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.

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.

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.

Three Successfully Treated Cases of Lodderomyces elongisporus Fungemia: Case Reports and a Review of the Literature.

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

Nationwide surveillance of bacterial respiratory pathogens conducted by the surveillance committee of the Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology in 2019-2020: General view of the pathogens' antibacterial susceptibility.

The trends and prevalence of antimicrobial susceptibility of pathogens vary by country, region, and time. Long-term regular surveillance is required to investigate trends in the antimicrobial resistance of various isolated bacterial pathogens. We report the results of a nationwide surveillance on the antimicrobial susceptibility of bacterial respiratory pathogens in Japan conducted by the Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology. The isolates were collected from clinical specimens obtained from adult patients who visited a collaborating medical facility between June 2019 and December 2020 and were diagnosed with respiratory tract infections by a physician. Antimicrobial susceptibility testing was performed in a centralized laboratory according to the methods recommended by the Clinical and Laboratory Standards Institute. Susceptibility testing was performed for 932 strains (201 Staphylococcus aureus, 158 Streptococcus pneumoniae, 6 S. pyogenes, 136 Haemophilus influenzae, 127 Moraxella catarrhalis, 141 Klebsiella pneumoniae, and 163 Pseudomonas aeruginosa) collected from 32 facilities in Japan. The proportions of methicillin-resistant S. aureus and penicillin-resistant S. pneumoniae were 35.3% and 0%, respectively. In H. influenzae, 16.2% and 16.9% were ß-lactamase-producing ampicillin resistant and ß-lactamase-negative ampicillin resistant, respectively. Extended-spectrum ß-lactamase-producing K. pneumoniae accounted for 5.0% of all K. pneumoniae infections. Carbapenemase-producing K. pneumoniae and multi-drug-resistant P. aeruginosa with metallo-ß-lactamase were not detected in this study. This surveillance will be a useful reference for treating respiratory infections in Japan and will provide evidence to enhance the appropriate use of antimicrobial agents.

A Gap of Patients with Infective Endocarditis between Clinical Trials and the Real World.

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

[Relationship between Serotypes and Biotypes of Yersinia enterocolitica and the Names of Identified Bacteria in the Microbial Identification and Susceptibility Testing Devices].

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

Could quick SOFA and SOFA score be a predictive tool for 30-day and in-hospital mortality in acute empyema?

While acute empyema is a critical infectious disease showing a high mortality rate, there are no prognostic tools to evaluate the disease severity and prognosis for patients. We conducted a retrospective cohort to determine whether quick Sequential Organ Failure Assessment (qSOFA) and SOFA score can predict the disease severity and prognosis of acute empyema. A total of 53 patients were enrolled in the study. The mean age was 69 years and 41 patients (77%) were male. Twenty-two patients (42%) had multiple underlying diseases with the Charlson comorbidity index ≥3. The-30 days, and in-hospital deaths were 7 (13%) and 10 (19%), respectively. The area under the ROC curve of SOFA score and CCI for 30-day and in-hospital deaths were 0.814 (p = 0.073) and 0.752 (p = 0.082), 0.848 (p = 0.07) and 0.762 (p = 0.011), respectively. Univariate analysis showed that qSOFA ≥2 and SOFA score ≥2, isolation of potentially drug-resistant (PDR) pathogen, high CCI (≥3), performance status of 2-4, surgical intervention, and anaerobic bacteria involvement were prognostic factors. Of these, multivariate logistic regression analysis showed that qSOFA ≥2 and SOFA score ≥2 (p = 0.011), isolation of PDR pathogen (p = 0.005), and high CCI (≥3) (p = 0.015) were independently poor prognostic factors. We concluded that qSOFA and SOFA scores could predict the disease severity and prognosis in acute empyema. Additionally, isolation of PDR pathogens and high CCI could be poor prognostic factors for patients.

Risk factors of first recurrence of Clostridioides difficile infection.

OBJECTIVES: Clostridioides difficile infection (CDI) often recurs. Approximately 25% of patients have recurrences after the initial treatment, and patients who have relapsed once are more likely to relapse. We aimed to identify the risk factors for initial CDI recurrence. METHODS: We performed a retrospective survey of patient backgrounds and treatment-related factors. Risk factors were analyzed using single and multiple logistic regression analyses. RESULTS: A total of 134 patients were included in the study. Prophylactic probiotic use and nasogastric tube feeding were independent risk factors for the initial recurrence of CDI. Patients using prophylactic probiotics had significantly higher recurrence rates than those not using prophylactic probiotics. CONCLUSION: Prophylactic probiotic use and nasogastric tube placement may be risk factors for the initial recurrence of CDI. It is noteworthy that CDI that occurs during the use of prophylactic probiotics may be prone to recurrence.

A Large Gap in Patients' Characteristics and Outcomes between the Real-World and Clinical Trial Settings in Community-Acquired Pneumonia and Healthcare-Associated Pneumonia.

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

Novel approach for rapid detection of extended spectrum ß-lactamase and metalloid-ß-lactamase using drug susceptibility testing microfluidic device (DSTM).

BACKGROUND/PURPOSE: Rapid detection of ß-lactamases is important in a recent situation where resistant bacteria are increasing. By using the drug susceptibility testing microfluidic device (DSTM), rapid screening of extended spectrum ß-lactamases (ESBLs) and metallo-ß-lactamases (MBLs) has become possible. METHODS: ß-lactams and ß-lactamase inhibitors were pre-fixed in the DSTM for use. A bacterial suspension in Mueller-Hinton broth (McF 0.25) was introduced into the device, and the effects of ß-lactamase inhibitor on morphological changes caused by ß-lactam were evaluated after 3 h incubation. RESULTS: Clinical isolates genetically confirmed to produce ß-lactamase were used. Of the 84 ESBL-producing strains, 80 strains (95%) turned to be ESBL positive, and five strains (6%) of them MBL were positive as well as ESBL. Four strains (5%) were negative for both ESBL and MBL. Of the 24 MBL-producing strains, 23 strains (96%) were positive for MBL. All the 43 AmpC-producing strains were negative for both ESBL and MBL. Of the 156 ESBL- and MBL-nonproducing strains, 155 strains (99%) were negative for both ESBL and MBL, and one strain was positive for ESBL. With this method, the detection sensitivity was 95% and the specificity was 100% for ESBL, whereas the detection sensitivity was 96% and the specificity was 98% for MBL. These results were not significantly different from the results of the disc diffusion method. CONCLUSION: The DSTM method allows rapid detection of ß-lactamases in 3 h and may be a useful replacement for the disc diffusion method.

Empyema and bacteremia caused by Aeromonas hydrophila: Case report and review of the literature.

INTRODUCTION: Despite the advance in antibiotics and widespread chest tube drainage, acute empyema still shows a high mortality rate, accounting for 10-25%. We experienced a case of acute empyema caused by A. hydrophila, which is extremely uncommon, and reviewed all previously published articles. CASE PRESENTATION: A 76-year older man with a medical history of liver cirrhosis (LC) due to chronic hepatitis C and hepatic cell carcinoma was admitted to our institute. Elevated inflammatory reaction and effusions on chest CT were seen, and he was suspected of having acute empyema. Although an empiric antibiotic therapy of meropenem with chest tube drainage was performed as an initial treatment, he died within 8 hours of admission. Postmortem, both blood and left pleural fluid cultures yielded Aeromonas hydrophila. The final diagnosis was acute empyema caused by A. hydrophila. We reviewed previously reported empyema caused by Aeromonas species cases (4 A. hydrophila, and 1 A. veronii) in 4 previous reports written in English, including ours. Of 5, all were male, and the mean age was 52 years (range 27-76 years). All patients had LC due to alcohol or viral infections. As for antibiotics initially prescribed, third-generation cephalosporins were most frequently used in 3/5 (60%). Thoracentesis was performed in all patients (100%). As for prognosis, 2 (40%) survived, and 3 (60%) died. CONCLUSION: Physicians should be aware of the possibility of acute empyema caused by A. hydrophila among patients with chronic hepatic disease.

Efficacy and validity of guideline-concordant treatment according to the JRS guidelines for the managements of pneumonia in adults updated in 2017 for nursing and healthcare-associated pneumonia. A propensity-matching score analysis.

INTRODUCTION: Patients with nursing and healthcare-associated pneumonia (NHCAP) commonly receive empiric antibiotic therapy according to the guideline's recommendation corresponding to the patient's deteriorated conditions. However, it is unclear whether guideline-concordant treatment (GCT) could be effective or not. PATIENTS AND METHODS: To evaluate the efficacy and validity of GCT according to the current guideline for pneumonia, we conducted this retrospective study. NHCAP patients who were admitted to our institute between 2014 and 2017 were enrolled. Based on the initial antibiotic treatment, these patients were divided into two groups, the GCT group (n = 83) and the non-GCT group (n = 146). Propensity score matching (PSM) was used to balance the baseline characteristics and potential confounders between the two groups. After PSM, patients' characteristics, microbial profiles, and clinical outcomes were evaluated. RESULTS: Both groups were well-balanced after PSM, and 78 patients were selected from each group. There were no differences in patients' characteristics or microbial profiles between the two groups. As for outcomes, there were no differences in 30-day, in-hospital mortality rate, duration of antibiotic treatment, or admission. The severity of pneumonia was more severe in patients with the GCT group than those with the non-GCT group. Anti-pseudomonal agents as initial treatment were more frequently seen in patients with the GCT group than those in the non-GCT group. CONCLUSION: Unlike previous studies, GCT's recommendation for management of pneumonia by the JRS in 2017 would appear to be valid and does not increase the mortality rate.

To what degree could clinical trials in evidence based medicine reflect reality in the treatment of candidemia?

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.

In Vivo Pharmacodynamics of ß-Lactams/Nacubactam against Carbapenem-Resistant and/or Carbapenemase-Producing Enterobacter cloacae and Klebsiella pneumoniae in Murine Pneumonia Model.

Carbapenem-resistant Enterobacterales (CRE) and carbapenemase-producing Enterobacterales (CPE) have become global threats. CRE- and CPE- derived infections have been associated with high mortality due to limited treatment options. Nacubactam is a ß-lactamase inhibitor and belongs to the new class of diazabicyclooctane. The agent has an in vitro antimicrobial activity against several classes of ß-lactamase-producing Enterobacterales. This study evaluated antimicrobial activity of combination therapies including ß-lactams (aztreonam, cefepime, and meropenem) and nacubactam against four Enterobacter cloacae and six Klebsiella pneumoniae isolates with murine pneumonia model. Based on changes in bacterial quantity, antimicrobial activities of some regimens were assessed. Combination therapies including ß-lactams (aztreonam, cefepime, and meropenem) with nacubactam showed enhanced antimicrobial activity against CRE E. cloacae (-3.70 to -2.08 Δlog10 CFU/lungs) and K. pneumoniae (-4.24 to 1.47 Δlog10 CFU/lungs) with IMP-1, IMP-6, or KPC genes, compared with aztreonam, cefepime, meropenem, and nacubactam monotherapies. Most combination therapies showed bacteriostatic (-3.0 to 0 Δlog10 CFU/lungs) to bactericidal (<-3.0 Δlog10 CFU/lungs) activities against CRE isolates. This study revealed that combination regimens with ß-lactams (aztreonam, cefepime, and meropenem) and nacubactam are preferable candidates to treat pneumonia due to CRE and CPE.

Ceftriaxone versus tazobactam/piperacillin and carbapenems in the treatment of aspiration pneumonia: A propensity score matching analysis.

INTRODUCTION: Aspiration pneumonia (AP) accounts for 5.0-53.2% of hospitalized pneumonia and the treatment commonly used is by broad-spectrum antibiotics to cover anaerobes. Since ceftriaxone (CTRX) could generally cover oral streptococcus and anaerobes implicated in AP, it could be a useful option in the treatment of AP, instead of piperacillin-tazobactam/(PIPC/TAZ) or Carbapenems. PATIENTS AND METHODS: For the purpose of examining whether CTRX is as effective as broad-spectrum antibiotics for the treatment of AP, this retrospective study included consecutive community-onset patients who were admitted to our institute between 2014 and 2017. These patients were divided into two groups, a CTRX group (n = 25) and a PIPC/TAZ or carbapenems group (n = 97) based on the initial antibiotic treatment. Propensity score matching (PSM) was used to balance the potential confounders, and 23 patients were selected from each group. Patients among CTXR group received CTRX, while those among PIPC/TAZ or carbapenems group received PIPC/TAZ, or carbapenems and/or other agents. RESULTS: Both groups were well-balanced after PSM. There were no differences in 30-day mortality, duration of hospital stay or antibiotic treatments in the between them. The medical costs were much more expensive in the PIPC/TAZ or carbapenems group than in the CTR group (35,582 v. s. 8678 Japanese yen, p < 0.001). CONCLUSION: CTRX is one of the most useful antibiotic treatment for AP, which is not inferior to broad-spectrum antibiotic treatment. In addition, usage of CTRX in the treatment of AP is more economical than broad-spectrum antibiotic treatment, and could contribute to reduction of medical costs.

Efficacy and validity of automated quantitative chemiluminescent enzyme immunoassay for SARS-CoV-2 antigen test from saliva specimen in the diagnosis of COVID-19.

INTRODUCTION: The pandemic of a novel coronavirus disease 2019 (COVID-19) caused by a severe acute respiratory coronavirus 2 (SARS-CoV-2) infection has been problematic worldwide. A new SARS-CoV-2 antigen test (LUMIPULSEⓇ) was licensed and widely used in Japan since May 2020. We conducted this study intending to whether the automated quantitative CLEIA antigen test using a saliva sample is effective and valid for the diagnosis of COVID-19. PATIENTS AND METHODS: We analyzed and compared the diagnostic accuracy of both the automated quantitative CLEIA antigen test and real-time RT-PCR (rRT-PCR) using a saliva sample from individuals suspected as having COVID-19. RESULTS: A total of 305 samples were collected and tested in Aichi Medical University Hospital and affiliated facilities from December 2020 until January 2021 at our institute. Using reverse-transcription PCR as a reference, the AUROC of the automated quantitative CLEIA antigen test was 0.903 (95% confidential interval 0.845-0.962, p < 0.001). The appropriate cut-off antigen level was 4.0 pg/mL and had a sensitivity of 77.8%, a specificity of 99.6%, a positive predictive value of 98%, and a negative predictive value of 94.5%. On the other hand, the diagnostic accuracy of the antigen test decreased among patients among patients with COVID-19 with threshold cycle (Ct-value)≥27, which shows the AUROC was 0.795 (95%CI 0.687-0.907, p < 0.001). CONCLUSION: While the automated quantitative CLEIA antigen test from saliva specimen could be one of the most useful diagnostic tests for the diagnosis of COVID-19 in general practice, clinicians should know the limitations of the antigen test.

Pharmacodynamic evaluation of meropenem, cefepime, or aztreonam combined with a novel ß-lactamase inhibitor, nacubactam, against carbapenem-resistant and/or carbapenemase-producing Klebsiella pneumoniae and Escherichia coli using a murine thigh-infection model.

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-ß-lactam diazabicyclooctane ß-lactamase inhibitor with in vitro activity against some Enterobacterales expressing classes of ß-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 ß-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 ß-lactams and NAC administered in the murine thigh-infection model showed greater efficacy against CRE+/CPE+, CRE+/CPE-, and CRE-/CPE+ isolates harboring various ß-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 ß-lactams and NAC are potential candidates for the treatment of CRE and/or CPE infections.

The combined score of quick SOFA and the charlson comorbidity index could be a poor prognostic indicator for in-hospital mortality among patients with necrotizing fasciitis.

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.

In vivo pharmacodynamics of lascufloxacin and levofloxacin against Streptococcus pneumoniae and Prevotella intermedia in a pneumonia mixed-infection mouse model.

This study aimed to evaluate the antimicrobial activity of a new quinolone, lascufloxacin, for the treatment of complicated pneumonia caused by Streptococcus pneumoniae and Prevotella intermedia using a neutropenic mice pneumonia mixed-infection model. In this study, one S. pneumoniae and four P. intermedia isolates were utilized. Antimicrobial efficacy was calculated for each isolate as the reduction of the bacterial count comparatively to the non-treated mice (log10 colony forming units (cfu)/mL) obtained in the lungs of the treated mice after 24 h. Consequently, the bacterial densities of S. pneumoniae (KY-9) and P. intermedia (335) in the lungs of control animals were 8.20 ± 0.19 log10 cfu/mL and 5.26 ± 1.50 log10 cfu/mL, respectively. At human-simulated doses, lascufloxacin and levofloxacin showed high antimicrobial activities against not only S. pneumoniae (lascufloxacin: 1.88 ± 0.43 log10 cfu/mL, p < 0.001; levofloxacin 4.30 ± 0.75 log10 cfu/mL, p < 0.001), but also P. intermedia (lascufloxacin: 1.54 ± 0.57 log10 cfu/mL, p < 0.001; levofloxacin: 2.79 ± 0.55 log10 cfu/mL, p = 0.0102). Additionally, levofloxacin demonstrated attenuated antimicrobial efficacies against S. pneumoniae in the mixed-infection model compared with that in the single infection model. In contrast, lascufloxacin showed enhanced antimicrobial activities against S. pneumoniae and P. intermedia in the mixed-infection model. In conclusion, lascufloxacin resulted in enhanced efficacies against S. pneumoniae and P. intermedia, in both the single and mixed-infection models used. These data support the clinical utility of lascufloxacin for use against S. pneumoniae and P. intermedia in the treatment of pneumonia.