Contamination rate of rare bacterial species detected by MALDI-TOFMS: a retrospective cohort study.

When rare bacterial species are identified in blood cultures, determining the clinical significance is sometimes difficult. This study aimed to analyze the clinical significance of rare bacterial species detected in blood cultures using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOFMS) by comparing their contamination rates with those of common species. We retrospectively analyzed medical records of adult patients with positive blood cultures at Kyoto City Hospital from 2014 to 2022. Rare species were defined by low detection rates and few PubMed reports. Of 4880 microorganisms identified from 3441 individuals, 1150 (23.6%) were classified as contamination. Meanwhile, 24 rare microorganisms were identified, of which 14 (58.3%) were classified as contamination, which was significantly higher than common species (odds ratio 4.56, 95% confidence Interval 1.88-11.50, P < 0.001). These findings may help in determining the clinical significance of rare bacterial species in blood cultures with few reported cases.

COVID-19 vaccine effectiveness against severe COVID-19 requiring oxygen therapy, invasive mechanical ventilation, and death in Japan: A multicenter case-control study (MOTIVATE study).

INTRODUCTION: Since the SARS-CoV-2 Omicron variant became dominant, assessing COVID-19 vaccine effectiveness (VE) against severe disease using hospitalization as an outcome became more challenging due to incidental infections via admission screening and variable admission criteria, resulting in a wide range of estimates. To address this, the World Health Organization (WHO) guidance recommends the use of outcomes that are more specific to severe pneumonia such as oxygen use and mechanical ventilation. METHODS: A case-control study was conducted in 24 hospitals in Japan for the Delta-dominant period (August-November 2021; "Delta") and early Omicron (BA.1/BA.2)-dominant period (January-June 2022; "Omicron"). Detailed chart review/interviews were conducted in January-May 2023. VE was measured using various outcomes including disease requiring oxygen therapy, disease requiring invasive mechanical ventilation (IMV), death, outcome restricting to "true" severe COVID-19 (where oxygen requirement is due to COVID-19 rather than another condition(s)), and progression from oxygen use to IMV or death among COVID-19 patients. RESULTS: The analysis included 2125 individuals with respiratory failure (1608 cases [75.7%]; 99.2% of vaccinees received mRNA vaccines). During Delta, 2 doses provided high protection for up to 6 months (oxygen requirement: 95.2% [95% CI:88.7-98.0%] [restricted to "true" severe COVID-19: 95.5% {89.3-98.1%}]; IMV: 99.6% [97.3-99.9%]; fatal: 98.6% [92.3-99.7%]). During Omicron, 3 doses provided high protection for up to 6 months (oxygen requirement: 85.5% [68.8-93.3%] ["true" severe COVID-19: 88.1% {73.6-94.7%}]; IMV: 97.9% [85.9-99.7%]; fatal: 99.6% [95.2-99.97]). There was a trend towards higher VE for more severe and specific outcomes. CONCLUSION: Multiple outcomes pointed towards high protection of 2 doses during Delta and 3 doses during Omicron. These results demonstrate the importance of using severe and specific outcomes to accurately measure VE against severe COVID-19, as recommended in WHO guidance in settings of intense transmission as seen during Omicron.

A case of amebic colitis and liver abscesses that occurred after treatment of coronavirus disease 2019 with dexamethasone.

Entamoeba histolytica infections, which can be asymptomatic, are endemic to developing countries; traveling to such countries is a risk factor for contracting these infections. A 65-year-old Japanese man was hospitalized for coronavirus disease 2019 (COVID-19)-associated respiratory distress, and was treated with remdesivir, dexamethasone, and oxygen supplementation. Although his respiratory condition improved and the oxygen support was discontinued, he developed a fever, severe abdominal pain, and diarrhea on day 13 of hospitalization. Fifteen years ago, he was hospitalized for diarrhea of an unknown origin in Suzhou, China, and had a history of passing loose stools for 1 year. Contrast-enhanced abdominal and pelvic computed tomography revealed liver abscesses in both lobes and intestinal edema from the ascending colon to the descending colon. The abscesses were suspected to be amebic based on the characteristics of the drained abscess fluid. The patient was treated with cefotaxime and metronidazole, and his temperature declined and abdominal pain improved. A culture analysis of abscess fluid yielded negative findings; however, polymerase chain reaction analyses of abscess and stool samples were positive for Entamoeba histolytica. We speculated that the patient was infected with Entamoeba histolytica while in China, and that the corticosteroid usage for COVID-19 had exacerbated the infection. Clinicians should be aware that corticosteroid treatments can lead to recurrent invasive amebiasis in asymptomatic amebic carriers.

Pre-emptive antifungal therapy versus empirical antifungal therapy for febrile neutropenia in people with cancer.

BACKGROUND: Intensive cytotoxic chemotherapy for people with cancer can cause severe and prolonged cytopenia, especially neutropenia, a critical condition that is potentially life-threatening. When manifested by fever and neutropenia, it is called febrile neutropenia (FN). Invasive fungal disease (IFD) is one of the serious aetiologies of chemotherapy-induced FN. In pre-emptive therapy, physicians only initiate antifungal therapy when an invasive fungal infection is detected by a diagnostic test. Compared to empirical antifungal therapy, pre-emptive therapy may reduce the use of antifungal agents and associated adverse effects, but may increase mortality. The benefits and harms associated with the two treatment strategies have yet to be determined.  OBJECTIVES: To assess the relative efficacy, safety, and impact on antifungal agent use of pre-emptive versus empirical antifungal therapy in people with cancer who have febrile neutropenia. SEARCH METHODS: We searched CENTRAL, MEDLINE Ovid, Embase Ovid, and ClinicalTrials.gov to October 2021. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared pre-emptive antifungal therapy with empirical antifungal therapy for people with cancer. DATA COLLECTION AND ANALYSIS: We identified 2257 records from the databases and handsearching. After removing duplicates, screening titles and abstracts, and reviewing full-text reports, we included seven studies in the review. We evaluated the effects on all-cause mortality, mortality ascribed to fungal infection, proportion of antifungal agent use (other than prophylactic use), duration of antifungal use (days), invasive fungal infection detection, and adverse effects for the comparison of pre-emptive versus empirical antifungal therapy. We presented the overall certainty of the evidence for each outcome according to the GRADE approach. MAIN RESULTS: This review includes 1480 participants from seven randomised controlled trials. Included studies only enroled participants at high risk of FN (e.g. people with haematological malignancy); none of them included participants at low risk (e.g. people with solid tumours).  Low-certainty evidence suggests there may be little to no difference between pre-emptive and empirical antifungal treatment for all-cause mortality (risk ratio (RR) 0.97, 95% confidence interval (CI) 0.72 to 1.30; absolute effect, reduced by 3/1000); and for mortality ascribed to fungal infection (RR 0.92, 95% CI 0.45 to 1.89; absolute effect, reduced by 2/1000). Pre-emptive therapy may decrease the proportion of antifungal agent used more than empirical therapy (other than prophylactic use; RR 0.71, 95% CI 0.47 to 1.05; absolute effect, reduced by 125/1000; very low-certainty evidence). Pre-emptive therapy may reduce the duration of antifungal use more than empirical treatment (mean difference (MD) -3.52 days, 95% CI -6.99 to -0.06, very low-certainty evidence). Pre-emptive therapy may increase invasive fungal infection detection compared to empirical treatment (RR 1.70, 95% CI 0.71 to 4.05; absolute effect, increased by 43/1000; very low-certainty evidence). Although we were unable to pool adverse events in a meta-analysis, there seemed to be no apparent difference in the frequency or severity of adverse events between groups. Due to the nature of the intervention, none of the seven RCTs could blind participants and personnel related to performance bias. We identified considerable clinical and statistical heterogeneity, which reduced the certainty of the evidence for each outcome. However, the two mortality outcomes had less statistical heterogeneity than other outcomes. AUTHORS' CONCLUSIONS: For people with cancer who are at high-risk of febrile neutropenia, pre-emptive antifungal therapy may reduce the duration and rate of use of antifungal agents compared to empirical therapy, without increasing over-all and IFD-related mortality; but the evidence regarding invasive fungal infection detection and adverse events was inconsistent and uncertain.

Association between serum alkaline phosphatase and bacteraemia in haemodialysis outpatients: a multicentre retrospective cross-sectional study.

OBJECTIVES: Elevated baseline serum alkaline phosphatase (ALP) may correlate with higher medium-term to long-term mortality in the general population and in patients with chronic kidney disease. However, few data are available on the association between serum ALP and the short-term prognosis of patients on haemodialysis (HD). We verified the association of ALP levels and bacteraemia or death in maintenance HD patients suspected of bacteraemia in an outpatient setting. DESIGN: We analysed 315 consecutive HD patients suspected of having bacteraemia with two sets of blood culture drawn on admission. SETTING: Admission to two tertiary-care university medical centres from January 2013 to December 2015. PARTICIPANTS: Consecutive cases on maintenance HD aged≥18 years. Cases of hospitalised patients who had been transferred from another hospital, had a dialysis vintage<2 months, were also undergoing peritoneal dialysis, and/or were receiving HD less than once a week were excluded. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome measure was bacteraemia and secondary outcome was in-hospital death. RESULTS: Among 315 cases included in the study, 187 had baseline-measured ALP levels, with a cut-off value on ROC analysis of 360 U/L (Area Under the Curve (AUC) 0.60, sensitivity 0.49, specificity 0.76). In multivariate analysis, there was a statistically significant association between a higher ALP in hospital visit and bacteraemia (OR: 2.37, 95% CI: 1.17 to 4.83). However, there were no statistically significant associations between higher ALP and in-hospital death (OR: 1.20, 95% CI: 0.57 to 2.54). A sensitivity analysis of 187 patients with no missing ALP values also demonstrated a significant association between elevated ALP and bacteraemia, but no significant association between ALP and in-hospital death. CONCLUSIONS: Elevated ALP is a predictor of bacteraemia. In HD patients suspected of bacteraemia in outpatient settings, increased ALP levels were associated with increased likelihood of confirmed disease.

Two cases of pyelonephritis with bacteremia by Staphylococcus epidermidis in male patients with nephrolithiasis: Case reports and a literature review.

BACKGROUND: Staphylococcus epidermidis is a common cause of health care-associated bacteremia, especially in patients with an indwelling medical device. However, S. epidermidis is an uncommon causative organism in catheter-associated urinary tract infection, and rare pyelonephritis without any indwelling urinary device. To our knowledge, there are few cases reported of bacteremia secondary to urinary tract infection. We report two cases of pyelonephritis with bacteremia by S. epidermidis in male patients with unilateral nephrolithiasis and review prior case reports. CASE PRESENTATION: Case 1: 74-year-old man with a history of diabetes and overactive bladder had fever and pyuria with a right nephrolithiasis on abdominal CT scan. Case 2: 79-year-old man with a history of diabetes and post-myocardial infarction status had fever with a left nephrolithiasis on abdominal CT scan. In both cases, both the urine culture collected at ureteral stenting and blood culture were positive for S. epidermidis. We initiated intravenous antibiotics in these patients in addition to ureteral stenting. CONCLUSIONS: S. epidermidis is acknowledged as an uncommon pathogen that can cause bacteremia secondary to pyelonephritis without an indwelling urinary device. Clinicians should consider the possibility of pyelonephritis due to S. epidermidis if the pathogen is identified in blood and urine in patients with nephrolithiasis.

Cervical abscess caused by Mycobacterium tilburgii in a patient carrying anti-interferon gamma autoantibody: A case report and literature review.

Mycobacterium tilburgii, a nonculturable mycobacterium, is an important nontuberculous mycobacterium that occasionally causes serious infections in patients with cellular immune deficiencies. Due to its nonculturable nature, information about its drug susceptibility is not available, and data about its clinical response to antimycobacterial treatment remains insufficient. Here, we report a case of a patient who presented with neck swelling and was finally diagnosed with cervical abscess caused by M. tilburgii carrying anti-interferon gamma autoantibodies using a molecular method. The relevant literature was reviewed in the context of epidemiological and clinical data on M. tilburgii infections. In this report, 15 patients were reported to be infected with M. tilburgii. Almost all patients had a cellular immune deficiency and presented with disseminated infections. Multiple refractory or relapse cases that often required prolonged antimycobacterial treatment have been reported, although a few fatal cases have also been reported. In conclusion, M. tilburgii is an important pathogen in patients with cellular immune deficiency. Physicians should thoroughly investigate cellular immune deficiency, including adult-onset immune deficiency with anti-interferon gamma autoantibodies, in patients with M. tilburgii infection.

Two Cases of Kikuchi Disease Presenting with Aseptic Meningitis and Encephalitis.

Kikuchi disease, also called histiocytic necrotizing lymphadenitis, is an idiopathic and generally self-limiting disease affecting young adults and children. Kikuchi disease does not commonly manifest neurological complications at its initial presentation. We herein report two cases of Kikuchi disease that initially presented with aseptic meningitis and encephalitis rather than the more common signs of lymphadenopathy, rash, and arthritis. A 15-year-old boy presented with aseptic meningitis with an extremely high intracranial pressure. A 28-year-old man presented with dysesthesia of the right lower extremity, coinciding with abnormal magnetic resonance imaging findings. In both cases, painful cervical lymphadenopathy was observed following the central nervous system symptoms. Both patients improved after treatment with steroids. Kikuchi disease occasionally affects the central nervous system, to which lymphadenitis may be observed subsequently. A repeated, careful physical examination of the cervical lymph nodes may be helpful for the diagnosis.

Non-typhoidal Salmonella bacteremia in COVID-19 with recrudescence of fever after corticosteroid discontinuation: A case report.

It is challenging for clinicians to determine the cause of occurrence of fever in COVID-19 patients after corticosteroid discontinuation. Blood cultures help us distinguish between secondary infections and rebound phenomena. We report a case of non-typhoidal Salmonella bacteremia in a 34-year-old male COVID-19 patient who developed fever after discontinuing corticosteroids.

Influence of anti-coronavirus disease 2019 policies on 10 pediatric infectious diseases.

BACKGROUND: To combat the coronavirus disease 2019 pandemic, many countries, including Japan, implemented policies limiting social activities and encouraging preventive behaviors. This study examines the influence of such policies on the trends of 10 infectious pediatric diseases: pharyngoconjunctival fever; group A streptococcal pharyngitis; infectious gastroenteritis; chickenpox; erythema infectiosum; hand, foot, and mouth disease; herpangina; respiratory syncytial virus; exanthem subitum; and mumps. METHODS: The research adopted a retrospective cohort study design. We collected data from Japan's National Epidemiological Surveillance Program detailing the incidences of the 10 diseases per pediatric sentinel site for a period beginning at 9 weeks before government-ordered school closures and ending at 9 weeks after the end of the state of emergency. We obtained corresponding data for the equivalent weeks in 2015-2019. We estimated the influence of the policies using a difference-in-differences regression model. RESULTS: For seven diseases (pharyngoconjunctival fever; group A streptococcal pharyngitis; infectious gastroenteritis; chickenpox; erythema infectiosum; hand, foot, and mouth disease; and herpangina), the incidence in 2020 decreased significantly during and after the school closures. Sensitivity analysis, in which the focus area was limited to the policy-implementation period or existing trend patterns, replicated these significant decreases for one of the above mentioned seven diseases - infectious gastroenteritis. CONCLUSIONS: Policies such as school closures and encouragement of preventive behaviors were associated with significant decreases in the incidences of most of the 10 diseases, which sensitivity analysis replicated in infectious gastroenteritis. To determine the long-term effects of these policies, prospective cohort studies are needed.

Development and external validation of a deep learning-based computed tomography classification system for COVID-19.

BACKGROUND: We aimed to develop and externally validate a novel machine learning model that can classify CT image findings as positive or negative for SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR). METHODS: We used 2,928 images from a wide variety of case-control type data sources for the development and internal validation of the machine learning model. A total of 633 COVID-19 cases and 2,295 non-COVID-19 cases were included in the study. We randomly divided cases into training and tuning sets at a ratio of 8:2. For external validation, we used 893 images from 740 consecutive patients at 11 acute care hospitals suspected of having COVID-19 at the time of diagnosis. The dataset included 343 COVID-19 patients. The reference standard was RT-PCR. RESULTS: In external validation, the sensitivity and specificity of the model were 0.869 and 0.432, at the low-level cutoff, 0.724 and 0.721, at the high-level cutoff. Area under the receiver operating characteristic was 0.76. CONCLUSIONS: Our machine learning model exhibited a high sensitivity in external validation datasets and may assist physicians to rule out COVID-19 diagnosis in a timely manner at emergency departments. Further studies are warranted to improve model specificity.

Added value of clinical prediction rules for bacteremia in hemodialysis patients: An external validation study.

INTRODUCTION: Having developed a clinical prediction rule (CPR) for bacteremia among hemodialysis (HD) outpatients (BAC-HD score), we performed external validation. MATERIALS & METHODS: Data were collected on maintenance HD patients at two Japanese tertiary-care hospitals from January 2013 to December 2015. We enrolled 429 consecutive patients (aged ≥ 18 y) on maintenance HD who had had two sets of blood cultures drawn on admission to assess for bacteremia. We validated the predictive ability of the CPR using two validation cohorts. Index tests were the BAC-HD score and a CPR developed by Shapiro et al. The outcome was bacteremia, based on the results of the admission blood cultures. For added value, we also measured changes in the area under the receiver operating characteristic curve (AUC) using logistic regression and Net Reclassification Improvement (NRI), in which each CPR was added to the basic model. RESULTS: In Validation cohort 1 (360 subjects), compared to a Model 1 (Basic Model) AUC of 0.69 (95% confidence interval [95% CI]: 0.59-0.80), the AUC of Model 2 (Basic model + BAC-HD score) and Model 3 (Basic model + Shapiro's score) increased to 0.8 (95% CI: 0.71-0.88) and 0.73 (95% CI: 0.63-0.83), respectively. In validation cohort 2 (96 subjects), compared to a Model 1 AUC of 0.81 (95% CI: 0.68-0.94), the AUCs of Model 2 and Model 3 increased to 0.83 (95% CI: 0.72-0.95) and 0.85 (95% CI: 0.76-0.94), respectively. NRIs on addition of the BAC-HD score and Shapiro's score were 0.3 and 0.06 in Validation cohort 1, and 0.27 and 0.13, respectively, in Validation cohort 2. CONCLUSION: Either the BAC-HD score or Shapiro's score may improve the ability to diagnose bacteremia in HD patients. Reclassification was better with the BAC-HD score.

Longitudinal association between mental health and future antibiotic prescriptions in healthy adults: Results from the LOHAS.

OBJECTIVES: To investigate the association of mental health and subjective physical functioning with future antibiotic prescriptions. DESIGN: Prospective cohort study. SETTING: A rural town in Japan. PARTICIPANTS: Participants who completed the baseline survey (2008-2010) of the Locomotive Syndrome and Health Outcomes in the Aizu Cohort Study (LOHAS) were recruited. Participants were limited to those without comorbidities according to the Charlson comorbidity index. Participants using antibiotics at baseline were excluded. Mental health and physical functioning were assessed using the Mental Health and Physical Functioning domains of the Short-Form 12 Health Survey, and depressive symptoms were assessed using the Mental Health Inventories at baseline. MAIN OUTCOME MEASURES: The main outcome was antibiotic prescriptions found in claims data during 1 year after the baseline survey. RESULTS: A total of 967 participants were included in the analysis, and 151 (15.6%) participants with at least one missing variable for the confounding factors were excluded, leaving 816 participants for the primary analysis. Among the 816 participants, 65 (8.0%) were newly prescribed at least one antibiotic during the 1-year follow-up period. The most frequently prescribed antibiotics were third-generation cephalosporins (44 prescriptions; 35.5%), macrolides (28 prescriptions; 22.6%), and quinolones (23 prescriptions; 18.6%). A multivariable logistic regression analysis showed an association between higher mental health scores and future antibiotic prescriptions (adjusted odds ratio [AOR], 1.40 per 1 standard deviation [SD] increase; 95% confidence interval [CI], 1.03-1.90), whereas no significant relationship was observed between Physical Functioning scores and future antibiotic prescriptions (AOR, 0.95 per 1 SD increase; 95% CI, 0.75-1.22). During the secondary analysis, adults with depressive symptoms were less likely to be prescribed antibiotics (AOR, 0.27; 95% CI, 0.11-0.70). CONCLUSIONS: Better mental health was associated with increased future antibiotic prescriptions for healthy community-dwelling Japanese adults, suggesting that mentally healthier adults could be a target population for reducing antimicrobial use.

Imported and locally transmitted mild SARS-CoV-2 pneumonia cases in Japan.

Here, we describe two mild SARS-CoV-2 pneumonia cases. One was imported from Wuhan, and the other was locally transmitted in Japan without recent travel to China. In both cases, lower respiratory tract symptoms were observed first, and high fever progressed in about one week. The laboratory findings revealed normal WBC and CRP despite apparent lung infiltrations, and typical observations on CT imaging were important diagnostic clues. In the domestic endemic situation, a comprehensive evaluation of the clinical course, and laboratory and radiological findings was required for diagnosis.

Clinical and Molecular Characteristics of Klebsiella pneumoniae Isolates Causing Bloodstream Infections in Japan: Occurrence of Hypervirulent Infections in Health Care.

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

Development of Delayed Hemolytic Anemia After Treatment with Oral Artemether-Lumefantrine in Two Patients with Severe Falciparum Malaria.

AbstractRecently, reports of delayed hemolytic anemia after treatment with artemisinin and its derivatives have emerged. Here we report two cases of delayed hemolytic anemia in a patient with severe falciparum malaria after treatment with oral artemether-lumefantrine (AL). The first patient, a 20-year-old Japanese male student, was diagnosed with falciparum malaria and was administered AL. As having a high parasitemia rate (20.6%) was the only severe malaria criterion met in this case and his general condition was stable, we continued with AL treatment. Despite disappearance of malarial parasites after 4 days of AL administration, a persistent fever remained. On days 13 and 16, a diagnosis of hemolytic anemia was made (lactate dehydrogenase [LDH]: 1,466 U/L, hemoglobin [Hb]: 7.2 g/dL). A blood smear at that time revealed no parasites. He recovered naturally from delayed hemolysis. The second patient, a 27-year-old Japanese female student, was diagnosed with falciparum malaria (parasitemia: 4.5%) and treated initially with oral quinine hydrochloride and doxycycline. The following day, parasitemia increased to 7.9% and oral AL was initiated. She was discharged on day 4 after achieving parasite clearance and afebrility. However, on day 5, fever (body temperature > 38°C) recurred, and on day 11, a diagnosis of hemolytic anemia was made (LDH: 712 U/L, Hb: 8.8 g/dL). A follow-up confirmed that her condition improved gradually. AL treatment of severe malaria can cause delayed hemolytic anemia. Patients should be followed up for up to 4 weeks to detect signs of hemolysis and provide appropriate symptomatic treatment.