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Infection and Immunity Mar 2020is a Gram-negative bacterium found ubiquitously in the environment that has historically been regarded as nonpathogenic. is increasingly observed in patient sputa in...
is a Gram-negative bacterium found ubiquitously in the environment that has historically been regarded as nonpathogenic. is increasingly observed in patient sputa in cystic fibrosis (CF), and while existing epidemiology indicates that patients with have poorer diagnoses, its clinical significance remains unclear. Moreover, as multidrug resistance is common among isolates, treatment options for these infections may be limited. Here, we investigated the pathogenicity of alone and during polymicrobial infection with Colonization, persistence, and virulence of were assessed in experimental respiratory infections of mice. The results of this study indicate that transiently colonizes the lung accompanied by significant weight loss and immune cell infiltration and the expression of early inflammatory markers, including interleukin 6 (IL-6), IL-1α, and tumor necrosis factor alpha (TNF-α). Importantly, polymicrobial infection with elicited significantly higher counts in bronchoalveolar lavages and lung tissue homogenates. This increase in bacterial load was directly correlated with the density of the population and required viable bacteria. Microscopic analysis of biofilms formed revealed that formed well-integrated biofilms with , and these organisms colocalize in the lung during dual-species infection. Based on these results, we conclude that active cellular processes by afford a significant benefit to during polymicrobial infections. Furthermore, these results indicate that may have clinical significance in respiratory infections.
Topics: Animals; Bacterial Load; Body Weight; Bronchoalveolar Lavage Fluid; Coinfection; Disease Models, Animal; Gram-Negative Bacterial Infections; Immunity, Innate; Lung; Mice; Microbial Interactions; Pneumonia, Bacterial; Pseudomonas aeruginosa; Stenotrophomonas maltophilia
PubMed: 31932329
DOI: 10.1128/IAI.00855-19 -
Antimicrobial Agents and Chemotherapy Mar 2021Cefiderocol is a novel siderophore cephalosporin antibiotic with broad coverage against difficult-to-treat Gram-negative bacteria, including those resistant to...
Cefiderocol is a novel siderophore cephalosporin antibiotic with broad coverage against difficult-to-treat Gram-negative bacteria, including those resistant to carbapenems. Its activity against was investigated against clinical isolates and in lung infection models using strains either resistant (SR202006) or susceptible (SR201934, SR200614) to trimethoprim-sulfamethoxazole. Cefiderocol demonstrated potent activity against all 217 clinical isolates tested (MIC, 0.063 μg/ml; MIC, 0.25 μg/ml). Cefiderocol also demonstrated low MICs against the trimethoprim-sulfamethoxazole-resistant strains (i.e., SR202006; MIC, 0.125 μg/ml). In a neutropenic mouse lung infection model, cefiderocol (30 mg/kg body weight and 100 mg/kg) demonstrated a significant, dose-dependent reduction in the lung viable bacteria cell count compared with untreated controls in infection and was the only antibiotic tested to show a similar significant effect in a trimethoprim-sulfamethoxazole-resistant infection. In immunocompetent rat lung infection models of , humanized dosing of cefiderocol (2 g every 8 h) and meropenem (1 g every 8 h) revealed pharmacokinetic profiles similar to those in human subjects, and the humanized cefiderocol dosing significantly reduced the lung viable bacteria cell count compared with baseline controls, which received no intervention. Together, the results from these studies suggest that cefiderocol could provide an effective alternative treatment option for infections in the lower respiratory tract, particularly strains resistant to empirical antibiotics, such as trimethoprim-sulfamethoxazole or minocycline.
Topics: Animals; Anti-Bacterial Agents; Cephalosporins; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Microbial Sensitivity Tests; Rats; Stenotrophomonas maltophilia; Cefiderocol
PubMed: 33526491
DOI: 10.1128/AAC.01436-20 -
Polish Journal of Microbiology Sep 2023This work investigated the genetic relationship among strains in fecal samples from dairy cows in northeast China and identified the dominant β-lactamase genotype. One...
This work investigated the genetic relationship among strains in fecal samples from dairy cows in northeast China and identified the dominant β-lactamase genotype. One hundred and six samples were collected from two randomly selected cow farms in northeast China, and the isolates were identified with MALDI-TOF/MS. Whole-genome sequencing was conducted using Illumina HiSeq 4000-PE150 platform (Illumina, Inc., USA). The antimicrobial resistance genes were detected using CGE services. The phylogenetic analysis of strains was performed by Roary and MEGA X. In total, 24 isolates were isolated. The results of resistome analysis showed all strains carrying gene, which was the only β-lactamase genotype. In addition, the aminoglycoside resistance genes and were found. The phylogenetic tree indicated the clonal diversity of in these two regions and the clonal relatedness of the strains from these regions. This study first investigated the dissemination and characterization of isolates from dairy cows in northeast China and provided evidence of the potential transmission between two provinces. Furthermore, it indicated was the most prevalent genotype of β-lactamase in these regions.
Topics: Animals; Female; Cattle; Stenotrophomonas maltophilia; Phylogeny; China; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; beta-Lactamases
PubMed: 37725894
DOI: 10.33073/pjm-2023-032 -
Infectious Diseases (London, England) May 2024() is a nosocomial pathogen causing life-threatening invasive infections with a high mortality rate in some patient populations, especially those who are severely ill... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
() 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 bacteremia.
OBJECTIVE
In this meta-analysis, we aimed to investigate risk factors for mortality in bacteremia.
METHODS
Studies comparing patients who died from 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 bacteremia. Indwelling central venous catheter, neutropenia, hematological malignancies and chronic kidney disease were also risk factors for mortality.
Topics: Humans; Stenotrophomonas maltophilia; Retrospective Studies; Gram-Negative Bacterial Infections; Risk Factors; Anti-Bacterial Agents; Hematologic Neoplasms; Bacteremia; Cross Infection; Neutropenia; Renal Insufficiency, Chronic
PubMed: 38436567
DOI: 10.1080/23744235.2024.2324365 -
Clinics in Chest Medicine Dec 2022Patients with cystic fibrosis (CF) often develop respiratory tract infections with pathogenic multidrug-resistant organisms (MDROs) such as methicillin-resistant... (Review)
Review
Patients with cystic fibrosis (CF) often develop respiratory tract infections with pathogenic multidrug-resistant organisms (MDROs) such as methicillin-resistant Staphylococcus aureus, and a variety of gram-negative organisms that include Pseudomonas aeruginosa, Burkholderia sp., Stenotrophomonas maltophilia, Achromobacter xylosoxidans, and nontuberculous mycobacteria (NTM). Despite the introduction of new therapies to address underlying cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction, MDRO infections remain a problem and novel antimicrobial interventions are still needed. Therapeutic approaches include improving the efficacy of existing drugs by adjusting the dose based on differences in CF patient pharmacokinetics/pharmacodynamics, the development of inhaled formulations to reduce systemic adverse events, and the use of newer beta-lactam/beta-lactamase combinations. Alternative innovative therapeutic approaches include the use of gallium and bacteriophages to treat MDRO pulmonary infections including those with extreme antibiotic resistance. However, additional clinical trials are required to determine the optimal dosing and efficacy of these different strategies and to identify patients with CF most likely to benefit from these new treatment options.
Topics: Humans; Cystic Fibrosis; Methicillin-Resistant Staphylococcus aureus; Stenotrophomonas maltophilia; Pseudomonas aeruginosa; Respiratory Tract Infections; Anti-Bacterial Agents; Pseudomonas Infections
PubMed: 36344073
DOI: 10.1016/j.ccm.2022.06.008 -
Iranian Journal of Microbiology Apr 2024is an opportunistic pathogen causing nosocomial infections. Diclofenac is an anti-inflammatory drug that is considered a non-antibiotic drug. This study assessed the...
BACKGROUND AND OBJECTIVES
is an opportunistic pathogen causing nosocomial infections. Diclofenac is an anti-inflammatory drug that is considered a non-antibiotic drug. This study assessed the antibacterial and antibiofilm effects of diclofenac and levofloxacin/diclofenac combination against levofloxacin resistant isolates.
MATERIALS AND METHODS
Minimum inhibitory concentration was determined using broth microdilution method for levofloxacin, diclofenac, and levofloxacin/diclofenac combination. Biofilm forming capacity and biofilm inhibition assay were determined. Relative gene expression was measured for efflux pump genes; , and genes and biofilm related genes , and without and with diclofenac and the combination.
RESULTS
Diclofenac demonstrated MIC of 1 mg/ml. The combination-with ½ MIC diclofenac-showed synergism where levofloxacin MIC undergone 16-32 fold decrease. All the isolates that overexpressed and showed a significant decrease in gene expression in presence of diclofenac or the combination. The mean percentage inhibition of biofilm formation with diclofenac and the combination was 40.59% and 46.49%, respectively. This agreed with biofilm related genes expression investigations.
CONCLUSION
Diclofenac showed an antibacterial effect against The combination showed synergism, significant reduction in biofilm formation and in the relative level of gene expression. Furthermore, it can potentiate the levofloxacin activity or revert its resistance.
PubMed: 38854979
DOI: 10.18502/ijm.v16i2.15349 -
Research in Microbiology 2022Maltocin P28, produced by Stenotrophomonas maltophilia P28, is an R-type phage tail-like bacteriocin (PTLB). Its gene cluster consists of 23 putative genes, including...
Maltocin P28, produced by Stenotrophomonas maltophilia P28, is an R-type phage tail-like bacteriocin (PTLB). Its gene cluster consists of 23 putative genes, including nine nonstructural genes and fourteen structural genes. In this work, three nonstructural genes, mpsA, mpsH and mpsR, were found to encode transcriptional regulators to control maltocin P28 synthesis. MpsA activated the transcription of mpsH and lysis genes. MpsH activated the transcription of structural genes. Under normal growth conditions, MpsR repressed the transcription of mpsA and the structural genes, as well as its own. When S. maltophilia P28 was treated with mitomycin C, an immediate and significant decrease in the amount of MpsR was observed, followed by derepressed expression of mpsA, mpsR and structural genes, a marked rise in the expression of all regulatory and structural genes, and finally a clear increase in the maltocin P28 production. Neither the recA gene nor the lexA gene was found to be involved in the induced synthesis of maltocin P28. Our study indicated that a unique mechanism regulates the expression of maltocin genes in S. maltophilia, representing a novel strategy for balancing the expression of PTLB genes in bacteria.
Topics: Bacteriocins; Multigene Family; Stenotrophomonas maltophilia
PubMed: 35569725
DOI: 10.1016/j.resmic.2022.103956 -
Antibiotics (Basel, Switzerland) Oct 2021is an urgent global threat due to its increasing incidence and intrinsic antibiotic resistance. Antibiotic development has focused on carbapenem-resistant... (Review)
Review
is an urgent global threat due to its increasing incidence and intrinsic antibiotic resistance. Antibiotic development has focused on carbapenem-resistant Enterobacteriaceae, Pseudomonas, and Acinetobacter, with approved antibiotics in recent years having limited activity for Stenotrophomonas. Accordingly, novel treatment strategies for Stenotrophomonas are desperately needed. We conducted a systemic literature review and offer recommendations based on current evidence for a treatment strategy of Stenotrophomonas infection.
PubMed: 34680807
DOI: 10.3390/antibiotics10101226 -
Journal of Applied Genetics May 2023Stenotrophomonas maltophilia is a species with immensely broad phenotypic and genotypic diversity that could widely distribute in natural and clinical environments....
Stenotrophomonas maltophilia is a species with immensely broad phenotypic and genotypic diversity that could widely distribute in natural and clinical environments. However, little attention has been paid to reveal their genome plasticity to diverse environments. In the present study, a comparative genomic analysis of S. maltophilia isolated from clinical and natural sources was systematically explored its genetic diversity of 42 sequenced genomes. The results showed that S. maltophilia owned an open pan-genome and had strong adaptability to different environments. A total of 1612 core genes were existed with an average of 39.43% of each genome, and the shared core genes might be necessary to maintain the basic characteristics of those S. maltophilia strains. Based on the results of the phylogenetic tree, the ANI value, and the distribution of accessory genes, genes associated with the fundamental process of those strains from the same habitat were found to be mostly conserved in evolution. Isolates from the same habitat had a high degree of similarity in COG category, and the most significant KEGG pathways were mainly involved in carbohydrate and amino acid metabolism, indicating that genes related to essential processes were mostly conserved in evolution for the clinical and environmental settings. Meanwhile, the number of resistance and efflux pump gene was significantly higher in the clinical setting than that of in the environmental setting. Collectively, this study highlights the evolutionary relationships of S. maltophilia isolated from clinical and environmental sources, shedding new light on its genomic diversity.
Topics: Stenotrophomonas maltophilia; Phylogeny; Phenotype; Genomics; Genetic Variation
PubMed: 36892794
DOI: 10.1007/s13353-023-00752-0 -
Virus Research Jun 2022Stenotrophomonas maltophilia (S. maltophilia) is an important Gram-negative opportunistic pathogen that is widely distributed in nature. S. maltophilia is highly...
Stenotrophomonas maltophilia (S. maltophilia) is an important Gram-negative opportunistic pathogen that is widely distributed in nature. S. maltophilia is highly drug-resistant because of its intrinsic properties and acquired drug resistance involving multiple molecular mechanisms, which creates a critical situation for infection therapy. Hence, there is an urgent need for alternative antimicrobial strategies to combat S. maltophilia. Herein, a novel S. maltophilia bacteriophage (phage) in family Podoviridae, named BUCT598, was isolated from hospital sewage and characterized to evaluate its potential as an antibacterial agent. The one-step growth curve showed that its latent period and burst size were approximately 30 min and 165 PFU/cell, respectively. Furthermore, phage BUCT598 survived within an extremely broad pH range (1-11), indicating its outstanding tolerance to both extremely acidic and extremely alkaline conditions. The whole-genome sequence of phage BUCT598 showed that it was a linear double-stranded DNA genome of 43,581 bp and 60% GC content. We identified 55 putative gene products involved in DNA replication, packaging, structure, and cell lysis. Whole-genome sequence comparisons among closely related phages indicated that phage BUCT598 had the highest sequence similarity with S. maltophilia phage BUCT609, with 52% query coverage and 76.40% identity, suggesting that it is a novel phage. Our findings indicate the great potential of phage BUCT598 as an alternative antimicrobial agent to eliminate S. maltophilia, and provide additional evidence that will help to understand how phages adapt and evolve under extreme environmental conditions, thereby opening up more extensive biotechnology applications of phages.
Topics: Bacteriophages; Genome, Viral; Hydrogen-Ion Concentration; Podoviridae; Stenotrophomonas maltophilia
PubMed: 35307481
DOI: 10.1016/j.virusres.2022.198751