Maltophilia Culture Research Articles

Clinical Characteristics and Prognostic Factors of Patients With Stenotrophomonas maltophilia Pneumonia: 10-Year Experience From a Single Center.

Stenotrophomonas maltophilia infection is gaining importance as an important cause of nosocomial pneumonia. S. maltophilia infection occurs especially in patients with a history of immunosuppression, comorbidity, or multiple antibiotherapy uses. A retrospective 10-year study was carried out to determine the clinical characteristics of all patients with S. maltophilia pneumonia, antibiotic resistance pattern, and risk factors associated with hospital mortality. Hospitalized pneumonia patients with S. maltophilia culture positivity were identified, and their medical records were reviewed. Risk factors associated with hospital mortality were analyzed. Any variable with a significant association with mortality in the univariate analysis was entered in a multivariate forward stepwise logistic regression model to identify independent risk factors for death. Seventy-two patients (mean age: 67.3 years, 65.2% males) with S. maltophilia pneumonia were included in the study. All patients had at least one comorbidity. The most common comorbidities were chronic obstructive pulmonary disease, diabetes mellitus, chronic renal failure, malignancy, and cardiac diseases. Percentage resistance to trimethoprim-sulfamethoxazole (5.5%) was lower than that for fluoroquinolones (12.5%). By using multivariate analysis, respiratory insufficiency needed mechanical ventilation, low hemoglobin level, age>65 years, previous antibiotic usage, and hypotension were the independent prognostic factors for mortality. S. maltophilia is emerging as an important pathogen with an increased risk of mortality in patients with respiratory insufficiency who need mechanical ventilation, a low hemoglobin level, >65 years of age, previous antibiotic usage, and hypotension. Empiric therapy should include agents active against S. maltophilia, such as newer fluoroquinolones and trimethoprim-sulfamethoxazole.

Inhalable Excipient-Free Dry Powder of Tigecycline for the Treatment of Pulmonary Infections.

Tigecycline (TIG) is a broad-spectrum antibiotic that has been approved for the treatment of a number of complicated infections, including community-acquired bacterial pneumonia. Currently it is available only as an intravenous injection that undergoes rapid chemical degradation and limits the use to in-patient scenarios. The use of TIG as an inhaled dry powder inhaler may offer a promising treatment option for patients with multidrug-resistant respiratory tract infections, such as Stenotrophomonas maltophilia (S. maltophilia). This study explores the feasibility of engineering an inhaled powder formulation of TIG that could administer relevant doses at a wide range of inhalation flow rates while maintaining stability of this labile drug. Using air-jet milling, micronized TIG had excellent aerosolization efficiency, with over 80% of the device emitted dose being within the respirable range. TIG was also readily dispersed using different inhaler devices even when tested at different pressure drops and flow rates. Additionally, micronized TIG was stable for 6 months at 25 °C/60% RH and 40 °C/75% RH. Micronized TIG maintained a low minimum inhibitory concentration (MIC) and minimum biofilm eradication concentration (MBEC) of 0.8 μM and >0.5 μM, respectively in S. maltophilia cultures in vitro. These results strongly suggest that the micronization of TIG results in a stable and respirable formulation that can be delivered via the pulmonary route for the treatment of lung infections.

Treatment, clinical outcomes, and predictors of mortality among a national cohort of hospitalized patients with Stenotrophomonas maltophilia infection

ObjectivesTo analyze treatment, clinical outcomes, and predictors of inpatient mortality in hospitalized patients with Stenotrophomonas maltophilia infection. Study designRetrospective cohort study. MethodsWe included patients admitted to Veterans Affairs hospitals nationally with S. maltophilia cultures and treatment from 2010 to 2019. We described patient and clinical characteristics, antibiotic treatment, and clinical outcomes. Univariate and multivariable logistic regression were used to evaluate predictors of inpatient mortality. ResultsWe identified 3891 hospitalized patients treated for an S. maltophilia infection, of which 13.7% died during admission. The most common antibiotic agents were piperacillin/tazobactam (39.7%), sulfamethoxazole/trimethoprim (23.3%), and levofloxacin (23.2%). Combination therapy was used in 16.6% of patients. Independent predictors of inpatient mortality identified in multivariable analysis included the following: presence of current acute respiratory failure (adjusted odds ratio [aOR] 4.74, 95% confidence interval [CI] 3.63–6.19), shock (aOR 3.00, 95% CI 2.31–3.90), acute renal failure (aOR 2.06, 95% CI 1.64–2.60), and septicemia (aOR 1.90, 95% CI 1.49–2.42), age 65 years and older (aOR 2.05, 95% CI 1.07–3.94, reference age 18–49 years), hospital-acquired infection (aOR 1.87, 95% CI 1.48–2.37), Black (aOR 1.58, 95% CI 1.21–2.06) and other races (aOR 1.65, 95% CI 1.41–2.41, reference White), liver disease (aOR 1.51, 95% CI 1.02–2.22), and median Charlson comorbidity score or higher (aOR 1.36, 95% CI 1.08–1.71, reference less than median). Clinical outcomes were similar between patients infected with sulfamethoxazole/trimethoprim-resistant, levofloxacin-resistant, and multidrug-resistant S. maltophilia strains compared to non-resistant strains. ConclusionsIn our national cohort of hospitalized patients with S. maltophilia infection, 13.7% of patients died during admission and several predictors of inpatient mortality were identified. Predictors related to the severity of infection were among the strongest identified. It is important that in severely ill patients presenting to the hospital, S. maltophilia be considered as a cause.

Phenotypical resistance profile of Stenotrophomonas maltophilia insolated from farm amimals

Stenotrophomonas maltophilia is a multidrug‐resistant opportunistic pathogen. Infections caused by resistant strains of bacteria in animals are characterized by a more severe manifestation, increased duration of treatment and often leads to recurrence. Isolation, identification and determination of pathogens and interpretation of their antibioticograms are the basis of effective and rational antibiotic therapy. The aim of the study was to analyze the antibiotic resistance of Stenotrophomonas maltophilia cultures isolated in cases of respiratory diseases in livestock. The materials for the study were nose scrapings collected from 50 postpartum period cows and 69 newborn calves, and 30 horses up to 3 years old. Primary cultures of tracheal and nasal swabs from horses, cows, and calves were incubated on meat‐peptone broth with 1% glucose and horse serum at 37℃ for 24 hours. After that the culture was inoculated on nutrient media such as columbia ram blood agar, chocolate agar, Endo medium and then incubated at 37℃ for 24 hours. Identification of the isolated cultures and study of their biochemical properties were performed using Nefermtest 24 (Erba Lachema, Czech Republic) test systems. Antibiotics resistance measurement was carried out by the MIC method using MicroScan WalkAway 40 plus (Siemens, Germany) automatic analyzer and GN3F, RUSTEF, NF Sensititre (Trek Diagnostic Systems, Great Britain) plates. Disk diffusion test with Mueller‐Hinton agar was performed according to the recommendations of the European Committee for the determination of antibiotic susceptibility (EUCAST). Pathogenicity of cultures was studied by in vivo testing on white mice. The total number of multidrug resistant S. maltophilia isolates made up less than 5% of 149 clinical samples. Following groups of antibiotics were selected to test the antibiotic sensitivity of this bacterium based on the study’s results: penicillins combined with β‐lactamase inhibitors (co‐amoxiclav, ampicillin/sulbactam, ticarcillin/clavulanic acid), quinolone antibiotics (levofloxacin, moxifloxacin, ciprofloxacin, enrofloxamethacin (trimethoxoprimolamines), sulfanilamylamines (TMP/SMX), nitrofurans (nitrofurantoin), tetracyclines (doxycycline), and macrolides (erythromycin). S. maltophilia cultures isolated from livestock were sensitive only to levofloxacin and moxifloxacin. Interpretation of antibioticograms is one of the main factors that determine the effectiveness of antibiotic therapy.

Trimethoprim-Sulfamethoxazole Versus Levofloxacin for Stenotrophomonas maltophilia Infections: A Retrospective Comparative Effectiveness Study of Electronic Health Records from 154 US Hospitals.

BackgroundTrimethoprim-sulfamethoxazole (TMP-SMX) is considered first-line therapy for Stenotrophomonas maltophilia infections based on observational data from small studies. Levofloxacin has emerged as a popular alternative due to tolerability concerns related to TMP-SMX. Data comparing levofloxacin to TMP-SMX as targeted therapy are lacking.MethodsAdult inpatient encounters January 2005 through December 2017 with growth of S maltophilia in blood and/or lower respiratory cultures were identified in the Cerner Healthfacts database. Patients included received targeted therapy with either levofloxacin or TMP-SMX. Overlap weighting was used followed by downstream weighted regression. The primary outcome was adjusted odds ratio (aOR) for in-hospital mortality or discharge to hospice. The secondary outcome was number of days from index S maltophilia culture to hospital discharge.ResultsAmong 1581 patients with S maltophilia infections, levofloxacin (n = 823) displayed statistically similar mortality risk (aOR, 0.76 [95% confidence interval {CI}, .58–1.01]; P = .06) compared to TMP-SMX (n = 758). Levofloxacin (vs TMP-SMX) use was associated with a lower aOR of death in patients with lower respiratory tract infection (n = 1452) (aOR, 0.73 [95% CI, .54–.98]; P = .03) and if initiated empirically (n = 89) (aOR, 0.16 [95% CI, .03–.95]; P = .04). The levofloxacin cohort had fewer hospital days between index culture collection and discharge (weighted median [interquartile range], 7 [4–13] vs 9 [6–16] days; P < .0001).ConclusionsBased on observational evidence, levofloxacin is a reasonable alternative to TMP-SMX for the treatment of bloodstream and lower respiratory tract infections caused by S maltophilia.

Antimicrobial Susceptibility, Minimum Inhibitory Concentrations, and Clinical Profiles of Stenotrophomonas maltophilia Endophthalmitis.

Stenotrophomonas maltophilia has been reported in various ocular infections, including keratitis, conjunctivitis, preseptal cellulitis, and endophthalmitis, all of which may lead to vision loss. However, the S. maltophilia strain is resistant to a wide variety of antibiotics, including penicillins, third-generation cephalosporins, aminoglycosides, and imipenem. In this study, we retrospectively reviewed the clinical characteristics, antibiotic susceptibility, antimicrobial minimum inhibitory concentrations (MICs), and visual outcomes for S. maltophilia endophthalmitis. The data of 9 patients with positive S. maltophilia cultures in a tertiary referral center from 2010 to 2019 were reviewed. Cataract surgery (n = 8, 89%) was the most common etiology, followed by intravitreal injection (n = 1, 11%). S. maltophilia’s susceptibility to levofloxacin and moxifloxacin was observed in 6 cases (67%). Seven isolates were resistant to sulfamethoxazole-trimethoprim (78%). The MIC90 for S. maltophilia was 256, 256, 256, 8, 12, 12, 12, and 8 μg/mL for amikacin, cefuroxime, ceftazidime, tigecycline, sulfamethoxazole-trimethoprim, levofloxacin, galtifloxacin, and moxifloxacin, respectively. Final visual acuity was 20/200 or better in 5 patients (56%). Fluoroquinolones and tigecycline exhibited low antibiotic MIC90. Therefore, the results suggest that fluoroquinolones can be used as first-line antibiotics for S. maltophilia endophthalmitis.

847. Trends in Stenotrophomonas maltophilia Antibiotic Resistance Rates

BackgroundStudies from the 1990’s and 2000’s identified increasing rates of Stenotrophomonas maltophilia, particularly among respiratory isolates and in intensive care populations. Additionally, resistance in S. maltophilia was found to be worsening. We aimed to quantify recent trends in prevalence and resistance of S. maltophilia in the national Veterans Affairs (VA) Healthcare system.MethodsWe identified positive S. maltophilia clinical cultures among VA adult patients from 2010 to 2018, collected in either VA medical centers (VAMCs), community living centers (CLCs), or the outpatient (Outpt) setting. Multidrug resistance (MDR) was defined as resistance to sulfamethoxazole/trimethoprim (SMX/TMP) and minocycline or levofloxacin. Time trends were assessed with regression analyses to estimate annual average percent changes (AAPC) with 95% confidence intervals using Joinpoint Software.ResultsOver the 9-year study period, we identified 18,285 S. maltophilia cultures (57% VAMCs, 3% CLCs, 40% Outpt). S. maltophilia cultures made up 0.4% of all positive cultures in the VA. In VAMCs and CLCs, the number of S. maltophilia cultures decreased 5.1% and 8.5% per year, respectively. Alternatively, of all positive cultures in VAMCs, the proportion that were S. maltophilia increased significantly by 2.6% per year.SMX/TMP resistance decreased significantly by 8.5% (2010, 15%; 2018, 6%) per year in VAMCs, and decreased non-significantly by 8.7% (2010, 13%, 2018, 6%) per year in CLCs and 6.0% (2010, 12%; 2018, 7%) in the outpatient setting. No other significant changes in resistance were observed over the study period. MDR increased non-significantly by 1.2% per year.ConclusionWhile previous studies found increasing rates of S. maltophilia, the number of positive S. maltophilia cultures decreased in the national VA Healthcare System between 2010 and 2018. However, S. maltophilia is making up a greater proportion of positive culture over time. During the study period, resistance to SMX/TMP decreased and now more closely reflects previously reported resistance rates worldwide (0-10%).Disclosures Aisling Caffrey, PhD, Merck (Research Grant or Support)Pfizer (Research Grant or Support)Shionogi (Research Grant or Support) Haley J. Appaneal, Pharm.D, Shionogi, Inc. (Research Grant or Support) Kerry LaPlante, PharmD, Merck (Advisor or Review Panel member, Research Grant or Support)Ocean Spray Cranberries, Inc. (Research Grant or Support)Pfizer Pharmaceuticals (Research Grant or Support)Shionogi, Inc. (Research Grant or Support)

1585. Stenotrophomonas maltophilia Infections and Approaches to Treatment

BackgroundCurrent knowledge of the epidemiology of Stenotrophomonas maltophilia is limited to studies from several small international medical centers. Additionally, real-world approaches to treatment are not well described.MethodsWe included admissions to any Veterans Affairs (VA) medical center nationally, with positive S. maltophilia cultures collected from any culture site between January 2010 and April 2019. We reviewed epidemiologic factors of clinical characteristics and treatment. Treatment was assessed by mapping out all antibiotic exposures each day, and identifying differences (heterogeneity) in the antibiotics used and duration of their use.ResultsOver the study period, we identified 8,225 hospital admissions with positive S. maltophilia cultures. Patients were older (mean age 68.2 year) and male (97.6%), with 25.8% in the intensive care and 56.1% admitted from other healthcare settings. Respiratory cultures were most common (47.4%), followed by urine (21.4%), skin and soft tissue (17.4%), and blood (5.1%). Admissions were mostly 11 days long (median), with an inpatient mortality rate of 13.9%.The median time to culture collection from admission was day 3 of the hospitalization, and the median time to culture completion was 4 days. Changes in therapy occurred before culture completion for 67.3% of admissions. Most admissions utilized different treatment approaches (antibiotic drug and duration treatment heterogeneity 89.7%), with a median of 4 changes in therapy. Fluroquinolones were utilized in 40.6% of admissions (initiated median 4 days from admission) and sulfamethoxazole/trimethoprim in 26.3% (initiated median 7 days from admission). Inpatient mortality was significantly higher among those with changes in therapy versus those without changes (15.0% vs 5.7%, p< 0.0001), and among those without changes, mortality was significantly higher with monotherapy versus combination therapy (16.2% vs 2.6%, p< 0.0001).ConclusionAmong more than 8,000 admissions with positive S. maltophilia cultures in the VA nationally, identification of the organism and targeted therapy did not occur until 4-7 days from admission. Differences in clinical outcomes were observed among the different treatment approaches.Disclosures Aisling Caffrey, PhD, Merck (Research Grant or Support)Pfizer (Research Grant or Support)Shionogi (Research Grant or Support) Haley J. Appaneal, PharmD, Shionogi, Inc. (Research Grant or Support) Kerry LaPlante, PharmD, Merck (Advisor or Review Panel member, Research Grant or Support)Ocean Spray Cranberries, Inc. (Research Grant or Support)Pfizer Pharmaceuticals (Research Grant or Support)Shionogi, Inc. (Research Grant or Support)

488. Epidemiology and Outcomes for Stenotrophomonas maltophilia Infections at a Tertiary Care Center in Detroit, MI

Background Stenotrophomonas maltophilia is a gram-negative, biofilm-forming bacterium. The increasing use of antibiotics has allowed this bacterium to become a predominant nosocomial pathogen with inherent resistance to several antibiotics. In this study, we describe the epidemiology and outcomes for patients treated for S. maltophilia infections who were admitted to Detroit Medical Center from January 1, 2010 to August 31, 2018.MethodsThis was a retrospective cohort study that included S. maltophilia cultures isolated from sterile body sites from January 1, 2010 to August 31, 2018. Nonsterile body sites and tissue cultures were excluded, as well as cultures that were deemed to be colonization based upon clinical evaluation. Appropriate empiric antibiotic therapy was defined as a regimen administered three days prior to or four days following the S. maltophilia culture date. Appropriate definitive therapy was defined as antibiotic treatment administered five to fourteen days following the culture date. Patient data were extracted from the electronic medical record which included demographic information, length of stay and outcome data. Bivariate analysis was performed using SAS database.Results126 patients with S. maltophilia infections were analyzed: 89 had bacteremia, 22 had lung infections, and 15 had other infections. The median length of stay was 16 days (IQR 6–30 days). Sixty-one patients (48%) admitted to the ICU had a median length of stay of 10 days (Table 2). Among the patients that were followed after discharge, 21 were readmitted within 30 days. Table 1 highlights the bivariate analysis of patients who died within 30 days vs. survived. Patients who received definitive antibiotic therapy had lower 30-day mortality (Table 1; CI 95%, OR=0.37, P = 0.03). In addition, patients who were bacteremic had a lower 30-day mortality (Table 1; CI 95%, OR=0.40, P = 0.04). There was no significant difference in mortality among patients who received appropriate empiric antibiotic therapy (P = 0.67).ConclusionThis study demonstrates that nonbacteremic patients infected with Stenotrophomonas have higher 30-day mortality than those with bacteremia. This necessitates that diseases associated with this bacterium should be taken seriously and treated with definitive appropriate antibiotics. Disclosures All authors: No reported disclosures.

Cystic fibrosis related diabetes is not independently associated with increased Stenotrophomonas maltophilia infection: Longitudinal data from the UK CF Registry

IntroductionStenotrophomonas maltophilia is common in the sputum of people with cystic fibrosis related diabetes (CFRD), raising the question as to whether this is a risk factor for its acquisition. We investigated this at a population level. MethodsWe analysed national Cystic Fibrosis Registry data 2011–2015 for 8047 people with CF > age 6 years, looking at demographics, diagnosis of CFRD, lung function and sputum microbiology; using descriptive and multivariate strategies to establish independent predictors for S. maltophilia culture and associated outcomes. ResultsS. maltophilia was present in 1148 (14.1%). Although univariate analysis confirmed it was more prevalent in those with CFRD, when adjusted for other clinical parameters there was no longer a relationship. Markers of more severe lung disease were independent risk-factors for S. maltophilia. ConclusionAlthough S. maltophilia is more common in people with CFRD, it is not an independent risk-factor for S. maltophilia acquisition.

Identification of immunogenic outer membrane proteins and evaluation of their protective efficacy against Stenotrophomonas maltophilia

BackgroundStenotrophomonas 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.MethodsOmps 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.ResultsOuter 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.ConclusionsThe 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.

Stenotrophomonas maltophilia infection among young children in a cardiac intensive care unit: a single institution experience.

Stenotrophomonas maltophilia can present as bacteremia, respiratory tract infection, urinary tract infection, soft tissue and wound infections, bone and joint infections, meningitis, and endocarditis especially in immunosuppressed patients and those with underlying medical conditions. The incidence and impact of S. maltophilia in young children with heart disease are poorly defined. A single center retrospective observational study was conducted in infants <180days of age with positive S. maltophilia cultures over a period of 5years. The overall incidence for S. maltophilia infection was 0.8% (n=32/3656). Among 32 identified infants, there were 47 episodes of S. maltophilia infection 66% of infants had prior exposure to broad spectrum antibiotics. 97% of positive isolates were susceptible to trimethoprim/sulfamethoxazole and 91% to levofloxacin as well as ticarcillin/clavulanate. Ventilator-free days and absolute lymphocyte count prior to acquiring infection were significantly lower in non-survivors than in survivors. 100% of survivors had clearance of positive cultures compared to 50% in non-survivors (p<0.05). The crude all-cause mortality rate was 37.5%. All non-survivors had increased length of ICU stay and duration of mechanical ventilation and had delayed clearance of infection and required longer duration of treatment.

Independent Predictors for Mortality in Patients with Positive Stenotrophomonas maltophilia Cultures

Stenotrophomonas maltophilia is an emerging pathogen in nosocomial infections that may result in high mortality. S. maltophilia often present as part of a polymicrobial culture and it is not well established when treatment is indicated. We aimed to identify predictors of mortality in patients with positive cultures of S. maltophilia. A retrospective cohort study in a tertiary care medical centre was performed in 150 adult patients with positive cultures of S. maltophilia. Patients' demographics, underlying diseases, severity of illness, length of hospitalisation, prior antibiotic exposure, number/types of indwelling catheters, culture sites, and appropriateness of empiric therapy were collected. Logistic regression was used to determine the independent risk factor(s) for infection-attributed mortality. Ninety-nine males and 51 females were studied. The mean (SD) age and APACHE II score of the patients were 61.9 (16.0) and 14.0 (6.1), respectively. The respiratory tract was the most frequent site (55.3%) where S. maltophilia was isolated. Infection-attributed mortality was observed in 22 of the 150 patients (14.7 %). Admission to ICU [Odds ratio (OR), 3.767; 95% confidence interval (CI), 1.277-11.116, P = 0.016], and delayed effective treatment (OR, 18.684; 95% CI, 4.050-86.188; P <0.001) were identified as independent risk factors for mortality. Predictors of mortality in patients with positive cultures of S. maltophilia were identified, which may guide clinicians in patient assessment and devising therapeutic decisions. Further studies are needed to validate our results.

Factors associated with mortality in patients with bloodstream infection and pneumonia due to Stenotrophomonas maltophilia

Severe infections caused by Stenotrophomonas maltophilia are associated with high mortality, and strategies to improve the clinical outcome for infected patients are needed. A retrospective cohort study of patients with bloodstream infection (BSIs) and pneumonia caused by S. maltophilia was conducted. Multivariate analysis was performed to access factors associated with 14-day mortality. A total of 60 infections were identified. Among these, eight (13%) were pneumonias and 52 were BSIs; 33.3% were primary, 13% were central venous catheter (CVC)-related and 40% were secondary BSIs. Fifty-seven (85%) patients had received previous antimicrobial therapy; 88% had CVC, 57% mechanical ventilation and 75% were in the intensive care unit at the onset of infection. Malignancy (45%) was the most frequent underlying disease. The mean of the Acute Physiology and Chronic Health Evaluation II (APACHE II) scores was 17 and for the Sepsis-related Organ Failure Assessment (SOFA) score, it was 7 points. The overall and 14-day mortality were, respectively, 75% and 48%. Forty-seven (78%) patients were treated and, of these, 74% received trimethoprim-sulfamethoxazole. Independent risk factors associated with mortality were SOFA index >6 points (0.005) and septic shock (0.03). The Kaplan-Meier estimations curves showed that patients with APACHE II score >20 and SOFA score >10 had a survival chance of, respectively, less than 8% and less than 10% (P<or=0.001) at 21 days after the first positive S. maltophilia culture. Our results suggest that the independent factors associated with outcome in patients with infection caused by S. maltophilia are septic shock and higher SOFA index.

Stenotrophomonas maltophilia infection of the central venous catheter and lysis of an old thrombosis in a post-bone marrow transplantation child: Implications in the fibrinolytic process

In this report, we describe an 11-y-old girl who developed jugular venous thrombosis after allogeneic bone marrow transplantation for lymphoma and then experienced dissolution of the thrombosis following catheter-related Stenothrophomonas maltophilia bactearemia. The lysis of the old thrombosis around the central venous catheter suggested a local fibrinolytic activity of S. maltophilia. The global fibrinolytic capacity (GFC) was also tested in vitro by using S. maltophilia cultures obtained from the present patient; GFC of the patient was compared to that of another isolate of S. maltophilia, other bacteria (S. pyogenes and E. coli), and control plasma. The fibrinolytic capasity of S. maltophilia was significantly higher than that of the control plasma (p<0.05) and almost equal to that of S. pyogenes (p>0.05). Thus, if a potent local fibrinolytic activity of S. maltophilia is evident, the use of the fibrinolytic enzyme of S. maltophilia as a thrombolytic agent may be a useful therapeutic adjunct in the future. Further studies are needed to comfirm the results obtained in the present study.

Cytotoxic activity of clinical Stenotrophomonas maltophilia

To determine the potential virulence factors produced by culture supernatants of clinical isolates of Stenotrophomonas maltophilia. Culture supernatants of clinical isolates of S. maltophilia were assayed for haemolytic, enzymatic (lipase, protease and phospholipase) and cytotoxic activity. Cytotoxic activity was assayed in Vero (African green monkey), HeLa (human cervix) and HEp-2 (human larynx epidermoid carcinoma) cells. Microscopic analyses revealed intensive rounding, loss of intercellular junctions and membrane alterations (blebbing) followed by death of HEp-2 cells. In Vero and HeLa cells, the cytotoxic effects were characterized by vigorous endocytosis and cell aggregation. The viability of cultured mammalian cells was determined with neutral red and demonstrated that the sensitivity among the cells was different. This activity was inactivated by heating at 56 degrees C for 15 min and protease inhibitors did not inhibit cytotoxic activity. The clinical S. maltophilia presented a cell-free haemolytic activity similar to the 'hot-cold' haemolysins. S. maltophilia culture supernatants caused vigorous endocytosis and cell aggregation in HeLa and Vero cells, produced haemolytic and enzymatic activities. This work revealed the presence of putative virulence factors that could be associated with human infections involving Stenotrophomonas maltophilia strains.

Physiological characterization of Mycobacterium sp. strain 1B isolated from a bacterial culture able to degrade high-molecular-weight polycyclic aromatic hydrocarbons.

The aim of this study was to further characterize a bacterial culture (VUN 10,010) capable of benzo[a]pyrene cometabolism. The bacterial culture, previously characterized as a pure culture of Stenotrophomonas maltophilia (VUN 10,010), was found to also contain another bacterial species (Mycobacterium sp. strain 1B), capable of degrading a similar range of PAH substrates. Analysis of its 16S rRNA gene sequence and growth characteristics revealed the strain to be a fast-growing Mycobacterium sp., closely related to other previously isolated PAH and xenobiotic-degrading mycobacterial strains. Comparison of the PAH-degrading characteristics of Mycobacterium sp. strain 1B with those of S. maltophilia indicated some similarities (ability to degrade phenanthrene and pyrene), but some differences were also noted (S. maltophilia able to degrade fluorene, but not fluoranthene, whereas Mycobacterium sp. strain 1B can degrade fluoranthene, but not fluorene). Unlike the S. maltophilia culture, there was no evidence of benzo[a]pyrene degradation by Mycobacterium sp. strain 1B, even in the presence of other PAHs (ie pyrene) as co-metabolic substrates. Growth of Mycobacterium sp. strain 1B on other organic carbon sources was also limited compared with the S. maltophilia culture. This study isolated a Mycobacterium strain from a bacterial culture capable of benzo[a]pyrene cometabolism. The Mycobacterium strain displays different PAH-degrading characteristics to those described previously for the PAH-degrading bacterial culture. It is unclear what role the two bacterial strains play in benzo[a]pyrene cometabolism, as the Mycobacterium strain does not appear to have endogenous benzo[a]pyrene degrading ability. This study describes the isolation and characterization of a novel PAH-degrading Mycobacterium strain from a PAH-degrading culture. Further studies utilizing this strain alone, and in combination with other members of the consortium, will provide insight into the diverse roles different bacteria may play in PAH degradation in mixed cultures and in the environment.

Differences in the permeability of high-flux dialyzer membranes for bacterial pyrogens.

The increasing use of high-flux membranes for hemodialysis has raised concerns that patients dialyzed with these membranes may be at higher risk of being exposed to cytokine-inducing bacterial substances in the dialysate than patients dialyzed with low-flux membranes. We investigated the permeability of various high-flux membranes for both purified E. coli lipopolysaccharide (LPS) as well as for LPS derived from Stenotrophomonas (Sten.) maltophilia. An in vitro dialysis circuit with saline in the blood compartment of 3 dialyzers containing different membranes (polysulfone, helixone and Diapes) was employed. The dialysate was challenged with increasing doses of sterile filtrates derived from Sten. maltophilia cultures or with purified LPS from E. coli. Samples from the blood compartment were tested for cytokine induction (IL-1beta, IL-6 and TNF) in mononuclear cells as well as for LPS by limulus amebocyte lysate test (LAL). IL-6 induction above sterile controls (< 0.02 ng/ml IL-6) was observed by samples from the blood side of DIAPES dialyzers (1.2 +/- 0.7 ng/ml IL-6) after challenging the dialysate with 4.1 +/- 3.6 U/ml E. coli LPS (9.9 +/- 4.5 ng/ml IL-6). In contrast, at the same challenge dose no significant IL-6 induction above sterile controls was observed by blood side samples of polysulfone (0.15 +/- 0.07 ng/ml) and helixone (0.09 +/- 0.05 ng/ml) dialyzers. Increasing the amount of E. coli LPS in the dialysate further augmented IL-6 induction by blood side samples of Diapes but not of polysulfone and helixone dialyzers. Similar results were obtained for IL-1beta and TNF. After challenging the dialysate with E. coli LPS as well as with cultures of Sten. maltophilia, significantly more LAL reactivity was observed in the blood compartment of Diapes compared to polysulfone and helixone. There are considerable differences between high-flux membranes regarding their permeability for cytokine-inducing substances from E. coli as well as for LPS derived from E. coli and Sten. maltophilia. Dialyzers that leak CIS under aqueous conditions in vivo should not be used unless the dialysate has passed through an ultrafilter.

Factors Affecting the Incidence of Stenotrophomonas maltophilia Isolation in Cystic Fibrosis

To identify factors predisposing cystic fibrosis (CF) patients to Stenotrophomonas maltophilia infection and to determine whether coinfection with S maltophilia affects the clinical response to therapy with tobramycin solution for inhalation (TSI), 300 mg bid. Retrospective review of data collected from two identical, 6-month, randomized, placebo-controlled trials. Sixty-nine CF centers in the United States. Active drug administration of 300 mg TSI. Five hundred twenty CF patients with chronic Pseudomonas aeruginosa endobronchial infections. A logistic regression analysis identified factors contributing to increased S maltophilia isolation frequency. In this multivariate analysis, the only significant predictors of S maltophilia isolation during the last month of the trial were the concomitant use of oral quinolones (primarily ciprofloxacin; p = 0.0015) and S maltophilia isolation prior to treatment (p < 0.0001). Treatment group, gender, age, use of systemic or inhaled steroids, use of oral sulfonamide, IV cephalosporins, or penicillin antibiotics, baseline FEV(1) percent predicted, and pretreatment Aspergillus isolation were not significant predictors of subsequent S maltophilia infection. In addition, S maltophilia-positive culture frequency was compared to the change in pulmonary function. Patients who either never had culture results positive for S maltophilia or who were positive at <25% of observations had greater clinical response to TSI at the final study visit compared to patients who were positive at > or = 25% of observations. TSI therapy did not result in a greater risk for isolation of S maltophilia than standard care alone. In contrast, oral quinolone antibiotic use during the trial was associated with a 2.7-fold increased risk of having a culture positive for S maltophilia (p = 0.0015). The use of TSI to suppress P aeruginosa resulted in improved lung function, regardless of S maltophilia culture frequency. However, improvement was not as great among patients who were persistently coinfected with S maltophilia.

Use of random amplified polymorphic DNA PCR to examine epidemiology of Stenotrophomonas maltophilia and Achromobacter (Alcaligenes) xylosoxidans from patients with cystic fibrosis.

Stenotrophomonas maltophilia and Achromobacter (Alcaligenes) xylosoxidans have been increasingly recognized as a cause of respiratory tract colonization in cystic fibrosis (CF). Although both organisms have been associated with progressive deterioration of pulmonary function, demonstration of causality is lacking. To examine the molecular epidemiology of S. maltophilia and A. xylosoxidans in CF, isolates from patients monitored for up to 2 years were fingerprinted using a PCR-based randomly amplified polymorphic DNA (RAPD-PCR) method. Sixty-one of 69 CF centers screened had 183 S. maltophilia culture-positive patients, and 46 centers had 92 A. xylosoxidans-positive patients. At least one isolate from each patient was genotyped, and patients with > or =10 positive cultures (12 S. maltophilia cultures, 15 A. xylosoxidans cultures) had serial isolates genotyped. In addition, centers with multiple culture-positive patients were examined for evidence of shared clones. There were no instances of shared genotypes among different CF centers. Some patients demonstrated isolates with a single genotype throughout the observation period, and others had intervening or sequential genotypes. At the six centers with multiple S. maltophilia culture-positive patients and the seven centers with multiple A. xylosoxidans-positive patients, there were three and five instances of shared genotypes, respectively. The majority of shared isolates were from pairs who were siblings or otherwise epidemiologically linked. These findings suggest RAPD-PCR typing can distinguish unique CF isolates of S. maltophilia and A. xylosoxidans, person-to-person transmission may occur, there are not a small number of clones infecting CF airways, and patients with long-term colonization may either have a persistent organism or may acquire additional organisms over time.