Stenotrophomonas maltophilia outbreak in a university hospital: epidemiological investigation and literature review of an emerging healthcare-associated infection.

Stenotrophomonas maltophilia was considered to be a low-virulence organism. But it has emerged as a prominent opportunistic pathogen in patients with certain risk factors. This study aimed to describe an outbreak experienced in our hospital with all dynamics while evaluating previous S. maltophilia outbreak reports. S. maltophilia isolates were obtained from a university hospital in Türkiye in a seven-months period. Antimicrobial resistance, type of infections, predisposing factors of infected patients, antibiotic therapy, outcome of infections, and outbreak source were investigated. Also, S. maltophilia outbreaks in the literature were reviewed. In the 12 months prior to the outbreak, prevalence rate of clinical samples including S. maltophilia was 7/1,000 patient per day, opposed to 113/1,000 patient per day during the outbreak. Although a large number of cases were observed in a short seven-month period, a source of contamination could not be detected. Stable mortality rates (or remaining close to the average) during outbreaks can be attributed to the careful attention paid by laboratory and clinic physicians during procedures. S. maltophilia has potential to spread outbreaks and infect patients in operating rooms and intensive care units during invasive procedures.

Determination of in vitro synergy and antibiofilm activities of antimicrobials and essential oil components.

Using existing adrentimicrobials with essential oil components to prevent antimicrobial resistance is an alternative strategy. This study aimed to evaluate the resistance status, synergistic combinations, and in vitro biofilm formation activities of clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA), Stenotrophomonas maltophilia and Candida albicans against antimicrobial agents and cinnamaldehyde, carvacrol, eugenol, limonene and eucalyptol. Antimicrobial activities were evaluated by microdilution, cytotoxicity by XTT, synergy by checkerboard and time-kill, and biofilm inhibition by microplate methods. Cinnamaldehyde and carvacrol showed strong antimicrobial activity. Synergistic effects were observed when using all essential oils with antimicrobials. Only two C. albicans isolates showed antagonism with cinnamaldehyde and fluconazole. The constituents showed cytotoxic effects in the L929 cell line (except limonene). A time-kill analysis revealed a bacteriostatic effect on S. maltophilia and MRSA isolates and a fungicidal effect on C. albicans isolates. These results are important for further research to improve antimicrobial efficacy or to develop new agents.

Antibacterial potential of Stenotrophomonas maltophilia complex cystic fibrosis isolates.

Over 160,000 people worldwide suffer from cystic fibrosis (CF), a genetic condition that causes mucus to accumulate in internal organs. Lung decline is a significant health burden for people with CF (pwCF), and chronic bacterial pulmonary infections are a major cause of death. Stenotrophomonas maltophilia complex (Smc) is an emerging, multidrug-resistant CF pathogen that can cause pulmonary exacerbations and result in higher mortality. However, little is known about the antagonistic interactions that occur between Smc isolates from pwCF and competitor bacteria. We obtained 13 Smc isolates from adult and pediatric pwCF located in the United States or Australia. We co-cultured these isolates with Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli. We also performed whole-genome sequencing of these Smc isolates and compared their genomes using average nucleotide identity analyses. We observed that some Smc CF isolates can engage in antagonistic interactions with P. aeruginosa and S. aureus but recovered a substantial number of P. aeruginosa and S. aureus cells following co-cultures with all tested Smc isolates. By contrast, we discovered that most Smc CF isolates display strong antibacterial properties against E. coli cells and reduce recovery below detectable limits. Finally, we demonstrate that Smc CF strains from this study belong to diverse phylogenetic lineages. IMPORTANCE: Antagonism toward competitor bacteria may be important for the survival of Stenotrophomonas maltophilia complex (Smc) in external environments, for the elimination of commensal species and colonization of upper respiratory tracts to enable early infections, and for competition against other pathogens after establishing chronic infections. These intermicrobial interactions could facilitate the acquisition of Smc by people with cystic fibrosis from environmental or nosocomial sources. Elucidating the mechanisms used by Smc to eliminate other bacteria could lead to new insights into the development of novel treatments.

Disinfection of sink drains to reduce a source of three opportunistic pathogens, during Serratia marcescens clusters in a neonatal intensive care unit.

OBJECTIVE: Evaluate the effects of five disinfection methods on bacterial concentrations in hospital sink drains, focusing on three opportunistic pathogens (OPs): Serratia marcescens, Pseudomonas aeruginosa and Stenotrophomonas maltophilia. DESIGN: Over two years, three sampling campaigns were conducted in a neonatal intensive care unit (NICU). Samples from 19 sink drains were taken at three time points: before, during, and after disinfection. Bacterial concentration was measured using culture-based and flow cytometry methods. High-throughput short sequence typing was performed to identify the three OPs and assess S. marcescens persistence after disinfection at the genotypic level. SETTING: This study was conducted in a pediatric hospitals NICU in Montréal, Canada, which is divided in an intensive and intermediate care side, with individual rooms equipped with a sink. INTERVENTIONS: Five treatments were compared: self-disinfecting drains, chlorine disinfection, boiling water disinfection, hot tap water flushing, and steam disinfection. RESULTS: This study highlights significant differences in the effectiveness of disinfection methods. Chlorine treatment proved ineffective in reducing bacterial concentration, including the three OPs. In contrast, all other drain interventions resulted in an immediate reduction in culturable bacteria (4-8 log) and intact cells (2-3 log). Thermal methods, particularly boiling water and steam treatments, exhibited superior effectiveness in reducing bacterial loads, including OPs. However, in drains with well-established bacterial biofilms, clonal strains of S. marcescens recolonized the drains after heat treatments. CONCLUSIONS: Our study supports thermal disinfection (>80°C) for pathogen reduction in drains but highlights the need for additional trials and the implementation of specific measures to limit biofilm formation.

Temporal analysis of prevalence and antibiotic-resistance patterns in Stenotrophomonas maltophilia clinical isolates in a 19-year retrospective study.

Stenotrophomonas maltophilia is a nonfermenting gram-negative bacterium associated with multiple nosocomial outbreaks. Antibiotic resistance increases healthcare costs, disease severity, and mortality. Multidrug-resistant infections (such as S. maltophilia infection) are difficult to treat with conventional antimicrobials. This study aimed to investigate the isolation rates, and resistance trends of S. maltophilia infections over the past 19 years, and provide future projections until 2030. In total, 4466 patients with S. maltophilia infection were identified. The adult and main surgical intensive care unit (ICU) had the highest numbers of patients (32.2%), followed by the cardiology department (29.8%), and the paediatric ICU (10%). The prevalence of S. maltophilia isolation increased from 7% [95% confidence interval (CI) 6.3-7.7%] in 2004-2007 to 15% [95% CI 10.7-19.9%] in 2020-2022. Most S. maltophilia isolates were resistant to ceftazidime (72.5%), levofloxacin (56%), and trimethoprim-sulfamethoxazole (14.05%), according to our study. A consistent and significant difference was found between S. maltophilia-positive ICU patients and non-ICU patients (P = 0.0017) during the three-year pandemic of COVID-19 (2019-2021). The prevalence of S. maltophilia isolates is expected to reach 15.08% [95% CI 12.58-17.59%] by 2030. Swift global action is needed to address this growing issue; healthcare authorities must set priorities and monitor infection escalations and treatment shortages.

The effects of methylparaben exposure on biofilm tolerance to chlorine disinfection.

Parabens are emerging contaminants that have been detected in drinking water. Their presence in DW distribution systems (DWDS) can alter bacterial behaviour, characteristics, and structure, which may compromise DW disinfection. This work provides insights into the impact of methylparaben (MP) on the tolerance to chlorine disinfection and antibiotics from dual-species biofilms formed by Acinetobacter calcoaceticus and Stenotrophomonas maltophilia isolated from DW and grown on high-density polyethylene (HDPE) and polypropylene (PPL). Results showed that dual-species biofilms grown on PPL were more tolerant to chlorine disinfection, expressing a decrease of over 50 % in logarithmic reduction values of culturable cells in relation to non-exposed biofilms. However, bacterial tolerance to antibiotics was not affected by MP presence. Although MP-exposed dual-species biofilms grown on HDPE and PPL were metabolically more active than non-exposed counterparts, HDPE seems to be the material with lower impact on DW risk management and disinfection, if MP is present. Overall, results suggest that MP presence in DW may compromise chlorine disinfection, and consequently affect DW quality and stability, raising potential public health issues.

Clinical characteristics and genome epidemiology of Stenotrophomonas maltophilia in Japan.

BACKGROUND: Stenotrophomonas maltophilia is a carbapenem-resistant Gram-negative pathogen increasingly responsible for difficult-to-treat nosocomial infections. OBJECTIVES: To describe the contemporary clinical characteristics and genome epidemiology of patients colonized or infected by S. maltophilia in a multicentre, prospective cohort. METHODS: All patients with a clinical culture growing S. maltophilia were enrolled at six tertiary hospitals across Japan between April 2019 and March 2022. The clinical characteristics, outcomes, antimicrobial susceptibility and genomic epidemiology of cases with S. maltophilia were investigated. RESULTS: In total, 78 patients were included representing 34 infection and 44 colonization cases. The median age was 72.5 years (IQR, 61-78), and males accounted for 53 cases (68%). The most common comorbidity was localized solid malignancy (39%). Nearly half of the patients (44%) were immunosuppressed, with antineoplastic chemotherapy accounting for 31%. The respiratory tract was the most common site of colonization (86%), whereas bacteraemia accounted for most infection cases (56%). The 30 day all-cause mortality rate was 21%, which was significantly higher in infection cases than colonization cases (35% versus 9%; adjusted HR, 3.81; 95% CI, 1.22-11.96). Susceptibility rates to ceftazidime, levofloxacin, minocycline and sulfamethoxazole/trimethoprim were 14%, 65%, 87% and 100%, respectively. The percentage of infection ranged from 13% in the unclassified group to 86% in genomic group 6A. The percentage of non-susceptibility to ceftazidime ranged from 33% in genomic group C to 100% in genomic groups 6 and 7 and genomic group geniculate. CONCLUSIONS: In this contemporary multicentre cohort, S. maltophilia primarily colonized the respiratory tract, whereas patients with bacteraemia had the highest the mortality from this pathogen. Sulfamethoxazole/trimethoprim remained consistently active, but susceptibility to levofloxacin was relatively low. The proportions of cases representing infection and susceptibility to ceftazidime differed significantly based on genomic groups.

Emergence of colistin-resistant Stenotrophomonas maltophilia with high virulence in natural aquatic environments.

The presence of Stenotrophomonas maltophilia in aquatic environments poses great health risks to immunocompromised individuals because of its multidrug resistance and resultant high mortality. However, a significant gap exists in the isolation and understanding of colistin-resistant S. maltophilia in aquatic environments. In this study, nine colistin-resistant S. maltophilia strains isolated from natural lakes were explored, and their phylogenetic relationship, biofilm formation, virulence, and antibiotic resistance profiles and underlying genetic determinants were assessed. After genome analysis, besides known multi-locus sequence typing (MLST) of ST532, new assigned ST965 and ST966 which phylogenetically clustered into soil isolates were found firstly. All the isolates exhibited resistance to multiple antibiotics, including aminoglycosides, beta-lactams, tetracyclines, and even colistin, with the highest minimum inhibitory concentration (MIC) against colistin reaching 640 mg/L. Comparative genomic analysis revealed aph(3')-Iic, blaL1, tetT, phoP, mcr-3, arnA, pmrE, and efflux pump genes as the genetic determinants underlying this multidrug resistance. Notably, the biofilm-forming capacities of the newly discovered ST965 and ST966 isolates were significant stronger than those of the known ST532 isolates (p < 0.01), resulting in the death of over 50 % of the Galleria mellonella population within 1 day of injection. The ST965 isolates demonstrated the highest virulence against G. mellonella, followed by the ST966 isolates and ST532 isolates which was phylogenetically clustered with clinical isolates, indicating that the novel S. maltophilia strains of ST965 and ST966 may pose considerable health risks to humans. Our findings provide insights into colistin-resistant S. maltophilia in aquatic environments and raise concerns about the health risks posed by the newly assigned sequence types of colistin-resistant S. maltophilia with potential high virulence in natural aquatic environments.

Evaluation of the presence of integrons, sul and smqnr genes and the prevalence of antibiotic resistance in Stenotrophomonas maltophilia clinical isolates.

OBJECTIVES: The objective of this investigation was to examine the mechanisms associated with antibiotic resistance in Stenotrophomonas maltophilia clinical isolates retrieved from hospitalized patients undergoing open heart surgery in a Heart Center located in Tehran, Iran. MATERIALS AND METHODS: This investigation encompassed a cross-sectional study of 60 S. maltophilia isolates, which were procured from diverse clinical specimens. Primary identification of the isolates was conducted through conventional microbiologic methods and subsequently verified by means of PCR primers. The E-test was utilized to establish the minimum inhibitory concentrations (MICs). PCR was then employed to ascertain the antibiotic resistance genes (sul1, sul2, Smqnr and intl1 - intl3). RESULTS: In this study, a total of sixty clinical isolates of S. maltophilia were collected, with the majority of them being obtained from Intensive Care Units (ICU) (n = 54; 90%). The disk diffusion method yielded results indicating that 55% of the isolates were sensitive to minocycline, whereas 30% were intermediate and 15% were found to be resistant. Additionally, the MIC results revealed that the resistant rates of the isolates towards ceftazidime, cotrimoxazole and levofloxacin were 46.7%, 1.7% and 5%, respectively. The PCR amplification of three classes of integrons genes indicated that fifteen (25%) of the isolates carried int1, while no detection for intl2 and intl3 was reported. Furthermore, the prevalence of antibiotic resistance genes (sul1, sul2, and Smqnr) was identified in 15 (25%), 6 (10%), and 28 (46.7%) isolates, respectively. CONCLUSION: The reported increasing rate of antibiotic resistance and mobile genetic elements that could extend the resistance genes to other strains in the hospital, finally it could be an alarming issue for healthcare settings that need special attention to this strain and the epidemiological study on this issue.

Multidrug-resistant Stenotrophomonas maltophilia in residential aged care facilities: An emerging threat.

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.

Antimicrobial activity of eravacycline and other comparative agents on aerobic and anaerobic bacterial pathogens in Taiwan: A clinical microbiological study.

OBJECTIVES: Eravacycline, a new tetracycline derivative, exhibits broad-spectrum antimicrobial susceptibility. This study aimed to comprehensively investigate in vitro activities of eravacycline, tigecycline, and ertapenem against various Gram-positive, Gram-negative, and anaerobic bacteria. METHODS: Minimum inhibitory concentrations (MICs) were determined using the broth microdilution method. The following bacterial species were collected: vancomycin-sensitive (VS) Enterococci species, vancomycin-resistant Enterococci species (VRE), Staphylococcus aureus, Streptococcus anginosus, Bacteroides species, Clostridioides difficile, Clostridium innocuum, Clostridium perfringens, Parabacteroides distasonis, and Stenotrophomonas maltophilia. RESULTS: We found that eravacycline exhibited superior in vitro activity compared to tigecycline and ertapenem. Notably, it exhibited the lowest MIC90 for several bacterial species, including VS E. faecalis (0.12 µg/mL), VS E. faecium (0.12 µg/mL), and others. Besides, VRE was susceptible to eravacycline (MIC90:0.12 µg/mL) and tigecycline (MIC90:0.12 µg/mL), but was all resistant to ertapenem (MIC90 > 64 µg/mL). S. aureus was also susceptible to eravacycline (MIC90:0.5 µg/mL) as well as tigecycline (MIC90:1.0 µg/mL). Furthermore, S. anginosus showed higher susceptibility to eravacycline (MIC90:2.0 µg/mL) and tigecycline (MIC90:4.0 µg/mL), but lower to ertapenem (MIC90:32.0 µg/mL). Eravacycline and tigecycline also demonstrated good susceptibility to anaerobes, including Bacteroides species (susceptibility rate: 100%), P. distasonis (100%), C. difficile (94.1‒100%), C. innocuum (94.1‒96.1%), and C. perfringens (88.9‒96.3%). For S. maltophilia, both tigecycline and eravacycline showed an MIC90 of 2 µg/mL. A moderate-to-strong correlation (rho = 0.608-0.804, P < 0.001) was noted between the MIC values of eravacycline and tigecycline against various bacterial species. CONCLUSIONS: Our study highlights the potential of eravacycline as an effective treatment option for multidrug-resistant bacterial infections.

Global mapping of antibiotic resistance rates among clinical isolates of Stenotrophomonas maltophilia: a systematic review and meta-analysis.

INTRODUCTION: Infections caused by Stenotrophomonas maltophilia are clinically important due to its intrinsic resistance to a broad range of antibiotics. Therefore, selecting the most appropriate antibiotic to treat S. maltophilia infection is a major challenge. AIM: The current meta-analysis aimed to investigate the global prevalence of antibiotic resistance among S. maltophilia isolates to the develop more effective therapeutic strategies. METHOD: A systematic literature search was performed using the appropriate search syntax after searching Pubmed, Embase, Web of Science and Scopus databases (May 2023). Statistical analysis was performed using Pooled and the random effects model in R and the metafor package. A total of 11,438 articles were retrieved. After a thorough evaluation, 289 studies were finally eligible for inclusion in this systematic review and meta-analysis. RESULT: Present analysis indicated that the highest incidences of resistance were associated with doripenem (97%), cefoxitin (96%), imipenem and cefuroxime (95%), ampicillin (94%), ceftriaxone (92%), aztreonam (91%) and meropenem (90%) which resistance to Carbapenems is intrinsic. The lowest resistance rates were documented for minocycline (3%), cefiderocol (4%). The global resistance rate to TMP-SMX remained constant in two periods before and after 2010 (14.4% vs. 14.6%). A significant increase in resistance to tigecycline and ceftolozane/tazobactam was observed before and after 2010. CONCLUSIONS: Minocycline and cefiderocol can be considered the preferred treatment options due to low resistance rates, although regional differences in resistance rates to other antibiotics should be considered. The low global prevalence of resistance to TMP-SMX as a first-line treatment for S. maltophilia suggests that it remains an effective treatment option.

Characterization of phage evolution and phage resistance in drug-resistant Stenotrophomonas maltophilia.

Phage therapy has become a viable antimicrobial treatment as an alternative to antibiotic treatment, with an increase in antibiotic resistance. Phage resistance is a major limitation in the therapeutic application of phages, and the lack of understanding of the dynamic changes between bacteria and phages constrains our response strategies to phage resistance. In this study, we investigated the changing trends of mutual resistance between Stenotrophomonas maltophilia (S. maltophilia) and its lytic phage, BUCT603. Our results revealed that S. maltophilia resisted phage infection through mutations in the cell membrane proteins, while the evolved phage re-infected the resistant strain primarily through mutations in structure-related proteins. Compared with the wild-type strain (SMA118), the evolved phage-resistant strain (R118-2) showed reduced virulence, weakened biofilm formation ability, and reduced resistance to aminoglycosides. In addition, the evolved phage BUCT603B1 in combination with kanamycin could inhibit the development of phage-resistant S. maltophilia in vitro and significantly improve the survival rate of S. maltophilia-infected mice. Altogether, these results suggest that in vitro characterization of bacteria-phage co-evolutionary relationships is a useful research tool to optimize phages for the treatment of drug-resistant bacterial infections.IMPORTANCEPhage therapy is a promising approach to treat infections caused by drug-resistant Stenotrophomonas maltophilia (S. maltophilia). However, the rapid development of phage resistance has hindered the therapeutic application of phages. In vitro evolutionary studies of bacteria-phage co-cultures can elucidate the mechanism of resistance development between phage and its host. In this study, we investigated the resistance trends between S. maltophilia and its phage and found that inhibition of phage adsorption is the primary strategy by which bacteria resist phage infection in vitro, while phages can re-infect bacterial cells by identifying other adsorption receptors. Although the final bacterial mutants were no longer infected by phages, they incurred a fitness cost that resulted in a significant reduction in virulence. In addition, the combination treatment with phage and aminoglycoside antibiotics could prevent the development of phage resistance in S. maltophilia in vitro. These findings contribute to increasing the understanding of the co-evolutionary relationships between phages and S. maltophilia.

Biofilm Eradication of Stenotrophomonas maltophilia by Levofloxacin and Trimethoprim-Sulfamethoxazole.

Stenotrophomonas maltophilia is a nonfermenting Gram-negative drug-resistant pathogen that causes healthcare-associated infections. Clinical isolates from Mexico were assessed for biofilm formation using crystal violet staining. Antimicrobial susceptibility was evaluated in planktonic and biofilm cells using the broth microdilution method. The effects of antibiotics on biofilms were visualized using fluorescence microscopy. Fifty isolates were included in this study, of which 14 (28%) were biofilm producers (9 [64%] from blood and 5 [36%] from respiratory samples). In planktonic cells 4/50 (8%) of isolates were resistant to levofloxacin (8.0%) and 22/50 (44%) were resistant to trimethoprim-sulfamethoxazole. All isolates were resistant to levofloxacin and trimethoprim-sulfamethoxazole in biofilm cells. Bacterial biofilms treated with different concentrations of both antibiotics were completely disrupted. In conclusion, S. maltophilia isolated from blood had higher biofilm production than those isolated from respiratory samples. Biofilm production was associated with increased antibiotic resistance. Antibiotic monotherapy might not be the best course of action for the treatment of S. maltophilia infections in Mexico, because it might cause biofilm production and antimicrobial resistance.

Interactions of hydrolyzed ß-lactams with the L1 metallo-ß-lactamase: Crystallography supports stereoselective binding of cephem/carbapenem products.

L1 is a dizinc subclass B3 metallo-ß-lactamase (MBL) that hydrolyzes most ß-lactam antibiotics and is a key resistance determinant in the Gram-negative pathogen Stenotrophomonas maltophilia, an important cause of nosocomial infections in immunocompromised patients. L1 is not usefully inhibited by MBL inhibitors in clinical trials, underlying the need for further studies on L1 structure and mechanism. We describe kinetic studies and crystal structures of L1 in complex with hydrolyzed ß-lactams from the penam (mecillinam), cephem (cefoxitin/cefmetazole), and carbapenem (tebipenem, doripenem, and panipenem) classes. Despite differences in their structures, all the ß-lactam-derived products hydrogen bond to Tyr33, Ser221, and Ser225 and are stabilized by interactions with a conserved hydrophobic pocket. The carbapenem products were modeled as Δ1-imines, with (2S)-stereochemistry. Their binding mode is determined by the presence of a 1ß-methyl substituent: the Zn-bridging hydroxide either interacts with the C-6 hydroxyethyl group (1ß-hydrogen-containing carbapenems) or is displaced by the C-6 carboxylate (1ß-methyl-containing carbapenems). Unexpectedly, the mecillinam product is a rearranged N-formyl amide rather than penicilloic acid, with the N-formyl oxygen interacting with the Zn-bridging hydroxide. NMR studies imply mecillinam rearrangement can occur nonenzymatically in solution. Cephem-derived imine products are bound with (3R)-stereochemistry and retain their 3' leaving groups, likely representing stable endpoints, rather than intermediates, in MBL-catalyzed hydrolysis. Our structures show preferential complex formation by carbapenem- and cephem-derived species protonated on the equivalent (ß) faces and so identify interactions that stabilize diverse hydrolyzed antibiotics. These results may be exploited in developing antibiotics, and ß-lactamase inhibitors, that form long-lasting complexes with dizinc MBLs.

A 20-year trend of prevalence and susceptibility to trimethoprim/sulfamethoxazole of Stenotrophomonas maltophilia in a single secondary care hospital in Korea.

Stenotrophomonas maltophilia is a Gram-negative opportunistic pathogen that can cause serious infection. We aimed to analyze the prevalence and susceptibility rates to trimethoprim/sulfamethoxazole of S. maltophilia. We conducted a retrospective study of S. maltophilia isolates from a university hospital from 2001 to 2020. Clinical information, the numbers of isolates and susceptibility rates were analyzed by year. Susceptibility rates and changes in respiratory and non-respiratory samples were compared. 1805 S. maltophilia isolates were identified, of which 81.4% (1469/1805) were from respiratory samples. There was a male predominance and 52% of the isolates were from general wards. The average susceptibility rate was 87.7% and there was no significant annual trend (P = .519). The susceptibility rate was 88.7% in respiratory samples and 84.1% in non-respiratory samples (P = .018). Susceptibility analyses using clinical data over long periods can guide the choice of antimicrobials especially for pathogen whose treatment options are limited.

Review on Stenotrophomonas maltophilia: An Emerging Multidrug- resistant Opportunistic Pathogen.

Stenotrophomonas maltophilia is an opportunistic pathogen that results in nosocomial infections in immunocompromised individuals. These bacteria colonize on the surface of medical devices and therapeutic equipment like urinary catheters, endoscopes, and ventilators, causing respiratory and urinary tract infections. The low outer membrane permeability of multidrug-resistance efflux systems and the two chromosomally encoded ß- lactamases present in S. maltophilia are challenging for arsenal control. The cell-associated and extracellular virulence factors in S. maltophilia are involved in colonization and biofilm formation on the host surfaces. The spread of antibiotic-resistant genes in the pathogenic S. maltophilia attributes to bacterial resistance against a wide range of antibiotics, including penicillin, quinolones, and carbapenems. So far, tetracycline derivatives, fluoroquinolones, and trimethoprim-sulfamethoxazole (TMP-SMX) are considered promising antibiotics against S. maltophilia. Due to the adaptive nature of the intrinsically resistant mechanism towards the number of antibiotics and its ability to acquire new resistance via mutation and horizontal gene transfer, it is quite tricky for medicinal contribution against S. maltophilia. The current review summarizes the literary data on pathogenicity, quorum sensing, biofilm formation, virulence factors, and antibiotic resistance of S. maltophilia.

Fosfomycin Resistance Evolutionary Pathways of Stenotrophomonas maltophilia in Different Growing Conditions.

The rise of multidrug-resistant Gram-negative pathogens and the lack of novel antibiotics to address this problem has led to the rescue of old antibiotics without a relevant use, such as fosfomycin. Stenotrophomonas maltophilia is a Gram-negative, non-fermenter opportunistic pathogen that presents a characteristic low susceptibility to several antibiotics of common use. Previous work has shown that while the so-far described mechanisms of fosfomycin resistance in most bacteria consist of the inactivation of the target or the transporters of this antibiotic, as well as the production of antibiotic-inactivating enzymes, these mechanisms are not selected in S. maltophilia fosfomycin-resistant mutants. In this microorganism, fosfomycin resistance is caused by the inactivation of enzymes belonging to its central carbon metabolism, hence linking metabolism with antibiotic resistance. Consequently, it is relevant to determine how different growing conditions, including urine and synthetic sputum medium that resemble infection, could impact the evolutionary pathways towards fosfomycin resistance in S. maltophilia. Our results show that S. maltophilia is able to acquire high-level fosfomycin resistance under all tested conditions. However, although some of the genetic changes leading to resistance are common, there are specific mutations that are selected under each of the tested conditions. These results indicate that the pathways of S. maltophilia evolution can vary depending on the infection point and provide information for understanding in more detail the routes of fosfomycin resistance evolution in S. maltophilia.

Infectious Diseases Society of America Guidance on the Treatment of AmpC ß-Lactamase-Producing Enterobacterales, Carbapenem-Resistant Acinetobacter baumannii, and Stenotrophomonas maltophilia Infections.

The Infectious Diseases Society of America (IDSA) is committed to providing up-to-date guidance on the treatment of antimicrobial-resistant infections. A previous guidance document focused on infections caused by extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-E), carbapenem-resistant Enterobacterales (CRE), and Pseudomonas aeruginosa with difficult-to-treat resistance (DTR-P. aeruginosa). Here, guidance is provided for treating AmpC ß-lactamase-producing Enterobacterales (AmpC-E), carbapenem-resistant Acinetobacter baumannii (CRAB), and Stenotrophomonas maltophilia infections. A panel of 6 infectious diseases specialists with expertise in managing antimicrobial-resistant infections formulated questions about the treatment of AmpC-E, CRAB, and S. maltophilia infections. Answers are presented as suggested approaches and corresponding rationales. In contrast to guidance in the previous document, published data on the optimal treatment of AmpC-E, CRAB, and S. maltophilia infections are limited. As such, guidance in this document is provided as "suggested approaches" based on clinical experience, expert opinion, and a review of the available literature. Because of differences in the epidemiology of resistance and availability of specific anti-infectives internationally, this document focuses on the treatment of infections in the United States. Preferred and alternative treatment suggestions are provided, assuming the causative organism has been identified and antibiotic susceptibility results are known. Approaches to empiric treatment, duration of therapy, and other management considerations are also discussed briefly. Suggestions apply for both adult and pediatric populations. The field of antimicrobial resistance is highly dynamic. Consultation with an infectious diseases specialist is recommended for the treatment of antimicrobial-resistant infections. This document is current as of 17 September 2021 and will be updated annually. The most current version of this document, including date of publication, is available at www.idsociety.org/practice-guideline/amr-guidance-2.0/.

Subtractive genomics and molecular docking approach to identify drug targets against Stenotrophomonas maltophilia.

Stenotrophomonas maltophilia is a multidrug resistant pathogen associated with high mortality and morbidity in patients having compromised immunity. The efflux systems of S. maltophilia include SmeABC and SmeDEF proteins, which assist in acquisition of multiple-drug-resistance. In this study, proteome based mapping was utilized to find out the potential drug targets for S. maltophilia strain k279a. Various tools of computational biology were applied to remove the human-specific homologous and pathogen-specific paralogous sequences from the bacterial proteome. The CD-HIT analysis selected 4315 proteins from total proteome count of 4365 proteins. Geptop identified 407 essential proteins, while the BlastP revealed approximately 85 non-homologous proteins in the human genome. Moreover, metabolic pathway and subcellular location analysis were performed for essential bacterial genes, to describe their role in various cellular processes. Only two essential proteins (Acyl-[acyl-carrier-protein]-UDP-N acetyl glucosamine O-acyltransferase and D-alanine-D-alanine ligase) as candidate for potent targets were found in proteome of the pathogen, in order to design new drugs. An online tool, Swiss model was employed to model the 3D structures of both target proteins. A library of 5000 phytochemicals was docked against those proteins through the molecular operating environment (MOE). That resulted in to eight inhibitors for both proteins i.e. enterodiol, aloin, ononin and rhinacanthinF for the Acyl-[acyl-carrier-protein]-UDP-N acetyl glucosamine O-acyltransferase, and rhazin, alkannin beta, aloesin and ancistrocladine for the D-alanine-D-alanine ligase. Finally the ADMET was done through ADMETsar. This study supported the development of natural as well as cost-effective drugs against S. maltophilia. These inhibitors displayed the effective binding interactions and safe drug profiles. However, further in vivo and in vitro validation experiment might be performed to check their drug effectiveness, biocompatibility and their role as effective inhibitors.