BackgroundThe Gram stain has been used as an essential tool for antimicrobial stewardship in our hospital since the 1970s. The objective of this study was to clarify the difference in the targeted therapies selected based on the Gram stain and simulated empirical therapies based on the antimicrobial guidelines used in Japan.MethodsA referral-hospital-based prospective descriptive study was undertaken between May 2013 and April 2014 in Okinawa, Japan. All enrolled patients were adults who had been admitted to the Division of Infectious Diseases through the emergency room with suspected bacterial infection at one of three sites: respiratory system, urinary tract, or skin and soft tissues. The study outcomes were the types and effectiveness of the antibiotics initially selected, and their total costs.ResultsTwo hundred eight patients were enrolled in the study. The median age was 80 years. A significantly narrower spectrum of antibiotics was selected based on the Gram stain than was selected based on the Japanese guidelines. The treatments based on the Gram stain and on the guidelines were estimated to be equally highly effective. The total cost of antimicrobials after Gram-stain testing was less than half the cost after the guidelines were followed.ConclusionsCompared with the Japanese guidelines, the Gram stain dramatically reduced the overuse of broad-spectrum antimicrobials without affecting the effectiveness of the treatment. Drug costs were reduced by half when the Gram stain was used. The Gram stain should be included in all antimicrobial stewardship programs.

The expression levels of various cytokines increase with the progression of HIV-1 infection. However, the effects of antiretroviral therapy (ART) on serum cytokine levels have not been fully determined. In this study we measured serum cytokine levels of 35 HIV-1-infected Japanese adults. We first performed a cross-sectional study and observed that TNF-α, IL-6, IL-10, IL-18, and IL-7 levels all showed significant increases in those with advanced disease, and that this had a significant negative correlation with the CD4 cell count. However, IFN-γ levels did not show this relationship. A longitudinal study in 18 HIV-1-infected patients with a CD4 cell count <350/μL revealed that the introduction of ART reduced cytokine levels. Significant reductions of IL-7, IL-10, IFN-γ, and IL-18 levels were observed on days 30, 60, 90, and 90 after the initiation of ART, respectively. These results indicate a discrepancy between cross-sectional and longitudinal studies of serum levels of IFN-γ. To clarify this, we investigated serum IFN-γ levels in each patient. In 5 of the 15 patients IFN-γ levels did not decrease, even after ART initiation, and remained at 5 pg/mL or higher on day 120 after ART initiation. Higher IFN-γ levels (>5 pg/mL) were also observed in 2 of 7 asymptomatic patients, and 2 of 11 patients who underwent ART for 1 year or longer. These data demonstrate that IFN-γ levels in some patients increased and remained high even after the initiation of ART, which was a specific observation different from those of the other cytokines.

Severe fever with thrombocytopenia syndrome (SFTS) is a bunyavirus infection with high mortality. Favipiravir has shown effectiveness in preventing and treating SFTS virus (SFTSV) infection in animal models. A multicenter non-randomized, uncontrolled single arm trial was conducted to collect data on the safety and the effectiveness of favipiravir in treatment of SFTS patients. All participants received favipiravir orally (first-day loading dose of 1800 mg twice a day followed by 800 mg twice a day for 7–14 days in total). SFTSV RT-PCR and biochemistry tests were performed at designated time points. Outcomes were 28-day mortality, clinical improvement, viral load evolution, and adverse events (AEs). Twenty-six patients were enrolled, of whom 23 were analyzed. Four of these 23 patients died of multi-organ failure within one week (28-day mortality rate: 17.3%). Oral favipiravir was well tolerated in the surviving patients. AEs (abnormal hepatic function and insomnia) occurred in about 20% of the patients. Clinical symptoms improved in all patients who survived from a median of day 2 to day10. SFTSV RNA levels in the patients who died were significantly higher than those in the survivors (p = 0.0029). No viral genomes were detectable in the surviving patients a median of 8 days after favipiravir administration. The 28-day mortality rate in this study was lower than those of the previous studies in Japan. The high frequency of hepatic dysfunction as an AE was observed. However, it was unclear whether this was merely a side effect of favipiravir, because liver disorders are commonly seen in SFTS patients. The results of this trial support the effectiveness of favipiravir for patients with SFTS.

Meningitis caused by enteric flora is a known complication of strongyloidiasis, and human T-lymphotropic virus-1 (HTLV-1) predisposes individuals to severe strongyloidiasis. We reviewed the clinical features of bacterial meningitis associated with strongyloidiasis seen at a single center in subtropical Japan, in an area endemic for both strongyloidiasis and HTLV-1. We found 33 episodes in 21 patients between 1990 and 2010. The results were remarkable for the high incidence of meningitis due to Gram-positive cocci (27.3 %), especially Streptococcus bovis, and culture-negative cases (42.4 %). Given the high incidence of Gram-positive meningitis, a modified approach to corticosteroid use would be advisable in areas where strongyloidiasis is endemic, due to the potentially adverse consequences of glucocorticoid therapy.

PurposesThe difference in predictors of bacteremia between elderly and non-elderly patients is unclear despite the aging of society. The objective was to determine predictors of bacteremia among elderly patients aged 80 years and older compared to non-elderly patients aged 18 to 79 years.MethodsA referral hospital-based retrospective descriptive study from April 2012 to March 2013 in Okinawa, Japan. All enrolled patients were adults suspected of having bacterial infection who had been newly admitted into the Division of Infectious Diseases. HIV- infected patients were excluded. Exposures were a history of shaking chills, prior antibiotics use within 48 hours, vital signs, and laboratory inflammation markers on admission. Outcome was blood culture positivity.ResultsThree hundred and sixty-six patients were enrolled. Median age was 78.5 (interquartile range [IQR]: 62–88). Among patients aged 18 to 79 years, shaking chills (adjusted odds ratio [AOR] 2.22, 95% confidence interval [CI]: 1.09–4.51) and previous antibiotics use (AOR 0.08, 95% CI: 0.01–0.68) were significant. However, among patients aged 80 years and older, shaking chills (AOR 3.06, 95% CI: 1.30–7.19) and body temperature above 38.5°C (AOR 2.98, 95% CI: 1.30–6.83) were significant.ConclusionsA history of shaking chills and vital signs indicating high body temperature were two findings that were useful in predicting bacteremia, especially in elderly patients aged 80 years and older. Further study is needed to assess whether the result is applicable in other regions and populations.