Hidekazu Mizuno

Preemptive Therapy in Nonneutropenic Patients with Candida Infection Using the Japanese Guidelines

Background: The Japanese Guidelines for the Diagnosis and Treatment of Deep-Seated Mycosis were established in 2003. Proven Candida infection (CI) is defined as at least one positive blood culture yielding a Candida species. Clinically documented CI requires documentation of more than 2 sites of colonization and a positive plasma β-O-glucan test. Possible CI is diagnosed by one of the above criteria in febrile, nonneutropenic critically ill patients. Objective: To assess the use of definitions of clinically documented and possible CI for guiding preemptive antifungal therapy in critically ill patients. Methods: The patients treated in our intensive care unit (ICU) for at least 48 hours between 2000 and 2004 were investigated. The administration of antifungal agents and ICU mortality were compared among proven, clinically documented, and possible CI groups for age, sex, APACHE II score, diagnosis, length of ICU stay, treatment, number of colonization sites, and plasma β-D-glucan level. Results: Six patients were diagnosed with proven CI, 25 were diagnosed with clinically documented CI, and 104 with possible CI. The patients with clinically documented CI were compared with those with possible CI, and statistically significant differences were found in the following variables: APACHE II score (p = 0.018), length of ICU stay (p < 0.01), use of ventilator (p = 0.027), tracheotomy (p = 0.027), number of colonization sites (p < 0.001), plasma β-D-glucan level (p < 0.001), and administration of antifungal agents (p < 0.001); incidence of mortality was not statistically significant (p = 0.33). The shorter length of ICU stay, use of ventilator, and continuous hemodiafiltration were risk factors for death after adjusting for APACHE II score, admission before/after 2003, antifungal therapy, and other factors. Although the frequency of the administration of preemptive antifungal therapy was higher after 2003 than before, the mortality rate did not differ significantly, Conclusions: The use of the definitions of clinically documented and possible CI may be beneficial for determining when it is appropriate to initiate preemptive antifungal therapy. However, use of the guidelines did not lead to prevention of possible CI proceeding to clinically documented CI or to improved mortality.

Colonization of an acid resistant Kingella denitrificans in the stomach may contribute to gastric dysbiosis by Helicobacter pylori

In the stomach of a gastric ulcer patient who had been administered an anti-acid, a gram-negative and urease-negative bacillus similar in size to Helicobacter pylori was infected together with H. pylori. According to biochemical test and 16S rRNA gene analysis, the urease-negative bacterium was identified as Kingella denitrificans, a human nasopharyngeal commensal. In contrast to the standard strain of K. denitrificans, the isolate showed catalase activity, did not produce acid from glucose, and exhibited acid tolerance. Acid tolerance of H. pylori was increased by cocultivation with the K. denitrificans isolate, but not with other isolates of K. denitrificans. Disruption of physiological and immunological niche by dysbiotic colonization of bacterium may provide pathological attributes to human stomach. Collectively, a careful administration of anti-acids to the elderly, especially those with atrophic gastritis, is necessary to avoid repression of the gastric barrier to bacteria.

Limited detectability of linezolid-resistant Staphylococcus aureus by the Etest method and its improvement using enriched media.

The aim of this study was to evaluate Etest for detectability of linezolid-resistant meticillin-resistant Staphylococcus aureus (MRSA). The MIC of linezolid obtained by the Etest method in 18 linezolid-resistant strains of MRSA was compared with that obtained using standard agar and broth dilution methods according to Clinical and Laboratory Standards Institute guidelines. The mean linezolid MIC obtained by Etest in 18 linezolid-resistant strains of MRSA using Mueller-Hinton (MH) agar was 12.6-fold lower than that obtained by the agar dilution method, with the result that 78 % of the linezolid-resistant strains were incorrectly classified as linezolid-susceptible. The MIC of linezolid by Etest on brain-heart infusion (BHI) agar had a mean value 2.5-fold lower than that obtained by the agar dilution method, suggesting that replacing MH agar with BHI agar considerably improved the detectability of linezolid-resistant MRSA. Use of blood agar (MH agar supplemented with 5 % sheep blood) and 48 h of incubation resulted in 100 % agreement with the agar and broth dilution methods. Thus, this study revealed that the Etest on MH agar and BHI agar yielded false-negative results in a significant fraction of the linezolid-resistant MRSA. Hence, the use of blood agar and prolonged incubation is highly recommended for the accurate detection of linezolid-resistant MRSA using Etest.

TROY is a promising prognostic biomarker in patients with colorectal cancer

Tumor necrosis factor receptor superfamily member 19 (TROY) is involved in the Wnt/β-catenin signaling pathway and interacts with leucine-rich repeat containing G-protein-coupled receptor 5 (LGR5), which is a well-known biomarker of cancer stem cells and a prognostic marker of colorectal cancer (CRC). Because there have been no studies to evaluate the prognostic significance of TROY, we performed the present study to determine whether TROY can be a prognostic biomarker in CRC patients. We evaluated TROY expression levels in 100 CRC tissues by quantitative real-time PCR and investigated the association of TROY expression levels with clinicopathologic features. Cancer stage and TROY expression level were found to be independent prognostic factors of disease-free survival. Moreover, TROY overexpression was the sole independent prognostic factor of disease-free survival in patients with stage II and III CRC. These results suggest that analysis of TROY might help predict clinical outcome in patients with CRC. To support our findings, confirmatory studies using independent data sets are needed.