Tumor-associated macrophages (TAMs) and microvessel density (MVD) play an essential role for tumor progression in prostate cancer (PCa). In this study, we evaluated the association between TAMs, the infiltration with tumor angiogenesis and the response to androgen deprivation therapies (ADTs) in PCa to evaluate TAM infiltration as a predictive factor for PCa survival. Fifty-four specimens were collected and stained with CD 68 antibody to investigated TAM infiltration in tumor. Von Willebrand factor was stained to evaluate MVD around the cancer foci. We assessed the association between patient's age, preoperative serum prostate-specific antigen, pathologic Gleason sum (GS), TAM infiltration, MVD, and the response to ADT for 5 years after PCa diagnosis. The median TAM was observed in 28 (6-76)/high power field (x400). Increasing TAM correlated with increasing tumor angiogenesis (P < 0.001, r = 0.61), and the response to ADT was significantly better in patients with fewer TAMs (28) (P = 0.003). TAM infiltration was significantly higher in those with higher serum prostate-specific antigen, higher GS, and metastasis. Multivariate analysis showed that GS, ADT type, and MVD number were significant prognostic factors for response to ADT in PCa (P < 0.0001). An increased infiltration of TAM [hazards ratio (HR) = 4.47; 95% confidence interval (CI): 1.97–10.15], MVD (HR = 2.66; 95% CI: 1.27–5.61), metastatic status (HR = 2.29; 95% CI: 0.14-0.60), and prostate volume (HR = 2.19; 95% CI: 1.27–3.12) significantly correlated with shorter survival in PCa patients by univariate analysis (P < 0.05). Multivariate analyses revealed that TAM and metastatic status significantly correlated with poor overall survival. TAM infiltration is associated with response to ADT and increased tumor angiogenesis in PCa. GS, ADT type, and MVD in PCa specimens are useful predictive factors for poor response to ADT. Increasing TAM and positive metastatic status were prognostic factors for a poorer survival in PCa patients.

The incidence of bacteremia caused by Enterococcus faecium, which is highly resistant to multiple antibiotics, is increasing in Japan. However, risk factors for the acquisition of E. faecium infection and mortality due to enterococcal bacteremia are not well known. We compared demographic, microbiological, and clinical characteristics using a Cox regression model and univariate analysis. We performed a multivariate analysis to identify risk factors for patients treated between 2014 and 2018. Among 186 patients with enterococcal bacteremia, two groups included in the Kaplan–Meier analysis (E. faecalis (n = 88) and E. faecium (n = 94)) showed poor overall survival in the E. faecium group (HR: 1.92; 95% confidence interval: 1.01–3.66; p = 0.048). The median daily antibiotic cost per patient in the E. faecium group was significantly higher than that in the E. faecalis group ($23 ($13–$34) vs. $34 ($22–$58), p < 0.001). E. faecium strains were more frequently identified with previous use of antipseudomonal penicillins (OR = 4.04, p < 0.001) and carbapenems (OR = 3.33, p = 0.003). Bacteremia from an unknown source (OR = 2.79, p = 0.025) and acute kidney injury (OR = 4.51, p = 0.004) were associated with higher risks of 30-day mortality in patients with enterococcal bacteremia. Therefore, clinicians should provide improved medical management, with support from specialized teams such as those assisting antimicrobial stewardship programs.

Cefazolin is an essential antibiotic used for treating bacteremia; in particular, it is recommended as a first-line agent for infections caused by methicillin-susceptible Staphylococcusaureus (MSSA). In March 2019, problems with a major antibiotic supplier caused a critical shortage of cefazolin in Japan; however, the impact of the cefazolin shortage on clinical outcomes remains unknown. This study aimed to evaluate the effect of the cefazolin shortage in patients with MSSA bacteremia. Data from 75 patients were compared between the pre-shortage (March 2018–January 2019, n = 39) and post-shortage (March 2019–January 2020, n = 36) periods. There were no significant differences in the demographic characteristics between the two groups, and the cefazolin shortage did not worsen clinical outcomes such as adverse drug reactions, treatment failure, and 30-day mortality. In the post-shortage group, ampicillin/sulbactam and benzylpenicillin were more frequently administered as alternative antibiotics for empirical and definitive therapy (10% vs. 31%, p = 0.042; 0% vs. 19%, p = 0.004, respectively). Multivariate analysis revealed that the broad-spectrum antibiotics for definitive therapy, such as antipseudomonal penicillin, were associated with treatment failure in patients with MSSA bacteremia (OR = 17, p = 0.003). Hence, narrow-spectrum antibiotics should be prescribed for MSSA bacteremia as alternatives during a cefazolin shortage.

Antimicrobial stewardship teams (ASTs) have been well-accepted in recent years; however, their clinical outcomes have not been fully investigated in urological patients. The purpose of this study was to evaluate the outcomes of intervention via a retrospective review of urological patients, as discussed in the AST meetings, who were treated with broad-spectrum antibiotics between 2014 and 2018 at the Department of Urology, Kobe University Hospital in Japan. Interventions were discussed in AST meetings for patients identified by pharmacists as having received inappropriate antibiotic therapy. The annual changes in numbers of inappropriate medications and culture submissions over five years at the urology department were statistically analyzed. Among 1,033 patients audited by pharmacists, inappropriate antibiotic therapy was found in 118 cases (11.4%). The numbers of inappropriate antibiotic use cases and of interventions for indefinite infections had significantly decreased during the study period (p = 0.012 and p = 0.033, respectively). However, the number of blood and drainage culture submissions had significantly increased (p = 0.009 and p = 0.035, respectively). Our findings suggest that urologists have probably become more familiar with infectious disease management through AST intervention, leading to a decrease in inappropriate antibiotic use and an increase in culture submissions.

Imipenemase-6 (IMP-6) type carbapenemase-producing Enterobacteriaceae is regarded as dangerous due to its unique lack of antimicrobial susceptibility. It is resistant to meropenem (MEPM) but susceptible to imipenem (IPM). In addition to carbapenemase, outer membrane porins and efflux pumps also play roles in carbapenem resistance by reducing the antimicrobial concentration inside cells. Extended-spectrum β-lactamase (ESBL) is transmitted with IMP-6 by the plasmid and broadens the spectrum of antimicrobial resistance. We collected 42 strains of IMP-6-producing Escherichia coli and conducted a molecular analysis of carbapenemase, ESBL, porin, efflux, and epidemiological characteristics using plasmid replicon typing. Among the 42 isolates, 21 strains were susceptible to IPM (50.0%) and 1 (2.4%) to MEPM. Seventeen strains (40.5%) co-produced CTX-M-2 type ESBL. We found that the relative expression of ompC and ompF significantly correlated with the MIC of IPM (p = 0.01 and p = 0.03, respectively). Sixty-eight% of CTX-M-2-non-producing strains had IncI1, which was significantly different from CTX-M-2-producing strains (p < 0.001). In conclusion, 50.0% of our IMP-6-producing strains were non-susceptible to IPM, which is different from the typical pattern and can be attributed to decreased porin expression. Further studies investigating other types of carbapenemase are warranted.

Since 2014, several global and national guidelines have been introduced to address the problem of antimicrobial resistance. We conducted a campaign in a tertiary hospital to promote appropriate quinolone use through educational lectures in 2018. The aim of this retrospective study was to evaluate the changes in the following: prescription characteristics, trend of oral quinolone use, and antibiotic susceptibility of bacteria from 2013 to 2020. Antimicrobial use was assessed as days of therapy per 1000 patient-days. We found a significant reduction in unnecessary antibiotic prescriptions between December 2013 and December 2020. Significant negative trends were detected in the use of quinolones over 8 years (outpatients, coefficient = −0.15655, p < 0.001; inpatients, coefficient = −0.004825, p = 0.0016). In particular, the monthly mean use of quinolones among outpatients significantly decreased by 11% from 2013 to 2014 (p < 0.05) and reduced further by 31% from 2017 to 2020 (p < 0.001). A significant positive trend was observed in the susceptibility of Pseudomonas aeruginosa to levofloxacin (p < 0.001). These results demonstrate that the use of oral quinolones was further reduced following educational intervention and the bacterial susceptibility improved with optimal quinolone usage compared to that in 2013.