Appropriate antimicrobial therapy significantly reduced 14-day mortality for A. baumannii bacteremia in severely ill patients.

BackgroundThe incidence of fungal healthcare-associated infection (HAI) has increased in a major teaching hospital in the northern part of Taiwan over the past decade, especially in the intensive care units (ICUs). The purpose of this study was to determine the factors that were responsible for the outbreak and trend in the ICU.MethodsSurveillance fungal cultures were obtained from “sterile” objects, antiseptic solutions, environment of infected patients and hands of medical personnel. Risk factors for comparison included age, gender, admission service, and total length of stay in the ICU, Acute Physiology and Chronic Health Evaluation (APACHE) II scores at admission to the ICU, main diagnosis on ICU admission, use of invasive devices, receipt of hemodialysis, total parenteral nutrition (TPN) use, history of antibiotic therapy before HAI or during ICU stay in no HAI group, and ICU discharge status (ie, dead or alive). Univariable analysis followed by multiple logistic regression analysis was performed to identify the independent risk factors for ICU fungal HAIs and ICU mortality.ResultsThere was a significant trend in ICU fungal HAIs from 1998 to 2009 (P < 0.001). A total of 516 episodes of ICU fungal HAIs were identified; the rates of various infections were urinary tract infection (UTI) (54.8%), blood stream infection (BSI) (30.6%), surgical site infection (SSI) (6.6%), pneumonia (4.5%), other sites (3.5%). The fungi identified were: yeasts (54.8%), Candida albicans (27.3%), Candida tropicalis (6.6%), Candida glabrata (6.6%), Candida parapsilosis (1.9%), Candida species (0.8%), and other fungi (1.9%). Candida albicans accounted for 63% of all Candida species. Yeasts were found in the environment of more heavily infected patients. The independent risk factors (P < 0.05) of developing ICU fungal HAIs from all sites were TPN use, sepsis, surgical patients, mechanical ventilation and an indwelling urinary catheter. The independent risk factors for ICU fungal UTI included TPN use, mechanical ventilation and an indwelling urinary catheter. The independent risk factors for ICU fungal BSI included TPN use, sepsis, and higher APACHE II score. The independent risk factors for ICU fungal pneumonia included TPN use, surgical patients. The independent risk factors for ICU fungal SSI included surgical patients, and TPN use. The odds ratios of TPN use in various infection types ranged from 3.51 to 8.82. The risk of mortality in patients with ICU fungal HAIs was over 2 times that of patients without ICU HAIs in the multiple logistic regression analysis (P < 0.001).ConclusionsThere was a secular trend of an increasing number of fungal HAIs in our ICU over the past decade. Patients with ICU fungal HAIs had a significantly higher mortality rate than did patients without ICU HAIs. Total parenteral nutrition was a significant risk factor for all types of ICU fungal HAIs, and its use should be monitored closely.

The phenotypically indistinguishable Acinetobacter baumannii and Acinetobacter nosocomialis have become leading pathogens causing nosocomial pneumonia in critically ill patients. A. baumannii and A. nosocomialis nosocomial pneumonias were grouped as a single clinical entity previously. This study aimed to determine whether they are the same or a different clinical entity. A total of 121 patients with A. baumannii and 131 with A. nosocomialis bacteremic nosocomial pneumonia were included during an 8-year period. Despite the similar Charlson co-morbidity scores at admission, patients with A. baumannii pneumonia were more likely to have abnormal haematological findings, lobar pneumonia, significantly higher Acute Physiology and Chronic Health Evaluation II scores and higher frequency of shock at the onset of bacteraemia than those with A. nosocomialis pneumoni. A. baumannii isolates were resistant to more classes of antimicrobials, except colistin, and therefore the patients with A. baumannii pneumonia were more likely to receive inappropriate antimicrobial therapy. The 14-day mortality was significantly higher in patients with A. baumannii pneumonia (34.7% vs. 15.3%, p 0.001). A. baumannii was an independent risk factor for mortality (OR, 2.03; 95% CI, 1.05-3.90; p 0.035) in the overall cohort after adjustment for other risk factors for death, including inappropriate antimicrobial therapy. The results demonstrated the difference in clinical presentation, microbial characteristics and outcomes between A. baumannii and A. nosocomialis nosocomial pneumonia, and supported that they are two distinct clinical entities.

Pseudomonas putida was metabolically engineered to produce medium chain length polyhydroxyalkanoate (mcl-PHA) from acetate, a promising carbon source to achieve cost-effective microbial processes. As acetate is known to be harmful to cell growth, P. putida KT2440 was screened from three Pseudomonas strains (P. putida KT2440, P. putida NBRC14164, and P. aeruginosa PH1) as the host with the highest tolerance to 10 g/L of acetate in the medium. Subsequently, P. putida KT2440 was engineered by amplifying the acetate assimilation pathway, including overexpression of the acs (encoding acetyl-CoA synthetase) route and construction of the ackA-pta (encoding acetate kinase-phosphotransacetylase) pathway. The acs overexpressing P. putida KT2440 showed a remarkable increase of mcl-PHA titer (+ 92%), mcl-PHA yield (+ 50%), and cellular mcl-PHA content (+ 43%) compared with the wild-type P. putida KT2440, which indicated that acetate could be a potential substrate for biochemical production of mcl-PHA by engineered P. putida.

Anthocyanins have been shown to inhibit the growth and metastatic potential of breast cancer (BC) cells. However, the effects of individual anthocyanins on triple-negative breast cancer (TNBC) have not yet been studied. In this study, we found that cyanidin-3-o-glucoside (Cy-3-glu) preferentially promotes the apoptosis of TNBC cells, which co-express the estrogen receptor alpha 36 (ERα36) and the epidermal growth factor receptor (EGFR). We demonstrated that Cy-3-glu directly binds to the ligand-binding domain (LBD) of ERα36, inhibits EGFR/AKT signaling, and promotes EGFR degradation. We also confirmed the therapeutic efficacy of Cy-3-glu on TNBC in the xenograft mouse model. Our data indicates that Cy-3-glu could be a novel preventive/therapeutic agent against the TNBC co-expressed ERα36/EGFR.