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We report a case of Burkholderia mallei causing glanders in a 73-year-old patient from the Northeast Region of Brazil. The patient was hospitalized with severe pneumonia. PCR and genomic sequencing confirmed B. mallei in pleural drainage. Genotyping revealed a novel genotype, emphasizing the need for genetic surveillance in zoonotic infections. [ABSTRACT FROM AUTHOR]

Burkholderia pseudomallei (Bpm) is the causative agent of the disease melioidosis. As a facultative intracellular pathogen, Bpm has a complex lifestyle that culminates in cell-to-cell fusion and multinucleated giant cells (MNGCs) formation. The virulence factor responsible for MNGC formation is the type 6 secretion system (T6SS), a contractile nanomachine. MNGC formation is a cell-to-cell spread strategy that allows the bacteria to avoid the extracellular immune system and our previous data highlighted cell death, apoptosis, and inflammation as pathways significantly impacted by T6SS activity. Thusly, we investigated how the T6SS influences these phenotypes within the macrophage and pulmonary models of infection. Here we report that the T6SS is responsible for exacerbating apoptotic cell death during infection in both macrophages and the lungs of infected mice. We also demonstrate that although the T6SS does not influence differential macrophage polarization, the M2 polarization observed is potentially beneficial for Bpm pathogenesis and replication. Finally, we show that the T6SS contributes to the severity of inflammatory nodule formation in the lungs, which might be potentially connected to the amount of apoptosis that is triggered by the bacteria. Author summary: Burkholderia pseudomallei (Bpm) is an intracellular pathogen and is the etiological agent of melioidosis. This neglected tropical disease results in an estimated 89,000 fatalities a year, however, this number is believed to be severely underreported. The complex intracellular lifestyle and host response to infection is poorly understood, basic cell interactions and responses are critical to defense against infection. Bpm utilizes an array of virulence factors to successfully replicate and disseminate cell-to-cell, one of these is the T6SS which is responsible for MNGC formation and cell-to-cell spread. In this work, we characterized how macrophages respond to infection in the presence or absence of the critical T6SS virulence factor. Macrophages are a primary replicative niche for Bpm but how intracellular replication disrupts macrophages response to infection is poorly understood. By understanding macrophage cell death patterns and polarization, we can dissect responses that are triggered by T6SS activity with the expectation of finding exploitable responses for host directed therapies. [ABSTRACT FROM AUTHOR]

Ice machines can harbor water-related organisms, and the use of ice or tap water for clinical care activities has been associated with infections in health care settings. During 2021–2022, a total of 23 cases of infection by Burkholderia multivorans (sequence type ST659) were reported at two southern California hospitals and linked to contaminated ice and water from ice machines. In addition to these 23 cases, this report also includes 23 previously unreported cases of B. multivorans ST659 infections that occurred during 2020–2024: 13 at a northern California hospital, eight at a hospital in Colorado, and two additional cases at one of the southern California hospitals. The same brand of ice machine and brands of filters, descaling, and sanitizing products were used by all four hospitals; B. multivorans was isolated from samples collected from ice machines in two of the hospitals. Whole genome sequencing indicated that all clinical and ice machine isolates were highly genetically similar (0–14 single nucleotide variant differences across 81% of the selected reference genome). Recommendations from public health officials to halt the outbreak included avoiding ice and tap water during clinical care activities. An investigation is ongoing to determine possible sources of ice machine contamination. During outbreaks of water-related organisms in health care facilities, health care personnel should consider avoiding the use of tap water, including ice and water from ice machines, for patient care. [ABSTRACT FROM AUTHOR]

Herbaspirillum huttiense is an opportunistic pathogen associated with rare cases of bacteremia. In this case report, H huttiense was isolated from blood samples collected from an intravenous catheter (incubated for 20.8 hours) and a peripheral vein (incubated for 14.16 hours) of a lung adenocarcinoma patient. Positive blood culture bottles were subjected to smear preparation, and Gram staining and microscopic examination revealed the presence of gram-negative rods in both aerobic bottles. We used the VITEK MS automatic microbial mass spectrometry system, VITEK 2 Compact automatic microbial analysis system, and high-throughput nucleic acid sequencing for accurate identification of the isolate. It is noteworthy that although the VITEK 2 Compact identified the isolate as Burkholderia cepacia , confirmation through VITEK MS mass spectrometry and 16S ribosomal DNA (rDNA) sequencing identified it as H huttiense. Subsequently, antimicrobial susceptibility testing was performed using the broth microdilution method, following the guidelines for nonfermenting gram-negative bacilli provided by the Clinical and Laboratory Standards Institute. This case highlights the possibility of misidentification of H huttiense as B cepacia by VITEK 2 Compact in certain situations, emphasizing the importance of considering uncommon pathogens, such as H huttiense , in the context of bacteremia in cancer patients. [ABSTRACT FROM AUTHOR]

Burkholderia cepacia complex (Bcc) is a bacterial group with 'natural' multi-antimicrobial resistance. This complex has generated epidemic outbreaks across the world. In people with cystic fibrosis (CF), Bcc can cause severe lung infections that lead to accelerated lung damage, which can be complicated by necrotizing pneumonia accompanied by high fevers, leucocytosis, and bacteraemia, which commonly causes fatal outcomes. Specifically, infection by Burkholderia cenocepacia is considered an exclusion criterion for lung transplantation. The species of Bcc exhibit both genetic and phenotypic hypervariability that complicate their accurate microbiological identification. Automated methods such as MALDI-TOF can err in the determination of species. Their slow growth even in selective agars and the absence of international consensuses on the optimal conditions for their isolation make early diagnosis a difficult challenge to overcome. The absence of correlations between antibiograms and clinical results has resulted in the absence of standardized cut-off values of antimicrobial susceptibility, a fact that brings a latent risk since incorrect antibiotic therapy can induce the selection of more aggressive variants that worsen the clinical picture of the host, added to the absence of a clear therapeutic guide for the eradication of pulmonary infections by Bcc in patients with CF, resulting in frequently ineffective treatments. There is an urgent need to standardize methods and diagnostic tools that would allow an early and accurate diagnosis, as well as to perform clinical studies of the effectiveness of available antibiotics to eradicate Bcc infections, which would allow us to establish standardized therapeutic schemes for Bcc-infected patients. [ABSTRACT FROM AUTHOR]

Introduction: The Burkholderia cepacia complex encompasses a group of gram-negative opportunistic pathogens that cause chronic lung infections in people with cystic fibrosis. Distinct from other respiratory pathogens, Burkholderia causes a unique clinical disease in a subset of patients known as 'cepacia syndrome', fulminant pneumonia accompanied by bacteraemia and sepsis with a mortality rate of up to 75%. Due to the bacteraemia associated with this disease, the mechanisms that allow Burkholderia to resist the bactericidal effects of serum complement-depending killing are vital. Antibodies usually promote serum killing; however, we have described 'cloaking antibodies', specific for lipopolysaccharides that paradoxically protect serum-sensitive bacteria from complement-mediated lysis. Cloaking antibodies that protect Pseudomonas aeruginosa have been found in 24%-41% of patients with chronic lung diseases. The presence of these antibodies is also associated with worse clinical outcomes. Here, we sought to determine the relevance of cloaking antibodies in patients with Burkholderia infection. Methods: Twelve Burkholderia spp. were isolated from nine pwCF and characterised for susceptibility to healthy control serum. Patient serum was analysed for the titre of the cloaking antibody. The ability of the patient serum to prevent healthy control serum (HCS) killing of its cognate isolates was determined. Results: We found that several of the Burkholderia strains were shared between patients. Ten of the 12 isolates were highly susceptible to HCS killing. Four of nine (44%) patients had cloaking antibodies that protected their cognate strain from serum killing. Depleting cloaking antibodies from patient serum restored HCS killing of Burkholderia isolates. Discussion: Cloaking antibodies are prevalent in patients with Burkholderia pulmonary infection and protect these strains from serum killing. Removal of cloaking antibodies via plasmapheresis, as previously described for individuals with life-threatening Pseudomonas infection, may be a useful new strategy for those with serious and life-threatening Burkholderia infection. [ABSTRACT FROM AUTHOR]

Background: Burkholderia pseudomallei, an environmental saprophyte bacterium, causes melioidosis in humans and animals. It was first discovered in Iran between 1967 and 1976 in small ruminants, equines, environments and humans. No subsequent studies have been conducted to determine the existence and prevalence of this pathogen in the country. Objectives: The present study aims to monitor the presence of B. pseudomallei in the ruminant population of the Golestan province of Iran, which largely depends on pastures. The ruminants can serve as sentinels to indicate the presence of the bacteria in the environment and its potential impact on human health in the One Health triad. Methods: Liver and lung abscesses from domestic sheep, cattle and goats in three industrial and three conventional slaughterhouses were sampled and analysed using 23S ribosomal DNA polymerase chain reaction (rDNA PCR) with primers CVMP 23‐1 and CVP‐23‐2 for B. pseudomallei, Burkholderia cepacia and Burkholderia vietnamiensis, as well as B. pseudomallei–specific TTS1 real‐time PCR, along with microbiological and biochemical assays. Results: Out of the 97 animals sampled, only 14 (15%) tested positive for 23S rDNA PCR. However, the follow‐up evaluation using TTS1 real‐time PCR and microbiological and biochemical assays did not confirm the presence of B. pseudomallei in the samples. Conclusions: Although B. pseudomallei was not detected in the current survey, conducting abattoir‐based surveillance of ruminants is a cost‐effective One Health approach to monitor pathogenic Burkholderia. Developing standards of clinical and laboratory good practices for Burkholderia infections is crucial for One Health surveillance. [ABSTRACT FROM AUTHOR]

The interactions between a virus and its host vary in space and time and are affected by the presence of molecules that alter the physiology of either the host or the virus. Determining the molecular mechanisms at the basis of these interactions is paramount for predicting the fate of bacterial and phage populations and for designing rational phage-antibiotic therapies. We study the interactions between stationary phase Burkholderia thailandensis and the phage ΦBp-AMP1. Although heterogeneous genetic resistance to phage rapidly emerges in B. thailandensis, the presence of phage enhances the efficacy of three major antibiotic classes, the quinolones, the beta-lactams and the tetracyclines, but antagonizes tetrahydrofolate synthesis inhibitors. We discovered that enhanced antibiotic efficacy is facilitated by reduced antibiotic efflux in the presence of phage. This new phage-antibiotic therapy allows for eradication of stationary phase bacteria, whilst requiring reduced antibiotic concentrations, which is crucial for treating infections in sites where it is difficult to achieve high antibiotic concentrations. Author summary: Bacteriophages are viruses that infect and kill bacteria and therefore are considered to be a very valuable alternative to the antibiotic molecules that are currently employed in the clinic but towards which bacteria are becoming increasingly resistant. Here we show that when infected with a bacteriophage termed ΦBp-AMP1, the bacterium Burkholderia thailandensis becomes more susceptible to three major antibiotic classes routinely employed to treat infections caused by Burkholderia. We discovered that enhanced antibiotic efficacy in the presence of this bacteriophage is due to a decreased capability of the bacterium to expel antibiotics when it is infected with this bacteriophage. Understanding how bacteriophages and antibiotic molecules interact with each other is essential for optimizing bacteriophage-antibiotic therapy against bacterial infections. [ABSTRACT FROM AUTHOR]

Background and objectives. Optimal management requires an understanding of Burkholderia infections demographic, clinical, microbiological, and antibiotic features. This study aims to improve treatment and infection control strategies by investigating the clinical profiles and antibiotic susceptibilities of Burkholderia infections in a tertiary care context. Material and methods. A retrospective analysis of 48 individuals with Burkholderia infections was carried out in a tertiary care environment. We gathered and analyzed data on antimicrobial susceptibility, clinical presentation, microbiological identification, and demographic features. Results. The mean age of the participants was 49.27 years, and their gender distribution was equal. Diabetes, heart disease, and hypertension are common comorbidities. The most typical symptoms were fever and cough, with infections varying in severity from minor to severe. Burkholderia was predominantly found in urine, blood, and respiratory secretions. Testing for antibiotic susceptibility showed inconsistent findings; some drugs, including ceftazidime and meropenem, were more successful than others. Conclusion. The research highlights the broad demographics impact of Burkholderia infections, in addition to their acute and occasionally fatal characteristics. It highlights how important it is to treat every patient differently, accounting for comorbidities and the severity of symptoms. The results emphasize how much more study is required to improve treatment options and learn more about the origins of Burkholderia infections.

Melioidosis is a bacterial infection caused by Burkholderia pseudomallei, that is common in tropical and subtropical countries including Southeast Asia and Northern Australia. The magnitude of undiagnosed and untreated melioidosis across the country remains unclear. Given its proximity to regions with high infection rates, Riau Province on Sumatera Island is anticipated to have endemic melioidosis. This study reports retrospectively collected data on 68 culture-confirmed melioidosis cases from two hospitals in Riau Province between January 1, 2009, and December 31, 2021, with full clinical data available on 41 cases. We also describe whole genome sequencing and genotypic analysis of six isolates of B. pseudomallei. The mean age of the melioidosis patients was 49.1 (SD 11.5) years, 85% were male and the most common risk factor was diabetes mellitus (78%). Pulmonary infection was the most common presentation (39%), and overall mortality was 41%. Lung as a focal infection (aOR: 6.43; 95% CI: 1.13–36.59, p = 0.036) and bacteremia (aOR: 15.21; 95% CI: 2.59–89.31, p = 0.003) were significantly associated with death. Multilocus sequence typing analysis conducted on six B.pseudomallei genomes identified three sequence types (STs), namely novel ST1794 (n = 3), ST46 (n = 2), and ST289 (n = 1). A phylogenetic tree of Riau B. pseudomallei whole genome sequences with a global dataset of genomes clearly distinguished the genomes of B. pseudomallei in Indonesia from the ancestral Australian clade and classified them within the Asian clade. This study expands the known presence of B. pseudomallei within Indonesia and confirms that Indonesian B. pseudomallei are genetically linked to those in the rest of Southeast Asia. It is anticipated that melioidosis will be found in other locations across Indonesia as laboratory capacities improve and standardized protocols for detecting and confirming suspected cases of melioidosis are more widely implemented. Author summary: Melioidosis is a disease caused by the bacterium Burkholderia pseudomallei. This disease can affect various organs such as the lungs, skin and soft tissues, central nervous system, internal organs, and others. The clinical manifestations vary, and the lack of laboratory examination support in some countries leads to underreporting of the disease. This also results in a varied death rate, ranging from 10–40% and even higher in some countries. The disease is endemic in the Southeast Asian region and northern Australia and is increasingly recognised in other tropical and sub-tropical locations globally. Indonesia has reported over 100 cases from at least 5 diverse regions. One province in Indonesia, Riau, located on the island of Sumatera bordering Malaysia, has been experiencing a relatively high number of melioidosis cases. This study reports melioidosis cases obtained from two referral hospitals in the province of Riau. The research explores the characteristics of patients, clinical manifestations, and outcomes in these cases. Additionally, the study analyzes factors influencing mortality from melioidosis in Riau. Phylogenetic analysis of six isolates of B. pseudomallei determined that B. pseudomallei in the province of Riau, Indonesia is genetically linked to those from neighbouring countries in Southeast Asia. [ABSTRACT FROM AUTHOR]

Early diagnosis is essential for the successful management of Burkholderia pseudomallei infection, but it cannot be achieved by the current gold standard culture technique. Therefore, this study aimed to develop a lateral flow immunoassay (LFIA) targeting B. pseudomallei capsular polysaccharide. The development was performed by varying nitrocellulose membrane reaction pads and chase buffers. The prototype LFIA is composed of Unisart CN95 and chase buffer containing tris-base, casein, and Surfactant 10G. The assay showed no cross-reactivity with E. coli, S. aureus, P. aeruginosa, and P. acne. The limit of detections (LODs) of the prototype LFIA was 107 and 106 CFU/mL B. pseudomallei in hemoculture medium and artificial urine, respectively. These LODs suggest that this prototype can detect melioidosis from positive hemoculture bottles but not straight from urine. Additionally, these LODs are still inferior compared to Active Melioidosis Detect (AMDTM). Overall, this prototype holds the potential to be used clinically with hemoculture bottles. However, further improvements should be considered, especially for use with urine samples. [ABSTRACT FROM AUTHOR]

Background: Melioidosis, a tropical infectious disease caused by Burkholderia pseudomallei, is epidemic in most region in Southeast Asia with high case fatality. However, there is scanty information regarding the disease's epidemiological pattern, demographics, and underlying risk factors. Method: This 5-year retrospective study of 185 confirmed cases which were taken from the Negeri Sembilan Melioidosis Registry between 2018 and 2022. We aim to describe the incidence, mortality rate, case fatality, relationship with meteorology, and factors that influence mortality in this central region of Peninsular Malaysia. Results: Incidence rate (IR) of melioidosis in Negeri Sembilan is varied at 1.9 to 5.1 with mean of 3.1 in 100,000 population per year. IR varied between districts in the state from zero to 22.01 in 100,000 population per year. Mortality rate were ranged from 0.17 to 0.74 cases with mean of 0.44 cases in 100,000 population per year. The case fatality rate of this state scattered from 8.70% to 16.67%. There were no significant linear associations between cases and deaths with monthly rainfall and humidity. The mean age of patients was 52.8 years, predominated with age around 41–60 years old. Males (77.8%) predominated, and the majority of cases were Malays (88.9%) and had exposed to soil related activities (74.6%). Mortality from melioidosis was more likely in Bumiputera and non-Malaysians (p<0.05). Patients who had at least one comorbidity were at a higher risk of death from melioidosis (p<0.05). Diabetes mellitus was found in 41.1% of all identified cases, making it a major underlying risk factor for both developing and dying from melioidosis (aOR:19.32, 95%CI:1.91–195.59, p<0.05). Hypertension and mortality status in melioidosis are also significantly correlated (aOR: 7.75, 95% CI: 2.26–26.61, p<0.05). Conclusion: The epidemiological patterns of cases reported from Negeri Sembilan are consistent for the most part from previous studies in other states in Malaysia and global with regard to its incidence, case fatality, demographic and predisposing chronic diseases. Diabetes mellitus and hypertension were significantly linked to increased mortality among all determinants. Author summary: Melioidosis is an environmentally acquired infection caused by Burkholderia pseudomallei, with the global distribution of this bacteria is comparatively restricted to temperate zones. The details on epidemiological pattern, demographics, and underlying risk factors of the disease, however, are still scarce. This study examines a 5-year retrospective analysis of 185 confirmed cases that were obtained between 2018 and 2022 from the Negeri Sembilan Melioidosis Registry. In this central region of Peninsular Malaysia, the authors detailed the incidence, death rate, case fatality, correlation with meteorology, and factors influencing mortality. Findings indicated that the state had a 3.1 in 100,000 population yearly mean incidence rate of melioidosis, with a case fatality rate ranging from 8.70% to 16.67%. The incidences vary throughout districts. Nevertheless, no significant relationships were found between monthly humidity and rainfall and the number of cases and fatalities. The main factors found to be associated with a higher mortality rate included bumiputra ethnicities, underlying comorbidities and diabetes mellitus. Remarkably, there was also a correlation found between the mortality status in melioidosis with hypertension. Despite a few limitations, these findings could contribute to improving healthcare professionals' knowledge of the illness and for better prevention care. [ABSTRACT FROM AUTHOR]

Background The autotransporter protein Burkholderia intracellular motility A (BimA) facilitates the entry of Burkholderia pseudomallei into the central nervous system (CNS) in mouse models of melioidosis. Its role in the pathogenesis of human cases of CNS melioidosis is incompletely defined. Methods Consecutive culture-confirmed cases of melioidosis at 2 sites in tropical Australia after 1989 were reviewed. Demographic, clinical, and radiological data of the patients with CNS melioidosis were recorded. The bimA allele (bimA Bm or bimA Bp ) of the B. pseudomallei isolated from each patient was determined. Results Of the 1587 cases diagnosed at the 2 sites during the study period, 52 (3.3%) had confirmed CNS melioidosis: 20 (38.5%) had a brain abscess, 18 (34.6%) had encephalomyelitis, 4 (7.7%) had isolated meningitis, and 10 (19.2%) had extra-meningeal disease. Among the 52 patients, there were 8 (15.4%) deaths; 17/44 (38.6%) survivors had residual disability. The bimA allele was characterized in 47/52; 17/47 (36.2%) had the bimA Bm allele and 30 (63.8%) had the bim A Bp allele. Patients with a bimA Bm variant were more likely to have a predominantly neurological presentation (odds ratio [OR]: 5.60; 95% confidence interval: 1.52–20.61; P  = .01), to have brainstem involvement (OR: 7.33; 1.92–27.95; P  = .004), and to have encephalomyelitis (OR: 4.69; 1.30–16.95; P  = .02). Patients with a bimA Bm variant were more likely to die or have residual disability (OR: 4.88; 1.28–18.57; P  = .01). Conclusions The bimA allele of B. pseudomallei has a significant impact on the clinical presentation and outcome of patients with CNS melioidosis. [ABSTRACT FROM AUTHOR]

Bacteriophages (phages), viruses that infect bacteria, are found in abundance not only in the environment but also in the human body. The use of phages for the diagnosis of melioidosis, a tropical infectious disease caused by Burkholderia pseudomallei, is emerging as a promising novel approach, but our understanding of conditions under which Burkholderia prophages can be induced remains limited. Here, we first demonstrated the isolation of Burkholderia phages from the hemocultures of melioidosis patients. The B. pseudomallei-positive hemoculture bottles were filtered to remove bacteria, and then phages were isolated and purified by spot and double agar overlay plaque assays. Forty blood samples (hemoculture-confirmed melioidosis) were tested, and phages were found in 30% of the samples. Transmission electron microscopy and genome analysis of the isolated phages, vB_HM387 and vB_ HM795, showed that both phages are Myoviruses. These two phages were stable at a pH of 5-7 and temperatures of 25-37°C, suggesting their ability to survive in human blood. The genome sizes of vB_HM387 and vB_HM795 are 36.3 and 44.0 kb, respectively. A phylogenetic analysis indicated that vB_HM387 has homologs, but vB_HM795 is a novel Myovirus, suggesting the heterogeneity of Burkholderia phages in melioidosis patients. The key finding that Burkholderia phages could be isolated from the blood of melioidosis patients highlights the potential application of phage-based assays by detecting phages in blood as a pathogen-derived biomarker of infection. [ABSTRACT FROM AUTHOR]

Rationale: Rates of viral respiratory infection (VRI) are similar in people with cystic fibrosis (CF) and the general population; however, the associations between VRI and CF pulmonary exacerbations (PEx) require further elucidation. Objectives: To determine VRI prevalence during CF PEx and evaluate associations between VRI, clinical presentation, and treatment response. Methods: The STOP2 (Standardized Treatment of Pulmonary Exacerbations II) study was a multicenter randomized trial to evaluate different durations of intravenous antibiotic therapy for PEx. In this ancillary study, participant sputum samples from up to three study visits were tested for respiratory viruses using multiplex polymerase chain reactions. Baselines and treatment-associated changes in mean lung function (percent predicted forced expiratory volume in 1 s), respiratory symptoms (Chronic Respiratory Infection Symptom Score), weight, and C-reactive protein were compared as a function of virus detection. Odds of PEx retreatment within 30 days and future PEx hazard were modeled by logistic and Cox proportional hazards regression, respectively. Results: A total of 1,254 sputum samples from 621 study participants were analyzed. One or more respiratory viruses were detected in sputum samples from 245 participants (39.5%). Virus-positive participants were more likely to be receiving CF transmembrane conductance regulator modulator therapy (45% vs. 34%) and/or chronic azithromycin therapy (54% vs. 44%) and more likely to have received treatment for nontuberculous Mycobacterium infection in the preceding 2 years (7% vs. 3%). At study visit 1, virus-positive participants were more symptomatic (mean Chronic Respiratory Infection Symptom Score, 53.8 vs. 51.1), had evidence of greater systemic inflammation (log10 C-reactive protein concentration, 1.32 log10 mg/L vs. 1.23 log10 mg/L), and had a greater drop in percent predicted forced expiratory volume in 1 second from the prior 6-month baseline (5.8 vs. 3.6). Virus positivity was associated with reduced risk of future PEx (hazard ratio, 0.82; 95% confidence interval, 0.69–0.99; P = 0.034) and longer median time to next PEx (255 d vs. 172 d; P = 0.021) compared with virus negativity. Conclusions: More than one-third of STOP2 participants treated for a PEx had a positive test result for a respiratory virus with more symptomatic initial presentation compared with virus-negative participants, but favorable long-term outcomes. More refined phenotyping of PEx, taking VRIs into account, may aid in optimizing personalized management of PEx. Clinical trial registered with www.clinicaltrials.gov (NCT 02781610). [ABSTRACT FROM AUTHOR]

Background: Chronic infection and consequent airway inflammation are the leading causes of morbidity and early mortality for people living with cystic fibrosis (CF). However, lower airway infections across a range of chronic respiratory diseases, including in CF, do not follow classical 'one microbe, one disease' concepts of infection pathogenesis. Instead, they are comprised of diverse and temporally dynamic lung infection microbiota. Consequently, temporal dynamics need to be considered when attempting to associate lung microbiota with changes in disease status. Set within an island biogeography framework, we aimed to determine the ecological patterns and processes of temporal turnover within the lung microbiota of 30 paediatric and adult CF patients prospectively sampled over a 3-year period. Moreover, we aimed to ascertain the contributions of constituent chronic and intermittent colonizers on turnover within the wider microbiota. Results: The lung microbiota within individual patients was partitioned into constituent chronic and intermittent colonizing groups using the Leeds criteria and visualised with persistence-abundance relationships. This revealed bacteria chronically infecting a patient were both persistent and common through time, whereas intermittently infecting taxa were infrequent and rare; respectively representing the resident and transient portions of the wider microbiota. It also indicated that the extent of chronic colonization was far greater than could be appreciated with microbiological culture alone. Using species-time relationships to measure temporal turnover and Vellend's rationalized ecological processes demonstrated turnover in the resident chronic infecting groups was conserved and underpinned principally by the deterministic process of homogenizing dispersal. Conversely, intermittent colonizing groups, representing newly arrived immigrants and transient species, drove turnover in the wider microbiota and were predominately underpinned by the stochastic process of drift. For adult patients, homogenizing dispersal and drift were found to be significantly associated with lung function. Where a greater frequency of homogenizing dispersal was observed with worsening lung function and conversely drift increased with better lung function. Conclusions: Our work provides a novel ecological framework for understanding the temporal dynamics of polymicrobial infection in CF that has translational potential to guide and improve therapeutic targeting of lung microbiota in CF and across a range of chronic airway diseases. AWnQWdeG2wJZnAAmwW9_w- Video Abstract [ABSTRACT FROM AUTHOR]

Melioidosis, a potentially fatal disease caused by the bacterium Burkholderia pseudomallei continues to be neglected in the Indian Subcontinent despite bearing about 44% of the global burden. Diagnosis poses a significant challenge since the disease presents a wide range of symptoms and closely mimics tuberculosis and pneumonia both of which are endemic in India. Sophisticated diagnosis and treatment often become unaffordable for patients from rural or low-income backgrounds. We present five cases of melioidosis from a tertiary care hospital (Mahatma Gandhi Medical College and Research Institute) in Pondicherry that exhibited predominantly high-grade fever, abdominal pain, and vomiting. Radiological imaging revealed abnormalities in the brain (1/5, 20%), lung (3/5, 60%), liver (2/5, 40%), spleen (2/5, 40%), kidney (2/5, 40%), and prostate gland (1/5, 20%). Burkholderia pseudomallei infection was confirmed through blood culture. Treatment with meropenem or ceftazidime was initiated immediately. Neuromelioidosis was confirmed in one patient. The clinical diagnoses for the remaining cases were as follows: septic shock, melioidosis with urosepsis, and refractory shock. Three patients required intensive care and of the five, one patient was discharged, one died, and three discontinued treatments against medical advice. In the case of the deceased patient, the clinical diagnosis encompassed refractory shock accompanied by lactic acidosis, melioidosis, and community-acquired pneumonia, which subsequently progressed to acute respiratory distress syndrome (ARDS). Notably, this patient presented with co-morbidities, notably type 2 diabetes mellitus. This exemplifies the difficulty faced by patients from low-income backgrounds which forces them to discontinue expensive treatment. The true burden of melioidosis in the Indian Subcontinent is uncertain as many cases remain undiagnosed. Unawareness of the disease, low index of suspicion among medical professionals, incorrect treatment, and discontinuation contribute to the disease burden. It is therefore imperative that melioidosis is brought to the attention of healthcare policymakers to determine the true burden of the disease by prioritizing nationwide surveillance and diagnosis. [ABSTRACT FROM AUTHOR]

Burkholderia spp. are often resistant to antibiotics, and infections with these organisms are difficult to treat. A potential alternative treatment for Burkholderia spp. infections is bacteriophage (phage) therapy; however, it can be difficult to locate phages that target these bacteria. Prophages incorporated into the bacterial genome have been identified within Burkholderia spp. and may represent a source of useful phages for therapy. Here, we investigate whether prophages within Burkholderia spp. clinical isolates can kill conspecific and heterospecific isolates. Thirty-two Burkholderia spp. isolates were induced for prophage release, and harvested phages were tested for lytic activity against the same 32 isolates. Temperate phages were passaged and their host ranges were determined, resulting in four unique phages of prophage origin that showed different ranges of lytic activity. We also analyzed the prophage content of 35 Burkholderia spp. clinical isolate genomes and identified several prophages present in the genomes of multiple isolates of the same species. Finally, we observed that Burkholdera cenocepacia isolates were more phage-susceptible than Burkholderia multivorans isolates. Overall, our findings suggest that prophages present within Burkholderia spp. genomes are a potentially useful starting point for the isolation and development of novel phages for use in phage therapy. [ABSTRACT FROM AUTHOR]

Retrospective observational study. To determine the efficacy and safety of bioactive glass ceramics mixed with autograft in the treatment of spondylodiscitis. Thirty-four patients with spondylodiscitis underwent surgery using autologous bone graft augmented by antibiotic loaded bioactive glass ceramic granules. Twenty-five patients aging 6 to 77, completed 1-year follow-up. The lumbosacral junction was affected in 3, lumbar spine in 13, one each in the dorso-lumbar junction and sacrum, and 7 dorsal spines. The organism isolated was Mycobacterium tuberculosis in 15, Methicillin sensitive Staphylococcus aureus (MSSA) in 4, Pseudomonas aeruginosa in 4, Klebsiella pneumoniae in one, Burkholderia pseudomallei in 1, and mixed infections in 2. All patients had appropriate antibiotic therapy based on culture and sensitivity. Clinical and radiological evaluation of all the patients was done at 6 weeks, 3 months, 6 months, and 12 months after the surgery. Twenty-three patients improved clinically and showed radiographic fusion between 6 and 9 months. The patient with Burkholderia infection died due to fulminant septicemia with multi organ failure while another patient died at 9 months due to an unrelated cardiac event. The mean Visual Analogue Score (VAS) at the end of 1-year was 2 with radiological evidence of fusion in all patients. There were no re-infections or discharging wounds, and the 30-day re-admission rate was 0. Bioactive glass ceramics is a safe and effective graft expander in cases of spondylodiscitis. The absorption of antibiotics into the ceramic appears to help the elimination of infection. [ABSTRACT FROM AUTHOR]

In recent years, the number of spinal internal fixation operations has increased significantly, correlating with an elevated risk of postoperative surgical site infection and a rising incidence rate. While the conventional treatment approach involves surgical debridement combined with antibiotic administration, there is a notable gap in reported strategies for Burkholderia cepacia infection and patients exhibiting multidrug resistance. Surgical site infection occurred in a patient following internal fixation surgery for thoracic vertebral fractures. Despite the application of systemic antibiotics and regular dressing changes, no improvement was observed. Bacterial culture and drug sensitivity experiments revealed a multidrug-resistant Burkholderia cepacia infection. Two comprehensive debridement procedures were performed along with continuous post-operative irrigation combined with antibiotic administration; however, no significant improvement was observed. The patient's infection was significantly controlled following treatment with vancomycin loaded bone cement. Following spinal internal fixation surgery, the management of a B. cepacian infection with multidrug resistance presented a significant challenge, despite the application of debridement procedures and systemic antibiotics. In this case, after 20 days of treatment with vancomycin-loaded bone cement, the patient's C-reactive protein level decreased to 54 mg/L, was normalized by February, and normal levels were maintained in the surgical area 1 month and 6 months after bone cement removal. The use of vancomycin-loaded bone cement proves effective in treating postoperative B. cepacian infection in a multidrug-resistant case following spinal internal fixation surgery. [ABSTRACT FROM AUTHOR]

Objective: This study aims to determine the pattern of germs and antibiotic sensitivity in septic patients treated with culture-based antibiotics. Design: This study was designed for observational- descriptive retrospective. Setting: The medical record of Dr. Wahidin Sudirohusodo Hospital from January 2018 to January 2022. Patient and participants: All patients who were diagnosed with sepsis and had data on bacterial culture and treatment with antibiotics. Interventions: We took blood culture data of patients diagnosed with sepsis from medical records. Measurement and results: The pattern of bacteria found was Gram-negative bacteria, with the most abundant bacteria being Burkholderia cepacia (37.93%), followed by Acinetobacter baumannii (24.14%), and Klebsiella pneumoniae (10.34%). The highest antibiotic sensitivity was obtained for tigecycline with 88.89% followed by levofloxacin with 78.57%. The lowest antibiotic sensitivity was found in ampicillin, ampicillin/ sulbactam, and cefoperazone/sulbactam as much as 0% or all of these antibiotics showed results that were resistant to culture results. Conclusions: Gram-negative bacteria are the main cause of septic patients with varying antibiotic sensitivity depending on the type of antibiotic used. [ABSTRACT FROM AUTHOR]

Rationale: 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) use is associated with a lower risk of incident pneumonia and, less robustly, with nonpulmonary infections. Whether statin use is associated with a lower risk of pneumonia than other clinical presentations of infection with the same pathogen is unknown. Objectives: To assess whether preadmission statin use is associated with a lower risk of pneumonia than nonpneumonia presentations among patients hospitalized with Burkholderia pseudomallei infection (melioidosis). Methods: We performed a secondary analysis of a prospective multicenter cohort study of patients hospitalized with culture-confirmed B. pseudomallei infection (melioidosis). We used Poisson regression with robust standard errors to test for an association between statin use and pneumonia.We then performed several sensitivity analyses that addressed healthy user effect and indication bias. Results: Of 1,372 patients with melioidosis enrolled in the parent cohort, 1,121 were analyzed. Nine hundred eighty (87%) of 1,121 were statin nonusers, and 141 (13%) of 1,121 were statin users. Forty-six (33%) of 141 statin users presented with pneumonia compared with 432 (44%) of 980 statin nonusers. Statin use was associated with a lower risk of pneumonia in unadjusted analysis (relative risk, 0.74; 95% confidence interval, 0.58--0.95; P = 0.02) and, after adjustment for demographic variables, comorbidities, environmental exposures, and symptom duration (relative risk, 0.73; 95% confidence interval, 0.57--0.94; P = 0.02). The results of sensitivity analyses, including active comparator analysis and inverse probability of treatment weighting, were consistent with the primary analysis. Conclusions: In hospitalized patients with melioidosis, preadmission statin use was associated with a lower risk of pneumonia than other clinical presentations of melioidosis, suggesting a lung-specific protective effect of statins. [ABSTRACT FROM AUTHOR]

We describe bedside-to-bench immunological and genetic elucidation of defective pyroptosis attributable to novel caspase 4 defect mediating pathogen-triggered inflammatory programmed cell death, in the setting of severe pneumonia and abscess-forming melioidosis in an overtly healthy host failing to clear Burkholderia pseudomallei infection, and how targeted adjunctive biological therapy led to a successful outcome. [ABSTRACT FROM AUTHOR]

Background and objectives. Optimal management requires an understanding of Burkholderia infections demographic, clinical, microbiological, and antibiotic features. This study aims to improve treatment and infection control strategies by investigating the clinical profiles and antibiotic susceptibilities of Burkholderia infections in a tertiary care context. Material and methods. A retrospective analysis of 48 individuals with Burkholderia infections was carried out in a tertiary care environment. We gathered and analyzed data on antimicrobial susceptibility, clinical presentation, microbiological identification, and demographic features. Results. The mean age of the participants was 49.27 years, and their gender distribution was equal. Diabetes, heart disease, and hypertension are common comorbidities. The most typical symptoms were fever and cough, with infections varying in severity from minor to severe. Burkholderia was predominantly found in urine, blood, and respiratory secretions. Testing for antibiotic susceptibility showed inconsistent findings; some drugs, including ceftazidime and meropenem, were more successful than others. Conclusion. The research highlights the broad demographics impact of Burkholderia infections, in addition to their acute and occasionally fatal characteristics. It highlights how important it is to treat every patient differently, accounting for comorbidities and the severity of symptoms. The results emphasize how much more study is required to improve treatment options and learn more about the origins of Burkholderia infections. [ABSTRACT FROM AUTHOR]

Pantoea dispersa is a plant-associated bacterium that often has beneficial effects on plants. In this study, we demonstrated that P. dispersa BB1, a previously identified potential biocontrol agent against the seedling rot pathogen Burkholderia glumae, could effectively suppress the symptoms of seedling blight caused by Burkholderia plantarii. To facilitate the isolation and utilization of P. dispersa as a biocontrol agent, a comparative genome analysis was performed to develop novel PCR primer sets for specifically detecting P. dispersa genes. Among the developed primer sets, the Pd725 set could detect 0.3 pg of genomic DNA of P. dispersa and evaluate the colonization of P. dispersa in plants. Using this primer set, we demonstrated that the colonization of P. dispersa in rice seeds infected with B. glumae and B. plantarii was significantly higher than that in non-infected seeds. This suggested that infection by Burkholderia pathogens promoted the colonization of P. dispersa. The Pd725 primer set could serve as a valuable tool for monitoring the colonization of P. dispersa in crops and evaluating potential new biocontrol strains. [ABSTRACT FROM AUTHOR]

Background: Melioidosis, an infectious disease caused by Burkholderia pseudomallei, is endemic in tropical countries. In nonendemic areas, the disease is rarely suspected because of varying clinical presentations and only a few attempts are made to isolate the pathogen. Many cases are left underdiagnosed or underreported in geographical areas where the disease is not endemic. This study aimed to analyze the clinical presentations, comorbidities, and antibiotic susceptibility patterns in patients with melioidosis in a tertiary care center. Materials and Methods: A retrospective study was done on culture‑confirmed melioidosis patients admitted to a tertiary care center, from January 2015 to December 2022. Relevant information on clinical presentations, mortality rate, comorbidities, and antibiogram was collected from hospital medical records. Results: A total of 73 culture‑confirmed cases of melioidosis were included in the study. Common clinical presentations were pneumonia (n = 35, 47.9%), septicemia (n = 13, 17.8%), and deep abscesses (n = 9, 12.3%). The mortality rate from melioidosis was 15.1% (n = 11). No significant difference was found in the mortality rate between pneumonia and septicemia groups (P = 0.716). Diabetes mellitus (DM) was the major comorbidity detected (n = 56, 76.7%). Isolates were susceptible to ceftazidime (n = 71, 97.3%), meropenem (n = 71, 97.3%), and co‑trimoxazole (n = 60, 82.2%). Conclusions: Common clinical presentations of melioidosis in our setting were pneumonia and septicemia. DM was the major comorbidity. Nearly one in six patients died. Ceftazidime and meropenem were the effective antibiotics. These findings may help physicians to make an early microbiological diagnosis which is essential to reduce mortality. [ABSTRACT FROM AUTHOR]

Melioidosis, a severe tropical illness caused by Burkholderia pseudomallei, poses significant treatment challenges due to limited therapeutic options and the absence of effective vaccines. The pathogen's intrinsic resistance to numerous antibiotics and propensity to induce sepsis during acute infections further complicate management strategies. Thus, exploring alternative methods for prevention and treatment is crucial. Monoclonal antibodies (mAbs) have emerged as a promising strategy for the prevention and treatment of infectious diseases. This study focused on generating three mAbs (13F1, 14G11, and 15D9) targeting hemolysin-coregulated protein 1 (Hcp1), a protein involved in the type VI secretion system cluster 1 (T6SS1) of B. pseudomallei. Notably, pretreatment with 13F1 mAb significantly reduced the intracellular survival of B. pseudomallei and inhibited the formation of macrophage-derived multinucleated giant cells (MNGCs). This protective effect was also observed in vivo. We identified a sequence of amino acids (Asp95-Leu114) within Hcp1 as the likely binding site for 13F1 mAb. In summary, our findings reveal that 13F1 mAb counteracts infection by targeting Hcp1, offering potential new targets and insights for melioidosis prevention. [ABSTRACT FROM AUTHOR]

Burkholderia pseudomallei is the causative agent of melioidosis, which is increasingly being reported worldwide. Mortality rates as high as 40% have been reported based on clinical patient outcomes in the endemic areas of Australia and Thailand. Novel therapies are needed to reduce treatment duration and adverse effects and improve treatment outcomes. Epetraborole, a novel antibiotic, targets leucyl-tRNA synthetase (LeuRS), an essential enzyme that catalyzes the attachment of leucine to transfer RNA. Epetraborole was evaluated for in vitro activity and efficacy in a murine model to assess clinical relevance against Burkholderia pseudomallei infections for possible treatment of melioidosis. Epetraborole was tested against 13 clinically derived and three reference B. pseudomallei strains that have a broad spectrum of susceptibilities to the standard-of-care (SoC) drugs for melioidosis, which showed that epetraborole exhibited minimal inhibitory concentrations of 0.5–4 μg/mL. Ex vivo studies using THP-1 macrophages confirmed the potency of epetraborole and demonstrated synergy between epetraborole and ceftazidime. In the acute pulmonary murine infection model of melioidosis, epetraborole demonstrated equivalent efficacy when delivered orally or subcutaneously, which compared well with the standard-of-care drug ceftazidime. In addition, adding epetraborole to ceftazidime significantly improved antimicrobial activity in this animal model. This work warrants further exploration of epetraborole as a candidate for treating melioidosis and substantiates LeuRS as a clinically relevant drug target in B. pseudomallei. Author summary: Our study suggests the repurposing of epetraborole for the treatment of the often rapidly progressing and fatal disease melioidosis is warranted. Melioidosis is caused by the bacterial pathogen Burkholderia pseudomallei, commonly found in Southeast Asia, Australia, Central and South America, Mexico, and recently in the Southern United States. The current clinical treatment of melioidosis involving multiple drugs is extensive, and a portion of infections will persist or relapse after the completion of treatment. Resistance to the majority of antibiotics limits the ability to treat and manage the disease effectively. However, Burkholderia pseudomallei is an under-recognized emerging pathogen with a general lack of resources and interest to drive research for new treatments. Epetraborole was initially identified with in vitro and in vivo activity against various medically important Gram-negative bacterial infections and was advanced to treat complicated urinary tract infections. Accordingly, we have assessed the use of epetraborole to treat melioidosis in a mouse model when administered alone or in combination with the current clinically used drug ceftazidime. [ABSTRACT FROM AUTHOR]

Treatment of infected wounds remains a major challenge for clinicians. Antimicrobial stewardship is an important pillar in wound treatment and, as the role of bacteria in wound repair is not well understood, new treatment options and products are constantly being developed to tackle local infection and biofilm. This case report describes a case of antibiotic-resistant Burkholderia cepacia skin infection and subsequent leg ulceration in an 86-year-old man during the COVID pandemic in Italy, which was successfully treated in a conservative way using 1% acetic acid and silver oxysalts in conjunction with compression bandage. [ABSTRACT FROM AUTHOR]

Melioidosis is an infection caused by Burkholderia pseudomallei known to be endemic in large portions of Asia, Sub-Sahara, and North Australia. Despite its endemicity in Malaysia, prompt diagnosis and subsequent treatment remain elusive especially in the more peripheral medical centres. This coupled with increasing risk to the population because of worsening climate crises renders early recognition and treatment more justifiable than ever. Here we present a case of melioidosis septic arthritis with systemic dissemination and discuss the factors involved in disease contraction, worsening prevalence, and diagnostic methods. [ABSTRACT FROM AUTHOR]

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Background: Melioidosis is an infectious disease caused by the bacterium Burkholderia pseudomallei. The two stages of melioidosis treatment are the intense intravenous phase and the oral eradication phase. Although co-trimoxazole has been in use for several years, the literature does not demonstrate uniformity of the drug doses, combinations, or durations suitable for the eradication phase of melioidosis. The safety profile of co-trimoxazole was not documented in the literature, nor have systematic studies of its effectiveness been done. This systematic review sought to study on the dose, duration and combination of co-trimoxazole therapy in view of clinical efficacy and safety in the eradication phase of melioidosis. Main body: This systematic review included all of the published articles that employed co-trimoxazole in the eradication phase after 1989, including, randomized clinical trials, case–control studies, cohorts, case reports, and case series. Throughout the eradication (maintenance) phase, co-trimoxazole usage was permissible in any dose for any period. A total of 40 results were included in the analysis which contained six clinical trials, one cohort study, one Cochrane review, and thirty-two case series/case reports. Clinical and microbial relapse rates are low when co-trimoxazole is used in single therapy than in combination. There were several adverse events of co-trimoxazole, however, a quantitative analysis was not conducted as the data did not include quantitative values in most studies. Short conclusion: The dose of co-trimoxazole, duration of the eradication phase, and other combinations used in the treatment was varying between studies. Compared to combined therapy patients treated with co-trimoxazole alone the mortality and relapse rates were low. The lowest relapse rate and lowest mortality rate occur when using co-trimoxazole 1920 mg twice daily. The duration of therapy varies on the focus of melioidosis and it is ranged from 2 months to one year and minimum treatment duration associated with low relapse rate is 3 months. The use of co-trimoxazole over the maintenance phase of melioidosis is associated with clinical cure but has adverse effects. [ABSTRACT FROM AUTHOR]

Burkholderia pseudomallei is a gram-negative bacterium that is the etiological agent of the tropical disease melioidosis. Currently, there is no licensed vaccine for melioidosis, but numerous candidates are being tested for protective efficacy and characterization of the elicited immune response. Our lab has previously reported the immunogenicity of a Bucl8-protein-based peptide antigen, designated L1-CRM197 (Cross-reacting material 197). When given subcutaneously, this vaccine formulation promoted a strong Th2 (IgG1) antibody response, however immunization did not protect from death. In this study, we hypothesized that an intranasally administered L1-CRM197 vaccine would induce protective mucosal immunity. To evaluate vaccine efficacy, we developed a surrogate Burkholderia infection model that employs outbred CD-1 mice which imitates the immunogenetic diversity of humans. Mice were immunized with either L1-CRM197 adjuvanted with fluorinated cyclic diguanosine monophosphate (FCDG) or with FCDG-only control. These mice were then challenged intranasally with an infectious dose of a luminescent strain of B. thailandensis E264 two weeks post-immunization, and correlates of protection were assessed in euthanized mice on days 1, 2, 3, and 7 postinfection. Overall, intranasal vaccination, compared to subcutaneous administration, induced a stronger Th1 (IgG2a/2b) to Th2 (IgG1) antibody response and promoted anti-L1 nasal, pulmonary, and systemic IgA. Additionally, sera IgG from L1-CRM197-vaccinated mice recognized whole-cell B. thailandensis and B. pseudomallei, a select agent exempt strain Bp82. Vaccination ameliorated disease indicators, including luminescent signal and bacterial cell counts, weight and temperature loss, and organ weight, which negatively correlated with IgG2a antibody levels and mucosa-stimulating cytokines IL-13 and IL-9. L1-CRM197-vaccinated mice also had earlier resolution of inflammatory and tissue-damaging cytokines compared to the FCDG-only controls. These results suggest a balanced humoral and cell-mediated response, along with mucosa-based immunity are beneficial for protection. Future efforts should further assess mucosal cellular and humoral mechanisms of protection and test such protection, using aerosolized B. pseudomallei select agent strain(s). [ABSTRACT FROM AUTHOR]

Prior infection with Burkholderia cepacia complex (BCC) has been associated with poorer outcomes after lung transplantation, posing an important dilemma for cystic fibrosis (CF). Although current guidelines consider BCC infection to be a relative contraindication, some centers continue to offer lung transplantation to BCC- infected CF patients. We conducted a retrospective cohort study which included all consecutive CF-LTR between 2000 and 2019 to compare the postoperative survival of BCC- infected CF lung transplant recipients (CF-LTR) to BCC -uninfected patients. We used a Kaplan-Meier analysis to compare survival of BCC -infected to BCC- uninfected CF-LTR and fitted a multivariable Cox model, adjusted for age, sex, BMI and year of transplantation as potential confounders. As an exploratory analysis, Kaplan-Meier curves were also stratified by the presence of BCC and urgency of transplantation. A total of 205 patients were included with a mean age of 30.5 years. Seventeen patients (8%) were infected with BCC prior to LT. Patients were infected with the following species: B. multivorans 5, B. vietnamiensis 3, combined B. multivorans and B. vietnamiensis 3 and others4. None of the patients were infected with B. cenocepacia. Three patients were infected with B. gladioli. One-year survival was 91.7% (188/205) for the entire cohort, 82.4% (14/17) among BCC -infected CF-LTR, and 92.5% (173/188) among BCC uninfected CF-LTR (crude HR = 2.19; 95%CI 0.99-4.85; p = 0.05). In the multivariable model, presence of BCC was not significantly associated with worse survival (adjusted HR 1.89; 95%CI 0.85-4.24; p = 0.12). In the stratified analysis for both presence of BCC and urgency of transplantation, urgency of transplantation among BCC -infected CF-LTR appeared to be associated with poorer outcome (p = 0.003 across the 4 subgroups). Our results suggest that non- cenocepacia BCC -infected CF-LTR have comparable survival rate to BCC -uninfected CF-LTR. [ABSTRACT FROM AUTHOR]

PurposeTo report a diffuse lamellar keratitis (DLK) cluster attributed to autoclave reservoir biofilm and to review the risk and prevention of DLK and toxic anterior segment syndrome (TASS) caused by such biofilms.SettingRefractive Surgery Center, University of California, Berkeley.DesignObservational case-control study and review of literature.MethodsEyes were evaluated for DLK following laser in situ keratomileusis (LASIK) over a 5-year period. Multiple changes in surgical and operating room protocols were prompted by a cluster of DLK cases. The autoclave reservoir chamber wall was cultured for microbial contamination. The MEDLINE database was used to identify relevant past publications.ResultsFrom January 7, 2010, to December 18, 2014, 1115 eyes received LASIK. Between September 2, 2010, and June 11, 2012, 147 eyes of 395 LASIK cases developed DLK (37.2%). Systematic modifications in surgical protocols were unsuccessful in ending the prolonged cluster of DLK cases until the STATIM 2000 autoclave was replaced with a new STATIM autoclave and a reservoir sterilization and surveillance protocol implemented. Over the subsequent 30 months, DLK incidence was reduced to 2.2% (14 DLK cases from 632 total LASIK cases, P < .0001). The retired autoclave reservoir chamber wall cultures grew Pseudomonas aeruginosa and the Burkholderia cepacia complex.ConclusionsFluid reservoirs of tabletop steam autoclaves can readily develop polymicrobial biofilms harboring microbial pathogens, whose inert molecular byproducts can cause DLK and TASS when introduced to the eye by surgical instruments. Stringent reservoir cleaning and maintenance may significantly reduce this risk by preventing and removing these biofilms.

Burkholderia cepacia infections are underreported and often seen in immunocompromised or cystic fibrosis patients. We describe a case of intra-abdominal abscesses and bacteraemia due to Burkholderia cepacia in a non-cystic fibrosis patient. A middle aged farmer with uncontrolled diabetes presented with 1 month of fever, abdominal pain, anorexia and weight loss. Examination revealed hepatosplenomegaly. Imaging showed multiple abscesses in liver and spleen. Burkholderia cepacia grew in the blood cultures. Patient showed clinical and radiological resolution post treatment with meropenem and subsequently co-trimoxazole. Clinicians' awareness, targeted investigations and early therapeutic intervention are essential for diagnosis and management of Burkholderia cepacia infections. [ABSTRACT FROM AUTHOR]

Background: There is increased interest in bacteriophage (phage) therapy to treat infections caused by antibiotic‐resistant bacteria. A lung transplant recipient with cystic fibrosis and Burkholderia multivorans infection was treated with inhaled phage therapy for 7 days before she died. Methods: Phages were given via nebulization through the mechanical ventilation circuit. Remnant respiratory specimens and serum were collected. We quantified phage and bacterial deoxyribonucleic acid (DNA) using quantitative polymerase chain reaction, and tested phage neutralization in the presence of patient serum. We performed whole genome sequencing and antibiotic and phage susceptibility testing on 15 B. multivorans isolates. Finally, we extracted lipopolysaccharide (LPS) from two isolates and visualized their LPS using gel electrophoresis. Results: Phage therapy was temporally followed by a temporary improvement in leukocytosis and hemodynamics, followed by worsening leukocytosis on day 5, deterioration on day 7, and death on day 8. We detected phage DNA in respiratory samples after 6 days of nebulized phage therapy. Bacterial DNA in respiratory samples decreased over time, and no serum neutralization was detected. Isolates collected between 2001 and 2020 were closely related but differed in their antibiotic and phage susceptibility profiles. Early isolates were not susceptible to the phage used for therapy, while later isolates, including two isolates collected during phage therapy, were susceptible. Susceptibility to the phage used for therapy was correlated with differences in O‐antigen profiles of an early versus a late isolate. Conclusions: This case of clinical failure of nebulized phage therapy highlights the limitations, unknowns, and challenges of phage therapy for resistant infections. [ABSTRACT FROM AUTHOR]

Burkholderia pseudomallei is a causative agent of melioidosis that can infect humans and animals in endemic countries, specifically in Southeast Asia and tropical Australia. A fundamental component for the pathogenesis of Burkholderia pseudomallei is the capability of the bacterium to enter, survive, replicate, and cause disease in a host cell by inducing the host cell fusion. Cell fusion results in multinucleated-giant cell formation, thus enabling the dissemination of Burkholderia pseudomallei intracellularly. cGAS reacts to Burkholderia pseudomallei infection by activating the cGAS-STING pathway and subsequently limiting host's aberrant cell division and cellular replication by inducing autophagic cell death. In this review, we discuss the host-pathogen interactions between the type VI secretion system 5 (T6SS-5) of Burkholderia pseudomallei and human cGAS pathway in melioidosis infections. Since T6SS- 5 is a main virulent factor in Burkholderia pseudomallei and the cGAS pathway is vital for host immune response, elucidating their functions is important for better understanding the pathogenesis of Burkholderia pseudomallei. [ABSTRACT FROM AUTHOR]

Burkholderia pseudomallei, the causative agent of the disease melioidosis, has been isolated from the environment in 45 countries. The treatment of melioidosis is complex, requiring lengthy antibiotic regimens, which can result in the relapse of the disease following treatment cessation. It is important that novel therapies to treat infections with B. pseudomallei be assessed in appropriate animal models, and discussions regarding the different protocols used between laboratories are critical. A 'deep dive' was held in October 2020 focusing on the use of the BALB/c mouse model and the inhalational route of infection to evaluate new antibiotic therapies. [ABSTRACT FROM AUTHOR]

Bacteria from the Burkholderia cepacia complex cause severe lung infections in people with cystic fibrosis (CF). The risk of epidemic spread of the infection led the CF centres to implement strict isolation precautions. Furthermore, it was imperative to identify the microbial agent correctly and timely which was made possible thanks to the methods of molecular microbiology. No new Burkholderia cenocepacia infections, caused by the ST-32 strain which had been responsible for a large outbreak in 1990s, were diagnosed in the Czech Republic in the last ten years. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Biofilm-associated Burkholderia pseudomallei infection contributes to antibiotic resistance and relapse of melioidosis. Burkholderia pseudomallei biofilm matrix contains extracellular DNA (eDNA) that is crucial for biofilm establishment. However, the contribution of eDNA to antibiotic resistance by B. pseudomallei remains unclear. In this study, we first demonstrated in vitro that DNase I with the administration of ceftazidime (CAZ) at 24 h considerably inhibited the 2-day biofilm formation and reduced the number of viable biofilm cells of clinical B. pseudomallei isolates compared to biofilm treated with CAZ alone. A 3–4 log reduction in numbers of viable cells embedded in the 2-day biofilm was observed when CAZ was combined with DNase I. Confocal laser-scanning microscope visualization emphasized the competence of DNase I followed by CAZ supplementation to significantly limit B. pseudomallei biofilm development and to eradicate viable embedded B. pseudomallei biofilm cells. Furthermore, DNase I supplemented with chitosan (CS) linked with CAZ (CS/CAZ) significantly eradicated shedding planktonic and biofilm cells. These findings indicated that DNase I effectively degraded eDNA leading to biofilm inhibition and dispersion, subsequently allowing CAZ and CS/CAZ to eradicate both shedding planktonic and embedded biofilm cells. These findings provide efficient strategies to interrupt biofilm formation and improve antibiotic susceptibility of biofilm-associated infections. [ABSTRACT FROM AUTHOR]

Background: Melioidosis is a bacterial infection caused by Burkholderia pseudomallei that is endemic in Southeast Asia, northern Australia, and Africa. Neurological involvement is rare and reported in 3–5% of total cases. Objective: The purpose of this study was to report a series of cases of melioidosis with neurological involvement and a brief review of the literature. Materials and Methods: We collected the data from six melioidosis patients having neurological involvement. Clinical, biochemical, and imaging findings were analyzed. Result: All patients in our study were adults (age range 27 to 73 years). The presenting symptoms were fever of varying duration (range 15 days to 2 months). Altered sensorium was noted in five patients. Four cases had brain abscess, one had meningitis, and one had a spinal epidural abscess. All cases of brain abscesses were T2 hyperintense with an irregular wall showing central diffusion restriction and irregular peripheral enhancement. The trigeminal nucleus was involved in one patient, but there was no enhancement of the trigeminal nerve. Extension along the white matter tract was noted in two patients. Magnetic resonance (MR) spectroscopy done in two patients showed increased lipid/lactate and choline peak in both of them. Conclusion: Melioidosis can present as multiple micro-abscesses in the brain. Involvement of the trigeminal nucleus and extension along the corticospinal tract may raise the possibility of infection by B. pseudomallei. Meningitis and dural sinus thrombosis, although rare, can be presenting features. [ABSTRACT FROM AUTHOR]

• This was a 40-year single-center collection of all Burkholderia cepacia complex (Bcc) cystic fibrosis airway isolates. • Infection control prevented nosocomial patient-to-patient transmission of Bcc. • Transient carriage of Bcc was 2.7 times more frequent than chronic infection. • Infections with B. cenocepacia or B. orbicola predispose patients to post-transplant sepsis. To resolve the epidemiology of airway infections with Burkholderia cepacia complex (Bcc) in patients with cystic fibrosis (pwCFs) over 40 years at a single treatment center. All Bcc and Burkholderia gladioli airway isolates were collected from pwCFs who presented at the cystic fibrosis outpatient and the lung transplantation clinics from 1983 to 2022. The collection of 1205 strains is dominated by B. multivorans (56%), followed by B. cenocepacia (16%), B. stabilis (10%), and B. orbicola (9%). A total of 27 pwCFs experienced a single self-limiting episode of airway infection with Bcc. A total of 13 pwCFs were harboring Bcc for 1.7-13.6 years and 15 pwCFs were persistently infected with Bcc. A total of 16 Bcc -positive pwCFs received a lung transplant. Fatal post-transplant sepsis happened in one patient with B. multivorans , two with B. cenocepacia , and two with B. orbicola. After the first acquisition of Bcc, transient carriage was 2.7 times more frequent than persistent colonization. Infections with B. cenocepacia or B. orbicola confer a higher risk for post-transplant sepsis than an infection with B. multivorans. [ABSTRACT FROM AUTHOR]

Burkholderia pseudomallei is a pathogen expanding in geographic range. We performed a retrospective study analyzing the clinical, microbiologic features of culture-proven melioidosis, and predictors of mortality based on data from a Singapore tertiary hospital between 2006- 2016. We found ICU admission, bacteremia, and mechanical ventilation to be associated with mortality. [ABSTRACT FROM AUTHOR]

• Central nervous system infections by Burkholderia cepacia complex are rare. • We report the first case of choroid plexitis caused by B. cepacia complex after severe COVID-19. • The patient recovered after long-term therapy with multiple antibiotics. Burkholderia cepacia complex (BCC) encompasses opportunistic pathogen with various clinical manifestations ranging from no symptoms to severe respiratory infections and septicemia. Central nervous system infections caused by BCC are rare. To the best of our knowledge, we present the first reported case of choroid plexitis caused by BCC after severe COVID-19. A 67-year-old woman who had been previously diagnosed with COVID-19 presented with a mild fever and headache. Gadolinium-enhanced T1-weighted brain magnetic resonance imaging showed contrast effects in the right choroid plexus and encapsulated abscess. Gram staining of cerebrospinal fluid revealed the presence of gram-negative rods. Broad-range polymerase chain reaction amplification of 16S ribosomal RNA from the cerebrospinal fluid, followed by sequence analysis, identified BCC; thus, choroid plexitis caused by BCC was diagnosed. After prolonged antimicrobial treatment with a multiantibiotic regimen, the patient recovered completely. This case highlights the importance of long-term therapy with a carefully selected multiantibiotic regimen to achieve complete recovery after BCC infection. [ABSTRACT FROM AUTHOR]

Background Burkholderia cepacia complex is a group of potential nosocomial pathogens often linked to contaminated water. We report on a cluster of 8 B. cepacia complex infections in cardiothoracic intensive care unit patients, which were attributed to contaminated extracorporeal membrane oxygenation (ECMO) water heaters. Methods In December 2020, we identified an increase in B. cepacia complex infections in the cardiothoracic intensive care unit at Brigham and Women's Hospital. We sought commonalities, sequenced isolates, obtained environmental specimens, and enacted mitigation measures. Results Whole-genome sequencing of 13 B. cepacia complex clinical specimens between November 2020 and February 2021 identified 6 clonally related isolates, speciated as Burkholderia contaminans. All 6 occurred in patients on ECMO. Microbiology review identified 2 additional B. contaminans cases from June 2020 that may have also been cluster related, including 1 in a patient receiving ECMO. All 8 definite or probable cluster cases required treatment; 3 patients died, and 3 experienced recurrent infections. After ECMO was identified as the major commonality, all 9 of the hospital's ECMO water heaters were cultured, and B. contaminans grew in all cultures. Cultures from air sampled adjacent to the water heaters were negative. Water heater touch screens were culture positive for B. contaminans, and the sink drain in the ECMO heater reprocessing room also grew clonal B. contaminans. Observations of reprocessing revealed opportunities for cross-contamination between devices through splashing from the contaminated sink. The cluster was aborted by removing all water heaters from clinical service. Conclusions We identified a cluster of 8 B. cepacia complex infections associated with contaminated ECMO water heaters. This cluster underscores the potential risks associated with water-based ECMO heaters and, more broadly, water-based care for vulnerable patients. [ABSTRACT FROM AUTHOR]

Background: Burkholderia cepacia (BC) has been detected more and more in infected patients in recent years. However, as a high-risk population, the clinical characteristics and prognosis of BC infection in hematopoietic stem cell transplantation (HSCT) patients have not been reported. The purpose of this study is to obtain data that will help fill in the gaps in this field, provide evidence for reducing the mortality rate of BC infection in HSCT patients, and guide the use of antibiotics in the future.Methods: Electronic medical records of patients with BC infection who underwent HSCT in Xiangya Hospital of Central South University from September 1, 2015 to August 31, 2021 were collected. At the same time, 1:1 case-control matching was conducted according to gender, age and disease type. Comparisons between patients with/without BC infection and respiratory failure were made respectively, and the sensitivity of BC to five clinically commonly used antibiotics was also evaluated. Univariate and multivariate analyses were performed to identify independent risk factors for death.Results: The most common site of BC infection in HSCT patients was the lung (75%). Although BC infection rate (3.74%) and antibiotic resistance were not significant, it was closely associated with a higher risk of death (P = 0.022), which even further increased to 90.9% when combined with respiratory failure (P = 0.008). Procalcitonin > 10 µg/L (HR = 40.88, 95% CI 6.51-256.63, P = 0.000) and septic shock (HR = 4.08, 95% CI 1.02-16.33, P = 0.047) were two independent risk factors for death.Conclusion: HSCT patients with BC infection are in critical condition, and the management of respiratory infection should be especially strengthened to improve the prognosis of these patients. [ABSTRACT FROM AUTHOR]