Nocardiosis in Japan: a Multicentric Retrospective Cohort Study.

Nocardia species cause a broad spectrum of infections, especially in immunocompromised patients. Given its relative rarity, data on the prognosis and distribution of nocardiosis from a large cohort are scarce. The present study aimed to scrutinize the clinical features and outcomes of nocardiosis in Japan, including 1-year mortality and microbiological data. The present multicentric, retrospective cohort study enrolled patients aged ≥18 years with nocardiosis diagnosed between January 2010 and December 2017 and recorded their clinical and microbiological characteristics. Factors associated with 1-year mortality were also determined using Cox proportional hazard analysis. In total, 317 patients were identified at 89 hospitals. Almost half (155/317, 48.9%) were receiving immunosuppressive agents, and 51 had disseminated nocardiosis (51/317, 16.1%). The 1-year all-cause mortality rate was 29.4% (80/272; lost to follow-up, n = 45). The most frequently isolated species was Nocardia farcinica (79/317, 24.9%) followed by the Nocardia nova complex (61/317, 19.2%). Selected antimicrobial agents were generally effective, with linezolid (100% susceptibility [S]) and amikacin (94% S) having the most activity against Nocardia species. In Cox proportional hazard analysis, factors independently associated with 1-year mortality were a Charlson comorbidity index score of ≥5 (adjusted hazard ratio [aHR], 3.61; 95% confidence interval [CI], 1.95 to 6.71, P < 0.001) and disseminated nocardiosis (aHR, 1.79; 95%CI, 1.01 to 3.18, P = 0.047). The presence of advanced comorbidities and disseminated infection, rather than variations in antimicrobial therapy or Nocardia species, was independently associated with 1-year mortality.

Prevalence and appropriateness of indwelling urinary catheters in Japanese hospital wards: a multicenter point prevalence study.

BACKGROUND: Indwelling urinary catheters are commonly used in hospitalized patients, which can lead to the development of urinary catheter complications, including catheter-associated urinary tract infection (CAUTI). Limited reports on the appropriateness of urinary catheter use exist in Japan. This study investigated the prevalence and appropriateness of indwelling urinary catheters, and the incidence of CAUTI in non-intensive care unit (non-ICU) wards in Japanese hospitals. METHODS: This prospective observational study was conducted in 7 non-ICU wards from 6 hospitals in Japan from October 2017 to June 2018. At each hospital the study teams evaluated urinary catheter prevalence through in-person bedside evaluation for at least 5 days of each week for 3 months. Catheter associated urinary tract infection (CAUTI) incidence and appropriateness of catheter use was collected via chart review. RESULTS: We assessed 710 catheter-days over 5528 patient-days. The mean prevalence of indwelling urinary catheter use in participating wards was 13% (range: 5% to 19%), while the mean incidence of CAUTI was 9.86 per 1000 catheter-days (range: 0 to 33.90). Approximately 66% of the urinary catheter days assessed had an appropriate indication for use (range: 17% to 81%). A physician's order for catheter placement was present in only 10% of catheterized patients. CONCLUSION: This multicenter study provides epidemiological information about the appropriate use of urinary catheters in Japanese non-ICU wards. A multimodal intervention may help improve the appropriate use of urinary catheters.

Experience of 101 patients with coronavirus infectious disease 2019 (COVID-19) at a tertiary care center in Japan.

INTRODUCTION: Clusters of novel coronavirus infectious disease of 2019 (COVID-19) have spread to become a global pandemic imposing a significant burden on healthcare systems. The lack of an effective treatment and the emergence of varied and complicated clinical courses in certain populations have rendered treatment of patients hospitalized for COVID-19 difficult. METHODS: Tokyo Metropolitan Tama Medical Center, a public tertiary acute care center located in Tokyo, the epicenter of COVID-19 in Japan, has been admitting patients with COVID-19 since February 2020. The present, retrospective, case-series study aimed to investigate the clinical course and outcomes of patients with COVID-19 hospitalized at the study institution. RESULTS: In total, 101 patients with COVID-19 were admitted to our hospital to receive inpatient care. Eleven patients (10.9%) received ECMO, and nine patients (8.9%) died during hospitalization after COVID-19 was diagnosed. A history of smoking and obesity were most commonly encountered among patients with a complicated clinical course. Most patients who died requested to be transferred to advanced palliative care in the early course of their hospitalization. CONCLUSIONS: Our experience of caring for these patients demonstrated a relatively lower mortality rate and higher survival rate in those with extracorporeal membrane oxygenation placement than previous reports from other countries and underscored the importance of proactive, advanced care planning in the early course of hospitalization.

Critical National Shortage of Cefazolin in Japan: Management Strategies.

The shortage of antimicrobials poses a global health threat. In Japan, for instance, the current, critical shortage of cefazolin, a first-line agent for the treatment of common infectious diseases and surgical antimicrobial prophylaxis, has had a substantial impact on inpatient care. A shortage of essential antimicrobial agents like cefazolin leads to increased consumption of alternative antimicrobial agents with broad-spectrum activity, with the unintended consequence of militating against antimicrobial stewardship efforts in inpatient settings and potentially promoting antimicrobial resistance. Although there is global awareness of the shortage of crucial antimicrobials, action to resolve this problem, especially with a view to preventing antimicrobial resistance and promoting antimicrobial stewardship, has been slow, possibly due to the failure to appreciate the urgency of the dilemma. A comprehensive plan for stabilizing antimicrobial access and international collaboration to secure a continuous supply of essential antimicrobials are urgently needed.

Performance of laboratory tests for detection for Clostridioides difficile: A multicenter prospective study in Japan.

BACKGROUND: The optimal and practical laboratory diagnostic approach for detection of Clostridioides difficile to aid in the diagnosis of C. difficile infection (CDI) is controversial. A two-step algorithm with initial detection of glutamate dehydrogenase (GDH) or nucleic acid amplification test (NAAT) alone are recommended as a predominant method for C. difficile detection in developed countries. The aim of this study was to compare the performance of enzyme immunoassays (EIA) detecting toxins A and B, NAAT detecting the toxin B gene, and GDH compared to toxigenic culture (TC) for C. difficile as the gold standard, in patients prospectively and actively assessed with clinically significant diarrhea in 12 medical facilities in Japan. METHODS: A total of 650 stool specimens were collected from 566 patients with at least three diarrheal bowel movements (Bristol stool grade 6-7) in the preceding 24 h. EIA and GDH were performed at each hospital, and NAAT and toxigenic C. difficile culture with enriched media were performed at the National Institute of Infectious Diseases. All C. difficile isolates recovered were analyzed by PCR-ribotyping. RESULTS: Compared to TC, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of EIA were 41%, 96%, 75% and 84%, respectively, and for NAAT were 74%, 98%, 91%, and 92%, respectively. In 439 specimens tested with GDH, the sensitivity, specificity, PPV, and NPV were 73%, 87%, 65%, and 91%, and for an algorithm (GDH plus toxin EIA, arbitrated by NAAT) were 71%, 96%, 85%, and 91%, respectively. Among 157 isolates recovered, 75% of isolates corresponded to one of PCR-ribotypes (RTs) 002, 014, 018/018", and 369; RT027 was not isolated. No clear differences in the sensitivities of any of EIA, NAAT and GDH for four predominant RTs were found. CONCLUSION: The analytical sensitivities of NAAT and GDH-algorithm to detect toxigenic C. difficile in this study were lower than most previous reports. This study also found low PPV of EIAs. The optimal method to detect C. difficile or its toxins to assist in the diagnosis of CDI needs further investigation.

Clostridioides (Clostridium) difficile infection burden in Japan: A multicenter prospective study.

Clostridioides (Clostridium) difficile is the leading cause of healthcare-associated infectious diarrhea in the developed world. Retrospective studies have shown a lower incidence of C. difficile infection (CDI) in Japan than in Europe or North America. Prospective studies are needed to determine if this is due lack of testing for C. difficile or a true difference in CDI epidemiology. A prospective cohort study of CDI was conducted from May 2014 to May 2015 at 12 medical facilities (20 wards) in Japan. Patients with at least three diarrheal bowel movements (Bristol stool grade 6-7) in the preceding 24 h were enrolled. CDI was defined by positive result on enzyme immunoassay for toxins A/B, nucleic acid amplification test for the toxin B gene or toxigenic culture. C. difficile isolates were subjected to PCR-ribotyping (RT), slpA-sequence typing (slpA-ST), and antimicrobial susceptibility testing. The overall incidence of CDI was 7.4/10,000 patient-days (PD). The incidence was highest in the five ICU wards (22.2 CDI/10,000 PD; range: 13.9-75.5/10,000 PD). The testing frequency and CDI incidence rate were highly correlated (R2 = 0.91). Of the 146 isolates, RT018/018″ was dominant (29%), followed by types 014 (23%), 002 (12%), and 369 (11%). Among the 15 non-ICU wards, two had high CDI incidence rates (13.0 and 15.9 CDI/10,000 PD), with clusters of RT018/slpA-ST smz-02 and 018"/smz-01, respectively. Three non-RT027 or 078 binary toxin-positive isolates were found. All RT018/018" isolates were resistant to moxifloxacin, gatifloxacin, clindamycin, and erythromycin. This study identified a higher CDI incidence in Japanese hospitals than previously reported by actively identifying and testing patients with clinically significant diarrhea. This suggests numerous patients with CDI are being overlooked due to inadequate diagnostic testing in Japan.

Reverse transcription polymerase chain reaction-based method for selectively detecting vegetative cells of toxigenic Clostridium difficile.

The laboratory diagnostic methods for Clostridium difficile infection (CDI) include toxigenic culture, enzyme immunoassays (EIAs) to detect the toxins of C. difficile, and nucleic acid amplification tests (NAATs) to detect C. difficile toxin genes, but each of these methods has disadvantages; toxigenic cultures require a long time to produce results, EIAs have low sensitivity, and NAATs that target DNA cannot distinguish vegetative cells from spores and dead cells. Here we report a new detection method that uses reverse transcription polymerase chain reaction to target the toxin-gene transcripts. This method was able to specifically detect the vegetative cells of toxigenic C. difficile in fecal samples in spike tests, with a minimum detection limit of 5 × 10(2) colony-forming units per 100 mg of stool specimen. The performance of this method was also demonstrated in a pilot scale evaluation using clinical fecal specimens, which showed that this method may be more sensitive than EIA and requires a shorter time than toxigenic culture. This method could potentially be applied in the clinical laboratory to detect C. difficile in fecal specimens. The ability of this method to discriminate the presence of vegetative cells from spores and dead cells could help to further the understanding of CDI.

Cerebrospinal fluid/blood glucose ratio as an indicator for bacterial meningitis.

BACKGROUND: Bacterial meningitis is an emergent disease requiring prompt diagnosis and treatment with appropriate antimicrobials. Although the lumbar puncture is widely used as a diagnostic tool for bacterial meningitis, it remains unclear which value in cerebrospinal fluid (CSF) analysis in emergency laboratory tests precisely predicts the presence of bacterial meningitis. METHODS: This is a single-center, retrospective review of medical records to determine which emergency laboratory CSF test results are useful for predicting bacterial meningitis. The diagnosis of meningitis is made when the white blood cell count in CSF exceeds 5 cells/µL, while the diagnosis of bacterial meningitis additionally requires the growth of a pathogen from a CSF culture or the identification of a pathogen in Gram staining of CSF specimen. RESULTS: We identified 15 patients with bacterial meningitis and 129 patients with aseptic meningitis. While neutrophil-predominant pleocytosis and a decreased glucose level in CSF can predict the presence of bacterial meningitis, the CSF/blood glucose ratio is more precise (optimal cut-off=0.36, sensitivity=92.9%, specificity=92.9%, area under the curve=.97) even after administration of antimicrobials prior to examination in the emergency department. CONCLUSION: This study suggests that the CSF/blood glucose ratio may be a better single indicator for bacterial meningitis. Since the CSF glucose and blood glucose values are promptly and easily obtained from a lumbar puncture, the CSF/blood glucose ratio should be considered as a timely diagnostic indicator of bacterial meningitis. It may also help exclude the diagnosis of bacterial meningitis especially in cases in which no microorganisms can be cultured.

Implementation of multifaceted diagnostic stewardship for Clostridioides difficile infection during the COVID-19 pandemic at a small Japanese hospital.

Objective: Clostridioides difficile infection (CDI) is a common, healthcare-associated infection. However, in Japan, testing for CDI is infrequent, suggesting that its incidence may be underestimated. This study aimed to examine the implementation of a multifaceted, diagnostic stewardship (DS) for CDI in a small Japanese hospital during the coronavirus 2019 pandemic. Design: Before-after study. Setting: A small Japanese community hospital. Participants: Healthcare workers including physicians, nurses, and pharmacists. Interventions: A multifaceted intervention including (1) the addition of CD testing criteria to the hospital guidelines; (2) provision of a tutorial on CD testing to physicians, nurses, and pharmacists; (3) assessment by clinical pharmacists and nurses of the need for CD testing in patients with nosocomial diarrhea and issuance of recommendations for CD testing to physicians; (4) reporting of data on the CD testing rate and CDI incidence in the study center. Results: The CD testing rate increased before the pandemic (+0.16/10,000 patient-days (PD); P = .28), decreased significantly during the pandemic (-0.79/10,000 PD; P = .02), and then increased significantly immediately after the implementation of the intervention (+29.6/10,000 PD; P < .01). Similarly, the CDI incidence increased significantly before the pandemic (+0.26/10,000 PD; P = .02) and decreased significantly during the pandemic (-0.49/10,000 PD; P = .01). Implementation of the intervention resulted in an immediate and significant increase in the CDI incidence (+6.2/10,000 PD; P < .01). Conclusion: Multifaceted DS involving multidisciplinary specialists was effective in improving CD testing, suggesting that appropriate testing can contribute to diagnosing CDI accurately.

Contact tracing in the hospital setting during the omicron wave of the coronavirus disease 2019 pandemic: persons and periods of concern for nosocomial infection prevention and control.

This study evaluating the efficacy of coronavirus disease 2019 contact tracing in the hospital setting during the omicron variant era found a high incidence of nosocomial severe acute respiratory coronavirus virus 2 (SARS-CoV-2) transmission in outbreaks, especially among individuals having close contact with infected persons. Identifying close contacts and outbreaks is essential to prevent nosocomial SARS-CoV-2 transmission.

Nosocomial outbreak of SARS-CoV-2 in a hospital ward during the Omicron variant-dominant wave with a review of the relevant literature.

Clusters of nosocomial coronavirus disease 2019 (COVID-19) were reported globally during the recent pandemic. Unfortunately, these clusters negatively impacted inpatient morbidity, mortality, and hospital functions. Using epidemiological data and whole genome sequencing (WGS) of SARS-CoV-2, the present study investigated an outbreak of COVID-19 at a university hospital. Eight inpatients and 13 healthcare workers tested positive for SARS-CoV-2 during a one-month period. Whole genome sequencing (WGS) of the virus in 11 patients revealed that two variants of concern belonging to the Omicron sublineages, BA.2.3 and BA1.1.2, had caused the outbreak during a time when the proportion of the Omicron lineage in the community was changing. When variants of concern are undergoing mutation, a response to the outbreak should be made with multiple variants in mind, even in the absence of epidemiological data showing close contact or other potential vectors of infection, and awareness about infection prevention and control should be raised to safeguard patient safety.

Absence of jolt accentuation of headache cannot accurately rule out meningitis in adults.

BACKGROUND: Meningitis is a common emergency disease. Signs and symptoms easily observed at the bedside are needed because early recognition of the possibility of meningitis is necessary for the decision to perform lumbar puncture. Jolt accentuation of headache has been reported to be the most sensitive diagnostic test; however, limited articles have reproduced its sensitivity. METHODS: This is a single-center retrospective medical record review between 2007 and 2012. We diagnosed meningitis based on the criterion standard that cerebrospinal fluid total cells is more than 5/mm(3), in accordance with previous studies. All diagnostic and management decisions including Kernig sign, nuchal rigidity, and jolt accentuation of headache were at the physician's discretion. We calculated the sensitivity and specificity of well-known signs and symptoms of meningitis and, especially, compared the efficacy of jolt accentuation of headache with previous studies. RESULTS: We investigated 531 adult patients who were suspected of meningitis and had lumbar puncture performed. Of these patients, 139 had meningitis. Background characteristics and vital signs were not clinically different between the 2 groups, although classic tetralogy of bacterial meningitis (fever, nuchal rigidity, mental disturbance, and headache) was worth investigated. The sensitivity and specificity of jolt accentuation of headache were 63.9% (95% confidence interval, 51.9%-76.0%) and 43.2% (34.7%-51.6%), respectively. CONCLUSION: The absence of jolt accentuation of headache test cannot, on its own, accurately rule out meningitis in adults. Further studies are warranted to reproduce this result and to discover better bedside diagnostic tests.

Effect of discontinuing ongoing education and postprescription feedback on antimicrobial prescriptions at discharge from the emergency department.

Multifaceted intervention is preferrable as an ASP strategy in the emergency department (ED). I assessed the effect of discontinuing multifaceted intervention for antimicrobial prescriptions at discharge in the emergency department. The proportion of appropriate prescriptions decreased quickly after discontinuation. Continuous commitment to appropriate antimicrobial prescriptions is needed for effective antimicrobial stewardship.

Multifaceted intervention for improving antimicrobial prescription at discharge in the emergency department.

The frequent prescription of antimicrobials, such as at discharge from the emergency department, calls for optimizing this practice through modifying physicians' prescribing behavior. A 1-year, multifaceted intervention implemented in an emergency department decreased the mean monthly antimicrobial prescription rate at discharge and increased the proportion of appropriate prescriptions.

Impact of coronavirus disease 2019 (COVID-19) pandemic on antimicrobial consumption and antimicrobial resistance at a small, local hospital in Japan.

The coronavirus disease 2019 (COVID-19) pandemic negatively affected antimicrobial stewardship programs at hospitals throughout Japan by diverting resources toward managing the pandemic. However, antimicrobial stewardship needs to continue regardless of hospital size or supervening crises. Herein, we discuss the impact of COVID-19 on antimicrobial stewardship at a small, local hospital in Japan.

Current in-hospital management for patients with tuberculosis in a high-income country: a retrospective cohort study.

OBJECTIVES: In Japan, most cases of tuberculosis (TB) occur among individuals aged 65 years or older. However, data on in-hospital adverse events (AEs) associated with TB management, especially in high-income nations with an ageing population, are scarce. The present study aimed to scrutinize the current TB unit practices, incidence of in-hospital AEs and predictors of in-hospital mortality. METHODS: This retrospective cohort study was conducted at a tertiary care centre in Tokyo, Japan from 2012 to 2017. Inpatients with the diagnosis of TB and aged >18 years were included. Quality of in-hospital care and factors associated with in-hospital mortality were investigated using multivariate logistic regression analysis. RESULTS: In total, 448 patients were enrolled. The in-hospital mortality rate was 16.7% (75/448). Miliary/disseminated TB was common (59/448, 13.2%), especially in those who died (17/75, 22.7%). Factors independently associated with in-hospital mortality were a low Karnofsky performance status score on admission (score: 40-10, adjusted odds ratio (aOR) 25.65, 95% CI 5.63-116.92 and score: 70-50, aOR 9.47, 95% CI 2.07-43.3), age over 89 years (aOR 3.68, 95% CI 1.08-12.46), Charlson Co-morbidity Index >5 (aOR 3.56, 95% CI 1.37-9.21), development of any health-care-associated infection (aOR 2.95, 95% CI 1.35-6.41), and development of any drug-related AE leading to discontinuation of anti-TB agents (seven patients were unable to resume treatment with anti-TB agents before death) (aOR 2.29, 95% CI 1.02-5.11). CONCLUSIONS: In-hospital AEs (i.e. health-care-associated infection and drug-related AEs), as well as patient-related variables, were associated with in-hospital mortality among TB patients.

Correlation of COVID-19 Severity and Immunoglobulin Presence Against Spike and Nucleocapsid Proteins in SARS-CoV-2.

Data on the human immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteins have been applied to vaccine development and diagnosing coronavirus disease 2019 (COVID-19), but little research has been done on the relationship between the human immune response and COVID-19 severity. We herein sought to determine whether there is a correlation between the immunoglobulin level and COVID-19 severity. Clinical samples were collected from 102 patients with COVID-19. Of these, 65 and 37 patients had mild and severe symptoms, respectively. An enzyme-linked immunosorbent assay using the recombinant SARS-CoV-2 nucleocapsid (N) protein, spike (S) protein, and synthetic peptides covering N and S as antigens was performed to measure the IgM and IgG levels. The correlation between the immunoglobulin level and COVID-19 severity was then analyzed. A significant difference in the level of IgG antibodies against N and of IgM antibodies against the receptor binding domain of the S protein was observed between patients with nonsevere and severe COVID-19 symptoms, and the level of IgG antibodies against N was found to be higher in patients with severe symptoms whereas the level of IgM antibodies against the S peptides was higher in patients with nonsevere symptoms. The level of specific antibodies against SARS-CoV-2 structural proteins might correlate with COVID-19 severity. If so, this fact may be useful for predicting the prognosis of the disease and in determining the appropriate treatment with greater precision.

A survey of preparedness against coronavirus disease 2019 (COVID-19) in hospitals in Tokyo, Japan, with healthcare personnel with COVID-19 and in-facility transmission.

A questionnaire was distributed to hospitals in Tokyo (N = 38) regarding their preparedness against and in-facility transmission of coronavirus disease 2019 (COVID-19). As of May 31, 2020, 284 HCP had contracted COVID-19, and in-facility COVID-19 transmission occurred at 13 hospitals, negatively impacting hospital functions and patient care.

Antimicrobial Time-Out for Vancomycin by Infectious Disease Physicians Versus Clinical Pharmacists: A Before-After Crossover Trial.

BACKGROUND: The present study assessed the impact of time-out on vancomycin use and compared the strategy's efficacy when led by pharmacists versus infectious disease (ID) physicians at a tertiary care center. METHODS: Time-out, consisting of a telephone call to inpatient providers and documentation of vancomycin use >72 hours, was performed by ID physicians and clinical pharmacists in the Departments of Medicine and Surgery/Critical Care. Patients in the Department of Medicine were assigned to the clinical pharmacist-led arm, and patients in the Department of Surgery/Critical Care were assigned to the ID physician-led arm in the initial, 6-month phase and were switched in the second, 6-month phase. The primary outcome was the change in weekly days of therapy (DOT) per 1000 patient-days (PD), and vancomycin use was compared using interrupted time-series analysis. RESULTS: Of 587 patients receiving vancomycin, 132 participated, with 79 and 53 enrolled in the first and second phases, respectively. Overall, vancomycin use decreased, although the difference was statistically nonsignificant (change in slope, -0.25 weekly DOT per 1000 PD; 95% confidence interval [CI], -0.68 to 0.18; P = .24). The weekly vancomycin DOT per 1000 PD remained unchanged during phase 1 but decreased significantly in phase 2 (change in slope, -0.49; 95% CI, -0.84 to -0.14; P = .007). Antimicrobial use decreased significantly in the surgery/critical care patients in the pharmacist-led arm (change in slope, -0.77; 95% CI, -1.33 to -0.22; P = .007). CONCLUSIONS: Vancomycin time-out was moderately effective, and clinical pharmacist-led time-out with surgery/critical care patients substantially reduced vancomycin use.