Timing and prediction of secondary bacteremia in patients with COVID-19: A retrospective cohort study.

Background: We aimed to aid the appropriate use of antimicrobial agents by determining the timing of secondary bacteremia and validating and updating clinical prediction models for bacteremia in patients with COVID-19. Methods: We performed a retrospective cohort study on all hospitalized patients diagnosed with COVID-19 who underwent blood culture tests from January 1, 2020, and September 30, 2021, at an urban teaching hospital in Japan. The primary outcome measure was secondary bacteremia in patients with COVID-19. Results: Of the 507 patients hospitalized with COVID-19, 169 underwent blood culture tests. Eleven of them had secondary bacteremia. The majority of secondary bacteremia occurred on or later than the 9th day after symptom onset. Positive blood culture samples collected on day 9 or later after disease onset had an odds ratio of 22.4 (95% CI 2.76-181.2, p < 0.001) compared with those collected less than 9 days after onset. The area under the receiver operating characteristic curve of the modified Shapiro rule combined with blood culture collection on or after the 9th day from onset was 0.919 (95% CI, 0.843-0.995), and the net benefit was high according to the decision curve analysis. Conclusions: The timings of symptom onset and hospital admission may be valuable indicators for making a clinical decision to perform blood cultures in patients hospitalized with COVID-19.

Oral mouthwashes for asymptomatic to mildly symptomatic adults with COVID-19 and salivary viral load: a randomized, placebo-controlled, open-label clinical trial.

BACKGROUND: Recent randomized clinical trials suggest that the effect of using cetylpyridinium chloride (CPC) mouthwashes on the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load in COVID-19 patients has been inconsistent. Additionally, no clinical study has investigated the effectiveness of on-demand aqueous chlorine dioxide mouthwash against COVID-19. METHODS: We performed a randomized, placebo-controlled, open-label clinical trial to assess for any effects of using mouthwash on the salivary SARS-CoV-2 viral load among asymptomatic to mildly symptomatic adult COVID-19-positive patients. Patients were randomized to receive either 20 mL of 0.05% CPC, 10 mL of 0.01% on-demand aqueous chlorine dioxide, or 20 mL of placebo mouthwash (purified water) in a 1:1:1 ratio. The primary endpoint was the cycle threshold (Ct) values employed for SARS-CoV-2 salivary viral load estimation. We used linear mixed-effects models to assess for any effect of the mouthwashes on SARS-CoV-2 salivary viral load. RESULTS: Of a total of 96 eligible participants enrolled from November 7, 2022, to January 19, 2023, 90 were accepted for the primary analysis. The use of 0.05% CPC mouthwash was not shown to be superior to placebo in change from baseline salivary Ct value at 30 min (difference vs. placebo, 0.640; 95% confidence interval [CI], -1.425 to 2.706; P = 0.543); 2 h (difference vs. placebo, 1.158; 95% CI, -0.797 to 3.112; P = 0.246); 4 h (difference vs. placebo, 1.283; 95% CI, -0.719 to 3.285; P = 0.209); 10 h (difference vs. placebo, 0.304; 95% CI, -1.777 to 2.385; P = 0.775); or 24 h (difference vs. placebo, 0.782; 95% CI, -1.195 to 2.759; P = 0.438). The use of 0.01% on-demand aqueous chlorine dioxide mouthwash was also not shown to be superior to placebo in change from baseline salivary Ct value at 30 min (difference vs. placebo, 0.905; 95% CI, -1.079 to 2.888; P = 0.371); 2 h (difference vs. placebo, 0.709; 95% CI, -1.275 to 2.693; P = 0.483); 4 h (difference vs. placebo, 0.220; 95% CI, -1.787 to 2.226; P = 0.830); 10 h (difference vs. placebo, 0.198; 95% CI, -1.901 to 2.296; P = 0.854); or 24 h (difference vs. placebo, 0.784; 95% CI, -1.236 to 2.804; P = 0.447). CONCLUSIONS: In asymptomatic to mildly symptomatic adults with COVID-19, compared to placebo, the use of 0.05% CPC and 0.01% on-demand aqueous chlorine dioxide mouthwash did not lead to a significant reduction in SARS-CoV-2 salivary viral load. Future studies of the efficacy of CPC and on-demand aqueous chlorine dioxide mouthwash on the viral viability of SARS-CoV-2 should be conducted using different specimen types and in multiple populations and settings.

Protocol for a Randomized, Open-Label Clinical Trial on the Effect of Mouthwash on Salivary SARS-CoV-2 Load.

Mouthwashes containing cetylpyridinium chloride (CPC) or on-demand aqueous chlorine dioxide (ACD) have potential to reduce the salivary severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) load in individuals with SARS-CoV-2 infection. This study will evaluate the effect of CPC and on-demand ACD mouthwashes on salivary SARS-CoV-2 levels in individuals with acute asymptomatic or mild SARS-CoV-2 infection (COVID-19) staying in a residential recuperation facility in Osaka, Japan. This randomized, open-label clinical trial will include three equal-sized groups (CPC mouthwash, on-demand ACD mouthwash, and placebo), with 30 participants per group. A stratified replacement block method will be used to ensure balanced allocation based on symptom presence and days since symptom onset. Participants will use mouthwash at set times for 7 days or until the end of recuperation. Saliva samples will be collected at multiple time points and tested for SARS-CoV-2 using quantitative reverse transcription polymerase chain reaction. The primary outcome will be changes in salivary SARS-CoV-2 viral load 2 h after the first mouthwash use compared with the pre-mouthwash level. Secondary outcomes will include changes in salivary viral load and clinical parameters at different time points. This study was registered with the Japan Registry of Clinical Trials on 18 October 2022 (jRCTs051220107).

Prehospital shock index predicts 24-h mortality in trauma patients with a normal shock index upon emergency department arrival.

BACKGROUND: The shock index (heart rate divided by systolic blood pressure) of trauma patients upon emergency department arrival predicts blood loss and death. However, some patients with normal shock indices (0.4 < shock index <0.9) upon emergency department arrival also have poor prognoses. This study aimed to determine whether abnormal prehospital shock indices in trauma patients with normal shock indices upon emergency department arrival were predictors of a high risk of mortality. METHODS: We conducted a retrospective cohort study of emergency department-admitted trauma patients from 2004 to 2017. The study included 89,495 consecutive trauma patients aged ≥16 years, with Abbreviated Injury Scale score of ≥3, who were transported to the emergency department directly from the field and had a normal shock index upon emergency department arrival. According to the prehospital shock index scores, the patients were categorized into low shock index (≤ 0.4), normal shock index, and high shock index (≥0.9) groups. Odds ratios and 95% confidence intervals were calculated using logistic regression analysis. RESULTS: The 89,495 patients had a median age of 64 (interquartile range: 43-79) years, and 55,484 (62.0%) of the patients were male. There were 1350 (1.5%) 24-h deaths in total; 176/4263 (4.1%), 1017/78,901 (1.3%), and 157/6331 (2.5%) patients were in the low, normal, and high prehospital shock index groups, respectively. The adjusted odds ratios for 24-h mortality compared with the normal shock index group were 1.63 (95% confidence interval: 1.34-1.99) in the low shock index group and 1.62 (95% confidence interval: 1.31-1.99) in the high shock index group. CONCLUSION: Trauma patients with abnormal prehospital shock indices but normal shock indices upon emergency department arrival are at a higher risk of 24-h mortality. Identifying these indices could improve triage and targeted care for patients.

Dose-response relationship between diarrhea quantity and mortality in critical care patients: A retrospective cohort study.

BACKGROUND: Previous studies have shown that diarrhea, defined as a dichotomized cutoff, is associated with increased mortality of patients in intensive care units (ICUs). This study aimed to examine the dose-response relationship between the quantity of diarrhea and mortality in ICU patients with newly developed diarrhea. METHODS: We conducted this single-center retrospective cohort study. We consecutively included all adult patients with newly developed diarrhea in the ICU between January 2017 and December 2018. Newly developed diarrhea was defined according to the World Health Organization definition. The consistency of diarrhea was evaluated by the Bristol stool chart scale, and the quantity of diarrhea was assessed on the day when patients newly developed diarrhea. The primary outcome was in-hospital mortality. The risk ratio (RR) and 95% confidence interval (CI) for the association between diarrhea quantity and mortality were estimated using multivariable modified Poisson regression models. RESULTS: Among the 231 participants, 68.4% were men; the median age was 72 years. The median diarrhea quantity was 401g (interquartile range [IQR] 230‒645g), and in-hospital mortality was 22.9%. More diarrhea at baseline was associated with higher in-hospital mortality; the adjusted RR (95% CI) per 200-g increase was 1.10 (1.01‒1.20), p = 0.029. In sensitivity analyses with near quartile categories of diarrhea quantity (<250g, 250-399g, 400-649g, ≥650g), the adjusted RRs for each respective category were 1.00 (reference), 1.02 (0.51-2.04), 1.29 (0.69-2.43), and 1.77 (0.99-3.21), p for trend = 0.033. CONCLUSIONS: A greater quantity of diarrhea was an independent risk factor for in-hospital mortality. The diarrhea quantity may be an indicator of disease severity in ICU patients.

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.

Association Between Empirical Anti-Pseudomonal Antibiotics for Recurrent Lower Respiratory Tract Infections and Mortality: A Retrospective Cohort Study.

Purpose: Whether the empirical use of anti-pseudomonal antibiotics actually improves patient outcomes is unclear. Hence, we aimed to determine whether empirical anti-pseudomonal antibiotics are better than anti-pseudomonal antibiotics in treating patients with recurrent lower respiratory tract infections (LRTIs). Patients and Methods: We extracted data from the Japanese nationwide database of the Real World Data Co., Ltd. Our target population was patients with LRTIs, defined as chronic obstructive pulmonary disease exacerbation and pneumonia. We included patients aged ≥40 years who were admitted for lower respiratory tract infections ≥2 times within 90 days. We excluded patients who had an event (death or transfer) within 24 h after admission. We ran a frailty model adjusted for the following confounding factors: number of recurrences, age, body mass index, activities of daily living, Hugh-Johns classification, altered mental status, oxygen use on admission, blood urea nitrogen, and systemic steroid use. Results: We included 893 patients with 1362 observations of recurrent LRTIs. There were 897 (66%) observations in the non-anti-pseudomonal antibiotic group and 465 (34%) in the anti-pseudomonal group; the numbers of in-hospital deaths were 86/897 (10%) and 63/465 (14%), respectively. Our frailty model yielded an adjusted hazard ratio (HR) (anti-pseudomonal group/non-anti-pseudomonal group) of 1.49 (95% confidence interval, 1.03-2.14). Conclusion: The empirical use of anti-pseudomonal antibiotics was associated with a higher HR of in-hospital mortality than the use of non-anti-pseudomonal antibiotics. Physicians might need to consider limiting the prescription of anti-pseudomonal antibiotics based on background factors such as the patient's baseline function and disease severity. Further studies are needed to evaluate the causal relationship between empirical anti-pseudomonal antibiotics and mortality, and identify specific patient population who benefit from empirical anti-pseudomonal antibiotics.

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.

Precisión de la prueba diagnóstica de acentuación de la cefalea mediante sacudidas cefálicas para el diagnóstico de meningitis aguda en urgencias / Diagnostic test accuracy of jolt accentuation for headache in acute meningitis in the emergency setting

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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.