Takahiro Takuma

Clinical viability of Fungitell, a new (1→3)-β-d-glucan measurement kit, for diagnosis of invasive fungal infection, and comparison with other kits available in Japan

Fungitell, a (1→3)-β-d-glucan (β-d-glucan) measurement kit, was approved in the United States in 2004. Three other kits for measurement of β-d-glucan, Fungitec G test MK (G-MK), β-Glucan test Wako (Wako), and β-Glucan test Maruha (Maruha), are commonly used for diagnosis of invasive fungal diseases in Japan. We evaluated the clinical viability of the Fungitell kit and compared it with the 3 kits generally used in Japan. The plasma β-d-glucan values measured with each kit showed some differences, possibly because different β-d-glucan standards, blood pretreatment methods, and kinds of horseshoe crab (a raw material for the main reagent) are used in each kit. Measures of diagnostic efficiency, for example the sensitivity, specificity, and positive and negative predictive values, varied among the kits. Although the areas under the receiver operating characteristic curves of the kits were not significantly different, the sensitivity of the Fungitell kit was the highest, followed by that of the G-MK kit. The sensitivity of the Wako and Maruha kits was low, but the specificity of these tests was higher than that of the G-MK or Fungitell kits. These inconsistent β-d-glucan measurements could interfere with diagnosis of invasive fungal infection. Early establishment of an international standard method for measurement of β-d-glucan is required.

Effect of interventions by an antimicrobial stewardship team on clinical course and economic outcome in patients with bloodstream infection.

BACKGROUND Bloodstream infections (BSIs) represent one of the most severe and clinically important conditions in the hospital setting. We have organized an interdisciplinary antimicrobial stewardship team (AST) at our hospital and performed consultations focusing on BSI patients since 2013. This study aimed to evaluate the impact of AST interventions on the diagnosis, treatment, and clinical outcomes of BSI patients. METHODS We conducted a retrospective quasi-experimental study of BSI patients at a single Japanese university hospital. AST provided recommendations to attending physicians regarding appropriate diagnosis, therapy, and management of BSI patients after reviewing medical charts. RESULTS We identified a total of 308 cases of BSI from January to December, 2012 (pre-intervention group) and 324 cases of BSI from April, 2013 to March, 2014 (post-intervention group). No significant differences in the in-hospital mortality or 30-day mortality rates were observed between both the groups. Inappropriate therapy was initiated in a significantly lower proportion of patients in the post-intervention group (18.5% vs. 11.4%; P = 0.012). Multivariate analysis confirmed that inappropriate therapy was significantly associated with in-hospital mortality (odds ratio, 2.62; 95% confidence interval, 1.42-4.82; P = 0.002). CONCLUSIONS An interdisciplinary AST intervention approach decreases the use of inappropriate therapy and may improve clinical outcomes in BSI patients.

More accurate measurement of vancomycin minimum inhibitory concentration indicates poor outcomes in meticillin-resistant Staphylococcus aureus bacteraemia

Meticillin-resistant Staphylococcus aureus (MRSA) is an important pathogen associated with community-acquired and nosocomial infections. The aim of this study was to validate the vancomycin (VAN) minimum inhibitory concentration (MIC) and administration of VAN that may affect the prognosis of patients with MRSA bacteraemia. In total, 140 clinical MRSA strains from blood cultures were collected from January 2009 to December 2013 at a university hospital in Tokyo (Japan). Patient background, their clinical situation and the susceptibility of isolates to anti-MRSA agents in all cases were reviewed, and factors contributing to 30-day mortality were analysed. Susceptibility to anti-MRSA agents was measured by a microdilution susceptibility testing method. The VAN MIC was further evaluated at 0.25 μg/mL intervals from 0.5 μg/mL to 2.0 μg/mL. Multiple logistic regression analysis revealed a 4-fold increase in mortality of patients with a VAN MIC ≥1.5 μg/mL [odds ratio (OR)=3.952, 95% confidence interval (CI) 1.471-10.614; P=0.006]. A one-score increase in the Charlson co-morbidity index resulted in a 1.2-fold increase in the risk of death (OR=1.199, 95% CI 1.054-1.364; P=0.006). However, no significant difference was found in the ratio of the VAN 24-h area under the concentration-time curve to MIC between VAN MIC ≥1.5 μg/mL and <1.5 μg/mL. A significant increase in the MICs of teicoplanin and daptomycin was observed in strains with high VAN MICs. For patients with high VAN MICs, administration of these anti-MRSA antibiotics may have a poor outcome owing to cross-resistance.

Changes in the Distribution of Capsular Serotypes of Streptococcus pneumoniae Isolated from Adult Respiratory Specimens in Japan

OBJECTIVE The objective of this study was to assess whether the distribution of pneumococcal capsular types has been changed, while also providing basic data on changes in the distribution after the introduction of Pneumococcal conjugated vaccine (PCV)13 in adult medical practice. METHODS We analyzed 431 Streptococcus pneumoniae strains (200 in 2006 and 231 in 2012) that had been isolated from respiratory infection specimens from adult patients. Capsular typing was performed by the Quellung reaction and multiplex polymerase chain reaction. RESULTS A comparison of the 2006 and 2012 strains revealed that the number and proportion of strains by serotype increased from 30 (15%) to 46 (20%) for serotype 3, from 4 (2%) to 14 (6%) for serotype 6A, and from 4 (2%) to 13 (6%) for serotype 6C, whereas the number and proportion of strains by serotype decreased from 8 (4%) to 0 (0%) for serotype 4 and from 24 (12%) to 17 (7%) for serotype 6B. From 2006 to 2012, the coverage rate significantly decreased from 39 to 28.1% for PCV7 (p=0.017). CONCLUSION Our study showed a decrease in the vaccine coverage of PCV7. However, PCV13 covered serotypes 3 and 6A, which are prevalent, as well as penicillin-resistant S. pneumoniae strains. At present, PCV13 in adult clinical practice seems to be highly significant. However, there is a possibility that the distribution has changed, and careful screening should be continued in the future.

Two-way analysis for detecting factors affecting ventilator-associated pneumonia

The “clinically required ventilation period” for assessing ventilator-associated pneumonia (VAP) has not been studied because this period could not be clinically predicted. We addressed this problem using both rate analysis and failure-time analysis. A total of 325 patients who had received mechanical ventilatory support in the intensive care unit of a university hospital were reviewed. The total ventilation period and the ventilation period before VAP were compared using logistic regression and the Cox proportional hazard model for univariate and multivariate analyses. The Frechet distribution model was also used. Fifty patients were excluded for having pneumonia before intubation or for being admitted to a department in which no VAP occurred; 12 patients had VAP. Discrepancies in both methods caused by time-dependent bias were observed in patients emergently admitted (odds ratio, 1.435; hazard ratio, 0.3928). This reduced hazard ratio remained with the multivariate Frechet distribution model. Longer operation time significantly increased the VAP rate in the logistic model only. Low body mass index increased the rate of VAP in both models, especially in female patients (hazard ratio, 0.1707; 95% confidence interval, 0.02105–0.6728). The results of rate analysis and failure-time analysis were similar for most factors but differed somewhat for several factors, such as emergency admission. Unknown factors might be obscured by this type of difference, and this two-way method might be able to reveal artificial effects.

Epidemiology and risk factors for mortality in bloodstream infections: A single-center retrospective study in Japan

Background: Few published data are available on the morbidity and mortality of bloodstream infections (BSIs) in Japan. We sought to investigate the epidemiology of BSIs, the involvement of antimicrobial resistance, and the factors that influence patient prognosis. Methods: This single‐center study retrospectively evaluated patients who were found to have positive blood cultures at a tertiary teaching hospital between January 2012 and December 2016. Results: A total of 2,105 patients with BSIs were included; 1,786 survived and 319 died, and the 30‐day mortality rate was 15.2% over the 5‐year study period. BSIs caused by yeasts were independently associated with 30‐day mortality. The 30‐day mortality rate of BSIs caused by extended‐spectrum beta lactamase–producing gram‐negative bacteria was significantly higher than that of BSIs caused by nonproducing bacteria. Discussion: The differences in mortality may be caused by differences in the distribution of pathogens and in the delivery of health care. Conclusions: This study reported epidemiology and antimicrobial resistance data of BSIs in Japan and identified several risk factors associated with 30‐day mortality. National surveillance of BSIs is required in Japan for comparison with other countries.