sulphamethoxazole (TMP-SMX) for preventing Pneumocystis jirovecii pneumonia (PJP) in paediatric patients at doses of 5-10 mg/kg/d of the TMP component, administered either daily, three times weekly, or twice weekly. However, limited studies describe the effectiveness and safety of these prophylactic regimens. Our study aimed to assess the clinical effectiveness and incidence of adverse events associated with each TMP-SMX regimen in paediatric patients, and to identify risk factors for adverse events. METHODS: We collected data regarding the onset of PJP, hyperkalaemia, and hepatotoxicity in patients aged 0-18 years who underwent prophylaxis with TMP-SMX from July 2018 to June 2023. RESULTS: A total of 215 paediatric patients met the inclusion criteria. No patients developed PJP. Hyperkalaemia occurred in 14.7%, patients receiving TMP-SMX daily, 15.4% receiving it three times weekly, and 15.5% receiving it twice weekly. Hepatotoxicity was most frequent in patients receiving TMP-SMX twice weekly (19%), followed by those receiving it three times weekly (7.7%), and daily (5.9%). Younger patients were significantly more prone to developing hyperkalaemia or hepatotoxicity. Patients aged <1 year had the highest incidences of hyperkalaemia (56.5%), and those aged 1-2 years had the highest incidence of hepatotoxicity (25%). CONCLUSIONS: No patient developed PJP under various dosage prophylactic regimens of TMP-SMX. However, our findings suggest the need to monitor potassium levels and hepatic function in patients undergoing any of the three TMP-SMX regimens. In particular, patients aged <1 year old and 1-2 years old face a higher risk of hyperkalaemia and hepatotoxicity, respectively.

Clinical evaluation of a modified SARS-CoV-2 rapid molecular assay, ID NOW ™ COVID-19 2.0.

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

Oral Clostridium butyricum on mice endometritis through uterine microbiome and metabolic alternations.

Endometritis occurs frequently in humans and animals, which can negatively affect fertility and cause preterm parturition syndrome. Orally administered Clostridium butyricum, a butyrate-producing gram-positive anaerobe, exhibits anti-inflammatory effects. However, the precise mechanism by which Clostridium butyricum attenuates endometritis remains unclear. This in vivo study evaluated the anti-inflammatory effects of orally administered Clostridium butyricum on uterine tissues. In addition, we conducted uterine microbiome and lipid metabolome analyses to determine the underlying mechanisms. Female Balb/c mice were divided into the following four groups (n = 5-20): (1) mock group, (2) only operation group (mice only underwent operation to exposed uterine horns from the side), (3) control group (mice underwent the same operation with the operation group + perfusion of lipopolysaccharide solution from uterine horns), and (4) Clostridium butyricum administration group (mice underwent the same operation with the control group + oral Clostridium butyricum administration from days 0 to 9). Clostridium butyricum was administered via oral gavage. On day 10, we investigated protein expression, uterine microbiome, and lipid metabolism in uterine tissues. Consequently, orally administered Clostridium butyricum altered the uterine microbiome and induced proliferation of Lactobacillus and Limosilactobacillus species. The effects can contribute to show the anti-inflammatory effect through the interferon-ß upregulation in uterine tissues. Additionally, oral Clostridium butyricum administration resulted in the upregulations of some lipid metabolites, such as ω-3 polyunsaturated fatty acid resolvin D5, in uterine tissues, and resolvin D5 showed anti-inflammatory effects. However, the orally administered Clostridium butyricum induced anti-inflammatory effect was attenuated with the deletion of G protein-coupled receptor 120 and 15-lipooxgenase inhibition. In conclusion, Clostridium butyricum in the gut has anti-inflammatory effects on uterine tissues through alterations in the uterine microbiome and lipid metabolism. This study revealed a gut-uterus axis mechanism and provided insights into the treatment and prophylaxis of endometritis.

Antimicrobial therapy and outcome of methicillin-resistant Staphylococcus aureus endocarditis: A retrospective multicenter study in Japan.

BACKGROUND: MRSA (methicillin-resistant Staphylococcus aureus)-infective endocarditis (IE) is associated with high morbidity and mortality. This study aimed to assess data from patients with MRSA-IE across multiple facilities in Japan, with a specific focus on antimicrobial therapy and prognosis. METHODS: This retrospective study enrolled patients with a confirmed diagnosis of IE attributed to MRSA, spanning the period from January 2015 to April 2019. RESULTS: Sixty-four patients from 19 centers were included, with a median age of 67 years. The overall mortality rate was 28.1% at 30 days, with an in-hospital mortality of 45.3%. The most frequently chosen initial anti-MRSA agents were glycopeptide in 67.2% of cases. Daptomycin and linezolid were selected as initial therapy in 23.4% and 17.2% of cases, respectively. Approximately 40% of all patients underwent medication changes due to difficulty in controlling infection or drug-related side effects. Significant prognostic factors by multivariable analysis were DIC for 30-day mortality and surgical treatment for 30-day and in-hospital mortality. For vancomycin as initial monotherapy, there was a trend toward a worse prognosis for 30-day and in-hospital mortality (OR, 6.29; 95%CI, 1.00-39.65; p = 0.050, OR, 3.61; 95%CI, 0.93-14.00; p = 0.064). Regarding the choice of initial antibiotic therapy, statistical analysis did not show significant differences in prognosis. CONCLUSION: Glycopeptide and daptomycin were the preferred antibiotics for the initial therapy of MRSA-IE. Antimicrobial regimens were changed for various reasons. Prognosis was not significantly affected by choice of antibiotic therapy (glycopeptide, daptomycin, linezolid), but further studies are needed to determine which antimicrobials are optimal as first-line agents.

Development of a therapeutic drug-monitoring algorithm for outpatients receiving voriconazole: A multicentre retrospective study.

AIMS: Although therapeutic drug monitoring (TDM) of voriconazole is performed in outpatients to prevent treatment failure and toxicity, whether TDM should be performed in all or only selected patients remains controversial. This study evaluated the association between voriconazole trough concentrations and clinical events. METHODS: We investigated the aggravation of clinical symptoms, incidence of hepatotoxicity and visual disturbances, change in co-medications and interaction between voriconazole and co-medications in outpatients receiving voriconazole between 2017 and 2021 in three facilities. Abnormal trough concentrations were defined as <1.0 mg/L (low group) and >4.0 mg/L (high group). RESULTS: A total of 141 outpatients (578 concentration measurements) met the inclusion criteria (treatment, 37 patients, 131 values; prophylaxis, 104 patients, 447 values). The percentages of patients with abnormal concentrations were 29.0% and 31.5% in the treatment and prophylaxis groups, respectively. Abnormal concentrations showed 50% of the concentrations at the first measurement in both therapies. Aggravation of clinical symptoms was most frequently observed in the low treatment group (18.2%). Adverse events were most common in the high group for both therapies (treatment, hepatotoxicity 6.3%, visual disturbance 18.8%; prophylaxis, hepatotoxicity 27.9%). No differences were found in changes to co-medications and drug interactions. In the prophylaxis group, prescription duration in the presence of clinical events tended to be longer than in their absence (47.4 ± 23.4 days vs 39.7 ± 21.9 days, P = .1132). CONCLUSIONS: We developed an algorithm based on clinical events for appropriate implementation of TDM in outpatients. However, future interventions based on this algorithm should be validated.

Co-infection with Neisseria mucosa in a patient with tuberculous otitis media.

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

Lung cancer progression alters lung and gut microbiomes and lipid metabolism.

Despite advances in medical technology, lung cancer still has one of the highest mortality rates among all malignancies. Therefore, efforts must be made to understand the precise mechanisms underlying lung cancer development. In this study, we conducted lung and gut microbiome analyses and a comprehensive lipid metabolome analysis of host tissues to assess their correlation. Alternations in the lung microbiome due to lung cancer, such as a significantly decreased abundance of Firmicutes and Deferribacterota, were observed compared to a mock group. However, mice with lung cancer had significantly lower relative abundances of Actinobacteria and Proteobacteria and higher relative abundances of Cyanobacteria and Patescibacteria in the gut microbiome. The activations of retinol, fatty acid metabolism, and linoleic acid metabolism metabolic pathways in the lung and gut microbiomes was inversely correlated. Additionally, changes occurred in lipid metabolites not only in the lungs but also in the blood, small intestine, and colon. Compared to the mock group, mice with lung cancer showed that the levels of adrenic, palmitic, stearic, and oleic (a ω-9 polyunsaturated fatty acid) acids increased in the lungs. Conversely, these metabolites consistently decreased in the blood (serum) and colon. Leukotriene B4 and prostaglandin E2 exacerbate lung cancer, and were upregulated in the lungs of the mice with lung cancer. However, isohumulone, a peroxisome proliferator-activated receptor gamma activator, and resolvin (an ω-3 polyunsaturated fatty acid) both have anti-cancer effects, and were upregulated in the small intestine and colon. Our multi-omics data revealed that shifts in the microbiome and metabolome occur during the development of lung cancer and are of possible clinical importance. These results reveal one of the gut-lung axis mechanisms related to lung cancer and provide insights into potential new targets for lung cancer treatment and prophylaxis.

Comparison of clinical efficacy and safety of baloxavir marboxil versus oseltamivir as the treatment for influenza virus infections: A systematic review and meta-analysis.

INTRODUCTION: Baloxavir marboxil (BXM), a newly developed cap-dependent endonuclease inhibitor, is widely used to treat influenza virus infections in inpatients and outpatients. A previous meta-analysis included only outpatients and patients suspected of having an influenza virus infection based on clinical symptoms. However, whether BXM or oseltamivir is safer and more effective for inpatients remains controversial. Therefore, we conducted a systematic review and meta-analysis validating the effectiveness and safety of BXM versus oseltamivir in inpatients with influenza virus. METHODS: The Scopus, EMBASE, PubMed, Ichushi, and CINAHL databases were systematically searched for articles published until January 2023. The outcomes were mortality, hospitalization period, incidence of BXM- or oseltamivir-related adverse events, illness duration, and changes of virus titers and viral RNA load in patients with influenza virus infections. RESULTS: Two randomized controlled trials with 1624 outpatients and two retrospective studies with 874 inpatients were enrolled. No deaths occurred in outpatients treated with BXM or oseltamivir. Among inpatients, BXM reduced mortality (p = 0.06) and significantly shortened hospitalization period (p = 0.01) compared to oseltamivir. In outpatients, BXM had a significantly lower incidence of adverse events (p = 0.03), reductions in influenza virus titers (p < 0.001) and viral RNA loads (p < 0.001), and a tendency to be a shorter illness duration compared with that of oseltamivir (p = 0.27). CONCLUSIONS: Our meta-analysis showed that BXM was safer and more effective in patients than oseltamivir; thus, supporting the use of BXM for the initial treatment of patients with proven influenza virus infection.

Derivation of clinical predictive factors (CHIEF) for first recurrent Clostridioides difficile infection.

BACKGROUND: Current models for predicting Clostridioides difficile infection (CDI) recurrence rates have a limited capacity to account for important risk factors. This study developed a clinical prediction rule for CDI recurrence. METHODS: This retrospective cohort study evaluated 209 patients with CDI at a university hospital in Japan. Logistic regression and receiver operating characteristic curve analyses were performed to identify potential predictors (age, sex, underlying diseases, antibiotic use, acid suppressants, immunosuppressants, CDI history) of CDI recurrence. RESULTS: Forty-five patients developed recurrent CDI. Univariate analyses identified several significant recurrence predictors (enteral feeding, inflammatory bowel diseases [IBD], community-onset CDI, severe CDI). Enteral feeding (odds ratio: 3.87, 95% confidence interval: 1.75-8.56) and IBD (odds ratio: 7.08, 95% confidence interval: 1.28-39.06) were significant factors in the multivariate analysis. The CHIEF predictive scoring system was developed using 5 relevant variables (carbapenem use, hematologic malignancy, IBD, enteral feeding, fluoroquinolone use); the area under the receiver operating characteristic curve for the CHIEF score was 0.70. DISCUSSION: The CHIEF score incorporates useful, clinically available factors and could help identify patients at risk of recurrent CDI. CONCLUSIONS: These findings contribute to the understanding of risk factors associated with CDI recurrence and provide support for the development of prevention strategies.

Clinical characteristics and antimicrobial susceptibility of Fusobacterium species isolated over 10 years at a Japanese university hospital.

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