Understanding the rationale and clinical impact of the revised CLSI 2024 minocycline susceptibility breakpoints against Stenotrophomonas maltophilia.

Stenotrophomonas maltophilia is challenging to treat due to the presence of multiple intrinsic and acquired resistance mechanisms. TMP-SMZ is the standard care of therapy for treating S. maltophilia infections; levofloxavin and minocycline are the preferred potential alternatives. Recently, in 2024, CLSI has lowered the susceptibility breakpoints for minocycline against S. maltophilia. Applying the revised minocycline's susceptibility breakpoint of ≤ 1 mg/L, susceptibility to minocycline dropped significantly from 77% (previous breakpoint, ≤ 4 mg/L) to 35% (revised breakpoint of ≤ 1 mg/L). In the wake of this change, minocycline's dependency has been questioned for treating S. maltophilia infections.

Preparation and optimization of hydrophilic modified pullulan encapsulated tetracycline for significant antibacterial and anti-biofilm activity against Stenotrophomonas maltophilia isolates.

The study aimed to assess the effectiveness of these formulations against  S. maltophilia in terms of their antimicrobial and anti-biofilm properties. The physicochemical characteristics of HM-PULL-Tetracycline were analyzed using a field scanning electron microscope, X-ray dispersion, Zeta potential, and dynamic light scattering analysis. The antibacterial and anti-biofilm activity was assessed using minimal biofilm inhibitory concentration and broth micro-dilution. In addition, the biocompatibility of HM-PULL-Tetracycline was assessed by investigating its cytotoxicity on the human diploid fibroblasts (HDF) normal cell line using the MTT test. The HM-PULL-Tetracycline formulation successfully prevented biofilm formation, measuring 179.7± 2.66 nm in size and with an encapsulation efficiency of 84.86± 3.14%. It exhibited a biofilm growth inhibition rating of 69% and significantly down-regulated the expression of the smf-1, rpfF, rmlA, and spgM biofilm genes in S. maltophilia strains (p<0.05). Furthermore, the HM-PULL-Tetracycline formulation exhibited a 4 to 6-fold increase in antibacterial efficacy compared to unbound tetracycline. The HM-PULL-Tetracycline formulation demonstrated cell viability of over 90% at all doses tested against HDF normal cells. The findings of the current investigation demonstrate that HM-PULL-Tetracycline enhances the bactericidal and anti-biofilm properties without causing harm to healthy human cells. This suggests that Could be a promising approach for medication administration.

Advances in the Microbiology of Stenotrophomonas maltophilia.

Stenotrophomonas maltophilia is an opportunistic pathogen of significant concern to susceptible patient populations. This pathogen can cause nosocomial and community-acquired respiratory and bloodstream infections and various other infections in humans. Sources include water, plant rhizospheres, animals, and foods. Studies of the genetic heterogeneity of S. maltophilia strains have identified several new genogroups and suggested adaptation of this pathogen to its habitats. The mechanisms used by S. maltophilia during pathogenesis continue to be uncovered and explored. S. maltophilia virulence factors include use of motility, biofilm formation, iron acquisition mechanisms, outer membrane components, protein secretion systems, extracellular enzymes, and antimicrobial resistance mechanisms. S. maltophilia is intrinsically drug resistant to an array of different antibiotics and uses a broad arsenal to protect itself against antimicrobials. Surveillance studies have recorded increases in drug resistance for S. maltophilia, prompting new strategies to be developed against this opportunist. The interactions of this environmental bacterium with other microorganisms are being elucidated. S. maltophilia and its products have applications in biotechnology, including agriculture, biocontrol, and bioremediation.

Characterization and Genomic Analysis of ɸSHP3, a New Transposable Bacteriophage Infecting Stenotrophomonas maltophilia.

This study describes a novel transposable bacteriophage, ɸSHP3, continuously released by Stenotrophomonas maltophilia strain c31. Morphological observation and genomic analysis revealed that ɸSHP3 is a siphovirus with a 37,611-bp genome that encodes 51 putative proteins. Genomic comparisons indicated that ɸSHP3 is a B3-like transposable phage. Its genome configuration is similar to that of Pseudomonas phage B3, except for the DNA modification module. Similar to B3-like phages, the putative transposase B of ɸSHP3 is a homolog of the type two secretion component ExeA, which is proposed to serve as a potential virulence factor. Moreover, most proteins of ɸSHP3 have homologs in transposable phages, but only ɸSHP3 carries an RdgC-like protein encoded by gene 3, which exhibits exonuclease activity in vitro Two genes and their promoters coding for ɸSHP3 regulatory proteins were identified and appear to control the lytic-lysogenic switch. One of the proteins represses one promoter activity and confers immunity to ɸSHP3 superinfection in vivo The short regulatory region, in addition to the canonical bacterial promoter sequences, displays one LexA and two CpxR recognition sequences. This suggests that LexA and the CpxR/CpxA two-component system might be involved in the control of the ɸSHP3 genetic switch.IMPORTANCES. maltophilia is an emerging global pathogenic bacterium that displays genetic diversity in both environmental and clinical strains. Transposable phages have long been known to improve the genetic diversity of bacterial strains by transposition. More than a dozen phages of S. maltophilia have been characterized. However, no transposable phage infecting S. maltophilia has been reported to date. Characterization of the first transposable phage, ɸSHP3, from S. maltophilia will contribute to our understanding of host-phage interactions and genetic diversity, especially the interchange of genetic materials among S. maltophilia.

Avibactam Restores the Susceptibility of Clinical Isolates of Stenotrophomonas maltophilia to Aztreonam.

Stenotrophomonas maltophilia is an emerging opportunistic pathogen, classified by the World Health Organization as one of the leading multidrug-resistant organisms in hospital settings. The need to discover novel compounds and/or combination therapies for S. maltophilia is urgent. We demonstrate the in vitro efficacy of aztreonam-avibactam (ATM-AVI) against S. maltophilia and kinetically characterize the inhibition of the L2 ß-lactamase by avibactam. ATM-AVI overcomes aztreonam resistance in selected clinical strains of S. maltophilia, addressing an unmet medical need.

Synthetic Peptides Derived from Bovine Lactoferricin Exhibit Antimicrobial Activity against E. coli ATCC 11775, S. maltophilia ATCC 13636 and S. enteritidis ATCC 13076.

Linear, dimeric, tetrameric, and cyclic peptides derived from lactoferricin B-containing non-natural amino acids and the RWQWR motif were synthesized, purified, and characterized using RP-HPLC, MALDI-TOF mass spectrometry, and circular dichroism. The antibacterial activity of peptides against Escherichia coli ATCC 11775, Stenotrophomonas maltophilia ATCC 13636, and Salmonella enteritidis ATCC 13076 was evaluated. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined. The synthetic bovine lactoferricin exhibited antibacterial activity against E. coli ATCC 11775 and S. enteritidis ATCC 13076. The dimeric peptide (RRWQWR)2K-Ahx exhibited the highest antibacterial activity against the tested bacterial strain. The monomeric, cyclic, tetrameric, and palindromic peptides containing the RWQWR motif exhibited high and specific activity against E. coli ATCC 11775. The results suggest that short peptides derived from lactoferricin B could be considered as potential candidates for the development of antibacterial agents against infections caused by E. coli.

Stenotrophomonas maltophilia Outbreak in an ICU: Investigation of Possible Routes of Transmission and Implementation of Infection Control Measures.

Stenotrophomonas maltophilia, a non-fermentative, ubiquitous, gram-negative aerobic bacterium, is associated with high mortality rates, particularly in immunocompromised or debilitated patients. The prevalence rate of ICU-acquired pneumonia episodes caused by this microorganism has been found to be 2%. S. maltophilia has been identified as one of the top 10 microorganisms responsible for such infections in EU/EEA countries. This study describes an outbreak of S. maltophilia in an intensive care unit of a hospital in northern Italy. This includes an epidemiological investigation of the cases, the environmental microbiological controls carried out, a comparison of the strains by multilocus sequence typing (MLST), and the measures taken to prevent and control the outbreak. Among the seven clinical isolates of S. maltophilia analyzed herein, six demonstrated susceptibilities to trimethoprim-sulfamethoxazole. Conversely, one isolate of S. maltophilia exhibited resistance to first-line antibiotics. ST was found to be identical for six patients (ST 4), as well as in the environmental feedback on the trolley of Box 2. The analysis of the temporal and spatial progression of the outbreak has suggested that the transmission of S. maltophilia may have occurred through cross-transmission during care practices.

Stenotrophomonas maltophilia contributes to smoking-related emphysema through IRF1-triggered PANoptosis of alveolar epithelial cells.

Cigarette smoke (CS), the main source of indoor air pollution and the primary risk factor for respiratory diseases, contains chemicals that can perturb microbiota through antibiotic effects. Although smoking induces a disturbance of microbiota in the lower respiratory tract, whether and how it contributes to initiation or promotion of emphysema are not well clarified. Here, we demonstrated an aberrant microbiome in lung tissue of patients with smoking-related COPD. We found that Stenotrophomonas maltophilia (S. maltophilia) was expanded in lung tissue of patients with smoking-related COPD. We revealed that S. maltophilia drives PANoptosis in alveolar epithelial cells and represses formation of alveolar organoids through IRF1 (interferon regulatory factor 1). Mechanistically, IRF1 accelerated transcription of ZBP1 (Z-DNA Binding Protein 1) in S. maltophilia-infected alveolar epithelial cells. Elevated ZBP1 served as a component of the PANoptosome, which triggered PANoptosis in these cells. By using of alveolar organoids infected by S. maltophilia, we found that targeting of IRF1 mitigated S. maltophilia-induced injury of these organoids. Moreover, the expansion of S. maltophilia and the expression of IRF1 negatively correlated with the progression of emphysema. Thus, the present study provides insights into the mechanism of lung dysbiosis in smoking-related COPD, and presents a potential target for mitigation of COPD progression.

Effects of various substances on the binding of keratin monomers to S. maltophilia DHHJ cells for the induction of keratinase production.

Biodegradation effectiveness of S. maltophilia DHHJ is determined by its ability to attach to the hydrolyzed feather keratin monomers. This binding capacity can be influenced by many components in the culture medium. Keratin monomers from feathers or those produced by gene overexpression can induce keratinase production in S. maltophilia DHHJ, and several proteases lack the ability to degrade keratin fragments and cysteines. In this study, we co-incubated FITC-labelled keratin monomers with S. maltophilia DHHJ cells in the presence of BSA, DNA, ATP, and several metal ions, and measured fluorescence values and keratinase activity. BSA was found to compete with keratins for cell binding sites, resulting in less keratinase production. DNA did not interfere with cellular binding to keratins revealing unchanged keratinase level. ATP, along with metal ions, enhanced the cellular binding capacity to keratins and increased the production of keratinase by S. maltophilia DHHJ. Fragments of keratin monomers degraded by proteases reduced the ability of cells to bind to keratin and affected enzyme production. Cysteine, a characteristic amino acid of feather keratin, did not have an effect on cellular binding to keratin monomer or on keratinase production. This study will facilitate the tweaking of catalytic parameters to improve feather biodegradation by S. maltophilia DHHJ.

Impact of Empirical Antimicrobial Treatment on Patients with Ventilator-Associated Pneumonia Due to Stenotrophomonas maltophilia.

This retrospective study was conducted to evaluate the characteristics and outcomes of patients with ventilator-associated pneumonia (VAP) caused by Stenotrophomonas maltophilia (S. maltophilia), focusing on the impact of appropriate empirical antimicrobial treatment. Of the enrolled 240 patients with VAP due to S. maltophilia (median age: 45 years) in a tertiary-care hospital in southern Thailand between January 2010 and December 2021, 90% had medical comorbidities and 91% had previously received carbapenems. In addition, only 45% of the patients were initially admitted to the intensive care unit. Patients administered appropriate empirical antimicrobial treatment including colistin alone and colistin plus TMP-SMX or fluoroquinolone-based regimens had significantly lower 14-day, 30-day, and in-hospital mortalities, compared with those who did not receive appropriate empirical antimicrobial treatment (21% and 2% vs. 31%; 30% and 5% vs. 44%; and 30% and 12% vs. 53%, respectively). Thus, the use of appropriate empirical antimicrobial treatments led to a significantly reduced length of hospital stay, duration of ventilation, and hospital costs. The current study suggests that the use of appropriate empirical antimicrobial treatment based on susceptibility testing without considering pharmacokinetic properties and administration dosages improves the outcomes of patients with VAP due to S. maltophilia.

Global prevalence and distribution of antibiotic resistance among clinical isolates of Stenotrophomonas maltophilia: A systematic review and meta-analysis.

OBJECTIVES: Stenotrophomonas maltophilia (S. maltophilia), an opportunistic pathogen, causes infection in patients undergoing immunosuppressive therapy, mechanical ventilation, or catheters and in long-term hospitalized patients. Due to its extensive resistance to various antibiotics and chemotherapeutic agents, S. maltophilia is challenging to treat. Using case reports, case series, and prevalence studies, the current study provides a systematic review and meta-analysis of antibiotic resistance profiles across clinical isolates of S. maltophilia. METHODS: A systematic literature search was performed for original research articles published in Medline, Web of Science, and Embase databases from 2000 to 2022. Statistical analysis was performed using STATA 14 software to report antibiotic resistance of S. maltophilia clinical isolates worldwide. RESULTS: 223 studies (39 case reports/case series and 184 prevalence studies) were collected for analysis. A meta-analysis of prevalence studies demonstrated that the most antibiotic resistance worldwide was to levofloxacin, trimethoprim-sulfamethoxazole (TMP/SMX), and minocycline (14.4%, 9.2%, and 1.4%, respectively). Resistance to TMP/SMX (36.84%), levofloxacin (19.29%), and minocycline (1.75%) were the most prevalent antibiotic resistance types found in evaluated case reports/case series studies. The highest resistance rate to TMP/SMX was reported in Asia (19.29%), Europe (10.52%), and America (7.01%), respectively. CONCLUSION: Considering the high resistance to TMP/SMX, more attention should be paid to patients' drug regimens to prevent the emergence of multidrug-resistant S. maltophilia isolates.

Assessment of the relative benefits of monotherapy and combination therapy approaches to the treatment of hospital-acquired Stenotrophomonas maltophilia pneumonia: a multicenter, observational, real-world study.

PURPOSE: Stenotrophomonas maltophilia is a Gram-negative pathogen that most commonly causes hospital-acquired infections that can be extremely challenging to treat, contributing to underrecognized mortality throughout the world. The relative benefits of monotherapy as compared to combination therapy in patients diagnosed with S. maltophilia pneumonia, however, have yet to be established. METHODS: Data from 307 patients diagnosed with S. maltophilia hospital-acquired pneumonia (HAP) across four Chinese teaching hospitals from 2016 to 2022 were retrospectively analyzed. RESULTS: Of the analyzed patients, 55.7% (171/307) were administered combination definitive therapy, with a 30-day all-cause mortality rate of 41.0% (126/307). A propensity score weighting analysis revealed that compared with monotherapy, combination definitive therapy was associated with a comparable 30-day mortality risk in the overall patient cohort (OR 1.124, 95% CI 0.707-1.786, P = 0.622), immunocompetent patients (OR 1.349, 95% CI 0.712-2.554, P = 0.359), and patients with APACHE II scores < 15 (OR 2.357, 95% CI 0.820-6.677, P = 0.111), whereas it was associated with a decreased risk of death in immunocompromised patients (OR 0.404, 95% CI .170-0.962, P = 0.041) and individuals with APACHE II scores ≥ 15 (OR 0.494, 95% CI 0.256-0.951, P = 0.035). CONCLUSION: The present data suggest that when treating S. maltophilia-HAP, immunocompromised patients and individuals with APACHE II scores ≥ 15 may potentially benefit from combination therapy.

Enterogenic Stenotrophomonas maltophilia migrates to the mammary gland to induce mastitis by activating the calcium-ROS-AMPK-mTOR-autophagy pathway.

BACKGROUND: Mastitis is an inflammatory disease of the mammary gland that has serious economic impacts on the dairy industry and endangers food safety. Our previous study found that the body has a gut/rumen-mammary gland axis and that disturbance of the gut/rumen microbiota could result in 'gastroenterogenic mastitis'. However, the mechanism has not been fully clarified. Recently, we found that long-term feeding of a high-concentrate diet induced mastitis in dairy cows, and the abundance of Stenotrophomonas maltophilia (S. maltophilia) was significantly increased in both the rumen and milk microbiota. Accordingly, we hypothesized that 'gastroenterogenic mastitis' can be induced by the migration of endogenous gut bacteria to the mammary gland. Therefore, this study investigated the mechanism by which enterogenic S. maltophilia induces mastitis. RESULTS: First, S. maltophilia was labelled with superfolder GFP and administered to mice via gavage. The results showed that treatment with S. maltophilia promoted the occurrence of mastitis and increased the permeability of the blood-milk barrier, leading to intestinal inflammation and intestinal leakage. Furthermore, tracking of ingested S. maltophilia revealed that S. maltophilia could migrate from the gut to the mammary gland and induce mastitis. Subsequently, mammary gland transcriptome analysis showed that the calcium and AMPK signalling pathways were significantly upregulated in mice treated with S. maltophilia. Then, using mouse mammary epithelial cells (MMECs), we verified that S. maltophilia induces mastitis through activation of the calcium-ROS-AMPK-mTOR-autophagy pathway. CONCLUSIONS: In conclusion, the results showed that enterogenic S. maltophilia could migrate from the gut to the mammary gland via the gut-mammary axis and activate the calcium-ROS-AMPK-mTOR-autophagy pathway to induce mastitis. Targeting the gut-mammary gland axis may also be an effective method to treat mastitis.

Aztreonam-avibactam synergy, a validation and comparison of diagnostic tools.

Introduction: Antimicrobial resistance is a growing problem that necessitates the development of new therapeutic options. Cefiderocol and aztreonam (AT) are often the last active ß-lactams for treating metallo-ß-lactamases (MBL)-producing Gram-negative bacilli. In these difficult-to-treat bacterial strains, AT resistance is frequently attributed to the co-occurrence of other resistance mechanisms. In the case of ß-lactamases they can often be inhibited by avibactam. In the present study, we evaluated the use of the double-disc synergy test (DDST) as a screening tool for the detection of synergy between AT-avibactam (ATA). We validated both the Gradient Diffusion Strips (GDSs) superposition method and the commercially available Liofilchem's ATA GDS. Materials and methods: We tested AT susceptibility in combination with ceftazidime-avibactam for 65 strains, including 18 Serine-ß-Lactamase (SBL)- and 24 MBL-producing Enterobacterales, 12 MBL-producing P. aeruginosa, and 11 S. maltophilia isolates. Interpretation was done with EUCAST breakpoints (version 13.0), AT breakpoints being used for ATA. The accuracy and validity of the GDSs superposition method and ATA GDS were evaluated using an AT GDS applied on Mueller Hinton Agar plates supplemented with avibactam (MH-AV). A DDST was performed to screen for synergy between antibiotic combinations. Results: Using MH-AV, all SBL- and MBL-positive Enterobacterales were susceptible or susceptible at increased exposure to the combination AT-avibactam. In contrast, only 2 out of the 12 (17%) P. aeruginosa strains and 9/11 (82%) of the S. maltophilia strains were susceptible- or susceptible at increased exposure for the combination of AT-avibactam. The DDST detected all synergies, demonstrating a 100% sensitivity and 100% negative predictive value for all bacterial strains. Conclusion: The DDST is a sensitive tool for screening for antibiotic synergy. Unlike S. maltophilia and SBL- and MBL-positive Enterobacterales, most MBL-positive P. aeruginosa strains remain resistant to AT-avibactam. ATA GDS should be preferred for MIC determination of the AT-avibactam combination, while the GDSs superposition method can be used as an alternative to the commercial test.

In Vitro Comparison of Aztreonam/Amoxicillin-Clavulanate Versus Aztreonam/Ceftazidime-Avibactam on Ceftazidime-Avibactam Resistant Stenotrophomonas maltophilia.

We investigated the in vitro susceptibility of ceftazidime-avibactam (CZA) resistant Stenotrophomonas maltophilia to the associations aztreonam/amoxicillin-clavulanate (ATM-AMC) and ATM-CZA. Forty clinical isolates of S. maltophilia recovered from sputum samples of 40 cystic fibrosis people were selected from the collection of the Nantes University Hospital, based on their resistance to CZA. Minimum inhibitory concentrations (MICs) of ATM-CZA and ATM-AMC were determined for each isolate by an Etest strip superposition method, and by Etest for each individual antibiotic. MICs of CZA, ATM, and AMC ranged from 12 to ≥256, ≥256, and 16 to ≥256 mg/L, respectively. Synergistic effects were observed with the ATM-CZA combination for all isolates (fractional inhibitory concentration index range of 0.01 to 0.27), with combination MICs ranging from 0.75 to 16 mg/L (MIC50/90 = 3/12 mg/L), corresponding to a decrease of at least 16-folds in the MIC of ATM. In 23 (57.5%) S. maltophilia isolates, the association of AMC to ATM was also synergistic and combination MICs were ≤16 mg/L (EUCAST breakpoint for ATM resistance in Pseudomonas aeruginosa). Our results show that ATM-CZA or ATM-AMC could be alternative therapeutic options against some highly resistant S. maltophilia. This encourages further experimental studies, in particular time-kill analyses, and clinical trials to delineate conditions required for use of these combinations in practice.

Prognosis of hospital-acquired pneumonia/ventilator-associated pneumonia with Stenotrophomonas maltophilia versus Klebsiella pneumoniae in intensive care unit: A retrospective cohort study.

INTRODUCTION: We collected data on ventilator-associated pneumonia (VAP) and hospital-acquired pneumonia (HAP) induced by Stenotrophomonas maltophilia (SM) and Klebsiella pneumoniae (KP) and compared differences between two bacteria in mortality, duration of ventilator use, length of hospital stay, and risk factors for infection. OBJECTIVES: This study aimed to evaluate the prognosis and to find risk factors of SM-HAP/VAP versus KP-HAP/VAP in the intensive care unit (ICU). METHODS: This retrospective cohort study included patients admitted to the ICU between June 2019 and June 2021 and diagnosed with SM-HAP/VAP or KP-HAP/VAP. The primary outcome was 28-day mortality. RESULTS: Ninety-two HAP/VAP patients (48 with SM-HAP/VAP and 44 with KP-HAP/VAP) were included. The 28-day mortality was 16.7% (8/48 patients) in SM-HAP/VAP and 15.9% (7/44 patients) in KP-HAP/VAP (P = 0.922). After adjustment for potential confounders, the hazard ratios for 28-day mortality in SM-HAP/VAP were 1.3 (95% CI:0.5-3.7), 1.0 (95% CI:0.4-3.0), 1.4 (95% CI:0.5-4.0), and 1.1 (95% CI:0.4-3.4), respectively. CONCLUSION: SM-HAP/VAP and KP-HAP/VAP patients in ICU might have a similar prognosis in mortality, the total duration of the artificial airway and ventilator use, the total length of ICU stay, and hospital stay. The risk factors of SM-HAP/VAP versus KP-HAP/VAP might be the artificial airway, ventilator use, gastric tube placement, acid suppressant and antibiotics (especially carbapenem).

Optimization of the incubation parameters for biogenic synthesis of WO3 nanoparticles using Taguchi method.

Green synthesis of metal nanoparticles is gathering attention due to eco-friendly processing. Tungsten oxide (WO3) nanoparticles have immense applications as semiconductors, antimicrobials and photo thermal materials but their synthesis using biological systems is hitherto unpublicized. The paper discusses synthesis of WO3 nanoparticles using Stenotrophomonas maltophilia and the optimization of physico-chemical parameters of incubation which influence the growth and metabolism of the bacterium and consequently the size of the WO3 nanoparticles. The biogenic synthesis of WO3 nanoparticles was confirmed by ATR-FTIR and X-ray diffraction analysis. Taguchi and analysis of variance method was applied to optimize the physico-chemical parameters (pH, temperature, time, aeration rate and concentration), considering particle size and poly dispersity index (PDI) of the nanoparticles as the experimental responses. Under the design of experiments technique, Taguchi's L27 array was selected to determine the optimal process parameters which could significantly reduce the particle size and PDI of WO3 nanoparticles. Statistical analysis by signal-to-noise ratio, regression analysis and ANOVA (95% confidence level) on experimental responses confirmed pH and aeration as most influential while temperature and time as least influential parameters. pH 8, Temperature 40 °C, aeration 200 RPM, time 3 days and concentration of sodium tungstate at 1 mM (p3t3r3d3c1) was the most effective level and parameters combination for smallest particle size and PDI of WO3 nanoparticles. Regression models developed for particle size and PDI exhibited a linear regression of 97.80% and 90.89% respectively, while the confirmation test validated the size and PDI of the experimental values against predicted results. SEM image of WO3 nanoparticles illustrated the same particle size as that predicted, further validating the model. The study can be applied to optimize any process parameters in the industry or on biological systems.

Healthcare-Associated Stenotrophomonas maltophilia Bacteraemia: Retrospective Evaluation of Treatment and Outcome.

Introduction Stenotrophomonas maltophilia (SM) is one of the common gram-negative pathogens that cause nosocomial infections. The aim of the present study is to evaluate the treatment and outcome of SM bacteraemia. Materials and Methods We retrospectively evaluated antimicrobial treatment in adult patients with nosocomial SM bacteraemia, with the 14th and 30th-day mortality as the outcome. Results In total, 140 adult patients with SM bacteraemia who were diagnosed between January 1, 2002, and December 31, 2016 were enrolled in the present study. Seventy-one (50.7%) patients were in the intensive care unit (ICU). The 14th and the 30th-day mortality rates were 32.9% (n=46) and 45.7% (n=64), respectively. Female sex (OR, 7.47; 95% CI 1.61-34.47, p<0.01), steroid use within the last month (OR, 10.2; 95% CI 1.27-82.27, p=0.029), Pittsburgh bacteraemia score (PBS) ≥4 (OR, 39.9; 95% CI 4.96-321.32, p<0.001) and solid organ malignancy (OR, 9.6; 95% CI 1.73-53.72, p<0.01) were independent risk factors for 14th day mortality. Removal of the catheter was an independent protective factor for both 14th (OR, 0.05; 95% CI 0.22-0.010, p<0.001) and 30th day (OR, 0.039;95% CI 0.164-0.009, p<0.001) mortality. We did not detect any difference between treatment regimens including trimethoprim-sulfamethoxazole (TMP/SMX) or levofloxacin in terms of mortality. We found that TMP/SMX and levofloxacin combination did not significantly improve patient prognosis. Conclusion  Due to the high mortality rates associated with nosocomial SM bacteraemia, adequate antibiotic therapy should be initiated immediately in the suspicion of infection, and prompt removal of any indwelling central venous catheter is important.

In-silico virtual screening for identification of potent inhibitor for L2-ß-lactamase from Stenotrophomonas maltophilia through molecular docking, molecular dynamics analysis study.

Stenotrophomonas maltophilia, a Multiple-Drug-Resistant proteobacterium found in healthy normal flora and fauna with an aerobic and non-fermentative respiratory process, is majorly involved in Healthcare-Associated Infections (HAI). The Multiple-Drug-Resistance takes place by secretion of the ß-Lactamase enzyme, which hydrolyzes the ß-Lactam antibiotics and currently serving as a significant clinical challenge by substantially effecting the mortality rate. In this study, involved 2D Similarity, Molecular docking, and Molecular Simulation for the commercially available ZINC database compounds to overcome this resistance mechanism and find out a proper potent inhibitor for the target L2-ß-Lactamase, which would not get cleaved by the hydrolytic activity of the L2-ß-Lactamase natural enzyme. The ZINC35053014 compound had the highest binding energy: -8.51Kcal/mol with hydrophobic interaction at THR235 and formation of hydrogen bonds at SER70, SER130, ASN170, LYS234, THR235, SER237, and ARG244. In total, 08 hit compounds subjected for the stability check of the protein-ligand complex (MD simulation) analysis which, concluded in the same RMSD, RMSF, and Rg values at the comparison between known compounds and the selected virtual hit compounds. These selected virtual hit compounds can be experimentally verified and used as lead compounds for the future search of ß-Lactamase potent inhibitors for S. maltophilia. Communicated by Ramaswamy H. Sarma.

Molecular Epidemiology, Antibiotic Resistance, and Virulence Traits of Stenotrophomonas maltophilia Strains Associated With an Outbreak in a Mexican Tertiary Care Hospital.

Stenotrophomonas maltophilia, an emerging opportunistic pathogen, is widely distributed in the environment the resistance mechanisms, and virulence factors of this bacterium facilitate its dissemination in hospitals. This study aimed to characterize the molecular epidemiology of S. maltophilia strains associated with an outbreak in the Children's Hospital of México Federico Gómez (HIMFG). Twenty-one clinical S. maltophilia strains were recovered from cultures of blood and urine samples from 10 pediatric patients at the emergency department, and nine environmental S. maltophilia strains recovered from faucets in the same area were also included. Two of the 10 patients were related with health care-associated infections (HCAIs), and the other eight patients (8/10) were infected with environmental S. maltophilia strains. The outbreak was controlled by monthly disinfection of the faucets in the emergency department. Typing using pulsed-field gel electrophoresis (PFGE) showed a 52% genetic diversity with seven pulsotypes denoted P1-P7 among all S. maltophilia strains. Three pulsotypes (P2, P3, and P7) were identified among both the clinical and environmental S. maltophilia strains and associated with two type sequences (STs), namely, ST304 and ST24. Moreover, 80% (24/30) of the strains exhibited resistance mainly to tetracycline, 76.66% (23/30) to trimethoprim-sulfamethoxazole, and 23.33% (7/30) to the extended-spectrum ß-lactamase (ESBL) phenotype. The main resistance genes identified by multiplex PCR were sul1 in 100% (30/30), qnr in 86.66% (26/30), and intl1 in 80% (24/30) of the samples, respectively. Furthermore, the pilU, hlylII, and rmlA genes were identified in 96.6% (29/30), 90% (27/30), and 83.33% (25/30) of the samples, respectively. Additionally, 76.66% (23/30) of the S. maltophilia strains exhibited high swimming motility, 46.66% (14/30) showed moderate biofilm formation capacity, 43.33% (13/30) displayed moderate twitching motility, and 20% (6/30) exhibited high adherence. The clinical S. maltophilia strains isolated from blood most strongly adhered to HTB-9 cells. In conclusion, the molecular epidemiology and some of the features such as resistance, and virulence genes associated with colonization patterns are pathogenic attributes that can promote S. maltophilia dissemination, persistence, and facilitate the outbreak that occurred in the HIMFG. This study supports the need for faucet disinfection as a control strategy for clinical outbreaks.