Human melioidosis caused by Burkholderia pseudomallei is a severe septic disease that is associated with high mortality, even under appropriate antibiotic treatment. The therapeutic effects of low-dose hydrocortisone plus ceftazidime, and of ceftazidime alone, have recently been investigated in the treatment of acute, severe sepsis caused by B. pseudomallei, both in normal BALB/c mice and in BALB/c mice with streptozotocin-induced diabetes. The mice were infected and then treated intravenously, from day 1 or day 2 post-infection, with saline (as a control, given twice daily for 10 days), low-dose hydrocortisone (given in twice-daily doses of 5 mg/kg, for 5 days) plus ceftazidime (given in twice-daily doses of 1200 mg/kg, for 10 days), or the same doses of ceftazidime alone. Although the infected, untreated mice all died within 14 days, almost all of the treated animals were still alive at the end of the follow-up, 30 days post-infection. The addition of the steroid appeared to have no benefit, with bacterial loads and plasma concentrations of tumour necrosis factor, aspartate aminotransferase, alanine aminotransferase and creatinine decreasing similarly in all the treated groups. The infected diabetic mice given hydrocortisone-ceftazidime from day 1 (but not those given just ceftazidime from day 1) showed an increase in their blood glucose concentrations. When infected mice were treated with the low-dose steroid and lower doses of the antibiotic (in twice-daily doses of 120-600 mg/kg), the steroid not only offered no apparent benefit but seemed to reduce survival. It therefore appears that low-dose hydrocortisone, as an adjunct to antibiotic treatment, does not provide benefit in the treatment of murine melioidosis and may have negative effects on human cases of the disease who have diabetes mellitus.

Burkholderia pseudomallei, the causative agent of melioidosis, is an important intracellular pathogen in tropical regions. TANK-binding kinase (TBK1), part of the pathway that induces transcription of Type I interferon genes, has been demonstrated to play an important role in controlling intracellular bacterial infections. To investigate the role of tbk1 in protecting against B. pseudomallei we developed tbk1-deficient cell lines by using shRNA for transient knockdown of the tbk1 gene in HeLa and RAW 264.7 cells. In tbk1-deficient RAW cells, the replication of invasive and non-invasive Escherichia coli was significantly increased at 48 h after infection compared with wild-type cells. The result was confirmed using Brucella melitensis in tbk1-deficient HeLa cells, which demonstrated a >1.5-2.0 log higher bacterial count at 6-48 h after infection compared to wild-type cells. By contrast, the growth of Burkholderia pseudomallei expressing either typical (A2) or atypical (G207) lipopolysaccharide was not significantly different between the tbk1-deficient and control cells. These results suggest that the tbk1 gene and its activation may be able to control invasive E. coli, non-invasive E. coli and B. melitensis growth but may not be able to control B. pseudomallei infection. The role of the tbk1 gene in proinflammatory cytokine induction and bacterial intracellular infection needs further investigation to identify mechanistic differences among the life cycles of various intracellular bacteria.

Background: Pseudomonas aeruginosa has become problematic because of an outbreak of multidrug-resistant (MDR) clone producing metallo-beta-lactamases (MBLs). It is crucial to determine the recent antimicrobial resistance trend in P. aeruginosa to prevent the spreading of MDR clone. We have performed nationwide surveillance on resistance to Fluoroquinolones (FQs) and other antimicrobials in many bacterial clinical isolates since 1994 in Japan. We report herein on surveillance data for P. aeruginosa isolates from patients with urinary tract infections (UTI) and with respiratory tract infections (RTI) collected between 1994 and 2010.Methods: A total of 8,058 clinical isolates (3,748 from UTI and 4,310 from RTI) were collected from 92 centers participating in the Levofloxacin Surveillance Group from 1994 to 2010 in Japan. The susceptibility to 14 antimicrobials was tested by broth microdilution methods according to the Clinical Laboratory Standards Institute (CLSI) guidelines. Metallo-␤-lactamases (MBL) were detected by phenotypic assay (MIC screening, Sodium mercaptoacetic acid (SMA) disk method) and PCR.Results: 1. UTI: The resistance rate for levofloxacin has decreased over time. Amikacin and ceftazidime also showed gradual decreases in the resistance rate. The susceptibility to imipenem remained nearly unchanged. The rate of the MDR clone decreased from 6.8% in 2004 to 2.3% in 2010.2. RTI: The resistance rates for levofloxacin, amikacin, ceftazidime and imipenem have been maintained constantly at levels of approximately 20%, 2%, 10% and 30%, respectively. The rate of the MDR clone was 1Conclusion: Hospital acquired infections by MDR-P. aeruginosa cause serious problems. The results of the present surveillance revealed a decrease in MDR-isolates. However, the presence of MDR-P. aeruginosa must continue to be monitored. http://dx. Burkholderia pseudomallei (B. pseudomallei) is the causative agent of melioidosis, a disease that can involve acute septicemia and chronic infection. Recent reports of a reduced susceptibility of B. pseudomallei to antibiotics. Background:Methods: The aim of this study was to test the antimicrobial activity of antibiotics applied to B. pseudomallei by standard disc diffusion and minimal inhibitory concentration (MIC). A total of 78 isolates of B. pseudomallei from patients admitted to Sapprasithiprasong Hospital between November 2010 and May 2011 were included in this study. In addition, medical records of these patients were reviewed.Results: It was shown that B. pseudomallei were susceptible to ceftazidime, cippofloxacin, piperacillin and imipemen by standard disc diffusion and MICs. Cefoparazone and aztreonam were found 100% susceptible by standard disc diffusion but MICs ≥ 16 were found 94.87% and 87.2% respectively. The mortality rate was found 7.69% and only 30.31% of patients receiving ceftazidime were recovered.Conclusion: Epidemiological study of drug susceptibility is important and still required for basic information. Study mechanisms of antibiotics resistance as well as associ...

Background: Burkholderia pseudomallei are the causative agent of melioidosis, a potentially life-threatening disease in humans and animals. It is a common public health threat in parts of Thailand. Objective: To summarizes the current knowledge regarding antimicrobial agents and B. pseudomallei. Methods: A literature search using MEDLINE (PubMed), SCOPUS, and OVID/LWWW databases. Results: B. pseudomallei are intrinsically resistant to a wide range of antimicrobial agents including β-lactam antibiotics, aminoglycosides, and macrolides. Antimicrobial therapy for melioidosis is divided into an acute phase and an eradication phase. The current recommendations for the acute phase are parenteral antimicrobial agents for ≥10 days using ceftazidime or a carbapenem. The eradication phase involves oral antimicrobial agents for ≥180 days using trimethoprim-sulfamethoxazole. Amoxicillin-clavulanic acid may be used as an alternative. Ceftazidime revealed rare primary resistance and a high relapse rate. Conclusion: Patients with acute melioidosis usually need intensive care and appropriate antibiotics for the acute and eradication phases. Ceftazidime is remains an effective agent in Thailand. A trend for decreasing susceptibility to antibiotics requires monitoring.