Vitamin D (1α,25(OH)2D3) supplementation minimized multinucleated giant cells formation and inflammatory response during Burkholderia pseudomallei infection in human lung epithelial cells.

Melioidosis is an infectious disease with high mortality rates in human, caused by the bacterium Burkholderia pseudomallei. As an intracellular pathogen, B. pseudomallei can escape from the phagosome and induce multinucleated giant cells (MNGCs) formation resulting in antibiotic resistance and immune evasion. A novel strategy to modulate host response against B. pseudomallei pathogenesis is required. In this study, an active metabolite of vitamin D3 (1α,25-dihydroxyvitamin D3 or 1α,25(OH)2D3) was selected to interrupt pathogenesis of B. pseudomallei in a human lung epithelium cell line, A549. The results demonstrated that pretreatment with 10-6 M 1α,25(OH)2D3 could reduce B. pseudomallei internalization to A549 cells at 4 h post infection (P < 0.05). Interestingly, the presence of 1α,25(OH)2D3 gradually reduced MNGC formation at 8, 10 and 12 h compared to that of the untreated cells (P < 0.05). Furthermore, pretreatment with 10-6 M 1α,25(OH)2D3 considerably increased hCAP-18/LL-37 mRNA expression (P < 0.001). Additionally, pro-inflammatory cytokines, including MIF, PAI-1, IL-18, CXCL1, CXCL12 and IL-8, were statistically decreased (P < 0.05) in 10-6 M 1α,25(OH)2D3-pretreated A549 cells by 12 h post-infection. Taken together, this study indicates that pretreatment with 10-6 M 1α,25(OH)2D3 has the potential to reduce the internalization of B. pseudomallei into host cells, decrease MNGC formation and modulate host response during B. pseudomallei infection by minimizing the excessive inflammatory response. Therefore, 1α,25(OH)2D3 supplement may provide an effective supportive treatment for melioidosis patients to combat B. pseudomallei infection and reduce inflammation in these patients.

Paravertebral abscess and bloodstream infection caused by Burkholderia pseudomallei after acupuncture: a case report.

BACKGROUND: Various pathogenic bacterial infections caused by acupuncture have raised widespread concern, but paravertebral abscesses and bloodstream infections of Burkholderia pseudomallei (B.pseudomallei) after acupuncture have not been reported. CASE PRESENTATION: A 49-year-old man was admitted to hospital with recurrent back pain and fever for 1 month, along with the finding of undiagnosed diabetes. He was considered to have tuberculosis because of unrelieved high fever and pulmonary nodules. Bilateral blood culture suggested B.pseudomallei infection, MRI of the lumbar spine suggested paravertebral abscess, and the final diagnosis was paravertebral abscess and bloodstream infection after acupuncture combined with migrating lung infection. He was discharged after abscess debridement and intensive anti-infective therapy, but no further oral antibiotics were administered because of his poor adherence. More than 5 months later, he was readmitted with the urine culture findings of B.pseudomallei. No other abscess formation was observed and he received oral antibiotics for more than 3 months without recurrence. CONCLUSIONS: Acupuncture may lead to B.pseudomallei infection in high-risk groups, and inadequate treatment can lead to recurrent infections.

Drug screening to identify compounds to act as co-therapies for the treatment of Burkholderia species.

Burkholderia pseudomallei is a soil-dwelling organism present throughout the tropics. It is the causative agent of melioidosis, a disease that is believed to kill 89,000 people per year. It is naturally resistant to many antibiotics, requiring at least two weeks of intravenous treatment with ceftazidime, imipenem or meropenem followed by 6 months of orally delivered co-trimoxazole. This places a large treatment burden on the predominantly middle-income nations where the majority of disease occurs. We have established a high-throughput assay for compounds that could be used as a co-therapy to potentiate the effect of ceftazidime, using the related non-pathogenic bacterium Burkholderia thailandensis as a surrogate. Optimization of the assay gave a Z' factor of 0.68. We screened a library of 61,250 compounds and identified 29 compounds with a pIC50 (-log10(IC50)) greater than five. Detailed investigation allowed us to down select to six "best in class" compounds, which included the licensed drug chloroxine. Co-treatment of B. thailandensis with ceftazidime and chloroxine reduced culturable cell numbers by two orders of magnitude over 48 hours, compared to treatment with ceftazidime alone. Hit expansion around chloroxine was performed using commercially available compounds. Minor modifications to the structure abolished activity, suggesting that chloroxine likely acts against a specific target. Finally, an initial study demonstrates the utility of chloroxine to act as a co-therapy to potentiate the effect of ceftazidime against B. pseudomallei. This approach successfully identified potential co-therapies for a recalcitrant Gram-negative bacterial species. Our assay could be used more widely to aid in chemotherapy to treat infections caused by these bacteria.

Tannic Acid-Stabilized Silver Nanoparticles Used in Biomedical Application as an Effective Antimelioidosis and Prolonged Efflux Pump Inhibitor against Melioidosis Causative Pathogen.

Burkholderia pseudomallei is the causative pathogen of melioidosis and this bacterium is resistant to several antibiotics. Silver nanoparticles (AgNPs) are an interesting agent to develop to solve this bacterial resistance. Here, we characterize and assess the antimelioidosis activity of AgNPs against these pathogenic bacteria. AgNPs were characterized and displayed a maximum absorption band at 420 nm with a spherical shape, being well-monodispersed and having high stability in solution. The average size of AgNPs is 7.99 ± 1.46 nm. The antibacterial efficacy of AgNPs was evaluated by broth microdilution. The bactericidal effect of AgNPs was further assessed by time-kill kinetics assay. Moreover, the effect of AgNPs on the inhibition of the established biofilm was investigated by the crystal violet method. In parallel, a study of the resistance induction development of B. pseudomallei towards AgNPs with efflux pump inhibiting effect was performed. We first found that AgNPs had strong antibacterial activity against both susceptible and ceftazidime-resistant (CAZ-resistant) strains, as well as being efficiently active against B. pseudomallei CAZ-resistant strains with a fast-killing mode via a bactericidal effect within 30 min. These AgNPs did not only kill planktonic bacteria in broth conditions, but also in established biofilm. Our findings first documented that the resistance development was not induced in B. pseudomallei toward AgNPs in the 30th passage. We found that AgNPs still showed an effective efflux pump inhibiting effect against these bacteria after prolonged exposure to AgNPs at sublethal concentrations. Thus, AgNPs have valuable properties for being a potent antimicrobial agent to solve the antibiotic resistance problem in pathogens.

An in situ high-throughput screen identifies inhibitors of intracellular Burkholderia pseudomallei with therapeutic efficacy.

Burkholderia pseudomallei (Bp) and Burkholderia mallei (Bm) are Tier-1 Select Agents that cause melioidosis and glanders, respectively. These are highly lethal human infections with limited therapeutic options. Intercellular spread is a hallmark of Burkholderia pathogenesis, and its prominent ties to virulence make it an attractive therapeutic target. We developed a high-throughput cell-based phenotypic assay and screened ∼220,000 small molecules for their ability to disrupt intercellular spread by Burkholderia thailandensis, a closely related BSL-2 surrogate. We identified 268 hits, and cross-species validation found 32 hits that also disrupt intercellular spread by Bp and/or Bm Among these were a fluoroquinolone analog, which we named burkfloxacin (BFX), which potently inhibits growth of intracellular Burkholderia, and flucytosine (5-FC), an FDA-approved antifungal drug. We found that 5-FC blocks the intracellular life cycle at the point of type VI secretion system 5 (T6SS-5)-mediated cell-cell spread. Bacterial conversion of 5-FC to 5-fluorouracil and subsequently to fluorouridine monophosphate is required for potent and selective activity against intracellular Burkholderia In a murine model of fulminant respiratory melioidosis, treatment with BFX or 5-FC was significantly more effective than ceftazidime, the current antibiotic of choice, for improving survival and decreasing bacterial counts in major organs. Our results demonstrate the utility of cell-based phenotypic screening for Select Agent drug discovery and warrant the advancement of BFX and 5-FC as candidate therapeutics for melioidosis in humans.

Oral eradication therapy for melioidosis: Important but not without risks.

OBJECTIVES: The purpose of this study was to quantify the adverse effects from oral eradication therapy for melioidosis, which is usually with high dose trimethoprim-sulfamethoxazole for 3-6 months. METHODS: This retrospective cohort study reviewed side effects from oral eradication therapy in patients presenting with first episode culture-confirmed melioidosis in the tropical north of Australia's Northern Territory between 1st October 2012 and 1st January 2017. RESULTS: 234 patients presented for the first time with culture-confirmed melioidosis. Of these, 16 (6.8%) died during the intensive phase treatment and 6 (2.6%) did not have complete treatment at Royal Darwin Hospital. Of the remaining 212 patients, 203 (95.8%) were initially prescribed trimethoprim-sulfamethoxazole as oral eradication therapy, 6 (2.8%) were prescribed doxycycline and 3 (1.4%) had no eradication therapy. Of the 203 prescribed trimethoprim-sulfamethoxazole, 61 (30.0%) experienced adverse effects, which necessitated a cessation, a change in antibiotic or reduction in dose. CONCLUSIONS: In patients treated for melioidosis in northern Australia there are high rates of adverse effects from oral trimethoprim-sulfamethoxazole, frequently necessitating a change in therapy or a reduction in dose. Given the side effects and low rates of oral therapy completion in our region we emphasise the importance of the prior often prolonged intensive phase intravenous therapy and using weight based trimethoprim-sulfamethoxazole dosing for eradication therapy.

Burkholderia pseudomallei: Challenges for the Clinical Microbiology Laboratory.

Melioidosis is a potentially fatal infection caused by the bacterium Burkholderia pseudomallei Clinical diagnosis of melioidosis can be challenging since there is no pathognomonic clinical syndrome, and the organism is often misidentified by methods used routinely in clinical laboratories. Although the disease is more prevalent in Thailand and northern Australia, sporadic cases may be encountered in areas where it is not endemic, including the United States. Since the organism is considered a tier 1 select agent according to the Centers for Disease Control and Prevention and the U.S. Department of Agriculture Animal and Plant Health Inspection Service, clinical laboratories must be proficient at rapidly recognizing isolates suspicious for B. pseudomallei, be able to safely perform necessary rule-out tests, and to refer suspect isolates to Laboratory Response Network reference laboratories. In this minireview, we report a case of melioidosis encountered at our institution and discuss the laboratory challenges encountered when dealing with clinical isolates suspicious for B. pseudomallei or clinical specimens from suspected melioidosis cases.

Guillaine-barre syndrome; a rare complication of melioidosis. a case report.

BACKGROUND: Melioidosis caused by Burkholderia pseudomellei is an infection with protean clinical manifestations. Guillain-Barré syndrome [GBS] associated with melioidosis is very rare. CASE PRESENTATION: A 42-year-old woman with diabetes presented with abdominal pain, vomiting and intermittent fever for one month. Six months before presentation she had recurrent skin abscesses. Three months before presentation she had multiple liver abscesses which were aspirated in a local hospital. The aspirate grew "coliforms" resistant to gentamicin and sensitive to ceftazidime. On presentation she had high fever and tender hepatomegaly. Ultra Sound Scan of abdomen showed multiple liver and splenic abscesses. Based on the suggestive history and sensitivity pattern of the previous growth melioidosis was suspected and high dose meropenem was started. Antibodies to melioidin were raised at a titre of 1:10240. The growth from the aspirate of liver abscess was confirmed as Burkholderia pseudomellei by polymerase chain reaction [PCR]. After a week of treatment, patient developed bilateral lower limb weakness. Deep tendon reflexes were absent. There was no sensory loss or bladder/bowel involvement. Analysis of the cerebro-spinal fluid showed elevated proteins with no cells. There was severe peripheral neuropathy with axonal degeneration. A diagnosis of GBS was made and she was treated with plasmapharesis with marked improvement of neurological deficit. Continuation of intravenous antibiotics lead to further clinical improvement with normalization of inflammatory markers and resolution of liver and splenic abscess. Eradication therapy with oral co-trimoxazole and co-amoxyclav was started on the seventh week. Patient was discharged to outpatient clinic with a plan to continue combination of oral antibiotics for 12 weeks. At the end of 12 weeks she was well with complete neurological resolution and no evidence of a relapse. CONCLUSIONS: Guillaine Barre syndrome is a rare complication of melioidosis and should be suspected in a patient with melioidosis who develop lower limb weakness. Plasmapharesis can be successfully used to treat GBS associated with active melioidosis.

The antibiotics of choice for the treatment of melioidosis in Indian set up.

Therapeutic options for the treatment of melioidosis caused by Burkholderia pseudomallei are limited due to the inherent resistance conferred by this pathogen to various groups of antibiotics. Witnessing an increase in the number of microbiological culture-confirmed cases of melioidosis at our settings in the past few years, we undertook this study to estimate the minimum inhibitory concentrations of clinical isolates of B. pseudomallei against the four commonly employed antimicrobial agents in the patient management at our settings, namely, ceftazidime, meropenem, trimethoprim-sulfamethoxazole and doxycycline. All isolates were susceptible to the antibiotics tested, except for one isolate which showed resistance to doxycycline (minimum inhibitory concentration [MIC]: 32 µg/ml). MIC50 and 90 for all the four antibiotics were estimated. From this study, we conclude that the clinical isolates of B. pseudomallei from the southern part of India are well susceptible to the commonly employed antimicrobial agents for therapy.

Acute pulmonary melioidosis presenting with multiple bilateral cavitary lesions in a healthy young adult: an authentic case report from Sri Lanka.

BACKGROUND: Melioidosis is an emerging infectious disease in Sri Lanka. This disease usually develops in a host with an immunocompromised state. Acute pulmonary melioidosis commonly presents as a lobar consolidation with or without pulmonary nodules or abscesses involving the upper lobes of the lungs. CASE PRESENTATION: We report a young healthy female who does not have known risk factors or immunocompromised state, presented with bilateral multiple cavitary lesions involving all three zones of the lungs. She used to involve in home gardening. Her initial relevant microbiological investigations were all negative. The diagnosis of melioidosis was made by broncho-alveolar lavage fluid culture positivity combined with a highly positive antibody titre. She showed dramatic response to intravenous high dose Meropenem. CONCLUSIONS: Melioidosis should be suspected early in patients with acute pulmonary involvement who show poor response to conventional antibiotics, even in the absence of known risk factors for disease. Other than known occupational exposures, household exposures such as home gardening should also be considered as a possible mode of exposure.

Anti-malarial and anti-inflammatory effects of Gleichenia truncata mediated through inhibition of GSK3ß.

Gleichenia truncata is a highland fern from the Gleicheniaceae family known for its traditional use among indigenous communities in Asia to treat fever. The scientific basis of its effect has yet to be documented. A yeast-based kinase assay conducted in our laboratory revealed that crude methanolic extract (CME) of G. truncata exhibited glycogen synthase kinase-3 (GSK3)-inhibitory activity. GSK3ß is now recognized to have a pivotal role in the regulation of inflammatory response during bacterial infections. We have also previously shown that lithium chloride (LiCl), a GSK3 inhibitor suppressed development of Plasmodium berghei in a murine model of malarial infection. The present study is aimed at evaluating G. truncata for its anti-malarial and anti-inflammatory effects using in vivo malarial and melioidosis infection models respectively. In a four-day suppressive test, intraperitoneal injections of up to 250 mg/kg body weight (bw) G. truncata CME into P.berghei-infected mice suppressed parasitaemia development by >60%. Intraperitoneal administration of 150 mg/kg bw G. truncata CME into Burkholderia pseudomallei-infected mice improved survivability by 44%. G. truncata CME lowered levels of pro-inflammatory cytokines (TNF-α, IFN-γ) in serum and organs of B. pseudomallei-infected mice. In both infections, increased phosphorylations (Ser9) of GSK3ß were detected in organ samples of animals administered with G. truncata CME compared to controls. Taken together, results from this study strongly suggest that the anti-malarial and anti-inflammatory effects elicited by G. truncata in part were mediated through inhibition of GSK3ß. The findings provide scientific basis for the ethnomedicinal use of this fern to treat inflammation-associated symptoms.

Thalassemia major is a major risk factor for pediatric melioidosis in Kota Kinabalu, Sabah, Malaysia.

BACKGROUND: Melioidosis is an important cause of community-acquired infection in Southeast Asia and northern Australia. Studies from endemic countries have demonstrated differences in the epidemiology and clinical features among children diagnosed with melioidosis. This suggests that local data are needed to determine the risk factors and outcome in specific areas. METHODS: This was a retrospective study of all children admitted to Likas Women's and Children Hospital, Kota Kinabalu, Sabah, Malaysia, with a blood or clinical sample positive for Burkholderia pseudomallei from 2001 to 2012. RESULTS: Of 28 children with confirmed melioidosis, 27 records were reviewed including 11 (41%) children with thalassemia major. Twenty of the children had bacteremia, and 16 (59%) had a fatal outcome. Six children had chronic disease, and none died. Empiric use of antibiotics not specific for B. pseudomallei was associated with increased risk of death (P < .001). The annual incidence of melioidosis in children with thalassemia major from 2001 to 2010 was 140 per 100 000/year vs 0.33 per 100 000/year for other children (P < .001). After institution of iron chelation therapy in 2010, no child with thalassemia major was diagnosed with melioidosis in 2011 or 2012. CONCLUSIONS: Pediatric melioidosis in Sabah is associated with a high proportion of bacteremia and death. Thalassemia major was a major risk factor for melioidosis among children from 2001 to 2010, but infections decreased markedly from 2011 to 2012 after universal availability of iron chelation therapy. Inappropriate empiric therapy was associated with an increased risk of death.

Glyburide reduces bacterial dissemination in a mouse model of melioidosis.

BACKGROUND: Burkholderia pseudomallei infection (melioidosis) is an important cause of community-acquired Gram-negative sepsis in Northeast Thailand, where it is associated with a ~40% mortality rate despite antimicrobial chemotherapy. We showed in a previous cohort study that patients taking glyburide ( = glibenclamide) prior to admission have lower mortality and attenuated inflammatory responses compared to patients not taking glyburide. We sought to define the mechanism underlying this observation in a murine model of melioidosis. METHODS: Mice (C57BL/6) with streptozocin-induced diabetes were inoculated with ~6 × 10(2) cfu B. pseudomallei intranasally, then treated with therapeutic ceftazidime (600 mg/kg intraperitoneally twice daily starting 24 h after inoculation) in order to mimic the clinical scenario. Glyburide (50 mg/kg) or vehicle was started 7 d before inoculation and continued until sacrifice. The minimum inhibitory concentration of glyburide for B. pseudomallei was determined by broth microdilution. We also examined the effect of glyburide on interleukin (IL) 1ß by bone-marrow-derived macrophages (BMDM). RESULTS: Diabetic mice had increased susceptibility to melioidosis, with increased bacterial dissemination but no effect was seen of diabetes on inflammation compared to non-diabetic controls. Glyburide treatment did not affect glucose levels but was associated with reduced pulmonary cellular influx, reduced bacterial dissemination to both liver and spleen and reduced IL1ß production when compared to untreated controls. Other cytokines were not different in glyburide-treated animals. There was no direct effect of glyburide on B. pseudomallei growth in vitro or in vivo. Glyburide directly reduced the secretion of IL1ß by BMDMs in a dose-dependent fashion. CONCLUSIONS: Diabetes increases the susceptibility to melioidosis. We further show, for the first time in any model of sepsis, that glyburide acts as an anti-inflammatory agent by reducing IL1ß secretion accompanied by diminished cellular influx and reduced bacterial dissemination to distant organs. We found no evidence for a direct effect of glyburide on the bacterium.

Present and future therapeutic strategies for melioidosis and glanders.

Burkholderia pseudomallei and Burkholderia mallei are the causative agents of melioidosis and glanders, respectively. Both Gram-negative pathogens are endemic in many parts of the world. Although natural acquisition of these pathogens is rare in the majority of countries, these bacteria have recently gained much interest because of their potential as bioterrorism agents. In modern times, their potential destructive impact on public health has escalated owing to the ability of these pathogens to cause opportunistic infections in diabetic and perhaps otherwise immunocompromised people, two growing populations worldwide. For both pathogens, severe infection in humans carries a high mortality rate, both species are recalcitrant to antibiotic therapy - B. pseudomallei more so than B. mallei - and no licensed vaccine exists for either prophylactic or therapeutic use. The potential malicious use of these organisms has accelerated the investigation of new ways to prevent and to treat the diseases. The availability of several B. pseudomallei and B. mallei genome sequences has greatly facilitated target identification and development of new therapeutics. This review provides a compilation of literature covering studies in antimelioidosis and antiglanders antimicrobial drug discovery, with a particular focus on potential novel therapeutic approaches to combat these diseases.

Dosing regimens of cotrimoxazole (trimethoprim-sulfamethoxazole) for melioidosis.

Melioidosis is an infectious disease with a propensity for relapse, despite prolonged antibiotic eradication therapy for 12 to 20 weeks. A pharmacokinetic (PK) simulation study was performed to determine the optimal dosing of cotrimoxazole (trimethoprim-sulfamethoxazole [TMP-SMX]) used in current eradication regimens in Thailand and Australia. Data for bioavailability, protein binding, and coefficients of absorption and elimination were taken from published literature. Apparent volumes of distribution were correlated with body mass and were estimated separately for Thai and Australian populations. In vitro experiments demonstrated concentration-dependent killing. In Australia, the currently used eradication regimen (320 [TMP]/1,600 [SMX] mg every 12 h [q12h]) was predicted to achieve the PK-pharmacodynamic (PD) target (an area under the concentration-time curve from 0 to 24 h/MIC ratio of >25 for both TMP and SMX) for strains with the MIC90 of Australian strains (< or = 1/19 mg/liter). In Thailand, the former regimen of 160/800 mg q12h would not be expected to attain the target for strains with an MIC of > or = 1/19 mg/liter, but the recently implemented weight-based regimen (<40 kg [body weight], 160/800 mg q12h; 40 to 60 kg, 240/1,200 mg q12h; >60 kg, 320/1,600 mg q12h) would be expected to achieve adequate concentrations for strains with an MIC of < or = 1/19 mg/liter. The results were sensitive to the variance of the PK parameters. Prospective PK-PD studies of Asian populations are needed to optimize TMP-SMX dosing in melioidosis.

[In vitro antibiotic susceptibility compliance with efficacy of chemotherapy in infections due to pathogenic Burkholderias].

Among the known species of Burkholderia only two are obligate pathogens, i.e., B. mallei and B. pseudomallei, causative agents of glanders and melioidosis respectively. The other species are saprophytes as natural inhabitants of water reservoirs and soil, still capable of causing opportunistic infections in humans and animals under definite conditions. All the species of Burkholderia are characterized by high resistance to antibacterials, including antibiotics. By the MICs, the most efficient chemotherapeutics against pathogenic burkholderias are tetracyclines, fluoroquinolones, penems and combined sulfanilamides. In the treatment of experimental glanders and melioidosis the set of the effective drugs had the inverse variation dependence on the infection severity and the desease process rate. Co-trimoxasole showed the best results, then followed doxicycline, ciprofioxacin and ceftazidime in the diminishing succession. The modification of the method for determination of antibiotic susceptibility with addition of native blood to the medium and the subculture under the atmosphere of 5% CO2 was shown useful in estimation of the prospects of the use of chemotherapeutics for the treatment of Burkholderia infections.

Melioidosis: antibiogram of cases in Singapore 1987-2007.

The antimicrobial susceptibility of Burkholderia pseudomallei isolates identified by the bacteriology laboratory at Singapore General Hospital was reviewed. Laboratory data were found to be available since 1987 and showed that ceftazidime, amoxicillin-clavulanate, chloramphenicol and tetracycline had remained effective through the years. Imipenem was added to the list of antimicrobials tested after 1989, and the isolates showed high susceptibility rates. Co-trimoxazole was found to be useful based on Etest results, but the isolates had low susceptibility rates when tested using disk diffusion.

Melioidosis: a review of orthopedic manifestations, clinical features, diagnosis and management.

Melioidosis is an infectious disease caused by gram-negative soil-dwelling bacillus Burkholderia pseudomallei. Musculoskeletal melioidosis mimics other infections both clinically and radiologically. An extensive literature review has been performed over musculoskeletal melioidosis through various search engines such as Pubmed, Embase, Medscape, Altavista and Google. Diagnosis requires a high index of clinical suspicion and is dependent on microbiological confirmation. Prompt treatment with long-term combination antibiotics in high dosages and surgical drainage of abscesses improves survival.

Activity of tigecycline in the treatment of acute Burkholderia pseudomallei infection in a murine model.

Burkholderia pseudomallei is the causative agent of melioidosis. Standard therapy includes ceftazidime alone or in combination with co-trimoxazole. Tigecycline, a novel agent, has displayed activity against B. pseudomallei. We evaluated the in vivo efficacy of tigecycline using a murine model of melioidosis. Mice were infected with either a high or low virulence B. pseudomallei isolate followed by administration of antibiotics alone or in combination (tigecycline, ceftazidime, tigecycline plus ceftazidime) for 7 days. Bacterial loads were assessed up to 7 days and survival was determined up to 7 days post infection. Tigecycline in combination with ceftazidime was the most effective and conferred the lowest mortality, suggesting the use of this new agent in B. pseudomallei infection.