Background: Invasive fungal infections, such as candidemia, caused by Candida species have been increasing. Candidemia is not only associated with a high mortality (30% to 40%) but also extends the length of hospital stay and increases the costs of medical care. Sepsis caused by Candida species is clinically indistinguishable from bacterial infections. Although, the clinical presentations of the patients with candidemia caused by Candida albicans and non-albicans Candida species (NAC) are indistinguishable, the susceptibilities to antifungal agents of these species are different. In this study, we attempted to identify the risk factors for candidemia caused by C. albicans and NAC in the hope that this may guide initial empiric therapy. Methods: A retrospective chart review was conducted during 1996 to 1999 at the Veterans General Hospital-Taipei. Results: There were 130 fatal cases of candidemia, including 68 patients with C. albicans and 62 with NAC. Candidemia was the most likely cause of death in 55 of the 130 patients (42.3 %). There was no significant difference in the distribution of Candida species between those died of candidemia and those died of underlying conditions. Patients who had one of the following conditions were more likely to have C. albicans, age ≧ 65 years, immunosuppression accounted to prior use of steroids, leukocytosis, in the intensive care unit (ICU), and intravascular and urinary catheters. Patients who had undergone cancer chemotherapy often appeared less critically ill and were more likely to have NAC. Conclusion: Clinical and epidemiological differences in the risk factors between candidemia caused by C. albicans and NAC may provide helpful clues to initiate empiric therapy for patients infected with C. albicans versus NAC.

Salmonella is a common intestinal pathogen that causes acute and chronic inflammatory response. Probiotics reduce inflammatory cytokine production and serve as beneficial commensal microorganisms in the human gastrointestinal tract. TGF-β (transforming growth factor β)/SMAD and NF-κB signaling play important roles in inflammation in intestinal cells. However, the involvement of the signaling in regulating inflammation between Salmonella and probiotics is not fully understood. L. acidophilus and prebiotic inulin were used to treat human intestinal Caco-2 cells prior to infection with Salmonella. The cells were harvested to examine the cytokines and MIR21 expression with immunoblotting and real-time PCR. NF-κB and SMAD3/4 reporter vectors were transfected into cells to monitor inflammation and TGF-β1 signaling, respectively. In this study, we showed that the probiotic L. acidophilus decreased Salmonella-induced NF-κB activation in human intestinal Caco-2 cells. Expression of the inflammatory cytokines, TNF-α and IL-8, in L. acidophilus-pretreated cells was also significantly lower than that in cells infected with Salmonella alone. Moreover, TGF-β1 and MIR21 expression was elevated in cells pretreated with L. acidophilus or synbiotic, a combination of inulin and L. acidophilus, compared to that in untreated cells or cells infected with S. typhimurium alone. By contrast, expression of SMAD7, a target of MIR21, was accordingly reduced in cells treated with L. acidophilus or synbiotics. Consistent with TGF-β1/MIR21 and SMAD7 expression, SMAD3/4 transcriptional activity was significantly higher in the cells treated with L. acidophilus or synbiotics. Furthermore, TGF-β1 antibody antagonized the SMAD3/4 and NF-κB transcriptional activity modulated by L. acidophilus in intestinal cells. Our results suggest that the TGF-β1/MIR21 signaling pathway may be involved in the suppressive effects of L. acidophilus on inflammation caused by S. typhimurium in intestinal Caco-2 cells.

Purpose: Few effective antibiotics are available for treating extensively drug-resistant Acinetobacter baumannii (XDRAB) sepsis. Phage therapy may show potential in treating XDRAB infections. Materials and methods: We studied ϕkm18p phage therapy in BALB/c and C57BL/6 mice models of XDRAB bacteremia. Results: We observed survival rates of nearly 100% in groups given phage therapy concurrent with XDRAB at different multiplicities of infection. In mice that received phage therapy after a 1-hour delay, the survival rate decreased to about 50%. The bacterial load in the blood decreased from 10⁸ to 10² and 10³ colony-forming units (CFU)/mL in the concurrent treatment group. In the phage therapy group, the levels of the cytokines, such as tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), were low at 3 hours after infection. Although some phage-resistant mutants were isolated after phage therapy, a cytotoxicity study showed that they had reduced fitness. Conclusion: Phage therapy in XDRAB bacteremia increased the animal survival rates, decreased the bacteremia loads, and decreased the levels of inflammatory markers TNF-α and IL-6. However, the reduced therapeutic effect with delayed administrations may be a concern in developing a successful phage therapy for treating acute infections of multidrug-resistant pathogens.

Extraintestinal pathogenic Escherichia coli (ExPEC) strains hold the responsibility for the majority of E. coli infections. Numerous extraintestinal virulence factors (VFs) were possessed by ExPEC which are involved in the pathogenesis of infection. However, the effect of comorbidities or infection syndrome in the association of VFs and mortality remains inconclusive. This study addressed whether specific sequence type (ST) and VFs of extended-spectrum beta-lactamase-producing E. coli (ESBL-EC) are associated with different outcomes in patients with bloodstream infection. 121 adults from southern Taiwan with ESBL-EC bloodstream infections were enrolled during a 6-year period. Demographic data, including infection syndromes, underlying disease and outcomes, were collected. The virulence factors in isolates were analyzed by PCR and multilocus sequence typing analyses were also performed. Positivity for the virulence genes iha, hlyD, sat, iutA, fyuA, malX, ompT, and traT was associated with ST131 positivity (P < 0.05). Some ESBL-EC virulence genes associated with urinary tract infection (UTI) were revealed. Positivity for ST405 and the virulence genes iroN and iss were significantly associated with increased 30-day mortality (death within 30 days) on univariate analysis (P < 0.05). Independent risk factors of 30-day mortality in bacteremic patients with UTI included underlying chronic liver disease and malignancy. ST131 was borderline associated with 30-day mortality. Independent risk factors associated with 30-day mortality among bacteremic patients without UTI included comorbidities and iroN positivity. In bacteremic patients with UTI, and the ST131 clone was borderline associated with mortality. Positivity for the virulence gene iroN may be linked to mortality in bacteremic patients without UTI.

Extended-spectrum β-lactamase (ESBL)-producing Escherichia coli sequence type ST131 has emerged as the leading cause of community-acquired urinary tract infections and bacteremia worldwide. Whether environmental water is a potential reservoir of these strains remains unclear. River water samples were collected from 40 stations in southern Taiwan from February to August 2014. PCR assay and multilocus sequence typing (MLST) analysis were conducted to determine the CTX-M group and sequence type, respectively. In addition, we identified the seasonal frequency of ESBL-producing E. coli strains and their geographical relationship with runoffs from livestock and poultry farms between February and August 2014. ESBL-producing E. coli accounted for 30% of the 621 E. coli strains isolated from river water in southern Taiwan. ESBL-producing E. coli ST131 was not detected among the isolates. The most commonly detected strain was E. coli CTX-M group 9. Among the 92 isolates selected for MLST analysis, the most common ESBL-producing clonal complexes were ST10 and ST58. The proportion of ESBL-producing E. coli was significantly higher in areas with a lower river pollution index ( P = 0.025) and regions with a large number of chickens being raised ( P = 0.013). ESBL-producing E. coli strains were commonly isolated from river waters in southern Taiwan. The most commonly isolated ESBL-producing clonal complexes were ST10 and ST58, which were geographically related to chicken farms. ESBL-producing E. coli ST131, the major clone causing community-acquired infections in Taiwan and worldwide, was not detected in river waters.

The emergence of multidrug-resistant (MDR) Escherichia coli (E. coli), particularly E. coli sequence type ST131, is becoming a global concern. Commensal bacteria, an important reservoir of antibiotic resistance genes, facilitate the spread of such genes to pathogenic bacterial strains. The objective of the study is to investigate the fecal carriage of MDR E. coli and ST131 E. coli in community children in Southern Taiwan. In this prospective study, stool samples from children aged 0–18 years were obtained within 3 days of hospitalization from October 2013 to September 2014. Children with a history of underlying diseases, antibiotic treatment, or hospitalization in the 3 months before specimen collection were excluded. E. coli colonies were selected and tested for antimicrobial susceptibility, and O25b-ST131, multilocus sequence typing, and blaCTX-M gene groups were detected. Among 157 E. coli isolates, the rates of nonsusceptibility to ampicillin, amoxycillin + clavulanate, trimethoprim–sulfamethoxazole, and cefazolin were 70, 65.6, 47.1, and 32.5%, respectively. Twenty-nine (18.5%) isolates were nonsusceptible to ciprofloxacin. MDR E. coli accounted for 58 (37%) of all isolates. Thirteen (8.3%) isolates produced extended-spectrum β-lactamase (ESBL). Furthermore, 26 (16.6%) and 13 (8.3%) isolates were O25b and ST131 positive, respectively. Five (38.5%) of the 13 ESBL-producing E. coli belonged to blaCTX-M group 9, among which were CTXM-14 and 4 (80%) were O25b–ST131 positive. Compared with the non-ESBL and ciprofloxacin-susceptible groups, the ESBL and ciprofloxacin-nonsusceptible groups showed significantly higher rates of O25b–ST131 positivity. The prevalence of the fecal carriage of nonsusceptible E. coli in children was high; among these E. coli, 37% were MDR, 18.5% were nonsusceptible to ciprofloxacin, and 8.3% produced ESBL. O25b–ST131 was the most common ESBL-producing E. coli clonal group present in the feces of children, and the ESBL and ciprofloxacin-nonsusceptible groups showed significantly higher rates of O25b–ST131 positivity.