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Background: Stenotrophomonas maltophilia ( S. maltophilia ) is a nosocomial pathogen causing life-threatening invasive infections with a high mortality rate in some patient populations, especially those who are severely ill or immunocompromised. There is a need for data on mortality in patients with S. maltophilia bacteremia., Objective: In this meta-analysis, we aimed to investigate risk factors for mortality in S. maltophilia bacteremia., Methods: Studies comparing patients who died from S. maltophilia bacteremia with patients who survived were considered for inclusion. Studies were included if they reported one or more risk factors for mortality. Mortality risk factors included clinical predisposing factors, predisposing comorbidities and appropriateness of antibiotic therapy., Results: Nineteen studies with 1248 patients were included in the meta-analysis. Five hundred and six (40.5%) patients died. The following risk factors for mortality were identified: ICU admission, septic shock, need for mechanical ventilation, indwelling central venous catheter, neutropenia, comorbid hematological malignancies, chronic kidney disease, inappropriate antimicrobial therapy and prior antibiotic use., Conclusions: Appropriate antimicrobial therapy had a protective effect against mortality in S. maltophilia bacteremia. Indwelling central venous catheter, neutropenia, hematological malignancies and chronic kidney disease were also risk factors for mortality.

A 60-year-old woman with myelodysplastic syndrome/myeloproliferative neoplasm-unclassifiable underwent unrelated bone marrow transplantation from a human leukocyte antigen (HLA) 8/8 allele-matched male donor. Neutrophil engraftment was achieved on day 29. Fluorescence in situ hybridization of sex chromosomes demonstrated complete donor chimerism. The red blood cell and platelet transfusion dependence continued, and the neutrophil count decreased gradually. Despite prolonged administration of broad-spectrum antibiotics for febrile neutropenia, blood cultures on days 46 and 58 returned positive for Stenotrophomonas maltophilia (SM). Contrast-enhanced computed tomography revealed multiple nodules of septic emboli in the lungs and kidneys, suggesting a disseminated SM infection. Antibiotic therapy was conducted based on antimicrobial susceptibility testing. However, the blood cell count failed to normalize and a secondary graft failure was diagnosed. A HLA-haploidentical peripheral-blood stem-cell transplantation from the patient's son was performed on day 134 after the initial transplantation. Neutrophil engraftment was achieved on day 11. Red blood cells and platelets were also engrafted. After the resolution of the SM bacteremia, the patient was discharged on day 63. The prognosis of the SM bacteremia with neutropenia is poor. Antibiotic treatment based on antimicrobial susceptibility testing and a second transplant from an HLA-haploidentical donor likely contributed to the successful outcome in this patient.

Background: Stenotrophomonas maltophilia is an opportunistic pathogen and a dreaded cause of bacteraemia with 30-day mortality rates ranging from 14 to 69%. The purpose of this cohort study was to evaluate outcomes of S. maltophilia bacteraemia, at Rigshospitalet, a tertiary hospital in Copenhagen, Denmark., Methods: We included all patients with a blood culture positive for S. maltophilia, from January 1, 2015 to April 1, 2020. We extracted data on antimicrobial susceptibility, treatment, central venous catheter intervention and severe haematological disease., Results: Sixty-one cases of S. maltophilia bacteraemia were identified. The overall 90-day mortality was 18%. Sixty percent of patients had a central venous catheter intervention performed. Seventy-nine percent of patients were treated with trimethoprim/sulfamethoxazole (TMP/SMX). Patients with central venous catheter intervention had significantly better survival than those without (HR: 0.16 [95% CI: 0.03-0.73]). Severe haematological disease and patients, who received intensive care unit (ICU) care, were at higher risk of death than other patients (HR: 5.93 [95% CI: 1.18 - 29.94] and HR: 8.37 [95% CI: 1.79 - 39.20], respectively). We found no evidence that any antibiotic regime was superior with regard to 90-day mortality., Conclusions: We did not find evidence to support a change in the current standard-of-care regimen of TMP/SMX and CVC removal. Larger clinical trials are needed to guide such recommendations.

Background: Fatal hemorrhagic pneumonia is one of the most severe manifestations of Stenotrophomonas maltophilia (SM) infections. Here, we aimed to investigate the clinical characteristics of SM bacteremia and to identify the risk factors of hemorrhagic pneumonia caused by SM in patients with hematologic diseases., Methods: The clinical records of 55 patients diagnosed with hematologic diseases and SM bacteremia were retrospectively reviewed. We compared patients' clinical characteristics and outcomes between the hemorrhagic pneumonia group and non-hemorrhagic pneumonia group., Results: Twenty-seven (49.1%) patients developed hemorrhagic pneumonia. The overall mortality rate of SM bacteremia was 67.3%. Hemorrhagic pneumonia (adjusted HR 2.316, 95% CI 1.140-4.705; P = 0.020) was an independent risk factor of 30-day mortality in hematological patients with SM bacteremia. Compared with the non-hemorrhagic pneumonia group, patients in the hemorrhagic pneumonia group were older and showed clinical manifestations as higher proportions of isolated SM in sputum culture, neutropenia and elevated procalcitonin (PCT). Multivariate analysis showed that neutropenia, high levels of PCT, prior tigecycline therapy within 1 month were independent risk factors associated with hemorrhagic pneumonia., Conclusions: Neutropenia, high level of PCT and prior tigecycline therapy within 1 month were significant independent predictors of hemorrhagic pneumonia in hematologic patients with SM bacteremia. Due to no effective antibiotics to prevent hemorrhagic pneumonia, prophylaxis of SM infection and its progression to hemorrhagic pneumonia is particularly important., (© 2021. The Author(s).)

Stenotrophomonas maltophilia is an opportunistic pathogen that most often infects patients requiring mechanical ventilation, indwelling central venous catheters and broad-spectrum antibiotics. The reported incidence of S. maltophilia infection has increased over the past two decades, and many of its risk factors are commonly seen in patients with severe COVID-19 infection. Our case regards a patient with severe COVID-19 pneumonia, who subsequently developed disseminated S. maltophilia infection, refractory to first-line treatment and optimal medical management. This case highlights the high index of suspicion required for diagnosing secondary complications in patients with COVID-19 infection and highlights the difficulty in treating disseminated S. maltophilia infection in critically ill patients., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Stenotrophomonas maltophilia is a multidrug-resistant bacterium with no precise clinical treatment. This bacterium can be a vital cause for death and different organ failures in immune-compromised, immune-competent, and long-time hospitalized patients. Extensive quorum sensing capability has become a challenge to develop new drugs against this pathogen. Moreover, the organism possesses about 789 proteins which function, structure, and pathogenesis remain obscured. In this piece of work, we tried to enlighten the aforementioned sectors using highly reliable bioinformatics tools validated by the scientific community. At first, the whole proteome sequence of the organism was retrieved and stored. Then we separated the hypothetical proteins and searched for the conserved domain with a high confidence level and multi-server validation, which resulted in 24 such proteins. Furthermore, all of their physical and chemical characterizations were performed, such as theoretical isoelectric point, molecular weight, GRAVY value, and many more. Besides, the subcellular localization, protein-protein interactions, functional motifs, 3D structures, antigenicity, and virulence factors were also evaluated. As an extension of this work, 'RTFAMSSER' and 'PAAPQPSAS' were predicted as potential T and B cell epitopes, respectively. We hope our findings will help in better understating the pathogenesis and smoothen the way to the cure., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Stenotrophomonas maltophilia (S. maltophilia) is an opportunistic and nosocomial pathogen that can cause an invasive and fatal infection, particularly in hospitalized and immunocompromised patients. However, little is known about the impact of S. maltophilia bacteremia in pediatric patients. Therefore, we aimed to identify risk factors for mortality, antibiotics susceptibility to S. maltophilia, and mortality rates in pediatric patients with S. maltophilia bacteremia., Methods: We conducted a retrospective cohort study by identifying all S. maltophilia positive blood cultures in the microbiology laboratory database between January 2007 and December 2018 from hospitalized pediatric patients (age 1-14 years). After identifying patients with S. maltophilia bacteremia, medical charts were reviewed for demographics, clinical data, and outcomes within seven days of bacteremia diagnosis. Risk factors associated with mortality in S. maltophilia bacteremia patients were determined using univariate and multivariate analyses., Findings: Sixty-eight pediatric patients with S. maltophilia bacteremia were identified. All infections were nosocomial infections, and (88.2%) bacteremia cases were catheter-related bloodstream infections. On multivariate analysis, ICU admission prior to bacteremia episode and neutropenia were the major risk factors associated with mortality. S. maltophilia was the most susceptible to trimethoprim and sulfamethoxazole (TMP/SMX, 94.1%), followed by levofloxacin (85.7%). The overall mortality rate within seven days of S. maltophilia bacteremia diagnosis was 33.8%., Conclusion: S. maltophilia bacteremia is a devastating emerging infection associated with high mortality among hospitalized children. Therefore, early diagnosis and prompt management based on local susceptibility data are crucial. Various risk factors, especially ICU admission prior to bacteremia episode and neutropenia, are associated with S. maltophilia bacteremia mortality.

Stenotrophomonas maltophilia is a ubiquitous environmental bacterium that has recently emerged as a multidrug-resistant opportunistic pathogen causing bloodstream, respiratory, and urinary tract infections. The connection between the commensal environmental S. maltophilia and the opportunistic pathogen strains is still under investigation. Bacterial toxin-antitoxin (TA) systems have been previously associated with pathogenic traits, such as biofilm formation and resistance to antibiotics, which are important in clinical settings. The same species of the bacterium can possess various sets of TAs, possibly influencing their overall stress response. While the TA systems of other important opportunistic pathogens have been researched, nothing is known about the TA systems of S. maltophilia . Here, we report the identification and characterization of S. maltophilia type II TA systems and their prevalence in the isolates of clinical and environmental origins. We found 49 putative TA systems by bioinformatic analysis in S. maltophilia genomes. Despite their even spread in sequenced S. maltophilia genomes, we observed that relBE , hicAB , and previously undescribed COG3832-ArsR operons were present solely in clinical S. maltophilia isolates collected in Lithuania, while hipBA was more frequent in the environmental ones. The kill-rescue experiments in Escherichia coli proved higBA , hicAB , and relBE systems to be functional TA modules. Together with different TA profiles, the clinical S. maltophilia isolates exhibited stronger biofilm formation, increased antibiotic, and serum resistance compared to environmental isolates. Such tendencies suggest that certain TA systems could be used as indicators of virulence traits.

Stenotrophomonas maltophilia is a multidrug-resistant, Gramnegative, and biofilm-forming pathogen. Information is limited concerning S. maltophilia bacteremia in children. Clinical data and microbiological test results collected in a tertiary children's hospital over a ten-year period were reviewed. Children 0-18 years old who had positive clinical specimen, blood and/or catheter cultures were included. We identified 20 S. maltophilia isolates from 12 pediatric patients with confirmed infections. The median age was 28 months (range: 3.1-187.3). The rate of previous use of antimicrobial therapy was 83 %. The median antibiotic number was 3 (range: 0-7) within 30 days prior to onset of S. maltophilia bacteremia. Catheter related infection was the main infectious source (66.6 %). The mortality rate was 33.3 %. The death of two non-survivors was associated with pneumonia. S. maltophilia should be considered a breakthrough agent for bacteremia in children with underlying disease exposed to broad-spectrum antibiotics during long-term hospitalization., Competing Interests: None, (Sociedad Argentina de Pediatría.)

Objective: Stenotrophomonas maltophilia (SM) is an important nosocomial pathogen, particularly in immunocompromised patients due to their adverse antimicrobial susceptibility pattern. The objective of this article was to investigate the clinical impact of SM bacteremia on the 30-day mortality rate and identify the risk factors of the cause of mortality in patients with hematologic disorders., Methods: We retrospectively reviewed the clinical data in patients diagnosed with hematological disorders and SM bacteremia over an 8-year period from July 2010 to July 2018 at a 248-bed hematology department. We compared patients' clinical characteristics and outcomes between the non-survivor and survivor groups., Results: The overall incidence of SM bacteremia was 25.1 per 10,000 admissions. There were 59 patients (median age: 35 years; 57.6% males) included in the study with an overall SM bacteremia-related 30-day mortality of 44.1%. Multi-drug resistance was common. In vitro susceptibility is higher to ceftazidime (72.9%), ciprofloxacin (66.1%) and cefoperazone/sulbactam (59.3%). The risk factors identified in the univariate analysis were catheter re-implantation, accompanying polymicrobial infection, inadequate initial antimicrobial treatment, APACHE II score, temperature > 39 °C, septic shock, respiratory failure, and non-remission post treatment for primary diseases. Multivariate analysis further confirmed that inadequate initial antimicrobial treatment, respiratory failure, and non-remission after treatment for hematological diseases are independent risk factors associated with mortality (P = 0.001, 0.002 and 0.007, respectively)., Conclusions: Our study suggests that SM bacteremia is highly associated with increased mortality in patients with hematologic diseases. Early detection, prompt comprehensive management including initiation of combined sensitive antibiotics, respiratory monitoring and support, platelet infusion, and strategies to improve patients' remission status are recommended to improve the overall survival in patients with SM bacteremia.

Accumulating evidence has revealed that lymphoid tissue-resident commensal bacteria (e.g. Alcaligenes spp.) survive within dendritic cells. We extended our previous study by investigating microbes that persistently colonize colonic macrophages. 16S rRNA-based metagenome analysis using DNA purified from murine colonic macrophages revealed the presence of Stenotrophomonas maltophilia. The in situ intracellular colonization by S. maltophilia was recapitulated in vitro by using bone marrow-derived macrophages (BMDMs). Co-culture of BMDMs with clinically isolated S. maltophilia led to increased mitochondrial respiration and robust IL-10 production. We further identified a 25-kDa protein encoded by the gene assigned as smlt2713 (recently renamed as SMLT_RS12935) and secreted by S. maltophilia as the factor responsible for enhanced IL-10 production by BMDMs. IL-10 production is critical for maintenance of the symbiotic condition, because intracellular colonization by S. maltophilia was impaired in IL-10-deficient BMDMs, and smlt2713-deficient S. maltophilia failed to persistently colonize IL-10-competent BMDMs. These findings indicate a novel commensal network between colonic macrophages and S. maltophilia that is mediated by IL-10 and smlt2713., (© The Author(s) 2019. Published by Oxford University Press on behalf of The Japanese Society for Immunology.)

Objective Hemorrhagic pneumonia due to Stenotrophomonas maltophilia (SM) in severely immunocompromised patients has a very poor prognosis. However, the risk factors for hemorrhagic pneumonia are not clear. Methods This study assessed the predictive factors of hemorrhagic pneumonia caused by SM. The medical records of patients admitted to Osaka City University Hospital with SM bacteremia between January 2008 and December 2017 were retrospectively reviewed. Patients All patients who had positive blood cultures for SM were included in this study. They were categorized into two groups: the SM bacteremia with hemorrhagic pneumonia group and the SM bacteremia without hemorrhagic pneumonia group. The clinical background characteristics and treatments were compared between these groups. Results The 35 patients with SM bacteremia included 4 with hemorrhagic pneumonia and 31 without hemorrhagic pneumonia. Hematologic malignancy (p=0.03) and thrombocytopenia (p=0.04) as well as the prior use of quinolone within 30 days (p=0.04) were more frequent in the SM bacteremia patients with hemorrhagic pneumonia than in those without hemorrhagic pneumonia. The mortality of the SM bacteremia patients with hemorrhagic pneumonia was higher than that of those without hemorrhagic pneumonia group (p=0.02). Conclusion Patients with SM bacteremia who have hematologic malignancy, thrombocytopenia, and a history of using quinolone within the past 30 days should be treated with deliberation.

A 44-year-old female was found to be systemically ill at dialysis and admitted to the hospital. Days into the hospitalization, her blood cultures from dialysis were positive with Stenotrophomonas maltophilia bacteremia with a levofloxacin minimum inhibitory concentration (MIC) of 1. She was discharged on ciprofloxacin 500 mg orally (PO) daily on hospital day 2 to complete a 14-day course. Weeks later, she was again found to be bacteremic at dialysis and sent back to the hospital. She was started on empiric antibiotics upon admission until further identification. Blood cultures again revealed S. maltophilia with a levofloxacin MIC of 32. Antibiotics were tailored to trimethoprim/sulfamethoxazole (TMP-SMX) until susceptibilities for additional agents were available. Further workup revealed mitral valve endocarditis. She was subsequently discharged on both minocycline 100 mg PO every 12 hours and TMP-SMX 1 DS PO daily with a planned duration of 6 weeks. Due to ongoing readmissions for hyperkalemia, TMP-SMX was discontinued and her regimen was modified to ceftazidime 1 g intravenously (IV) after HD plus minocycline 100 mg PO every 12 hours. She was deemed clinically and microbiologically cleared based on follow-up assessments. To our knowledge, this is the first case of S. maltophilia endocarditis treated with oral minocycline in combination with another antibiotic.

Stenotrophomonas maltophilia can cause serious infections in immunocompromised patients. The aim of this systematic review was to establish what invasive infections in humans are caused by S. maltophilia and to evaluate the optimal choice of antibiotics for their treatment. MEDLINE, EBSCO, SCOPUS, SCINDEKS and GOOGLE SCHOLAR were systematically searched for clinical trials, observational studies, case reports or case series describing invasive infections with S. maltophilia in patients of any age. S. maltophilia may cause invasive infections of various tissues in hospitalized patients. In the great majority of cases it was susceptible to co-trimoxazole, levofloxacin and ceftazidime. In about three fourths of the cases, the treatment was successful, while less than 20% of the patients died. S. maltophilia is increasingly associated with serious invasive infections in hospitalized patients and due to growing trend of resistance to almost all antibiotics requires a careful approach to patients who is harboring this bacterium.

Background: Stenotrophomonas maltophilia is an important nosocomial pathogen. This pathogen has intrinsic or acquired resistance to a number of antibiotics classes. Furthermore, Stenotrophomonas infections have been associated with high mortality, mainly in immunocompromised patients. Accordingly, we conducted a retrospective cohort study on the clinical data, microbiological characteristics, and outcomes of patients with S. maltophilia (SM) bacteremia., Methods: A retrospective cohort study was conducted at two tertiary care referral hospitals in Seoul, South Korea. Data were collected between January 2006 and December 2015 from electric medical records. Our analysis aimed to identify the risk factors associated with crude mortality, as well as the predictive factors of quinolone-resistant strains in SM bacteremia patients., Results: A total of 126 bacteremia patients were enrolled in the study. The mortality rate was 65.1%. On multivariable analysis, hypoalbuminemia (odds ratio [OR], 5.090; 95% confidence interval [CI], 1.321-19.621; P = 0.018), hematologic malignancy (OR, 35.567; 95% CI, 2.517-502.515; P = 0.008) and quinolone-resistant strains (OR, 7.785; 95% CI, 1.278-47.432; P = 0.026) were independent risk factors for mortality. Alternatively, usage of an empirical regimen with quinolone (OR, 0.172; 95% CI, 0.034-0.875; P = 0.034) was an independent protective factor for mortality. The multivariable analysis of predictive factors revealed that high Charlson comorbidity index (OR, 1.190; 95% CI, 1.040-1.361; P = 0.011) and indwelling of a central venous catheter (CVC) (OR, 3.303; 95% CI, 1.194-9.139; P = 0.021) were independent predisposing factors associated with quinolone-resistant strains in SM bacteremia patients., Conclusions: Our findings suggest that a high Charlson comorbidity score and indwelling of a CVC were significantly independent predictors of quinolone-resistant strains in SM bacteremia patients. Therefore, we need to carefully consider the antibiotic use in SM bacteremia patients with these predictive factors.

Objectives: Stenotrophomonas maltophilia is a gram-negative opportunistic bacterium that may cause a myriad of clinical diseases in immunocompromised individuals. We aimed to describe the clinical characteristics, risk factors, mortality, and treatment of S. maltophilia bacteremia in critically ill children, a topic on which data are sparse., Design: A multicenter observational retrospective study in which medical charts of critically ill children with S. maltophilia bacteremia were reviewed between 2012 and 2017., Setting: Data were collected from each of the four largest PICUs nationwide, allocated in tertiary medical centers to which children with complex conditions are referred regularly., Patients: A total of 68 suitable cases of S. maltophilia bacteremia were retrieved and reviewed., Measurements and Main Results: The total occurrence rate of S. maltophilia isolation had increased significantly during the study period (r = 0.65; p = 0.02). The crude mortality was 42%, and the attributed mortality was 18%. Significant risk factors for mortality were a longer length of hospital stay prior to infection (33 d in nonsurvivors vs 28 in survivors; p = 0.03), a nosocomial source of infection (p = 0.02), presentation with septic shock (p < 0.001), and treatment with chemotherapy (p = 0.007) or carbapenem antibiotics (p = 0.05) prior to culture retrieval. On multivariate analysis, septic shock (odds ratio, 14.6; 95% CI, 1.45-147.05; p = 0.023) and being treated with chemotherapy prior to infection (odds ratio, 5.2; 95% CI, 1.59-17.19; p = 0.006)] were associated with mortality. The combination of ciprofloxacin, trimethoprim-sulfamethoxazole, and minocycline resulted in the longest survival time (p < 0.01)., Conclusions: The significant attributed mortality associated with S. maltophilia bacteremia in critically ill children calls for an aggressive therapeutic approach. The findings of this investigation favor a combination of trimethoprim-sulfamethoxazole, ciprofloxacin, and minocycline.

Background: Acquired carbapenem resistance among non-fermenting Gram-negative bacilli (NFGNB), such as Pseudomonas aeruginosa and Acinetobacter calcoaceticus-Acinetobacter baumannii complex (ACB complex), is a serious problem in nosocomial infections. We previously reported that patients infected with the intrinsically carbapenem-resistant Elizabethkingia meningoseptica were associated with high mortality. However, little information is available regarding the clinical outcome of E. meningoseptica bacteremia when compared to that of other carbapenem-resistant NFGNB., Methods: We conducted an observational study that included consecutive patients with E. meningoseptica, carbapenem-resistant ACB complex, carbapenem-resistant P. aeruginosa, and Stenotrophomonas maltophilia bacteremia at a Taiwanese medical center in 2015. We compared the clinical characteristics and outcomes between patients with E. meningoseptica bacteremia and those with other carbapenem-resistant NFGNB bacteremia., Results: We identified 30 patients with E. meningoseptica, 71 with carbapenem-resistant ACB complex, 25 with S. maltophilia, and 17 with carbapenem-resistant P. aeruginosa bacteremia. The clinical characteristics, disease severity, and previous antibiotic exposures were similar between patients with bacteremia either due to E. meningoseptica or other carbapenem-resistant NFGNB. Patients with E. meningoseptica bacteremia had a higher rate of appropriate empirical antibiotics than those with other carbapenem-resistant NFGNB and was less associated with central venous catheterization. The 28-day mortality rates were similar between patients with E. meningoseptica and the other carbapenem-resistant NFGNB bacteremia (46.7% vs 46%, p = 0.949)., Conclusion: The mortality rate of E. meningoseptica bacteremia was as high as other carbapenem-resistant NFGNB infections. The emerging E. meningoseptica infection calls for active surveillance and continued awareness from clinical physicians for this serious carbapenem-resistant infection., (Copyright © 2018. Published by Elsevier B.V.)

Hemorrhagic pneumonia (HP) is known as the clinical manifestation of Stenotrophomonas maltophilia infection, while catheter-related blood stream infection (CRBSI) is the common clinical presentation of S. maltophilia bacteremia (SMB). The purpose of this study is to evaluate the risk factors for mortality in hematologic malignancy patients with SMB and to analyze clinical and microbiological characteristics of HP associated with SMB and CRBSI. SMB cases of patients with a hematologic malignancy were collected from 2006 through 2016. The overall 30-day mortality rate and mortality risk factors were assessed. The expression of major virulence-associated genes from S. maltophilia isolates, which included genes encoding type-1 fimbriae (smf-1), proteases (StmPr1 and StmPr2), and esterase (Smlt3773), from the blood of patients with HP and CRBSI was investigated. The phenotypic and genotypic traits were also compared. A total of 118 cases of SMB were included. The overall 30-day mortality rate was 61.0%. A multivariable analysis showed that HP was the most important risk factor for mortality (adjusted OR = 106.41; 95% CI = 5.18-2184.55). Although no statistical significance was observed in microbiological analysis, isolates from HP have a trend toward a higher protease activity (93.8% vs. 73.3%, P = 0.172). Clinical analysis showed that thrombocytopenia (P = 0.037) and prolonged neutropenia (P = 0.043) were significant factors associated with HP. Our data, which includes hematologic malignancy patients with SMB, suggest that HP is the significant risk factor for mortality and that the unique characteristics of patients and microbes contribute to the pathogenesis.

To understand the role of flagella of Stenotrophomonas maltophilia in lung infections, DBA/2N mice were challenged with aflagellate fliI- mutant and colonization, invasion and persistence, lung damage and inflammatory response compared, on days 1 and 3 post-exposure (p.e.), with that of the isogenic wild-type (wt). Following exposure to nebulized bacterial suspension, mice infected with wt and fliI- strains showed a comparable trend in body weight change, pulmonary persistence, lung damage and mortality rate over the study period considered. Interestingly, although on day 1 p.e. both strains colonized near all the spleens, on day 3 p.e. wt strain persisted in 40% of spleens, whereas fliI- mutant was completely cleared. No significant differences were found in MIP-2, IFN-γ and IL-6 pulmonary levels between groups over time, except for TNF-α whose levels on day 1 p.e. were significantly higher in mice infected with flagellated wt strain. Overall, our results indicate that in S. maltophilia flagella and motility might not represent virulence traits involved in the pathogenesis of lung infection. However, the evidence for a specific flagellar-induced TNF-α response warrants further study.

Purpose: Stenotrophomonas maltophilia has low pathogenicity potential, but if it causes bacteremia it can be fatal, because it has shown high resistance to many antibiotics and can be difficult to treat. Patient death from S. maltophilia bacteremia has increased since 2014 in our hospital. In this study, we investigated risk factors for death due to S. maltophilia bacteremia., Methods: Seventy patients from the hospital database with S. maltophilia bacteremia between January 2010 and July 2017 were investigated. We retrospectively analyzed risk factors including gender, age, wards, hospitalized duration, clinical history, devices, source of S. maltophilia identification, polymicrobial bacteremia, prior antimicrobial therapy, antimicrobial therapy after bacteremia, and resistance to antibiotics. The statistical analysis was performed to compare the period from 2010 to 2013 to from 2014 to 2017., Results: Comparing the 2010-2013 period to the 2014-2017 period, it revealed that history of hospitalization, identification of S. maltophilia from sputum, polymicrobial bacteremia, prior carbapenem use, and mortality was significantly different in S. maltophilia bacteremia (p = 0.028, p = 0.004, p < 0.001, p = 0.034, and p = 0.007, respectively). Comparison between non-survivors and survivors for 2010-2013 and 2014-2017 found ICU admission and ventilator use were seen more often in non-survivors (p = 0.030 vs p = 0.013 and p = 0.027 vs p = 0.010, respectively)., Conclusions: Our analyses showed increase in mortality from S. maltophilia bacteremia from 2014 to 2017, and that non-survivors had a higher frequency of ICU admission and ventilator use in both the 2010-2013 and 2014-2017 periods. There were more combination antimicrobial therapy cases after bacteremia in 2014-2017. Further prospective studies with larger numbers of patients should be undertaken for definitive conclusions., (Copyright © 2018 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Stenotrophomonas maltophilia (S. maltophilia) is an emerging global multiple-drug-resistant organism. It becomes increasingly challenging to treat S. maltophilia infection effectively. Novel therapeutic and preventive approaches targeting S. maltophilia infection are still lacking. This study aims to isolate outer membrane proteins (Omps) from S. maltophilia and use immunoproteomic technology to identify potential vaccine candidates of Omps against S. maltophilia infections., Methods: Omps from S. maltophilia culture were separated by two-dimensional electrophoresis and identified by matrix-assisted laser desorption/ionization time of flight mass spectrometry and nano liquid chromatography coupled fourier transform ion cyclotron resonance tandem mass spectrometry. Recombinant Omps were prepared and used to immunize mice, and the potency of mouse anti-Omp serum was tested in opsonophagocytic killing assay (OPKA). The effects of immunization with recombinant Omp on blood and tissue bacterial loads in a mouse model of S. maltophilia-induced infection were analyzed., Results: Outer membrane protein A (OmpA) and Smlt4123 were identified by mass spectrometry. Mouse anti-Smlt4123 serum significantly reduced the bacterial counts in healthy individuals' blood in OPKA (P < 0.05) but mouse anti-OmpA serum did not. Enzyme-linked immunosorbent assay revealed that the antibody subtype of mouse anti-Smlt4123 antibody was IgG1. Eight hours after an intraperitoneal challenge with S. maltophilia, the bacterial loads in mouse blood were significantly lower in the mice receiving immunization with recombinant Smlt4123 than in the control mice receiving no immunization (P < 0.05), whereas the bacterial loads in other organs, such as the liver, spleen, lung, and kidney were similar in the two groups., Conclusions: The results revealed that the immunoproteomic approach was an efficient way to screen the immunogenic protein of Stenotrophomonas maltophilia. Moreover, the recombinant Smlt4123 had potential to protect mice from bacteremia caused by S. maltophilia in the early stages.

Purpose: The aim of this study was to describe the clinical characteristics and antimicrobial patterns of Stenotrophomonas maltophilia bloodstream infections (BSI) and pneumonia episodes in patients with cancer., Methods: Patients with S. maltophilia BSI or pneumonia admitted from 1 Jan. 2000 to 31 Dec. 2016 were identified at the Instituto Nacional de Cancerología (INCan), a tertiary-care oncology hospital in Mexico City., Results: During the study period, there were 171 isolates identified. The mean age of the whole group was 46.9 ± 17.4 years; 99 (57.9%) were women. There were 95 BSI: 64 ambulatory catheter-related BSI (CRBSI), 20 nosocomial CRBSI, and 11 secondary BSI. Mortality was higher in nosocomial CRBSI (40%) vs. that in ambulatory CRBSI (7.8%) (p = 0.001). There were 76 pneumonia episodes; all were nosocomial acquired; 46 (60.5%) ventilator-associated. From all the group, nine strains (5.2%) were resistant to sulfamethoxazole/trimethoprim/(SMX/TMP). At the first month, 54 patients (31.6%) have died, 38 due to pneumonia (70%) and 16 due to BSI (30%, p < 0.001). Multivariate analysis showed that removal of central venous catheter was associated with a favorable outcome in patients with bacteremia. For patients with pneumonia, age ≥ 65 years and inappropriate antimicrobial treatment were risk factors associated with 30-day mortality., Conclusions: S. maltophilia related with ambulatory CRBSI have a better prognosis than other sources of BSI. Older patients with pneumonia who do not receive appropriate antibiotics have higher mortality. SMX/TMP is still the antibiotic of choice.

Stenotrophomonas maltophilia (SM) has emerged as an important nosocomial pathogen with high morbidity and mortality. Because of its unique antimicrobial susceptibility pattern, appropriate antimicrobial therapy for SM bacteremia is still challenging, especially in immunocompromised patients. The present study was performed to assess clinical predictors of SM bacteremia in adult patients with hematologic malignancy. From 2006 through 2016, a case-control study was performed at a tertiary-care hospital. Case patients were defined as SM bacteremia in patients with hematologic malignancy. Date- and location-matched controls were selected from among patients with gram-negative bacteremia (GNB) other than SM. A total of 118 cases of SM bacteremia were identified and compared to 118 controls. While pneumonia was the most common source of SM bacteremia, centralline-associated infection was most common in the controls. The overall 30-day mortality rate of cases with SM bacteremia was significantly higher than that of the controls (61.0 and 32.2%, respectively; P < 0.001). A multivariable analysis showed that polymicrobial infection, previous SM isolation, the number of antibiotics previously used ≥ 3, and breakthrough bacteremia during carbapenem therapy were significantly associated with SM bacteremia (all P < 0.01). Previous use of trimethoprim/sulfamethoxazole (TMP/SMX) was negatively association with SM bacteremia (P = 0.002). Our data suggest that SM is becoming a significant pathogen in patients with hematologic malignancy. Several clinical predictors of SM bacteremia can be used for appropriate antimicrobial therapy in hematologic patients with suspected GNB.

Background: Stenotrophomonas maltophilia (S. maltophilia) bacteremia causes significant morbidity and mortality in immunocompromised hosts. However, incidence and risk factors for mortality in S. maltophilia bacteremia following allogeneic hematopoietic stem cell transplantation (allo-HSCT) remain controversial. The primary aim of this study is to clarify factors associated with poor prognosis of allo-HSCT recipients with S. maltophilia bacteremia., Methods: From January 2005 to December 2014, patients with hematological diseases and S. maltophilia bacteremia at a single transplantation center in Japan were examined for incidence and 90-day mortality. Prognostic factors associated with 90-day mortality among allo-HSCT recipients were analyzed by log-rank test, and significant variables in the univariate analysis were included in the multivariate Cox proportional-hazards regression model., Results: A total of 65 patients, including 47 patients undergoing allo-HSCT, developed S. maltophilia bacteremia. The incidence of S. maltophilia bacteremia was significantly higher in allo-HSCT recipients compared to patients not receiving allo-HSCT (6.53 vs. 0.36 per 100 admissions, respectively; p < 0.01). The overall 90-day mortality in allo-HSCT recipients was 43%. Independent risk factors for 90-day mortality were low serum albumin (<3.0 g/dl) (HR = 10.86; 95% CI, 3.27-36.12) and high serum C-reactive protein (CRP) (≥10.0 mg/dl) (HR = 3.28; 95% CI, 1.00-10.72). Among 9 patients with both high CRP and low albumin, 5 had pneumonia at the onset of bacteremia and the remaining 4 patients developed pneumonia in a median of 3 days (range, 1 to 8 days) even under effective treatment. All 9 patients eventually died in a median of 2 days (range, 2 to 32 days). The probabilities of developing pneumonia in patients with or without high CRP and low albumin levels were 100% (9/9) and 10.5% (4/38), respectively (p < 0.01)., Conclusions: Allo-HSCT recipients had higher rates of S. maltophilia bacteremia than did patients not receiving allo-HSCT. High serum CRP and low serum albumin at the onset of bacteremia are predictive of disease progression to pneumonia and poor prognosis.

Stenotrophomonas maltophilia is an important opportunistic pathogen that affects immunocompromised individuals. Viable bacterial count method was used to count the number of adhered bacteria. The current study showed the efficiency of S. maltophilia (Sm2) adhesion on different parts of mouse intestinal tract (IT), small intestinal tract (SIT), large intestinal tract (LIT) and rectum (P<0.05) and this ability was equal for each part of IT [ANOVA test (P > 0.05)]. Moxifloxacin (0.03 x MIC) resulted a significant decrease in adhesion of S. maltophilia to SIT (P<0.05) versus control and other sub-inhibitory moxifloxacin concentrations (0.06 x and 1.2 x MIC). It can be concluded from the current study that the S. maltophilia (Sm2) has a good ability to adhere to mouse IT and the lowest concentrations of moxifloxacin (0.03 x MIC) reduced the ability of this bacterium to infect IT by reducing the ability of this bacterium to adhere to IT.

Background: Recently, Stenotrophomonas maltophilia has increasingly been reported as an important nosocomial opportunistic pathogen. Limited therapeutic options of S. maltophilia infections demand early identification and knowledge about the probable risk factors for controlling its spread., Study Design: The present study aimed to investigate the risk factors and trend of antibiotic susceptibility, along with genetic analysis in bacteraemia cases at pediatric intensive care units (PICUs)., Methods: A total of 16 S. maltophilia isolates were obtained, during 4 months from August to November 2015, from blood cultures of patients admitted to PICUs at Nemazee teaching hospital, Shiraz, Iran. S. maltophilia isolates were identified by conventional tests and confirmed by specific PCR primers. Minimum inhibitory concentrations (MICs) were determined by the MIC strip test as described by the Clinical and Laboratory Standards Institute's (CLSI) recommendation. The genetic relatedness among the isolates was assessed by ERIC-PCR., Results: All isolates of S. maltophilia were susceptible to ciprofloxacin, co-trimoxazole and colistin, and only 1 (6.2%) isolate was resistant against ceftazidime. The MIC50/MIC90 of ciprofloxacin, trimethoprim/sulfamethoxazole, colistin and ceftazidime was 0.25/0.38 mg/mL, 0.125/0.19 mg/mL, 0.25/0.38 mg/mL, and 2/4 mg/mL, respectively. Genotypic analysis of ERIC-PCR results revealed two distinct types of pattern. Interestingly, the only ceftazidime resistant isolate showed different patterns with other isolates., Conclusions: Our findings indicated the importance of routine surveillance in infection control, since early detection of pathogens prevented the spread of nosocomial infections and granted effectiveness to care practices. Moreover, the results suggest that the routine drug of choice for S. maltophilia was mostly active against clinical isolates in our region.

Background: Clusters of bloodstream infections caused by Burkholderia cepacia and Stenotrophomonas maltophilia are uncommon, but have been previously identified in hemodialysis centers that reprocessed dialyzers for reuse on patients. We investigated an outbreak of bloodstream infections caused by B cepacia and S maltophilia among hemodialysis patients in clinics of a dialysis organization., Study Design: Outbreak investigation, including matched case-control study., Setting & Participants: Hemodialysis patients treated in multiple outpatient clinics owned by a dialysis organization., Predictors: Main predictors were dialyzer reuse, dialyzer model, and dialyzer reprocessing practice., Outcomes: Case patients had a bloodstream infection caused by B cepacia or S maltophilia; controls were patients without infection dialyzed at the same clinic on the same day as a case; results of environmental cultures and organism typing., Results: 17 cases (9 B cepacia and 8 S maltophilia bloodstream infections) occurred in 5 clinics owned by the same dialysis organization. Case patients were more likely to have received hemodialysis with a dialyzer that had been used more than 6 times (matched OR, 7.03; 95% CI, 1.38-69.76) and to have been dialyzed with a specific reusable dialyzer (Model R) with sealed ends (OR, 22.87; 95% CI, 4.49-∞). No major lapses during dialyzer reprocessing were identified that could explain the outbreak. B cepacia was isolated from samples collected from a dialyzer header-cleaning machine from a clinic with cases and was indistinguishable from a patient isolate collected from the same clinic, by pulsed-field gel electrophoresis. Gram-negative bacteria were isolated from 2 reused Model R dialyzers that had undergone the facility's reprocessing procedure., Limitations: Limited statistical power and overmatching; few patient isolates and dialyzers available for testing., Conclusions: This outbreak was likely caused by contamination during reprocessing of reused dialyzers. Results of this and previous investigations demonstrate that exposing patients to reused dialyzers increases the risk for bloodstream infections. To reduce infection risk, providers should consider implementing single dialyzer use whenever possible., (Published by Elsevier Inc.)

Purpose: The aim of the study was to investigate the prevalence of plasmid-mediated quinolone resistance (PMQR) genes in an unselected collection of bloodstream isolates recovered over an 18-month period in a laboratory affiliated to a university hospital in Athens, Greece, and to assess their impact on the in vitro activity of ciprofloxacin and levofloxacin., Methods: Eight PMQR genes were screened by PCR and sequencing. All PMQR-positive isolates were submitted to isoelectric focusing for β-lactamase detection, conjugation or transformation, time-kill assays, mutant prevention concentrationand inoculum effect evaluation. PCR and sequencing of gyrA and parC were performed for detection of chromosomal mutations., Results: Among 96 Gram-negative isolates, 7 (7.3 %) carried one or more PMQR genes. qnrS1 was the most prevalent (5.2 %), followed by aac(6')-Ib-cr (4.2 %) and their combination (2 %). Cloning was successful for three isolates. The presence of a single PMQR determinant without any target modification was not associated with quinolone resistance with one exception, Stenotrophomonasmaltophilia carrying qnrS1, which was resistant to norfloxacin and ciprofloxacin, but in this isolate, additional mechanisms of quinolone resistance cannot be excluded. All PMQR-positive isolates showed a significant inoculum effect. The mutant prevention concentrations of ciprofloxacin against the quinolone-susceptible clinical isolates ranged from 0.38 to 32 mg l-1 and those of levofloxacin from 1 to 32 mg l-1., Conclusions: PMQRs compromised the bactericidal activity of ciprofloxacin and levofloxacin when expressed in Enterobactercloacae, S. maltophilia or Klebsiellapneumoniae and when more than one co-existed. PMQR determinants represent an unrecognized threat, capable to compromise the in vitro activity of quinolones if expressed in a favourable genetic environment and to favour selection of resistant mutants by widening the mutant selection window of these agents.

Background: Previous studies have shown an association between higher Stenotrophomonas maltophilia antibody levels and decreased lung function in patients with cystic fibrosis (CF). The purpose of this study was to assess the serologic response to S. maltophilia over time and to determine whether changes in antibody levels could predict clinical outcomes., Methods: Changes in S. maltophilia antibody levels in adult and pediatric patients with CF from 2008 to 2014 were assessed between groups of infection patterns. Regression models accounting for repeated measures were used to assess whether antibody levels could predict subsequent S. maltophilia microbiological status, and whether they are associated with lung function and subsequent pulmonary exacerbation., Results: A total of 409 S. maltophilia antibody samples from 135 CF patients showed that antibody levels did not change significantly between study visits, regardless of infection group. Higher antibody levels were independently associated with future culture positivity (OR 1.62; 95% CI 1.09, 2.41; p=0.02). While higher antibody levels were not independently associated with decreases in FEV 1 % predicted, they were associated with an increased hazard ratio for subsequent pulmonary exacerbation (HR 1.3; 95% CI 1.1, 1.6; p<0.001)., Conclusions: S. maltophilia antibody levels may be helpful to identify individuals at risk of exacerbation who may benefit from earlier antimicrobial treatment., (Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Objective Stenotrophomonas maltophilia is an emerging nosocomial pathogen that causes fatal infections in critically ill or immunocompromised patients. S. maltophilia bacteremia (SMB) is a rare condition, and its clinical characteristics in Japanese settings are not well known. Methods The medical charts of patients with SMB were retrospectively reviewed at two medical facilities (Okayama University Hospital and Tsuyama Chuo Hospital) for seven years. The data were analyzed along with those previously reported from other Japanese facilities. Result A total of 181 patients (110 men and 71 women) were evaluated. The major underlying diseases included hematologic malignancy (36.5%), solid organ malignancy (25.4%), and neutropenia (31.5%). The recent use of carbapenem was seen in 56.9% of the cases in total, and more than one-third of the patients in our hospitals were treated with carbapenem at the onset of SMB. Of 28 (63.6%) of 44 cases treated for S. maltophilia, those who did not survive were more likely to have been treated with broad-spectrum antibiotics. A multivariate analysis revealed that a higher updated Charlson Comorbidity Index [odds ratio (95% confidence interval), 1.75 (1.11-2.75); p=0.015] and intubation [odds ratio (95% confidence interval), 12.6 (1.62-97.9); p=0.016] were associated with mortality in our cases. Pathogens were often resistant to ceftazidime but susceptible to minocycline, trimethoprim/sulfamethoxazole, and fluoroquinolones. The overall mortality rates within 30 and 90 days were 37.5% and 62.5%, respectively. Conclusion The clinical characteristics of SMB in Japanese cases were similar to those reported from other countries. Clinicians should be aware that breakthrough infection by S. maltophilia may occur during administration of carbapenem.

Channel catfish (Ictalurus punctatus) is an important agricultural fish that has been plagued by Stenotrophomonas maltophilia (S. maltophilia) infections in recent years, some of them severe. The outer membrane proteins (OMPs) of S. maltophilia are one of the most immunogenic and highly conserved candidates for vaccine development in aquaculture. The present study investigated OMPs of S. maltophilia as vaccine on immune response and disease resistance against S. maltophilia of channel catfish and investigated the enhancement effect of natural adjuvants Propolis (Pro), FIG polysaccharide (Fcps), Glycyrrhizine (Gly) to OMPs of S. maltophilia for further study. The results indicated that channel catfish injected intraperitoneally with OMPs showed better immune response including leukocytes phagocytosis activity, serum bactericidal activity, complement C3, IgM level and an increasement of resistance against S. maltophilia compared to the control group. Moreover, Pro, Fcps and Gly could enhance the immune response of OMPs. The relative percent of survival (RPS) was 73.33%, 66.67%, 63.33%, 60%, 0% in fish injected OMPs + Pro, OMPs + Fcps, OMPs + Gly, OMPs and 0.65% normal saline, respectively. These results suggested that OMPs used as vaccine could induce and stimulate immune response and enhance disease resistance in channel catfish, especially for Pro as immunoenhancer. Results revealed that OMPs were an effective vaccine against S. maltophilia in channel catfish., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Stenotrophomonas maltophilia is a nosocomial pathogen associated with high morbidity and mortality, particularly in immunocompromised or critically ill patients. In this study, we investigated the risk factors for mortality in patients with S. maltophilia bacteremia.Retrospectively, medical records from all patients with S. maltophilia bacteremia between December 2005 and 2014 at Severance Hospital, a 2000-bed tertiary care hospital in Seoul, Korea, were reviewed. Analysis was performed to identify factors associated with 28-day mortality.In total, 142 bacteremia patients were enrolled in this study. The overall 28-day mortality rate was 36.6%. Based on the univariate analysis, hematologic malignancy (P = 0.015), Sepsis-related Organ Failure Assessment (SOFA) score (P < 0.001) and the removal of a central venous catheter (CVC) (P = 0.040) were significantly related to mortality. In the intensive care unit patients, the Acute Physiology and Chronic Health Evaluation II score (P = 0.001) also had significance. Based on the multivariate analysis, the SOFA score (odds ratio [OR] = 1.323; 95% confidence interval [CI]: 1.159, 1.509; P < 0.001) and removal of the CVC (OR = 0.330; 95% CI: 0.109, 0.996; P = 0.049) were independent factors associated with mortality.Our results suggest that removing a CVC may considerably reduce mortality in patients with S. maltophilia bacteremia.

Background/purpose: The impact of bacteremia due to the resistance of Stenotrophomonas maltophilia to trimethoprim-sulfamethoxazole (TMP-SXT) is uncertain. This study compared the clinical characteristics and outcomes of patients with TMP-SXT-susceptible (TSSSM) and TMP-SXT-resistant S. maltophilia (TSRSM) monomicrobial bacteremia., Methods: The medical records of adult patients with TSSSM and TSRSM monomicrobial bacteremia from January 2004 to December 2013 were reviewed and classified into two groups, namely, TSSSM and TSRSM., Results: There were 184 patients with monomicrobial S. maltophilia bacteremia. The mean age was 68.3 years. Most patients were males (72.8%), had high Charlson Comorbidity Index scores, previously prescribed antimicrobial agents, and indwelling medical devices. The 14-day and in-hospital mortality rates were 23.9% and 47.2%, respectively. There were 128 patients (69.6%) with TSSSM and 56 (30.4%) with TSRSM. The incidence of TSSSM bacteremia increased during the study period. The TSSSM and TSRSM groups had similar demographic and clinical characteristics and no significant differences in 14-day and in-hospital mortality (24.2% vs. 23.2%, p = 0.833; 50.0% vs. 41.1%, p = 0.264, respectively). Patients with TSSSM bacteremia had an increased risk of septic shock (p = 0.044) and neutropenia (p = 0.028) at bacteremia onset. Logistic regression analysis indicated that acquisition of TMP-SXT resistance was an independent risk factor for prolonged hospitalization (p = 0.018) and catheter-related S. maltophilia bacteremia was inversely associated with prolonged hospitalization after bacteremia (p = 0.032)., Conclusion: There were no significant differences in mortality for patients with TSSSM and TSRSM bacteremia, but patients with TSRSM bacteremia were associated with prolonged hospitalization after bacteremia onset., (Copyright © 2014. Published by Elsevier B.V.)

Background: Empiric antimicrobial coverage in compromised hosts commonly includes pseudomonal coverage but often lacks coverage against Stenotrophomonas maltophilia. Identification of risk factors specific for S. maltophilia infection may lead to prompt initiation of appropriate antibiotics and improved outcome., Methods: We conducted a retrospective analysis of pediatric patients with bacteremia due to S. maltophilia or Pseudomonas aeruginosa from April 2002 to July 2014 at a tertiary children's hospital. Patient demographics, underlying disease, clinical course, and treatment were compared between S. maltophilia and P. aeruginosa cases., Results: Nineteen children with S. maltophilia bacteremia and 49 children with P. aeruginosa bacteremia were identified. On multivariate logistic regression analysis, use of carbapenems within 7 days prior to onset (OR, 5.00; 95%CI: 1.25-20.07; P = 0.02) and previous intensive care unit stay (OR, 3.75; 95%CI: 1.13-12.47; P = 0.03) were significantly associated with S. maltophilia bacteremia compared with P. aeruginosa bacteremia. The majority of the S. maltophilia bacteremia patients had central line-associated bloodstream infection (79%), compared with the P. aeruginosa bacteremia patients (37%, P = 0.002). There were nine children (47%) who had polymicrobial infection in the S. maltophilia bacteremia group, in contrast to four (8%) in the P. aeruginosa bacteremia group (OR, 10.13; 95%CI: 2.59-39.56; P = 0.001). Consultation with an infectious diseases physician was associated with a lower rate of persistent S. maltophilia bacteremia (P = 0.04)., Conclusions: Stenotrophomonas maltophilia should be considered in breakthrough bacteremia in pediatric patients who receive carbapenems within 7 days prior to onset., (© 2015 Japan Pediatric Society.)

Stenotrophomonas maltophilia is a ubiquitous bacterium and an emerging nosocomial pathogen. This bacterium is resistant to many antibiotics, associated with a number of infections, and a significant health risk, especially for immunocompromised patients. Given that Caenorhabditis elegans shares many conserved genetic pathways and pathway components with higher organisms, the study of its interaction with bacterial pathogens has biomedical implications. S. maltophilia has been isolated in association with nematodes from grassland soils, and it is likely that C. elegans encounters this bacterium in nature. We found that a local S. maltophilia isolate, JCMS, is more virulent than the other S. maltophilia isolates (R551-3 and K279a) tested. JCMS virulence correlates with intestinal distension and bacterial accumulation and requires the bacteria to be alive. Many of the conserved innate immune pathways that serve to protect C. elegans from various pathogenic bacteria also play a role in combating S. maltophilia JCMS. However, S. maltophilia JCMS is virulent to normally pathogen-resistant DAF-2/16 insulin-like signaling pathway mutants. Furthermore, several insulin-like signaling effector genes were not significantly differentially expressed between S. maltophilia JCMS and avirulent bacteria (Escherichia coli OP50). Taken together, these findings suggest that S. maltophilia JCMS evades the pathogen resistance conferred by the loss of DAF-2/16 pathway components. In summary, we have discovered a novel host-pathogen interaction between C. elegans and S. maltophilia and established a new animal model with which to study the mode of action of this emerging nosocomial pathogen., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

Whole-genome sequences for Stenotrophomonas maltophilia serial isolates from a bacteremic patient before and after development of levofloxacin resistance were assembled de novo and differed by one single-nucleotide variant in smeT, a repressor for multidrug efflux operon smeDEF. Along with sequenced isolates from five contemporaneous cases, they displayed considerable diversity compared against all published complete genomes. Whole-genome sequencing and complete assembly can conclusively identify resistance mechanisms emerging in S. maltophilia strains during clinical therapy., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Background: To describe a simple quantitative immunofluorescence assay (IFA) for the detection of specific Stenotrophomonas maltophilia antibodies in serum of CF patients., Methods: A total of 100 sera (64 CF patients and 36 healthy subjects) were collected over a period of 2 years at the University Hospital Essen, Germany. Sputum culture status classified CF patients into groups. Serologic response was determined after Pseudomonas aeruginosa absorption by indirect IFA to Sm whole cell., Results: CF patients with "chronic S. maltophilia" showed significantly higher S. maltophilia antibody levels compared with healthy individuals (P<0.0001) and CF patients with "intermittent" (P=0.0315) or "never S. maltophilia/P. aeruginosa" (P=0.0002). A discriminant cut-off value of >1:120 titre was established to differentiate "CF chronic S. maltophilia" from the other groups. For "CF chronic S. maltophilia", the IFA showed sensitivity and specificity values of 70.7% and 84.7%, respectively., Conclusion: Our data demonstrated that quantitative IFA is a simple serological assay for the detection of specific S. maltophilia antibodies, which could be useful as a diagnostic tool for monitoring immune response of CF patients to S. maltophilia., (Copyright © 2013 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Background: Stenotrophomonas maltophilia is an emerging pathogen causing invasive infections in immunocompromised pediatric patients, including neonates and pediatric oncology patients. Information on innate immune responses to S. maltophilia and its potential modulation are scarce., Methods: We established an in vitro S. maltophilia whole blood sepsis model and studied the proinflammatory cytokine production of CD14-positive cells by flow cytometry. We compared the cytokine expression of term newborns (n = 13) and healthy adults (n = 10) and investigated in vitro responses of pediatric oncology patients after recovery from neutropenia (n = 10) with healthy adults (n = 10). We further evaluated the immunomodulatory role of the amino-acid derivative taurolidine in our in vitro sepsis model., Results: Proinflammatory cytokine responses to S. maltophilia were largely diminished in the neonatal population. No remarkable differences were noted for cytokine responses between pediatric oncology patients and healthy controls. Taurolidine inhibited immunoglobulin (IL)-6, IL-8 and tumor necrosis factor-alpha expression in a dose dependent-fashion in both, pediatric oncology patients and healthy controls., Conclusion: Deficient immune responses to S. maltophilia require optimized prevention strategies against infection in immunocompromised patients, including neonates. Taurolidine may be an effective immunomodulatory agent in a clinical setting., (Copyright © 2012. Published by Elsevier B.V.)

The role of Stenotrophomonas maltophilia fimbrin (SMF) to stimulate the bladder innate immune response was evaluated in this study. SMF was isolated and purified from clinical isolates of S .maltophilia. Different amounts of SMF (1, 5 and 15 μg) was instilled transurethrally. The innate immune response was evaluated in terms of IL-1β, TNF-α, IL-8 and NO concentrations, and mRNA expressions of IL-1β, TNF-α, IL-8 and iNOS in mouse bladder tissue. Moreover, neutrophil infiltration in urine, myeloperoxidase (MPO) activity in bladder tissue and bladder epithelial cells (BECs) activity to engulf and kill bacteria in vitro was studied. The maximum pro-inflammatory cytokines (IL-1β and TNF-α) and chemokine (IL-8) concentrations and their mRNA expressions were found in bladder homogenates of mice that were instilled with 15 μg of SMF transurethrally. The high levels of these mediators was concomitant with the high level of neutrophil infiltration in bladder tissue (MPO) and in collected urine (neutrophil count). The administration of SMF transurethrally activated the BECs in terms of bacterial uptake and intracellular bacterial killing in vitro. This study showed that the SMF administration increased the level of nitric oxide (NO) in bladder tissue. The present study proved for the first time that the administration of mice with SMF transurethrally induced cellular and molecular elements of innate immune response in mouse bladder.

A novel bacterium capable of growth on trichloroethylene as the sole carbon source was identified as Stenotrophomonas maltophilia PM102 by 16S rDNA sequencing (accession number of NCBI GenBank: JQ797560). In this paper, we report the growth pattern, TCE degradation, and total proteome of this bacterium in presence of various other carbon sources: toluene, phenol, glucose, chloroform, and benzene. TCE degradation was comparatively enhanced in presence of benzene. Densitometric analysis of the intracellular protein profile revealed four proteins of 78.6, 35.14, 26.2, and 20.47 kDa while the extracellular protein profile revealed two distinct bands at 14 kDa and 11 kDa that were induced by TCE, benzene, toluene, and chloroform but absent in the glucose lane. A rabbit was immunised with the total protein extracted from the bacteria grown in 0.2% TCE + 0.2% peptone. Antibody preadsorbed on proteins from peptone grown PM102 cells reacted with a single protein of 35.14 kDa (analysed by MALDI-TOF-mass-spectrometry) from TCE, benzene, toluene, or chloroform grown cells. No reaction was seen for proteins of PM102 grown with glucose. The PM102 strain was immobilised in calcium alginate beads, and TCE degradation by immobilised cells was almost double of that by free cells. The beads could be reused 8 times.

To clarify the clinical features and outcome of Stenotrophomonas maltophilia infection among hematopoietic SCT (HCT) recipients, we retrospectively reviewed the records of 1085 consecutive HCT recipients and identified 42 episodes in 31 HCT recipients with S. maltophilia infection. We compared these recipients with 30 non-HCT patients with S. maltophilia infection. The mortality rate in HCT recipients was significantly higher than that in non-HCT patients (relative risk 5.7, P=0.04), and we identified seven patients with pulmonary hemorrhage due to S. maltophilia, exclusively in the HCT cohort. Six of these latter seven patients died within 1 day from the onset of hemorrhage and the isolate was identified after death in most cases; one patient, who received empiric therapy for S. maltophilia and granulocyte transfusion, survived for more than 2 weeks. The patients with pulmonary hemorrhage had a more severe and longer duration of neutropenia, persistent fever despite of the use of broad-spectrum antibiotics, complication by pneumonia and higher C-reactive protein levels than those without pulmonary hemorrhage. In conclusion, S. maltophilia was associated with fulminant and fatal pulmonary hemorrhage in HCT recipients. Empiric therapy with antibiotics before the onset of pulmonary hemorrhage may be effective in HCT recipients who carry the conditions identified.

Stenotrophomonas maltophilia is an emerging drug-resistant pathogen. Here, we demonstrated that S. maltophilia flagellin could locally activate innate immunity thereby increase the resistance to respiratory tract infection (RTI) and improved bacterial clearance in the lungs of BALB/c mice. The test group consisted of BALB/c mice instilled with 5 μg of purified flagellin and challenged 4 h later with S. maltophilia. In this group, increased production of pro-inflammatory cytokines (IL-1β and TNF-α), myeloperoxidase activity, caspase-1 activity and nitric oxide (NO) was seen in lung homogenates in significant amounts (P < 0.05) as compared to control groups. On the contrary, low level of malondialdehyde was detected in the test group. Activation of alveolar macrophages in terms of bacterial engulfment and intracellular bacterial killing at an early stage and delayed production of anti-inflammatory cytokine (IL-10) was also detected. Concomitant with elevation of pro-inflammatory mediators, high number of leukocytes infiltration was detected in bronchoalveolar lavage of treated mice. The generated mucosal immune response was found to be protective against S. maltophilia as well as Staphylococcus aureus infection. In conclusion, this study emphasizes the nonspecific protection mediated by flagellin against homologous as well as heterologous bacterium that might be exploited therapeutically to prevent the development of RTI., (© 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.)

The flagellar protein (flagellin) was isolated and purified from strains of Pseudomonas aeruginosa, Burkholderia cepacia and Stenotrophomonas maltophilia. A significant difference was observed in the molecular weight of different flagellin preparations obtained from these bacterial isolates. Antiserum prepared against S. maltophilia flagellin did not react with flagellin of P. aeruginosa or/and B. cepacia on Immunoblot or in indirect ELISA. In addition the anti-flagellin did not agglutinate P. aeruginosa and B. cepacia. No inhibition of motility of P. aeruginosa and B. cepacia was observed in presence of antiserum; though the latter inhibited the motility of S. maltophilia. The results of the present study prove that no specific relationship existed among all the studied flagellar proteins obtained from closely related bacteria.

Background: The clinical consequences of chronic Stenotrophomonas maltophilia infection in cystic fibrosis (CF) patient are still unclear., Method: All patients treated in the Copenhagen CF centre (N=278) from 1 January 2008 to 31 December 2009 were included. Each patient chronically infected with S. maltophilia for at least 2 years without any other chronic Gram-negative infection were matched to two non-infected CF controls., Results: Twenty-one patients were chronically infected with S. maltophilia during the 2-year study period. Fifteen were infected for at least 2 years. The patients in the S. maltophilia group had a steeper decline (-3.2%/year vs. -0.3%/year) in FEV(1) compared to the non-infected CF controls (P=0.03). The rate of decline was the same as observed 3 years before the patients became chronically infected., Discussions: Chronic infection with S. maltophilia does not lead to a steeper decline in lung function when compared to the period before chronic infection., (Copyright © 2011 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

The cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel provides the glutathione and hypochlorous acid necessary for bactericidal/viricidal actions. CFTR mutations block these effects, diminishing pathogen defence and allowing extracellular pathogen accumulation, where antibody encounter is likely. KEGG pathway analysis of the CFTR interactome shows that CFTR is involved in pathogen entry pathways and immune defence as well as in pathways relevant to comorbid conditions (diabetes, cardiomyopathies and sexual organ development). Pseudomonas aeruginosa and Staphylococcus aureus infections decrease the lifespan of cystic fibrosis patients and Stenotrophomonas maltophilia colonization is increased. Autoantibodies, targeting myeloperoxidase, the bactericidal/permeability-increasing protein and calgranulin may further compromise pathogen defence. Short consensus sequences, within immunogenic extracellular regions of the CFTR protein, are homologous to proteins expressed by P. aeruginosa, S. aureus and S. maltophilia, and to several autoantigens, with a universal overlap between autoantigen/pathogen/CFTR consensi. Antibodies to pathogens are thus likely responsible for the creation of these autoantibodies, which, with pathogen antibodies, may target the CFTR protein acting as antagonists, further compromising its function. This creates a feedforward cycle, diminishing the function of the CFTR protein and increasing the probability of pathogen accumulation and antibody production at every turn. Interruption of this cycle by antibody adsorption or immunosuppressant therapy may be beneficial in cystic fibrosis., (© 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.)