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Antimicrobial Resistance and Infection... May 2024Stenotrophomonas maltophilia is a gram-negative bacterium that can cause hospital infections and outbreaks within hospitals. This study aimed to evaluate an outbreak of...
BACKGROUND
Stenotrophomonas maltophilia is a gram-negative bacterium that can cause hospital infections and outbreaks within hospitals. This study aimed to evaluate an outbreak of Stenotrophomonas maltophilia, caused by ready-to-use commercial syringes containing liquid lithium and heparin for arterial blood gas collection in a university hospital.
METHODS
Upon detecting an increase in Stenotrophomonas maltophilia growth in blood cultures between 15.09.2021 and 19.11.2021, an outbreak analysis and a case-control study (52 patients for the case group, 56 patients for the control group) were performed considering risk factors for bacteremia. Samples from possible foci for bacteremia were also cultured. Growing bacteria were identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. The genetic linkage and clonal relationship isolates were investigated with pulsed-field gel electrophoresis (PFGE) in the reference laboratory.
RESULTS
In the case-control study, the odds ratio for the central venous catheter [3.38 (95% confidence interval [CI]: 1.444, 8.705 ; p = 0.006)], for surgery [3.387 (95% confidence interval [CI]: 1.370, 8.373 ; p = 0.008)] and for arterial blood gas collection history [18.584 (95% confidence interval [CI]:4.086, 84.197; p < 0.001)] were identified as significant risk factors. Stenotrophomonas maltophilia growth was found in ready-to-use commercial syringes used for arterial blood gas collection. Molecular analysis showed that the growths in the samples taken from commercial syringes and the growths from blood cultures were the same. It was decided that the epidemic occurred because the method for sterilization of heparinized liquid preparations were not suitable. After discontinuing the use of the kits with this lot number, the outbreak was brought under control.
CONCLUSIONS
According to our results, disposable or sterile medical equipment should be included as a risk factor in outbreak analyses. The method by which injectors containing liquids, such as heparin, are sterilized should be reviewed. Our study also revealed the importance of the cooperation of the infection control team with the microbiology laboratory.
Topics: Stenotrophomonas maltophilia; Humans; Disease Outbreaks; Case-Control Studies; Gram-Negative Bacterial Infections; Male; Female; Cross Infection; Middle Aged; Aged; Adult; Risk Factors; Bacteremia; Hospitals, University; Syringes; Electrophoresis, Gel, Pulsed-Field; Aged, 80 and over; Heparin
PubMed: 38764050
DOI: 10.1186/s13756-024-01410-8 -
Microbiology Spectrum Jun 2024Malignant central airway stenosis is treated with airway stent placement, but post-placement microbial characteristics remain unclear. We studied microbial features in...
UNLABELLED
Malignant central airway stenosis is treated with airway stent placement, but post-placement microbial characteristics remain unclear. We studied microbial features in 60 patients post-stent placement, focusing on changes during granulation tissue proliferation. Samples were collected before stent ( = 29), after stent on day 3 ( = 20), and after granulation tissue formation (AS-GTF, = 43). Metagenomic sequencing showed significant respiratory tract microbiota changes with granulation tissue. The microbiota composition, dominated by , , and , was similar among the groups. At the species level, the AS-GTF group exhibited significant differences, with and enriched. Analysis based on tracheoesophageal fistula presence identified and as the main differential species, enriched in the fistula subgroup. Viral and fungal detection showed and as the main species, respectively. These findings highlight microbiota changes after stent placement, potentially associated with granulation tissue proliferation, informing stent placement therapy and anti-infective treatment optimization.
IMPORTANCE
Malignant central airway stenosis is a life-threatening condition that can be effectively treated with airway stent placement. However, despite its clinical importance, the microbial characteristics of the respiratory tract following stent insertion remain poorly understood. This study addresses this gap by investigating the microbial features in patients with malignant central airway stenosis after stent placement, with a specific focus on microbial changes during granulation tissue proliferation. The findings reveal significant alterations in the diversity and structure of the respiratory tract microbiota following the placement of malignant central airway stents. Notably, certain bacterial species, including and , exhibit distinct patterns in the after-stent granulation tissue formation group. Additionally, the presence of tracheoesophageal fistula further influences the microbial composition. These insights provide valuable references for optimizing stent placement therapy and enhancing clinical anti-infective strategies.
Topics: Humans; Stents; Female; Male; Microbiota; Middle Aged; Aged; Bacteria; Airway Obstruction; Respiratory System; Granulation Tissue; Adult; Aged, 80 and over; Tracheoesophageal Fistula
PubMed: 38747599
DOI: 10.1128/spectrum.03472-23 -
Frontiers in Microbiology 2024is an opportunistic pathogen intrinsically resistant to multiple and broad-spectrum antibiotics. Although the bacterium is considered a low-virulence pathogen, it can... (Review)
Review
is an opportunistic pathogen intrinsically resistant to multiple and broad-spectrum antibiotics. Although the bacterium is considered a low-virulence pathogen, it can cause various severe diseases and contributes significantly to the pathogenesis of multibacterial infections. During the COVID-19 pandemic, has been recognized as one of the most common causative agents of respiratory co-infections and bacteremia in critically ill COVID-19 patients. The high ability to adapt to unfavorable environments and new habitat niches, as well as the sophisticated switching of metabolic pathways, are unique mechanisms that attract the attention of clinical researchers and experts studying the fundamental basis of virulence. In this review, we have summarized the current knowledge on the molecular aspects of virulence and putative virulence factors, partially touched on interspecific bacterial interactions and iron uptake systems in the context of virulence, and have not addressed antibiotic resistance.
PubMed: 38741741
DOI: 10.3389/fmicb.2024.1385631 -
Annals of Intensive Care May 2024The efficacy and safety of cefiderocol in ICU patients with difficult-to-treat resistance (DTR) non-fermenting Gram-negative bacteria (Nf-GNB) are not as...
BACKGROUND
The efficacy and safety of cefiderocol in ICU patients with difficult-to-treat resistance (DTR) non-fermenting Gram-negative bacteria (Nf-GNB) are not as well-established. Consequently, we conducted a cohort study to compare Cefiderocol with the Best Available Therapy (BAT) in ICU patients.
METHODS
We included adult patients from 9 different ICUs, including a burn ICU unit, from 2019 to 2023 treated with Cefiderocol for DTR Nf-GNB isolated from the blood or lungs. We matched each patient at a 1:2 ratio based on the same DTR Nf-GBN isolated pathogen, and when possible, within the same type of ICU (burn unit or not). The primary endpoint of the study was the clinical cure at 15 days, with secondary endpoints including clinical cure at 30 days, relapse, and in-ICU mortality. For each outcome, adjusted odds ratios were estimated using bidirectional stepwise regression in a final model, which included 13 preselected confounders.
RESULTS
We included 27 patients with cefiderocol, matched with 54 patients receiving the BAT. Four patients were not exactly matched on the type of ICU unit. Characteristics were comparable between groups, mostly male with a Charlson Comorbidity Index of 3 [1-5], and 28% had immunosuppression. Cefiderocol patients were most likely to have higher number of antibiotic lines. The main DTR Nf-GNB identified was Pseudomonas aeruginosa (81.5%), followed by Acinetobater baumanii (14.8%) and Stenotrophomonas maltophilia (3.7%). Pneumonia was the identified infection in 21 (78.8%) patients in the Cefiderocol group and in 51 (94.4%) patients in the BAT group (p = 0.054). Clinical cure at 15 and 30-day and the in-ICU mortality was comparable between groups, however relapse was higher in the cefiderocol group (8-29.6% vs. 4-7.4%;aOR 10.06[1.96;51.53]) CONCLUSION: Cefiderocol did not show an improvement in clinical cure or mortality rates compared to BAT in the treatment of DTR Nf-GNB, but it was associated with a higher relapse rate.
PubMed: 38736016
DOI: 10.1186/s13613-024-01308-z -
ISME Communications Jan 2024While several environmental factors contribute to the evolutionary diversification of the pathogenic bacterium during cystic fibrosis lung infections, relatively little...
While several environmental factors contribute to the evolutionary diversification of the pathogenic bacterium during cystic fibrosis lung infections, relatively little is known about the impact of the surrounding microbiota. By using experimental evolution we show that the presence of , or them both, prevent the evolution of loss of virulence, which repeatedly occurs in the absence of these species due to mutations in regulators of the Quinolone Signal quorum sensing system, and . Moreover, the strength of the effect of co-occurring species is attenuated through changes in the physical environment by the addition of mucin, resulting in selection for phenotypes resembling those evolved in the absence of the co-occurring species. Together, our findings show that variation in mucosal environment and the surrounding polymicrobial environment can determine the evolutionary trajectory of , partly explaining its diversification and pathoadaptation from acute to chronic phenotype during cystic fibrosis lung infections.
PubMed: 38707844
DOI: 10.1093/ismeco/ycae043 -
AMB Express May 2024L-asparaginase is an important therapeutic enzyme that is frequently utilized in the chemotherapy regimens of adults as well as pediatric patients with acute...
L-asparaginase is an important therapeutic enzyme that is frequently utilized in the chemotherapy regimens of adults as well as pediatric patients with acute lymphoblastic leukemia. However, a high rate of hypersensitivity with prolonged use has limited its utilization. Stenotrophomonas maltophilia (S. maltophilia) EMCC2297 isolate was reported as a novel and promising source for L- asparaginase. The present study aimed at the production, purification, and characterization of L- asparaginase from S. maltophilia EMCC2297 isolate. The microbial production of L-asparaginase by the test isolate could be increased by pre-exposure to chloramphenicol at 200 µg/ml concentration. S. maltophilia EMCC2297 L-asparaginase could be purified to homogeneity by ammonium sulphate precipitation and the purified form obtained by gel exclusion chromatography showed total activity of 96.4375 IU/ml and specific activity of 36.251 IU/mg protein. SDS-PAGE analysis revealed that the purified form of the enzyme is separated at an apparent molecular weight of 17 KDa. Michaelis-Menten constant analysis showed a Km value of 4.16 × 10 M with L-asparagine as substrate and Vmax of 10.67 IU/ml. The antitumor activity of the purified enzyme was evaluated on different cell lines and revealed low IC50 of 2.2 IU/ml and 2.83 IU/ml for Hepatocellular cancer cell line (HepG-2), human leukemia cancer cell line (K-562), respectively whereas no cytotoxic effect could be detected on normal human lung fibroblast cells (MRC-5). However, mice treated with native L-asparaginase showed lower IgG titre compared to commercial L-asparaginase. This study highlights the promising characteristics of this enzyme making it a valuable candidate for further research and development to be an adduct in cancer chemotherapy.
PubMed: 38704453
DOI: 10.1186/s13568-024-01700-9 -
Frontiers in Microbiology 2024Chronic infection with in persons with cystic fibrosis (pwCF) has been linked to an increased risk of pulmonary exacerbations and lung function decline. We sought to...
RATIONALE
Chronic infection with in persons with cystic fibrosis (pwCF) has been linked to an increased risk of pulmonary exacerbations and lung function decline. We sought to establish whether baseline sputum microbiome associates with risk of incident infection and persistence in pwCF.
METHODS
pwCF experiencing incident infections attending the Calgary Adult CF Clinic from 2010-2018 were compared with -negative sex, age (+/-2 years), and birth-cohort-matched controls. Infection outcomes were classified as persistent (when the pathogen was recovered in ≥50% of cultures in the subsequent year) or transient. We assessed microbial communities from prospectively biobanked sputum using V3-V4 16S ribosomal RNA (rRNA) gene sequencing, in the year preceding (Pre) ( = 57), at (At) ( = 22), and after (Post) ( = 31) incident infection. We verified relative abundance data using -specific qPCR and 16S rRNA-targeted qPCR to assess bioburden. Strains were typed using pulse-field gel electrophoresis.
RESULTS
Twenty-five pwCF with incident (56% female, median 29 years, median FEV 61%) with 33 total episodes were compared with 56 uninfected pwCF controls. Demographics and clinical characteristics were similar between cohorts. Among those with incident infection, sputum communities did not cluster based on infection timeline (Pre, At, Post). Communities differed between the infection cohort and controls ( = 56) based on Shannon Diversity Index (SDI, = 0.04) and clustered based on Aitchison distance (PERMANOVA, = 0.01) prior to infection. At the time of incident isolation, communities did not differ in SDI but clustered based on Aitchison distance (PERMANOVA, = 0.03) in those that ultimately developed persistent infection versus those that were transient. abundance within sputum was increased in samples from patients (Pre) relative to controls, measuring both relative ( = 0.004) and absolute ( = 0.001). Furthermore, abundance was increased in sputum at incident infection in those who ultimately developed persistent infection relative to those with transient infection, measured relatively ( = 0.04) or absolute ( = 0.04), respectively.
CONCLUSION
Microbial community composition of CF sputum associates with infection acquisition as well as infection outcome. Our study suggests sputum microbiome may serve as a surrogate for identifying infection risk and persistence risk.
PubMed: 38690371
DOI: 10.3389/fmicb.2024.1353145 -
Journal of Chemical Information and... May 2024L2 β-lactamases, serine-based class A β-lactamases expressed by , play a pivotal role in antimicrobial resistance (AMR). However, limited studies have been conducted...
L2 β-lactamases, serine-based class A β-lactamases expressed by , play a pivotal role in antimicrobial resistance (AMR). However, limited studies have been conducted on these important enzymes. To understand the coevolutionary dynamics of L2 β-lactamase, innovative computational methodologies, including adaptive sampling molecular dynamics simulations, and deep learning methods (convolutional variational autoencoders and BindSiteS-CNN) explored conformational changes and correlations within the L2 β-lactamase family together with other representative class A enzymes including SME-1 and KPC-2. This work also investigated the potential role of hydrophobic nodes and binding site residues in facilitating the functional mechanisms. The convergence of analytical approaches utilized in this effort yielded comprehensive insights into the dynamic behavior of the β-lactamases, specifically from an evolutionary standpoint. In addition, this analysis presents a promising approach for understanding how the class A β-lactamases evolve in response to environmental pressure and establishes a theoretical foundation for forthcoming endeavors in drug development aimed at combating AMR.
Topics: beta-Lactamases; Molecular Dynamics Simulation; Deep Learning; Evolution, Molecular; Protein Conformation; Stenotrophomonas maltophilia
PubMed: 38687957
DOI: 10.1021/acs.jcim.4c00189 -
Respiratory Research Apr 2024Children with advanced pulmonary disease due to cystic fibrosis (CF) are at risk of acute respiratory failure due to pulmonary exacerbations leading to their admission...
Acute respiratory failure due to pulmonary exacerbation in children with cystic fibrosis admitted in a pediatric intensive care unit: outcomes and factors associated with mortality.
BACKGROUND
Children with advanced pulmonary disease due to cystic fibrosis (CF) are at risk of acute respiratory failure due to pulmonary exacerbations leading to their admission to pediatric intensive care units (PICU). The objectives of this study were to determine short and medium-term outcomes of children with CF admitted to PICU for acute respiratory failure due to pulmonary exacerbation and to identify prognosis factors.
METHODS
This retrospective monocentric study included patients less than 18 years old admitted to the PICU of a French university hospital between 2000 and 2020. Cox proportional hazard regression methods were used to determine prognosis factors of mortality or lung transplant.
RESULTS
Prior to PICU admission, the 29 patients included (median age 13.5 years) had a severe lung disease (median Forced Expiratory Volume in 1 s percentage predicted at 29%). Mortality rates were respectively 17%, 31%, 34%, 41% at discharge and at 3, 12 and 36 months post-discharge. Survival rates free of lung transplant were 34%, 32%, 24% and 17% respectively. Risk factors associated with mortality or lung transplant using the univariate analysis were female sex and higher pCO2 and chloride levels at PICU admission, and following pre admission characteristics: home respiratory and nutritional support, registration on lung transplant list and Stenotrophomonas Maltophilia bronchial colonization.
CONCLUSION
Children with CF admitted to PICU for acute respiratory failure secondary to pulmonary exacerbations are at high risk of death, both in the short and medium terms. Lung transplant is their main chance of survival and should be considered early.
Topics: Humans; Cystic Fibrosis; Female; Male; Retrospective Studies; Child; Adolescent; Respiratory Insufficiency; Intensive Care Units, Pediatric; Risk Factors; Disease Progression; France; Child, Preschool; Treatment Outcome
PubMed: 38685088
DOI: 10.1186/s12931-024-02778-2 -
MicrobiologyOpen Jun 2024Stenotrophomonas maltophilia is a multidrug-resistant (MDR), Gram-negative bacterium intrinsically resistant to beta-lactams, including last-resort carbapenems. As an...
Stenotrophomonas maltophilia is a multidrug-resistant (MDR), Gram-negative bacterium intrinsically resistant to beta-lactams, including last-resort carbapenems. As an opportunistic pathogen, it can cause serious healthcare-related infections. This study assesses the prevalence, resistance profiles, and genetic diversity of S. maltophilia isolated from residential aged care facilities (RACFs). RACFs are known for their overuse and often inappropriate use of antibiotics, creating a strong selective environment that favors the development of bacterial resistance. The study was conducted on 73 S. maltophilia isolates recovered from wastewater and facility swab samples obtained from three RACFs and a retirement village. Phenotypic and genotypic assessments of the isolates revealed high carbapenem resistance, exemplifying their intrinsic beta-lactam resistance. Alarmingly, 49.3% (36/73) of the isolates were non-wild type for colistin, with minimum inhibitory concentration values of > 4 mg/L, and 11.0% (8/73) were resistant to trimethoprim-sulfamethoxazole. No resistance mechanisms were detected for either antimicrobial. Genotypic assessment of known lineages revealed isolates clustering with Sm17 and Sm18, lineages not previously reported in Australia, suggesting the potential ongoing spread of MDR S. maltophilia. Lastly, although only a few isolates were biocide tolerant (2.7%, 2/73), their ability to grow in high concentrations (64 mg/L) of triclosan is concerning, as it may be selecting for their survival and continued dissemination.
Topics: Stenotrophomonas maltophilia; Drug Resistance, Multiple, Bacterial; Microbial Sensitivity Tests; Humans; Anti-Bacterial Agents; Gram-Negative Bacterial Infections; Genotype; Australia; Wastewater; Prevalence; Genetic Variation; Colistin; Carbapenems; Aged; Residential Facilities
PubMed: 38682784
DOI: 10.1002/mbo3.1409