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In most existing studies on the impact of infectious disease (ID) specialty care on bloodstream infections, ID consultations were started upon request or mandatory after notification of positive blood cultures; however, initial antibiotic therapy had already been administrated at that time by attending physicians. This study aimed to assess the impact of early ID consultation at the time of blood culture collection on therapeutic management and outcome of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. This retrospective cohort study investigated all patients with MRSA bacteremia (MRSAB) from 2011 to 2018. Proactive ID consultations were available 24 h per day, 7 days per week and obtained upon request by attending physicians, and patients were classed as having early ID consultation (at the time of blood culture collection) or late ID consultation (after notification of positive blood cultures), or none. A total of 55 first MRSAB episodes were included. In the ID consultation group, a significantly higher proportion of patients were treated for more than 14 days, and significantly more echocardiography and follow-up blood cultures were performed. Moreover, patients in the ID consultation group were hospitalized for a significantly shorter period overall. With respect to cost, we noted a possible association between ID consultation and lower hospital charges. Furthermore, relative to late ID consultation, patients receiving early ID consultation were more likely to receive appropriate empirical therapy and had significantly lower all-cause in-hospital mortality (odds ratio, 0.034; 95% confidence interval [CI], 0.0002–0.51; p = 0.015) and long-term mortality (hazard ratio, 0.17; 95% CI, 0.033–0.83; p = 0.028).

As of October 2020, there is still no specific drug to treat COVID-19 as it rages around the world. Favipiravir, indicated for the treatment of new and re-emerging influenza infections, has been suggested to be effective against SARS-CoV-2, although this has not yet been fully validated. We administered favipiravir to a 64-year-old female patient with COVID-19. Her symptoms resolved quickly after the start of treatment, with reduction of SARS-CoV-2 viral load, but she developed a fever again on day 12. Since the fever was relieved by discontinuation of favipiravir, and based on positive results with a drug-induced lymphocyte stimulation test, we diagnosed her with favipiravir-induced drug fever. Decrease in the serum concentration of favipiravir was observed along with resolution of the fever. The present case suggests that drug fever should be considered in the differential diagnosis of relapsing fever episodes in COVID-19 patients receiving favipiravir.

Adaptive immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) dynamics remain largely unknown. The neutralizing antibody (NAb) levels in patients with coronavirus disease 2019 (COVID-19) are helpful for understanding the pathology. Using SARS-CoV-2 pseudotyped virus, serum sample neutralization values in symptomatic COVID-19 patients were measured using the chemiluminescence reduction neutralization test (CRNT). At least two sequential serum samples collected during hospitalization were analyzed to assess NAbs neutralizing activity dynamics at different time points. Of the 11 patients, four (36.4%), six (54.5%), and one (9.1%) had moderate, severe, and critical disease, respectively. Fifty percent neutralization (N50%-CRNT) was observed upon admission in 90.9% (10/11); all patients acquired neutralizing activity 2–12 days after onset. In patients with moderate disease, neutralization was observed at earliest within two days after symptom onset. In patients with severe-to-critical disease, neutralization activity increased, plateauing 9–16 days after onset. Neutralization activity on admission was significantly higher in patients with moderate disease than in patients with severe-to-critical disease (relative % of infectivity, 6.4% vs. 41.1%; P = .011). Neutralization activity on admission inversely correlated with disease severity. The rapid NAb response may play a crucial role in preventing the progression of COVID-19.

This study aimed to determine the frequency of SARS‐CoV‐2 RNA in serum and its association with the clinical severity of COVID‐19. This retrospective cohort study performed at Toyama University Hospital included consecutive patients with confirmed COVID‐19. The prevalence of SARS‐CoV‐2 RNAemia and the strength of its association with clinical severity variables were examined. Fifty‐six patients were included in this study. RNAemia was detected in 19.6% (11/56) patients on admission, and subsequently in 1.0% (1/25), 50.0% (6/12), and 100.0% (4/4) moderate, severe, and critically ill patients, respectively. Patients with RNAemia required more frequent oxygen supplementation (90.0% vs. 13.3%), ICU admission (81.8% vs. 6.7%), and invasive mechanical ventilation (27.3% vs. 0.0%). Among patients with RNAemia, the median viral loads of nasopharyngeal (NP) swabs that were collected around the same time as the serum sample were significantly higher in critically ill (5.4 log10 copies/μl; interquartile range [IQR]: 4.2–6.3) than in moderate‐severe cases (2.6 log10 copies/μl; [IQR: 1.1–4.5]; p = 0.030) and were significantly higher in nonsurvivors (6.2 log10 copies/μl [IQR: 6.0–6.5]) than in survivors (3.9 log10 copies/μl [IQR: 1.6–4.6]; p = 0.045). This study demonstrated a relatively high proportion of SARS‐CoV‐2 RNAemia and an association between RNAemia and clinical severity. Moreover, among the patients with RNAemia, the viral loads of NP swabs were correlated with disease severity and mortality, suggesting the potential utility of combining serum testing with NP tests as a prognostic indicator for COVID‐19, with higher quality than each separate test.

ObjectivesVaccines against severe acute respiratory syndrome coronavirus-2 have been introduced. To investigate whether the vaccine provides protective immunity effectively, the amount and function of vaccine-induced antibodies were evaluated.MethodsSera from 13-17 days after the second dose of the Pfizer BNT162b2 vaccine were collected from healthcare workers at the University of Toyama (n=740). Antibody levels were quantitatively measured by the anti-receptor binding domain antibody test (anti-RBD test), and neutralising activity against pseudotyped viruses displaying wild-type (WT) and mutant spike proteins (B.1.1.7- and B.1.351-derived variants) were assayed using a high-throughput chemiluminescent reduction neutralising test (htCRNT). Basic clinical characteristics were obtained from questionnaires.ResultsAntibodies were confirmed in all participants in both the anti-RBD test (median 2112 U/mL, interquartile range [IQR] 1275–3390 U/mL) and the htCRNT against WT (median % inhibition >99.9, IQR >99.9 to >99.9). For randomly selected sera (n=61), 100.0% were positive for htCRNT against the B.1.1.7- and B.1.351-derived variants. Among those who answered the questionnaire (n=237), the values of the anti-RBD test were negatively correlated with age for females (pConclusionsThe BNT162b2 vaccine produced sufficient antibodies in terms of quality and quantity which could neutralise emerging variants. Antibody induction can be affected by age and sex but will still be at a sufficient level.

ObjectivesThis study aimed to evaluate the incidence and pattern of favipiravir-induced liver injury and the potential association between serum concentrations in hospitalized COVID-19 patients.Patients and methodsWe retrospectively reviewed laboratory-confirmed patients with COVID-19 for whom serum favipiravir trough concentration (Cmin) was measured under steady-state conditions during treatment. All patients were administered 1800 mg of favipiravir twice daily on the first day and 800 mg twice daily from the second day.ResultsThirty observed favipiravir concentrations were collected from nine patients. Of these, favipiravir-induced liver injury developed in three patients after 13 (11–14) days from the initiation of therapy, with two classified as cholestatic and one hepatocellular injury, with a score of four (possible), seven (probable), and three (possible) based on the CIMOS/RUCAM scoring system. Median (range) favipiravir Cmin at steady state was found to be significantly higher in patients with liver injury at 66.4 (47.8–72.4) mg/L than in those without injury at 12.8 (9.4–21.8) mg/L (P = 0.028).ConclusionsHigher favipiravir serum concentrations were observed in patients who developed favipiravir-induced liver injury than in those who did not. As the variations in favipiravir concentrations between patients were large, personalized optimal dosing strategies may be needed for safe use.

This study aimed to assess the nasopharyngeal viral load at discharge or time of discontinued isolation in coronavirus 2019 (COVID-19) patients admitted to our hospital and discharged under the current symptom-based criteria in Japan. Patients diagnosed with COVID-19 by reverse transcription polymerase chain reaction and hospitalized at Toyama University Hospital were included in the analysis. Nasopharyngeal viral load was measured when symptom-based criteria for discharge or end of isolation in the accommodations were met, and examined the relationship between viral load and days after onset or age. From the perspective of virus isolation limit, the amount of infectious viral load was defined at 50 copies/μL by nasopharyngeal sample. Thirty-three patients with laboratory-confirmed COVID-19 were included in the analysis, after excluding critical and fatal cases. Mean nasopharyngeal viral load at discharge or end of isolation was 1.90 log-copies/μL, and 64% of patients were discharged with over 50 copies/μL. No correlation was apparent between age and viral load at discharge, and viral load remained relatively high at discharge or end of isolation in all age groups. Although attempts at infectious virus isolation are necessary, infection control precautions even after discharge or discontinued isolation in accommodations may be needed, as the date of onset mostly depended on self-reporting by patients.

Background Linezolid is administered as a fixed dose to all patients despite evidence of overexposure and thrombocytopenia in renal impairment. The aims of this study were to evaluate the risk of thrombocytopenia and the utility of therapeutic drug monitoring (TDM), and to propose alternate dosing regimens in patients with renal impairment. Methods We retrospectively reviewed patients ≥13 years old for whom serum linezolid trough concentration (Cmin) was measured during linezolid treatment. Patients with episodes of infection were divided into groups by presence of renal impairment (RI group) or absence of renal impairment (non-RI group), and by use of Cmin-based TDM (TDM group) or not (non-TDM group) during linezolid treatment. Results In the 108 patients examined by multivariable analyses, renal impairment was independently associated with increased risk of thrombocytopenia (OR 3.17, 95%CI 1.10–9.12) and higher Cmin. Analysis of the utility of TDM in the RI group showed that clinical failure rate was significantly lower in the TDM subgroup than in the non-TDM subgroup. Furthermore, in the RI group, dosage adjustments were needed in 90.5% of the TDM subgroup. All episodes administered a reduced dose of 300 mg every 12 h in the RI group showed Cmin ≥ 2.0 mg/L. Additional analysis of 53 episodes in which Cmin was measured within 48 h after starting administration showed that the initial standard dose for 2 days was sufficient to rapidly reach an effective therapeutic concentration in the RI group. Conclusions Empirical dose reduction to 300 mg every 12 h after administration of the initial fixed dose for 2 days and Cmin-based TDM may improve safety outcomes while maintaining appropriate efficacy among patients with renal impairment.

ObjectiveThis study aimed to determine the frequency of SARS-CoV-2 RNA in serum and its association with the clinical severity of COVID-19.MethodsAn analytical cross-sectional study was performed in a single tertiary care hospital and included consecutive patients with confirmed COVID-19. The prevalence of SARS-CoV-2 RNAemia and the strength of its association with clinical severity variables, including required oxygen supplementation, ICU admission, invasive mechanical ventilation, and in-hospital mortality, were examined.ResultsFifty-six patients were included in the study. The median age was 54.5 years, and individuals with RNAemia were older than those without detectable SARS-CoV-2 RNA in serum (78 vs. 50 years; P = .0013). RNAemia was detected in 19.6% of patients (11/56) and in 1.0% (1/25), 50.0% (6/12), and 100.0% (4/4) of moderate, severe, and critically ill cases, respectively. Patients with RNAemia required more frequent oxygen supplementation (90.0% vs. 13.3%; P < .0001) and ICU admission (81.8% vs. 6.7%; P < .0001) and required invasive mechanical ventilation (27.3% vs. 0.0%; P < .0001). Among patients with RNAemia, the median viral loads of NP swabs that were collected around the same time as the serum were significantly higher in critically ill cases (5.4 Log10 copies/μL [IQR: 4.2–6.3]) than in moderate–severe cases (2.6 Log10 copies/μL [1.1–4.5]; P =.030) and were significantly higher in nonsurvivor cases (6.2 Log10 copies/μL [IQR: 6.0–6.5]) than in survivor cases (3.9 Log10 copies/μL [1.6–4.6]; P =.045).ConclusionsThis study demonstrated a relatively high proportion of SARS-CoV-2 RNAemia and an association between RNAemia and clinical severity. Moreover, among the patients with RNAemia, the viral loads of NP swabs were correlated with severity and mortality, thus suggesting the potential utility of combining serum testing with NP tests as a prognostic indicator for COVID-19 with a higher quality than each separate test.

To investigate the relationship between viral load and secondary transmission in novel coronavirus disease 2019 (COVID-19), we reviewed epidemiological and clinical data obtained from immunocompetent laboratory-confirmed patients with COVID-19 at Toyama University Hospital. In total, 28 patients were included in the analysis. Median viral load at the initial sample collection was significantly higher in adults than in children and in symptomatic than in asymptomatic patients. Among symptomatic patients, non-linear regression models showed that the estimated viral load at onset was higher in the index (patients who transmitted the disease to at least one other patient) than in the non-index patients (patients who were not the cause of secondary transmission; median [95% confidence interval]: 6.6 [5.2–8.2] vs. 3.1 [1.5–4.8] log copies/μL, respectively). High nasopharyngeal viral loads around onset may contribute to secondary transmission of COVID-19.Article Summary LineHigh nasopharyngeal viral load around the onset may contributes to secondary transmission of COVID-19.

Nocardia farcinica usually infects the respiratory tract and can sometimes cause central nervous system infections; however, it rarely infects the prostate. Here we report the first case of N. farcinica detected in the purulence specimen drained from a prostate abscess. A 70-year-old Japanese male receiving steroid and cyclosporine treatment came to our department with chief complaint of turbid urine. Computed tomography revealed a low-density lesion in his prostate. Antibiotic administration and prostatic drainage were effective. N. farcinica was detected in the cultures of urine and prostatic drainage purulence specimens. Nocardiosis should be included in the differential diagnosis in immunosuppressive patients with prostate abscess. Keywords: Nocardia farcinica, Prostate abscess, Immunocompromised host

Slackia exigua is an obligate anaerobic coccobacillus associated with dental infection, but rarely causes extraoral infection. We report two cases of monomicrobial bacteremia caused by S. exigua isolated from two institutions. The first case involved community-acquired bacteremia associated with pleural empyema in a 69-year-old man. The second case involved hospital-acquired bacteremia secondary to postoperative intra-abdominal abscess in a 73-year-old man with primary intestinal diffuse large B-cell lymphoma. S. exigua was finally identified by 16S ribosomal RNA gene sequencing analyses in both cases. In the first case, our attempts to identify the organism using commercial identification kits for anaerobes resulted in inaccurate identification as Gemella morbillorum. However, S. exigua was promptly identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometry in the second case. The epidemiology and clinical characteristics of S. exigua extraoral infection remain unclear because of the limitations in accurate identification and because only 19 cases of extraoral S. exigua infection have been reported previously, including four cases of bacteremia. Physicians should focus on this species, which can cause community-acquired infections and spread via various routes even in patients with no comorbidities. Further studies are needed to clarify the clinical characteristics of extraoral S. exigua infections.

Objective To investigate the relationship between viral load and secondary transmission in novel coronavirus disease 2019 (COVID-19). Methods Epidemiological and clinical data were obtained from immunocompetent laboratory-confirmed patients with COVID-19 who were admitted to and/or from whom viral loads were measured at Toyama University Hospital. Using a case-control approach, index patients who transmitted the disease to at least one other patient were analysed as “cases” (index patients) compared with patients who were not the cause of secondary transmission (non-index patients, analysed as “controls”). The viral load time courses were assessed between the index and non-index symptomatic patients using non-linear regression employing a standard one-phase decay model. Results In total, 28 patients were included in the analysis. Median viral load at the initial sample collection was significantly higher in symptomatic than in asymptomatic patients and in adults than in children. Among symptomatic patients (n = 18), non-linear regression models showed that the estimated viral load at onset was higher in the index than in the non-index patients (median [95% confidence interval]: 6.6 [5.2–8.2] vs. 3.1 [1.5–4.8] log copies/μL, respectively). In adult (symptomatic and asymptomatic) patients (n = 21), median viral load at the initial sample collection was significantly higher in the index than in the non-index patients (p = 0.015, 3.3 vs. 1.8 log copies/μL, respectively). Conclusions High nasopharyngeal viral loads around onset may contribute to secondary transmission of COVID-19. Viral load may help provide a better understanding of why transmission is observed in some instances, but not in others, especially among household contacts.