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Microbiology Spectrum Aug 2023Tuberculosis (TB) is an important infectious disease suffered by many countries, including China. In this stage, accurate diagnosis and treatment are key measures for...
Tuberculosis (TB) is an important infectious disease suffered by many countries, including China. In this stage, accurate diagnosis and treatment are key measures for the prevention and control of TB. Stenotrophomonas maltophilia is a global emerging Gram-negative, multidrug-resistant (MDR) organism characterized by its high contribution to the increase in crude mortality rates. By single cell preparation and strain identification, we isolated S. maltophilia from stored cultures of Mycobacterium tuberculosis (Mtb). We found that S. maltophilia could not be removed from sputum by alkali treatment or inhibited by antibiotic mixture added to MGIT 960 indicator tubes. When co-cultured with Mtb on a Löwenstein-Jensen (L-J) slant, it could inhibit the growth of Mtb and liquefy the medium. More seriously, it was resistant to 10 of the 12 anti-TB drugs, including isoniazid and rifampin, and made the mixed samples display multidrug-resistant Mtb (MDR-TB) results in the drug sensitivity test, which might change a treatment regimen and increase disease burden. Following, we conducted a small-scale surveillance which showed that the isolation rate of S. maltophilia in TB patients was 6.74%, but these patients had no special characteristics and the presence of S. maltophilia was hidden. The effect of on TB and its mechanism are unclear and require more attention. China is a high-burden country for tuberculosis (TB), multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB), and HIV-associated TB. Increasing the positive rate of culture and the accuracy of antibiotic susceptibility testing (AST) are important for diagnosis, treatment, and control of TB. In our study, we found that the isolation rate of Stenotrophomonas maltophilia in TB patients was not neglectable and that this bacterium affects the isolation and AST results of TB. Due to a lack of relevant research, the impact of S. maltophilia on the course and outcome of TB is unclear. However, the characteristics of S. maltophilia that increase disease mortality require attention. Therefore, in the clinical testing of TB, in addition to mycobacteria, it is recommended to increase the detection of co-infected bacteria and improve the awareness of TB clinicians of these bacteria.
Topics: Humans; Stenotrophomonas maltophilia; Antitubercular Agents; Tuberculosis; Mycobacterium tuberculosis; Rifampin; Tuberculosis, Multidrug-Resistant; Microbial Sensitivity Tests
PubMed: 37306591
DOI: 10.1128/spectrum.00944-23 -
Microbiology Spectrum Aug 2023Stenotrophomonas maltophilia is increasingly recognized as an important nosocomial pathogen among the Gram-negative bacteria. Intrinsic resistance to different classes...
Stenotrophomonas maltophilia is increasingly recognized as an important nosocomial pathogen among the Gram-negative bacteria. Intrinsic resistance to different classes of antibiotics makes treatment of infections challenging. A deeper understanding of S. maltophilia physiology and virulence requires molecular genetic tools. Here, we describe the implementation of tetracycline-dependent gene regulation ( regulation) in this bacterium. The exploited regulatory sequence of transposon Tn contained the gene and three intertwined promoters, one of which was required for regulated expression of a target gene or operon. The episomal architecture was tested with a variant as a quantifiable reporter. Fluorescence intensity was directly correlated with the concentration of the inducer anhydrotetracycline (ATc) applied and the duration of induction. Also, the expression of the operon of S. maltophilia K279a was subjected to control. These genes code for the synthesis of dTDP-l-rhamnose, an activated nucleotide sugar precursor of lipopolysaccharide (LPS) formation. A Δ mutant was complemented with a plasmid carrying this operon downstream of the sequence. In the presence of ATc, the LPS pattern was similar to that of wild-type S. maltophilia, whereas without the inducer, fewer and apparently shorter O-antigen chains were detected. This underscores the functionality and usefulness of the system for gene regulation and, prospectively, the validation of targets for new anti-S. maltophilia drugs. Stenotrophomonas maltophilia is an emerging pathogen in hospital settings and poses a threat to immunocompromised patients. Due to a high level of resistance to different types of antibiotics, treatment options are limited. We here adapted a tool for inducible expression of genes of interest, known as the system, to S. maltophilia. Genes relevant to producing surface carbohydrate structures (lipopolysaccharide [LPS]) were placed under the control of the system. In the presence of an inducer, the LPS pattern was similar to that of wild-type S. maltophilia, whereas in the "off" state of the system (without inducer), fewer and apparently shorter versions of LPS were detected. The system is functional in S. maltophilia and may be helpful to reveal gene-function relationships to gain a deeper understanding of the bacterium's physiology and virulence.
Topics: Humans; Stenotrophomonas maltophilia; Lipopolysaccharides; Anti-Bacterial Agents; Gene Expression
PubMed: 37378537
DOI: 10.1128/spectrum.01576-23 -
Cureus Jun 2022Stenotrophomonas maltophilia, a gram-negative bacillus well known to cause respiratory tract infections, is increasingly being reported to cause urinary tract infections... (Review)
Review
Stenotrophomonas maltophilia, a gram-negative bacillus well known to cause respiratory tract infections, is increasingly being reported to cause urinary tract infections (UTI). In our review of the literature comprising six articles, males were more prone to developing UTIs, with the mean age of the patients being 62.5 ±18.9 years. While several risk factors have been associated with the development of the disease, patients with underlying urological or nephrological diseases tend to develop a more severe illness. The organism was sensitive to trimethoprim-sulfamethoxazole (TMP-SMX) in the majority of cases. This systematic review also aims to shed light on the possible mechanisms of resistance adopted by the bacteria, modes of transmission, and strategies to prevent the transmission and development of the disease.
PubMed: 35891807
DOI: 10.7759/cureus.26184 -
Journal of Clinical Microbiology Aug 2021Stenotrophomonas maltophilia is intrinsically resistant to many beta-lactam antibiotics, including carbapenems, and is resistant to aminoglycosides, which limits the...
Stenotrophomonas maltophilia is intrinsically resistant to many beta-lactam antibiotics, including carbapenems, and is resistant to aminoglycosides, which limits the therapeutic repertoire for managing S. maltophilia infections. Additionally, employing automated susceptibility testing of S. maltophilia is challenging because commercial test systems' performance is limited (A. Khan, C. A. Arias, A. Abbott, J. Dien Bard, et al., J Clin Microbiol 59:e00654-21, 2021, https://doi.org/10.1128/JCM.00654-21). This commentary will briefly discuss the opportunity to use automated commercial susceptibility testing systems with S. maltophilia, with a focus on how to implement their use practically while mitigating risk of error.
Topics: Aminoglycosides; Anti-Bacterial Agents; Carbapenems; Gram-Negative Bacterial Infections; Humans; Microbial Sensitivity Tests; Stenotrophomonas maltophilia
PubMed: 34190573
DOI: 10.1128/JCM.01094-21 -
Infectious Diseases & Clinical... Dec 2022There are many difficulties in diagnosing and treating bacteremia. In this study, we aimed to evaluate "true" and "false-positive bacteremia" and assess mortality risk...
OBJECTIVE
There are many difficulties in diagnosing and treating bacteremia. In this study, we aimed to evaluate "true" and "false-positive bacteremia" and assess mortality risk factors and the impact of different treatment regimens.
MATERIALS AND METHODS
Hospitalized adult patients with -positive blood cultures were assessed by a two-stage analysis. First, the clinical significance of blood cultures was assessed, and patients were divided into "true" and "false-positive bacteremia" groups. Then, excluding false positives, we analyzed the antimicrobial regimens and the factors associated with 28-day mortality in true bacteremia cases performing univariate and multivariate analyses.
RESULTS
The study included 127 out of 138 patients with bacteremia. True bacteremia was identified in 51.2% and false-positive bacteremia in 48.8% of patients. In the true bacteremia group, hypotension, nosocomial bacteremia, concomitant infections, a source of bacteremia, two positive blood culture sets, and 28-day mortality were more common. The 28-day mortality was 50.7% among true bacteremia cases. In multivariate analysis, age and solid tumor were the independent predictors of 28-day mortality. Early effective antimicrobial therapy and different antimicrobial regimens, including trimethoprim-sulfamethoxazole (SXT), fluoroquinolones (FQs), and tigecycline (TGC), did not have any significant impact on survival.
CONCLUSION
Patients with bacteremia should first be assessed regarding clinical significance. Clinical findings, the presence of multiple positive blood culture sets and the primary sources of bacteremia are useful parameters while discriminating true from false-positive bacteremia. Patients with advanced age and solid tumors should be followed carefully in terms of mortality. Antimicrobial regimens, including SXT, FQs, or TGC, can be preferred in patients with bacteremia considering antimicrobial resistance and adverse effects or toxicity.
PubMed: 38633723
DOI: 10.36519/idcm.2022.187 -
Journal of Bacteriology Jan 2022Stenotrophomonas maltophilia has recently arisen as a prominent nosocomial pathogen because of its high antimicrobial resistance and ability to cause chronic respiratory...
Stenotrophomonas maltophilia has recently arisen as a prominent nosocomial pathogen because of its high antimicrobial resistance and ability to cause chronic respiratory infections. Often the infections are worsened by biofilm formation which enhances antibiotic tolerance. We have previously found that mutation of the gene, encoding the glycolytic enzyme phosphoglycerate mutase, impacts the formation of this biofilm on biotic and abiotic surfaces at early time points. This finding, indicating an association between carbon source and biofilm formation, led us to hypothesize that metabolism would influence S. maltophilia biofilm formation and planktonic growth. In the present study, we tested the impact of various growth substrates on biofilm levels and growth kinetics to determine metabolic requirements for these processes. We found that S. maltophilia wild type preferred amino acids versus glucose for planktonic and biofilm growth and that deletion inhibited growth in amino acids. Furthermore, supplementation of the Δ strain by glucose or ribose phenotypically complemented growth defects. These results suggest that S. maltophilia shuttles amino acid carbon through gluconeogenesis to an undefined metabolic pathway supporting planktonic and biofilm growth. Further evaluation of these metabolic pathways might reveal novel metabolic activities of this pathogen. Stenotrophomonas maltophilia is a prominent opportunistic pathogen that often forms biofilms during infection. However, the molecular mechanisms of virulence and biofilm formation are poorly understood. The glycolytic enzyme phosphoglycerate mutase appears to play a role in biofilm formation, and we used a mutant in its gene () to probe the metabolic circuitry potentially involved in biofilm development. The results of our study indicate that S. maltophilia displays unique metabolic activities, which could be exploited for inhibiting growth and biofilm formation of this pathogen.
Topics: Amino Acids; Bacterial Proteins; Biofilms; Culture Media; Gene Expression Regulation, Bacterial; Metabolic Networks and Pathways; Ribose; Stenotrophomonas maltophilia
PubMed: 34633868
DOI: 10.1128/JB.00398-21 -
Antimicrobial Resistance and Infection... Jan 2021Stenotrophomonas maltophilia (S. maltophilia) is an opportunistic and nosocomial pathogen that can cause an invasive and fatal infection, particularly in hospitalized...
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.
Topics: Adolescent; Anti-Bacterial Agents; Catheter-Related Infections; Child; Child, Preschool; Cross Infection; Female; Gram-Negative Bacterial Infections; Humans; Infant; Intensive Care Units; Male; Microbial Sensitivity Tests; Neutropenia; Retrospective Studies; Risk Factors; Saudi Arabia; Stenotrophomonas maltophilia
PubMed: 33482916
DOI: 10.1186/s13756-021-00888-w -
Ophthalmology and Therapy Sep 2021Stenotrophomonas maltophilia keratitis is an uncommon infectious disease of the cornea. The clinical features, antibiotic susceptibility, and clinical outcomes of S....
INTRODUCTION
Stenotrophomonas maltophilia keratitis is an uncommon infectious disease of the cornea. The clinical features, antibiotic susceptibility, and clinical outcomes of S. maltophilia keratitis were investigated in this study.
METHODS
Between January 2015 and February 2020, the medical records of 16 patients with culture-proven S. maltophilia-associated infectious keratitis were retrospectively reviewed. Clinical data were analyzed regarding risk factors, clinical presentation, antibiotic susceptibility, and clinical outcomes.
RESULTS
The average age of the patients was 56.24 ± 24.84 years. The most common risk factors for S. maltophilia keratitis were trauma (6/16, 37.5%), use of contact lenses (6/16, 37.5%), and herpes simplex virus keratitis (3/16, 18.8%), which caused ocular instability. Regarding the antibiotic sensitivities, most isolates (15/16, 93.8%) were susceptible to fluoroquinolones, 87.5% (14/16) of them to aminoglycosides, and 81.3% (13/16) of them to beta-lactams. Patients were classified into two groups according to the initial antibiotic eye drops, and there were significant differences in the final visual acuity between two groups: mixed fluoroquinolone, beta-lactam, aminoglycoside group, and mixed beta-lactam and aminoglycoside groups (p = 0.039).
CONCLUSION
Ocular infection due to S. maltophilia is an opportunistic infection followed by instability of the ocular surface. In cases of S. maltophilia infection, mixed use of fluoroquinolone, beta-lactam, and aminoglycoside should be considered for treatment of choice.
PubMed: 33982273
DOI: 10.1007/s40123-021-00348-z -
Open Forum Infectious Diseases May 2022is an underappreciated source of morbidity and mortality among gram-negative pathogens. Effective treatment options with acceptable toxicity profiles are limited.... (Review)
Review
is an underappreciated source of morbidity and mortality among gram-negative pathogens. Effective treatment options with acceptable toxicity profiles are limited. Phenotypic susceptibility testing via commercial automated test systems is problematic and no Food and Drug Administration breakpoints are approved for any of the first-line treatment options for . The lack of modern pharmacokinetic/pharmacodynamic data for many agents impedes dose optimization, and the lack of robust efficacy and safety data limits their clinical utility. Levofloxacin has demonstrated similar efficacy to trimethoprim-sulfamethoxazole, although rapid development of resistance is a concern. Minocycline demonstrates the highest rate of in vitro susceptibility, however, evidence to support its clinical use are scant. Novel agents such as cefiderocol have exhibited promising activity in preclinical investigations, though additional outcomes data are needed to determine its place in therapy for . Combination therapy is often employed despite the dearth of adequate supporting data.
PubMed: 35415194
DOI: 10.1093/ofid/ofac095 -
Acta Crystallographica. Section F,... Jul 2023The resistance of the emerging human pathogen Stenotrophomonas maltophilia to tetracycline antibiotics mainly depends on multidrug efflux pumps and ribosomal protection...
The resistance of the emerging human pathogen Stenotrophomonas maltophilia to tetracycline antibiotics mainly depends on multidrug efflux pumps and ribosomal protection enzymes. However, the genomes of several strains of this Gram-negative bacterium code for a FAD-dependent monooxygenase (SmTetX) homologous to tetracycline destructases. This protein was recombinantly produced and its structure and function were investigated. Activity assays using SmTetX showed its ability to modify oxytetracycline with a catalytic rate comparable to those of other destructases. SmTetX shares its fold with the tetracycline destructase TetX from Bacteroides thetaiotaomicron; however, its active site possesses an aromatic region that is unique in this enzyme family. A docking study confirmed tetracycline and its analogues to be the preferred binders amongst various classes of antibiotics.
Topics: Humans; Stenotrophomonas maltophilia; Crystallography, X-Ray; Anti-Bacterial Agents; Tetracycline; Oxytetracycline; Microbial Sensitivity Tests
PubMed: 37405486
DOI: 10.1107/S2053230X23005381