Maltophilia Infection Research Articles

Stenotrophomonas maltophilia natural history and evolution in the airways of adults with cystic fibrosis.

Stenotrophomonas maltophilia is an opportunistic pathogen infecting persons with cystic fibrosis (pwCF) and portends a worse prognosis. Studies of S. maltophilia infection dynamics have been limited by cohort size and follow-up. We investigated the natural history, transmission potential, and evolution of S. maltophilia in a large Canadian cohort of 321 pwCF over a 37-year period. One-hundred sixty-two isolates from 74 pwCF (23%) were typed by pulsed-field gel electrophoresis, and shared pulsotypes underwent whole-genome sequencing. S. maltophilia was recovered at least once in 82 pwCF (25.5%). Sixty-four pwCF were infected by unique pulsotypes, but shared pulsotypes were observed between 10 pwCF. In chronic carriage, longer time periods between positive sputum cultures increased the likelihood that subsequent isolates were unrelated. Isolates from individual pwCF were largely clonal, with differences in gene content being the primary source of genetic diversity objectified by gene content differences. Disproportionate progression of CF lung disease was not observed amongst those infected with multiple strains over time (versus a single) or amongst those with shared clones (versus strains only infecting one patient). We did not observe evidence of patient-to-patient transmission despite relatedness between isolates. Twenty-four genes with ≥ 2 mutations accumulated over time were identified across 42 sequenced isolates from all 11 pwCF with ≥ 2 sequenced isolates, suggesting a potential role for these genes in adaptation of S. maltophilia to the CF lung. Genomic analyses suggested common, indirect sources as the origins of S. maltophilia infections in the clinic population. The information derived from a genomics-based understanding of the natural history of S. maltophilia infection within CF provides unique insight into its potential for in-host evolution.

Steno-sphere: Navigating the enigmatic world of emerging multidrug-resistant Stenotrophomonas maltophilia.

Stenotrophomonas maltophilia is an opportunistic pathogen and frequent cause of serious nosocomial infections. Patient populations at greatest risk for these infections include the immunocompromised and those with chronic respiratory illnesses and prior antibiotic exposure, notably to carbapenems. Its complex virulence and resistance profile drastically limit available antibiotics, and incomplete breakpoint and pharmacokinetic/pharmacodynamic (PK/PD) data to inform dose optimization further complicates therapeutic approaches. Clinical comparison data of first-line agents, including trimethoprim-sulfamethoxazole (TMP-SMX), quinolones, and minocycline, are limited to conflicting observational data with no clear benefit of a single agent or combination therapy. Newer antibiotic approaches, including cefiderocol and aztreonam- avibactam, are promising alternatives for extensively drug-resistant isolates; however, clinical outcomes data are needed. The potential clinical utility of bacteriophage for compassionate use in treating S. maltophilia infections remains to be determined since data is limited to in-vitro and sparse in-vivo work. This article provides a review of available literature for S. maltophilia infection management focused on related epidemiology, resistance mechanisms, identification, susceptibility testing, antimicrobial PK/PD, and emerging therapeutic strategies.

In vitro susceptibilities of Stenotrophomonas maltophilia isolates to antimicrobial agents commonly used for related infections: Results from the Antimicrobial Testing Leadership and Surveillance (ATLAS) program, 2004-2020

Stenotrophomonas maltophilia is an emerging opportunistic pathogen and therapeutic options are limited because of intrinsic multidrug resistance. We collected S. maltophilia isolates as a part of the Antimicrobial Testing Leadership and Surveillance (ATLAS) program and determined minimuminhibitory concentrations (MICs) through broth microdilution methods. The susceptibility was interpreted according to the Clinical and Laboratory Standards Institute (CLSI) breakpoints. Isolates with tigecycline MIC ≤ 2 mg/L were defined as susceptible by using the United States Food and Drug Administration criteria of Enterobacterales. A total of 2,330 S. maltophilia isolates were collected from 47 countries worldwide during 2004-2020 in the ATLAS program. Most patients were hospitalized (92.3%, 2151/2330) and respiratory tract infections (47.8%, 1114/2330) was the leading source. Minocycline had the highest susceptibility rate (98.8%), followed by levofloxacin, TMP-SMX, and ceftazidime (85.0%, 84.4%, and 53.7%, respectively). A total of 98.3% (2290/2330) of S. maltophilia isolates had tigecycline MIC ≤ 2 mg/L. Among the S. maltophilia isolates exhibiting resistance to levofloxacin and ceftazidime, 89.3% (150/168) and 97.3% (692/711), respectively, were susceptible to tigecycline. Eight countries provided more than 30 isolates and were selected for comparison. The geographic difference in antimicrobial resistance was found for levofloxacin, minocycline, and tigecycline resistance (all p <0.05) but not for ceftazidime (p = 0.467). In conclusion, our in vitro susceptibility data demonstrated that minocycline had the best susceptible rate than ceftazidime and levofloxacin. Additionally, our findings demonstrated that tigecycline could be an alternative or salvage option for the treatment of S. maltophilia infections.

P230 The microbiome of cystic fibrosis (CF) sputum and its association with incident Stenotrophomonas maltophilia (SM) infections

In persons with CF (pwCF) SM infection associates with chronic inflammation and lung function decline. We sought to elucidate the factors of the CF lower airway microbiome that associate with SM incident infection and persistence risk.

Molecular Epidemiology of Stenotrophomonas maltophilia Strains Isolated from Bacteremia in Hospitalized Children.

The aim of this study was to determine the phenotypic and genotypic characteristics of Stenotrophomonas maltophilia isolates obtained from blood culture samples of pediatric patients hospitalized in Borujerd and Hamadan hospitals in western Iran. Oxidase-negative isolates were collected from the blood cultures of pediatric patients. S. maltophilia isolates were identified and confirmed by routine microbiological and molecular testing. Antibiotic susceptibility of the isolates was determined. The phenotypic and genotypic biofilm-forming ability of the isolates were investigated. Molecular typing of all isolates was performed by repetitive element sequence-based polymerase chain reaction. Out of 450 oxidase-negative bacilli, 72 (16.0%) were identified as S. maltophilia isolates. Biofilm assay results showed strong biofilm formation in 19 (26.4%) isolates, moderate in 38 (52.8%), weak in 10 (13.9%), and no biofilm formation in five (6.9%) isolates. Biofilm-associated genes rmlA, rpfF, and spgM were detected respectively in 59 (81.9%), 54 (75.0%), and 72 (100%) of isolates. Antimicrobial susceptibility testing showed that 67 (93.1%) isolates were sensitive to trimethoprim-sulfamethoxazole. All isolates were sensitive to levofloxacin and resistant to ceftazidime. The S. maltophilia isolates were grouped into 14 different types of repetitive sequence by repetitive element sequence-based polymerase chain reaction analysis. The results of this study indicate that S. maltophilia should be considered an important opportunistic pathogen in pediatric units. Different genotypes of S. maltophilia with the ability to form a biofilm (an important virulence factor) were circulating in the hospitals investigated. Levofloxacin and trimethoprim-sulfamethoxazole are recommended to treat S. maltophilia infections.

Improved mini-Tn7 Delivery Plasmids for Fluorescent Labeling of Stenotrophomonas maltophilia.

Fluorescently labeled bacterial cells have become indispensable for many aspects of microbiological research, including studies on biofilm formation as an important virulence factor of various opportunistic bacteria of environmental origin such as Stenotrophomonas maltophilia. Using a Tn7-based genomic integration system, we report the construction of improved mini-Tn7 delivery plasmids for labeling of S. maltophilia with sfGFP, mCherry, tdTomato and mKate2 by expressing their codon-optimized genes from a strong, constitutive promoter and an optimized ribosomal binding site. Transposition of the mini-Tn7 transposons into single neutral sites located on average 25 nucleotides downstream of the 3'-end of the conserved glmS gene of different S. maltophilia wild-type strains did not have any adverse effects on the fitness of their fluorescently labeled derivatives. This was demonstrated by comparative analyses of growth, resistance profiles against 18 antibiotics of different classes, the ability to form biofilms on abiotic and biotic surfaces, also independent of the fluorescent protein expressed, and virulence in Galleria mellonella. It is also shown that the mini-Tn7 elements remained stably integrated in the genome of S. maltophilia over a prolonged period of time in the absence of antibiotic selection pressure. Overall, we provide evidence that the new improved mini-Tn7 delivery plasmids are valuable tools for generating fluorescently labeled S. maltophilia strains that are indistinguishable in their properties from their parental wild-type strains. IMPORTANCE The bacterium S. maltophilia is an important opportunistic nosocomial pathogen that can cause bacteremia and pneumonia in immunocompromised patients with a high rate of mortality. It is now considered as a clinically relevant and notorious pathogen in cystic fibrosis patients but has also been isolated from lung specimen of healthy donors. The high intrinsic resistance to a wide range of antibiotics complicates treatment and most likely contributes to the increasing incidence of S. maltophilia infections worldwide. One important virulence-related trait of S. maltophilia is the ability to form biofilms on any surface, which may result in the development of increased transient phenotypic resistance to antimicrobials. The significance of our work is to provide a mini-Tn7-based labeling system for S. maltophilia to study the mechanisms of biofilm formation or host-pathogen interactions with live bacteria under non-destructive conditions.

Stenotrophomonas maltophilia Infections: A Systematic Review and Meta-Analysis of Comparative Efficacy of Available Treatments, with Critical Assessment of Novel Therapeutic Options.

PubMed/MEDLINE and Embase were searched from inception to 30 November 2022. The primary outcome was all-cause mortality. Secondary outcomes included clinical failure, adverse events, and length of stay. A random effects meta-analysis was performed. This study was registered with PROSPERO (CRD42022321893). Twenty-four studies, all retrospective, were included. A significant difference in terms of overall mortality was observed when comparing as a monotherapy TMP/SMX versus FQs (odds ratio (OR) 1.46, 95% confidence interval (CI) 1.15-1.86, I2 = 33%; 11 studies, 2407 patients). The prediction interval (PI) did not touch the no effect line (1.06-1.93), but the results were not robust for the unmeasured confounding (E-value for point estimate of 1.71). When comparing TMP/SMX with TDs, the former showed an association with higher mortality but not significant and with a wide PI (OR 1.95, 95% CI 0.79-4.82, PI 0.01-685.99, I2 = 0%; 3 studies, 346 patients). Monotherapies in general exerted a protective effect against death opposed to the combination regimens but were not significant (OR 0.71, 95% CI 0.41-1.22, PI 0.16-3.08, I2 = 0%; 4 studies, 438 patients). Against SM infections, FQs and, possibly, TDs seem to be reasonable alternative choices to TMP/SMX. Data from clinical trials are urgently needed to better inform therapeutic choices in this setting by also taking into account newer agents.

Stenotrophomonas maltophilia : An Emerging Pathogen in Chronic Granulomatous Disease.

Reports of infections with Stenotrophomonas maltophilia in primary immunodeficiency diseases are scarce. We report 3 children with chronic granulomatous disease (CGD) who developed infections due to S. maltophilia (1- septicemia and 2- pneumonia). We propose that CGD is a risk factor for the development of S. maltophilia infections and children with unexplained S. maltophilia infections need to be worked up for CGD.

&lt;i&gt;Stenotrophomonas maltophilia&lt;/i&gt; Infection in Trauma and Orthopedic Patients: Clinical Experience and Review

Background. Stenotrophomonas maltophilia (S. maltophilia) is a gram-negative non-fermenting bacillus and is a rare pathogen of orthopedic infection. Due to the relatively low virulence of S. maltophilia, many clinicians are still faced with the question of whether this bacterial species is simply a colonizing agent or the true cause of infection.&#x0D; Aim of the study to raise the awareness of practitioners about S. maltophilia as a rare pathogen of orthopedic infection.&#x0D; Methods. A retrospective analysis was performed concerning the frequency of S. maltophilia isolation from patients treated at the Vreden Center for periprosthetic infection and/or osteomyelitis from January 1, 2009 to October 31, 2022. The literature search by keywords was carried out in the PubMed/MEDLINE, Scopus, eLIBRARY, and Cyberleninka databases. The search retrieved 587 articles published in Russian or English over the period from 2012 to November 2022.&#x0D; Results. During the study period, 9 cases of orthopedic monoinfection with S. maltophilia were identified in 9 patients aged 36 to 83 years. At the time of admission, no leukocytosis was detected in patients, and only 2 of 9 patients had elevated C-reactive protein level. S. maltophilia is naturally resistant to many broad-spectrum antibiotics. Co-trimoxazole is considered the drug of choice for the treatment of S. maltophilia infection. The limited choice of drugs for targeted therapy, the presence of multiple determinants of antibiotic resistance, the existence of microbial associations and patient risks including implantation, chronic nature of infection, elderly age, as well as the presence of significant concomitant somatic pathology can lead to the ineffectiveness of the ongoing treatment of infections caused by S. maltophilia. Our experience shows that in the case of sensitivity of S. maltophilia strain to co-trimoxazole it is possible to prescribe this drug for a long course as monotherapy, provided that the radical surgical treatment of the focus is performed.

Fulminant Metastatic Cellulitis Caused by Stenotrophomonas Maltophilia Infection and Subsequent Candida Parapsilosis Fungemia After Cord Blood Transplantation

Stenotrophomonas maltophilia is known to be an opportunistic pathogen with intrinsic and acquired resistance mechanisms to multiple antibiotics. Bloodstream infection caused by S. maltophilia is a potentially fatal complication, especially in recipients of umbilical cord blood transplantation (CBT). Infrequent reports of S. maltophilia skin and soft tissue infections (SSTIs), including metastatic cellulitis and ecthyma gangrenosum, have been reported as wound infections. Metastatic cellulitis lesions due to S. maltophilia are typically reported to be tender, erythematous, and to show warm subcutaneous infiltration. There are only a few available reports about the clinical course of metastatic cellulitis due to S. maltophilia. We experienced a case involving the development of metastatic cellulitis with fulminant and extensive exfoliation in a patient who underwent CBT. Despite controlling the bloodstream infection caused by S. maltophilia, the patient succumbed to secondary fungal infection due to the devastation of the skin barrier. Our case highlights that SSTIs due to S.maltophilia can cause the unexpected development of fulminant metastatic cellulitis with systemic epidermal peeling in severely immunocompromised hosts, including CBT recipients undergoing steroid therapy.

Stenotrophomonas maltophilia İnfeksiyonu Geçiren Hastaların Klinik Özelliklerinin İncelenmesi ve Mortaliteyle İlişkili Risk Faktörlerinin Araştırılması

Introduction: It is important to know the risk factors for death in reducing mortality in patients with Stenotrophomonas maltophilia infections. The purpose of this study was to examine the risk factors associated with mortality in hospitalized patients with S. maltophilia infections. Materials and Methods: Patients with S. maltophilia infections aged 18 years and older who were hospitalized in Haseki Research and Training between January 1, 2017, and April 30, 2022, were included in the study. The patients were divided into two groups, non-survivors and survivors, and the clinical features and laboratory parameters of the groups were compared. Mortality risk factors were analyzed by logistic and Cox regression analyses. Results: A total of 75 patients with S. maltophilia infections were included. The mortality rate was 38.6% (n= 29). Advanced age (OR= 1.05, 95% CI= 1.012-1.085, p= 0.009), COVID-19 pneumonia (OR= 9.52, 95% CI= 1.255-72.223, p= 0.029), and presence of central venous catheter (CVC) (OR= 18.25, 95% CI= 2.187-152.323, p= 0.007) were risk factors for death. Conclusion: Physicians should be aware of the potential risk of S. maltophilia infections for mortality, particularly in patients with predefined risk factors such as advanced age, the presence of CVC, and COVID-19. Performing CVC care in accordance with infection prevention and control measures and timely removal of CVC may be beneficial in reducing deaths due to S. maltophilia infection.

Association between minimum inhibitory concentration values and mortality risk in patients with Stenotrophomonas maltophilia infections: a retrospective cohort study of electronic health records from 148 US hospitals.

Clinical data informing antimicrobial susceptibility breakpoints for Stenotrophomonas maltophilia infections are lacking. We sought to leverage real-world data to identify MIC values within the currently defined susceptible range that could discriminate mortality risk for patients with S. maltophilia infections and guide future breakpoint revisions. Inpatients with S. maltophilia infection who received single-agent targeted therapy with levofloxacin or trimethoprim/sulfamethoxazole were identified in the Cerner HealthFacts electronic health record database. Encounters were restricted to those with MIC values reported to be in the susceptible range for both agents. Curation for exact (non-range) MIC values yielded sequentially granular model populations. Logistic regression was used to calculate adjusted OR (aOR) of mortality or hospice discharge associated with different susceptible-range MICs, controlling for patient- and centre-related factors, and infection site, polymicrobial infection and receipt of empirical therapy. Seventy-three of 851 levofloxacin-treated patients had levofloxacin MIC of exactly 2 mg/L (current Clinical and Laboratory Standards Institute (CLSI) susceptibility breakpoint) and served as the reference category for levofloxacin breakpoint models. In breakpoint model I (n = 501), aOR of mortality associated with infection due to isolates with levofloxacin MIC of ≤1 versus 2 mg/L were similar [aOR = 1.79 (95% CI 0.88-3.62), P = 0.11]. In breakpoint model IIa (n = 358), aOR of mortality associated with MIC ≤0.5 versus 2 mg/L were also similar [aOR 0.1.36 (95% CI 0.65-2.83), P = 0.41]. However, breakpoint model IIb (n = 297) displayed higher aOR of mortality associated with an MIC of 1 versus 2 mg/L [aOR 2.36 (95% CI 1.14-4.88), P = 0.02]. Only 9/645 trimethoprim/sulfamethoxazole-treated patients had trimethoprim/sulfamethoxazole MIC of exactly 2/38 mg/L precluding informative models for this agent. In this retrospective study of real-world patients with S. maltophilia infection, risk-adjusted survival data do not appear to stratify patients clinically within current susceptible-range MIC breakpoint for levofloxacin (≤2 mg/L) by mortality.

Genotypic Diversity, Antibiotic Resistance, and Virulence Phenotypes of Stenotrophomonas maltophilia Clinical Isolates from a Thai University Hospital Setting.

Stenotrophomonas maltophilia is a multidrug-resistant organism that is emerging as an important opportunistic pathogen. Despite this, information on the epidemiology and characteristics of this bacterium, especially in Thailand, is rarely found. This study aimed to determine the demographic, genotypic, and phenotypic characteristics of S. maltophilia isolates from Maharaj Nakorn Chiang Mai Hospital, Thailand. A total of 200 S. maltophilia isolates were collected from four types of clinical specimens from 2015 to 2016 and most of the isolates were from sputum. In terms of clinical characteristics, male and aged patients were more susceptible to an S. maltophilia infection. The majority of included patients had underlying diseases and were hospitalized with associated invasive procedures. The antimicrobial resistance profiles of S. maltophilia isolates showed the highest frequency of resistance to ceftazidime and the lower frequency of resistance to chloramphenicol, levofloxacin, trimethoprim/sulfamethoxazole (TMP/SMX), and no resistance to minocycline. The predominant antibiotic resistance genes among the 200 isolates were the smeF gene (91.5%), followed by blaL1 and blaL2 genes (43% and 10%), respectively. Other antibiotic resistance genes detected were floR (8.5%), intI1 (7%), sul1 (6%), mfsA (4%) and sul2 (2%). Most S. maltophilia isolates could produce biofilm and could swim in a semisolid medium, however, none of the isolates could swarm. All isolates were positive for hemolysin production, whereas 91.5% and 22.5% of isolates could release protease and lipase enzymes, respectively. In MLST analysis, a high degree of genetic diversity was observed among the 200 S. maltophilia isolates. One hundred and forty-one sequence types (STs), including 130 novel STs, were identified and categorized into six different clonal complex groups. The differences in drug resistance patterns and genetic profiles exhibited various phenotypes of biofilm formation, motility, toxin, and enzymes production which support this bacterium in its virulence and pathogenicity. This study reviewed the characteristics of genotypes and phenotypes of S. maltophilia from Thailand which is necessary for the control and prevention of S. maltophilia local spreading.

Risk Factors for Infection and Mortality Associated With Stenotrophomonas maltophilia Bloodstream Infections in Children; Comparison With Pseudomonas aeruginosa Bloodstream Infections.

The increasing incidence of Stenotrophomonas maltophilia ( S. maltophilia ) infections raises concern because of the high fatality/case ratio. This study aimed to evaluate the risk factors for infection and mortality associated with S. maltophilia bloodstream infections (BSIs) in children and compare them with Pseudomonas aeruginosa BSIs. All BSIs caused by S. maltophilia (n:73) and P. aeruginosa (n:80) were enrolled in this study between January 2014 and December 2021 at the Medical School of Ege University. Previous Pediatric Intensive Care Unit (PICU) admission, prior glycopeptide, and carbapenem use were significantly more common in patients with S. maltophilia BSIs ( P = 0.044, P = 0.009, and P = 0.001, respectively) than with P. aeruginosa BSIs. C-reactive protein (CRP) levels were significantly higher in S. maltophilia BSIs ( P = 0.002). Multivariate analysis showed that prior carbapenem use was associated with S. maltophilia BSIs ( P = 0.014, adjusted odds ratio [AOR]: 2.710; 95% confidence interval [CI]: 1.225-5.992). PICU admission because of BSI, prior carbapenem and glycopeptide use, neutropenia, and thrombocytopenia were significantly more common in patients with mortality because of S. maltophilia BSIs ( P < 0.001, P = 0.010, P = 0.007, P = 0.008, P = 0.004, respectively), while only PICU admission because of BSI, and prior glycopeptide use were significant in multivariate analysis (AOR, 19.155; 95% CI: 2.337-157.018; P = 0.006 and AOR, 9.629; 95% CI: 1.053-88.013; P = 0.045, respectively). Prior carbapenem use is a significant risk factor for developing S. maltophilia BSIs. PICU admission because of BSI and prior glycopeptide use are risk factors associated with the mortality rate in patients with S. maltophilia BSIs. Therefore, S. maltophilia should be considered in patients with these risk factors, and empirical treatment should include antibiotics for S. maltophilia .

Stenotrophomonas maltophilia: A Case Series and Review for an Uncommon Cause of Peritoneal Dialysis-Associated Infection

Peritonitis is a common and potentially serious complication of peritoneal dialysis (PD). Common organisms include Staphylococcus Aureus, enterococci, and coagulase-negative staphylococcus. However, Stenotrophomonas maltophilia (S. maltophilia) is an uncommon cause of PD-related infection. We describe a series of three cases of S. maltophilia PD infection (two cases of PD peritonitis and one case of PD exit-site infection) that were identified over a seven-week period in a single centre. The cases were treated with antibiotics (the primary antibiotic being co-trimoxazole) for a mean duration of 30 ± 7.9 days. All of the patients required PD catheter removal due to treatment failure with antibiotics. Hospital admission was required in two of the cases and one case resulted in mortality, with the cause of death directly associated with complications from S. maltophilia infection. A multi-disciplinary team using root-cause analysis did not identify a common link between our cases but highlighted possible risk factors contributing to these presentations. Given the relative rarity of S. maltophilia, evidence on its management options remains limited. In this article, we draw upon our own experiences and examine the literature available from previously published case reports and series. These reports highlight S. maltophilia as a complex and challenging organism to treat. Our experience demonstrated the importance of early PD catheter removal in S. maltophilia PD infection, as this is likely more effective than prolonged antibiotic therapy and hence a safer management option, considering the resistant nature of S. maltophilia.

Stenotrophomonas maltophilia Epidemiology, Resistance Characteristics, and Clinical Outcomes: Understanding of the Recent Three Years' Trends.

Stenotrophomonas maltophilia is an emerging pathogen classified as a public health concern, that infects critically ill patients and has expressed resistance against antimicrobial therapy. The aim of this study was to examine the epidemiological pattern, resistance characteristics and clinical outcomes of S. maltophilia infections in hospitalized patients. The study included 393 S. maltophilia isolates from different clinical specimens as well as the clinical data of 209 Intensive Care Unit (ICU) patients. The patients' data were obtained from medical and laboratory files. Descriptive statistics and a univariate analysis were used to report and compare the demographics, clinical data, and outcomes. The S. maltophilia was mostly isolated from the respiratory specimens of ICU patients. The adult patients were more likely to develop serious infections and worse outcomes than were pediatric patients. The most common co-infecting pathogens were SARS-CoV2 and Pseudomonas aeruginosa. The death rate was 44.5% and increased to 47.1% in the case of a respiratory infection. Septic shock was the most significant predictor of mortality. Older age and mechanical ventilation were independent and significant risk factors that worsened the outcomes in patients with respiratory infections. The identification of S. maltophilia as a threat highlights the importance of surveillance studies in this region.

451: MANAGEMENT OF STENOTROPHOMONAS MALTOPHILIA PNEUMONIA IN MECHANICALLY VENTILATED PATIENTS

Introduction: Stenotrophomonas maltophilia is a gram negative opportunistic pathogen that most often causes infections in critically ill patients. S. maltophilia infections are associated with high morbidity and mortality. Common treatment options include sulfamethoxazole/trimethoprim (SMX/TMP), levofloxacin, and tetracyclines. SMX/TMP has been shown to have resistance rates up to 19%, and levofloxacin has shown minimal resistance rates (2%). Regardless of resistance rates, S. maltophilia is associated with a treatment failure rate of around 30%. The objective of this study is to evaluate the effectiveness of monotherapy treatment with SMX/TMP or levofloxacin in critically ill patients with S. maltophilia pneumonia on mechanical ventilation. Methods: Retrospective analysis of patients >/=18 years of age with a positive respiratory culture for S. maltophilia between January 1, 2018, to August 31, 2021. At the time of culture patients must have been on mechanical ventilation for at least 48 hours and treated with monotherapy SMX/TMP or levofloxacin for at least 48 hours. Patients were excluded if they received less than 48 hours of monotherapy, received concomitant treatment with an additional agent with activity agents S. maltophilia (minocycline, ceftazidime, cefiderocol), were pregnant, received combination therapy, had a diagnosis of cystic fibrosis, or had a history of S. maltophila positive culture within the previous 12 months. Results: A total of 105 patients were assessed for eligibility and 92 met inclusion criteria. Of these patients, 51 (55%) received SMX/TMP and 41 (45%) received levofloxacin. Treatment failure occurred more often in those treated with levofloxacin 20% compared to SMX/TMP 16%, p=0.045. Mortality was greater in the levofloxacin group 37% vs. 15%, p=0.011. Clinical cure, 30-day microbiological cure, ICU length of stay and hospital length of stay were similar between groups. Acute kidney injury occurred significantly more in patients treated with SMX/TMP. Conclusions: SMX/TMP was associated with less treatment failure and mortality compared to levofloxacin when treating S. maltophilia pneumonia in patients on mechanical ventilation. A large multicenter cohort study comparing SMX/TMP and levofloxacin is warranted to validate these findings.

Treatment, clinical outcomes, and predictors of mortality among a national cohort of hospitalized patients with Stenotrophomonas maltophilia infection

ObjectivesTo analyze treatment, clinical outcomes, and predictors of inpatient mortality in hospitalized patients with Stenotrophomonas maltophilia infection. Study designRetrospective cohort study. MethodsWe included patients admitted to Veterans Affairs hospitals nationally with S. maltophilia cultures and treatment from 2010 to 2019. We described patient and clinical characteristics, antibiotic treatment, and clinical outcomes. Univariate and multivariable logistic regression were used to evaluate predictors of inpatient mortality. ResultsWe identified 3891 hospitalized patients treated for an S. maltophilia infection, of which 13.7% died during admission. The most common antibiotic agents were piperacillin/tazobactam (39.7%), sulfamethoxazole/trimethoprim (23.3%), and levofloxacin (23.2%). Combination therapy was used in 16.6% of patients. Independent predictors of inpatient mortality identified in multivariable analysis included the following: presence of current acute respiratory failure (adjusted odds ratio [aOR] 4.74, 95% confidence interval [CI] 3.63–6.19), shock (aOR 3.00, 95% CI 2.31–3.90), acute renal failure (aOR 2.06, 95% CI 1.64–2.60), and septicemia (aOR 1.90, 95% CI 1.49–2.42), age 65 years and older (aOR 2.05, 95% CI 1.07–3.94, reference age 18–49 years), hospital-acquired infection (aOR 1.87, 95% CI 1.48–2.37), Black (aOR 1.58, 95% CI 1.21–2.06) and other races (aOR 1.65, 95% CI 1.41–2.41, reference White), liver disease (aOR 1.51, 95% CI 1.02–2.22), and median Charlson comorbidity score or higher (aOR 1.36, 95% CI 1.08–1.71, reference less than median). Clinical outcomes were similar between patients infected with sulfamethoxazole/trimethoprim-resistant, levofloxacin-resistant, and multidrug-resistant S. maltophilia strains compared to non-resistant strains. ConclusionsIn our national cohort of hospitalized patients with S. maltophilia infection, 13.7% of patients died during admission and several predictors of inpatient mortality were identified. Predictors related to the severity of infection were among the strongest identified. It is important that in severely ill patients presenting to the hospital, S. maltophilia be considered as a cause.

Combination Therapy versus Monotherapy in the Treatment of Stenotrophomonas maltophilia Infections: A Systematic Review and Meta-Analysis.

Stenotrophomonas maltophilia is a multidrug-resistant bacterium that is difficult to treat in hospitals worldwide, leading to high mortality. Published data describing the use of monotherapy or combination therapy and which one is better is still unclear. We aimed to investigate the efficacy of monotherapy and combination therapy in the treatment of S. maltophilia infections. We performed a systematic review of combination therapy and additionally a systematic review and meta-analysis to determine the effects of monotherapy versus combination therapy on mortality in S. maltophilia infections. Electronic databases: Cochrane Library, PubMed, Embase, ClinicalTrials.gov, Scopus, and OpenGrey were accessed. Of the 5030 articles identified, 17 studies were included for a systematic review of combination therapy, of which 4 cohort studies were finally included for meta-analysis. We found there is a trend of favorable outcomes with respect to mortality in the use of combination therapy to treat complex or severe S. maltopholia infections. A meta-analysis of monotherapy showed a statistical significance in the decreasing rate of mortality in hospital-acquired pneumonia (hazard ratio 1.42; 95% confidence interval, 1.04-1.94) compared to combination therapy, but not significant in bacteremia (hazard ratio 0.76; 95% confidence interval, 0.18-3.18). Further studies should continue to explore this association.

The sbiTRS Operon Contributes to Stenobactin-Mediated Iron Utilization in Stenotrophomonas maltophilia.

Iron is an essential micronutrient for various bacterial cellular processes. Fur is a global transcriptional regulator participating in iron homeostasis. Stenotrophomonas maltophilia is a ubiquitous environmental bacterium that has emerged as an opportunistic pathogen. To elucidate the novel regulatory mechanism behind iron homeostasis in S. maltophilia, wild-type KJ and KJΔFur, a fur mutant, were subjected to transcriptome assay. A five-gene cluster, sbiBA-sbiTRS, was significantly upregulated in KJΔFur. SbiAB is an ATP type efflux pump, SbiT is an inner membrane protein, and SbiSR is a two-component regulatory system (TCS). The sbiTRS operon organization was verified by reverse transcription-PCR (RT-PCR). Localization prediction and bacterial two-hybrid studies revealed that SbiT resided in the inner membrane and had an intramembrane interaction with SbiS. In iron-replete conditions, SbiT interacted with SbiS and maintained SbiSR TCS in a resting state. In response to iron depletion stress, SbiT no longer interacted with SbiS, leading to SbiSR TCS activation. The iron source utilization assay demonstrated the contribution of SbiSR TCS to stenobactin-mediated ferric iron utilization but notto the utilization of hemin and ferric citrate. Furthermore, SmeDEF and SbiAB pumps, known stenobactin secretion outlets, were members of the SbiSR regulon. Collectively, in an iron-depleted condition, SbiSR activation is regulated by Fur at the transcriptional level and by SbiT at the posttranslational level. Activated SbiSR contributes to stenobactin-mediated ferric iron utilization by upregulating the smeDEF and sbiAB operons. SbiSR is the first TCS found to be involved in iron homeostasis in S. maltophilia. IMPORTANCE Therapeutic options for Stenotrophomonas maltophilia infections are limited because S. maltophilia is intrinsically resistant to several antibiotics. Iron is an essential element for viability, but iron overload is a lethal threat to bacteria. Therefore, disruption of iron homeostasis can be an alternative strategy to cope with S. maltophilia infection. The intricate regulatory networks involved in iron hemostasis have been reported in various pathogens; however, little is known about S. maltophilia. Herein, a novel sbiTRS operon, a member of Fur regulon, was characterized. SbiT, an inner membrane protein, negatively modulated the SbiSR two-component regulatory system by intramembrane protein-protein interaction with SbiS. In response to iron-depleted stress, SbiSR was activated via the regulation of Fur and SbiT. Activated SbiSR upregulated smeDEF and sbiAB, which contributed to stenobactin-mediated ferric iron utilization. A novel fur-sbiT-sbiSR-smeDEF/sbiAB regulatory circuit in S. maltophilia was revealed.