Maltophilia Infection Research Articles

Stenotrophomonas maltophilia – A Threatening Nosocomial Pathogen

Abstract Stenotrophomonas maltophilia is a ubiquitous Gram-negative rod which has emerged as one of the major causes of nosocomial infections. It can cause pneumonia, septicemia, meningitis, urinary tract, and wound infections, and is associated with high mortality in immune-compromised patients. Pathogenesis in S. maltophilia infections is an outcome of multiple virulence factors, including outer membrane lipopolysaccharide, extracellular enzymes, porins, pilli, biofilm formation, motility, and small colony variants, among others. S. maltophilia shows high intrinsic and acquired resistance to all commonly used antibiotics, limiting the number of therapeutic choices. The aim of this review is to summarize the virulence factors, antibiotic resistance mechanisms, diagnosis, and treatment of S. maltophilia infections.

Characterization and genomic analysis of phage vB_SmaP_c9-N, a novel Stenotrophomonas maltophilia podophage with antibiofilm activity.

Stenotrophomonas maltophilia strains are increasingly emerging as multidrug-resistant pathogens. Moreover, S. maltophilia commonly produces biofilms that enhance antibiotic resistance in bacteria. Phages are effective alternative drugs for treating S. maltophilia infections. In this study, the lytic phage vB_SmaP_c9-N (abbreviated as Φc9-N), which is specific for S. maltophilia, was isolated from Nanhu Lake, Wuhan, China. Electron microscopy observation revealed that Φc9-N is a podophage. Φc9-N is stable over a wide pH range, from pH 4 to 10, and its activity did not change after storage at 4°C for 2months. The latency period of Φc9-N is 5 min, and its outbreak period is 35min. Antibacterial tests showed that Φc9-N could effectively inhibit the growth of S. maltophilia c24. Moreover, the biofilm production of S. maltophilia c24 decreased when Φc9-N was administered either to the forming biofilm or to the mature biofilm. These results suggest that Φc9-N has application potential in clinical treatment. The genome of Φc9-N is a dsDNA of 43,170 bp with 55 putative unidirectional genes, 18 of which were assigned putative functions, while other genes encoded hypothetical proteins. Genome sequence comparisons and phylogenetic analysis indicated that Φc9-N represents a new species, and, together with the Stenotrophomonas phages BUCT700, BUCT703, BUCT598, and vB_SmaS_P15, can be included in the newly proposed genus "Maltovirus" in the family Autographiviridae.

Analysis of Stenotrophomonas maltophilia infections in lower respiratory tract samples at a university hospital: 5 year data

Objectives Patients with reported Stenotrophomonas maltophilia (S. maltophilia) growth in lower respiratory tract samples were investigated. The results of these patients were assessed by clinicians as either infection or colonization. The data of patients considered to have S. maltophilia infection were compared to those considered to have colonization to explore factors associated with infection. Methods Parameters including as age, length of hospital stay, duration of S. maltophilia growth after hospital admission, sex, unit, department, specimen type, mechanical ventilation treatment status, antimicrobial susceptibility results, comorbidities, survival, and antimicrobials used during the period from hospital admission to S. maltophilia growth were investigated. Additionally, some biochemical parameters that were examined include the day of hospital admission, the day of sample collection when the bacterium was isolated (±1 day), and the day of discharge/died. Results The infection group had a significantly higher rate of admissions to internal medical departments and more cases of discharge/died. The infection group showed a lower amount of aminoglycoside antibiotic usage and significantly higher levels of BUN, creatinine, neutrophils, and neutrophil-to-lymphocyte ratio on their day of discharge/died. Conclusion Being admitted to internal medical departments and receiving aminoglycoside treatment were identified to be factors associated with S. maltophilia infection. These patients should be monitored for infection markers such as CRP and neutrophil count, as well as renal function tests. It should be noted that being infected with S. maltophilia is an independent risk factor for mortality. Bangladesh Journal of Medical Science Vol. 23 No. 04 October’24 Page : 1095-1103

A-254 Increase of Stenotrophomonas maltophilia Isolates Non-Susceptible to Trimethoprim-Sulfamethoxazole and/or Levofloxacin at Brazilian Hospitals

Abstract Background Stenotrophomonas maltophilia is an emerging multidrug-resistant pathogen that exhibits intrinsic and acquired resistance to a wide variety of antimicrobial agents such as β-lactams, aminoglycosides, quinolone, tetracyclines and disinfectants. In addition to that, the increased resistance to sulfamethoxazole/trimethoprim (SMX/TMP) and Levofloxacin has been reported in the past few years, leading to few therapeutic options. This study aimed to describe the increase of Stenotrophomonas maltophilia clinical isolates recovered from Brazilian hospitals over a 6-year analysis (January 2018 to December 2023). Methods This study design was a retrospective, observational analysis based on microbiological data of emergent BGN-NF isolates detected in several Brazilian tertiary hospitals. The bacterial identification was performed by Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF/MS) and the antimicrobial susceptibility profile to trimethoprim-sulfamethoxazole and levofloxacin was determined using disk-diffusion method and epsilometer method, respectively. Only one sample per patient was considered in this analysis. Results During the 6 year period, a total of 1,706 (2018; 221), (2019; 203), (2020; 294), (2021; 276), (2022; 294) and (2023; 418) Stenotrophomonas maltophilia strains were isolated from blood (n=626), respiratory tract (n=365), fluid and secretion (n=235), skin and soft tissue (n=162), urine (n=132), catheter tip (n=112), swab (n=36), bone fragment (n=29) and cerebrospinal fluid (n=9). The major frequency of S. maltophilia isolation occurred among man (52.6%) and the main age range was over 60 years (42.7%), while 0-10 comprised 16.6% of cases. Compared the 6-years period, the resistance rate to trimethoprim-sulfamethoxazole was 2.7%; 5.4%; 5.8%; 2.2%; 5.8%; 7.9% and levofloxacin was 3.6%; 3.4%; 3.1%; 3.3%; 1.7%; 2.9%, respectively. The resistance rate to trimethoprim-sulfamethoxazole and levofloxacin, simultaneously, was 0.23%. Conclusions The incidence rate of S. maltophilia infections has increased significantly, especially in the last year, followed by an increase in the pattern of resistance to trimethoprim-sulfamethoxazole. Regarding trimethoprim-sulfamethoxazole and levofloxacin co-resistance, very low rates were detected in our analysis. Our data point to a scenario wherein the presence of S. maltophilia may have been intensified by the covid-19 pandemic. Regional surveillance reports are extremely important and should be out to understand some aspects of the dynamics of bacterial resistance in both hospital and community settings.

Stenotrophomonas Maltophilia Infection in Cancer Patients Undergoing Major Surgery in A Tertiary Cancer Centre

Background: We aim to study the impact of postoperative Stenotrophomonas maltophilia infections among cancer patients undergoing major surgery. Methods: Ambispective, observational study. Study period from 1st November 2019 to 31st March 2024. The study population included patients with a definite diagnosis of cancer who underwent a major surgical procedure in a single, dedicated surgical unit and developed postoperative infection which showed a documented growth of Stenotrophomonas maltophilia. Clinical and laboratory parameters were collected and data represented as median values, percentages and range. Results: Nine patients were identified to have Stenotrophomonas maltophilia infection in the postoperative period among a total of 2506 patients. Co-morbid illnesses were noted in 33.3% patients; all were nosocomial infections. Fever was a manifestation in 77.8% patients, 44.4% had leukocytosis. Of all samples, 33.3% were respiratory ones. Co-infection was noted in 44.4% patients. Sensitivity to trimethoprim-sulphamethoxazole was seen in 44.4% and to levofloxacin in 66.7% isolates. Mortality rate was 11.1%. Conclusion: Stenotrophomonas maltophilia causes uncommon but clinically significant infections among cancer patients in the postoperative period.

Description, clinical impact and early outcome of S. maltophilia respiratory tract infections after lung transplantation, A retrospective observational study

Background and research questionS. maltophilia infections are associated with significant morbidity and mortality. Little is known regarding its presentation, management, and outcome in lung transplant recipients. Study design and MethodsThis retrospective case control study reviewed S. maltophilia respiratory tract infection in lung transplant recipients (01/01/2011-31/01/2020) and described the clinical, microbiological and outcome characteristics matched with lung transplant recipients without respiratory tract infection. Results and interpretationWe identified 63 S. maltophilia infections in lung transplant recipients. Among them none were colonized before transplantation. Infections occurred a median of 177 (IQR: 45- 681) days post transplantation. Fifty-four (85.7 %) patients received trimethoprim-sulfamethoxazole (400/80 mg three times a week) to prevent Pneumocystis jirovecii pneumonia (PJP). S. maltophilia strains were susceptible to trimethoprim-sulfamethoxazole, levofloxacin, minocycline and ceftazidime in respectively 85.7 %, 82.5 %, 96.8 % and 34.9 % of cases. Median duration of treatment was 9 days (IQR 7–11.5). Clinical and microbiological recurrence were observed in respectively 25.3 % and 39.7 % of cases. Combination therapy was not associated with a decrease in the risk of recurrence and did not prevent the emergence of resistance. S. maltophilia respiratory tract infection was associated with a decline in FEV-1 at one year. ConclusionS. maltophilia is an important cause of lower respiratory tract infection in lung transplant recipients. Trimethoprim-sulfamethoxazole use as prophylaxis for PJP doesn't prevent S. maltophilia infection among lung transplant recipients. Levofloxacin and trimethoprim-sulfamethoxazole appear to be the two molecules of choice for the treatment of these infections and new antibiotic strategies (cefiderocol, aztreonam/avibactam) are currently being evaluated for multi-resistant S. maltophilia infections.

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.

Effective strategies for managing trimethoprim-sulfamethoxazole and levofloxacin-resistant Stenotrophomonas maltophilia infections: bridging the gap between scientific evidence and clinical practice.

To discuss the therapeutic options available for the management of difficult-to-treat strains of Stenotrophomonas maltophilia (Sma), namely those resistant to trimethoprim-sulfamethoxazole and fluoroquinolones. Recent pharmacological studies have highlighted the fact that current breakpoints for first-line antibiotics against Sma are too high. In light of these data, it is likely that the prevalence of difficult-to-treat (DTR) Sma is underestimated worldwide. Two promising alternatives for treating DTR strains are cefiderocol and the combination of aztreonam and an L2 inhibitor. However, clinical trials are currently very limited for these antibiotics and no comparative studies have been carried out to date. It is important to note that the clinical efficacy of cefiderocol appears to be inferior to that initially anticipated from in-vitro and animal studies. Consequently, minocycline and ceftazidime may remain viable options if they are used against strains with a low minimum inhibitory concentration. We advise against the use of intravenous polymyxins and tigecycline. Finally, recent literature does not support the systematic use of combination therapy or long-course treatments. In the coming years, phage therapy may become a promising approach against DTR Sma infections. Overall, clinical comparative studies focused on DTR strains are required in order to provide more accurate and actionable information for therapeutic decisions.

A Case of Persistent Intra-Abdominal Stenotrophomonas maltophilia Infection Despite Bacteriophage Therapy.

Multidrug resistant infections are a challenge in the health care setting and a cause of patient morbidity and mortality. Bacteriophages (phages) are viruses that target and kill bacteria and have been used in patients to treat bacterial infections. We present a case of disseminated Stenotrophomonas maltophilia infection, with pulmonary, intra-abdominal and bloodstream involvement. The patient was treated with a combination of antibiotics and personalized phage therapy, administered daily for 12 days both intravenously as well as via intra-abdominal drains. Phage therapy was well-tolerated, the patient cleared S. maltophilia from their bloodstream and their intra-abdominal abscesses were stable or decreased in size. However, the intra-abdominal fluid cultures remained positive for S. maltophilia. Unfortunately, the patient passed away 2 months after completion of phage therapy due to multiorgan failure. These data highlight the difficulty of treating critically ill patients and clearing complex, biofilm mediated infections, even with phages. More information is needed regarding the optimal treatment protocols for phage therapy in complex multifocal infections.

A case of recurrent peritoneal dialysis-related peritonitis caused by Stenotrophomonas maltophilia during ongoing antibiotic treatment for Enterococcus faecalis-induced peritonitis.

Recurrent peritonitis is a serious complication of peritoneal dialysis (PD), which could result in PD withdrawal and mortality. However, cases of recurrent peritonitis occurring during ongoing antimicrobial therapy are rarely reported. Herein, we present a 71-year-old man who experienced initial peritonitis due to Enterococcus faecalis. Despite effective antimicrobial therapy, he developed recurrent peritonitis while on antimicrobial therapy. PD fluid culture analysis yielded Stenotrophomonas maltophilia (S. maltophilia). He was treated with multiple antimicrobials, and the peritoneal catheter was removed. To the best of our knowledge, this is the first case of recurrent peritonitis caused by S. maltophilia, which was developed during antimicrobial treatment. Our report findings suggest the importance of considering S. maltophilia infection in an atypical case of very early recurrent peritonitis.

A Retrospective Case Series of Stenotrophomonas maltophilia at an Acute Care Hospital in Alabama, July-November 2023

Background: In August 2023, an infection preventionist at an acute care hospital in Alabama recognized an increase in cases of Stenotrophomonas maltophilia, which is an emerging pathogen in clinical settings worldwide. It was not until the facility identified the pathogen in their water system in October that it was reported to ADPH as an outbreak. The outbreak investigation was brief due to the hospital’s rapid containment response and adherence to its established water management program (WMP). As a result of inappropriate antibiotic use in hospitals, pan-resistant strains have been increasing at an alarming rate. The pathogen can employ water used in hospital settings to cause a variety of nosocomial infections, including those found in the blood, respiratory tract, urinary tract, and on the skin. Hospitalized patients, especially those with immunocompromising conditions or implanted medical devices, are at increased risk of significant morbidity and mortality. The aim of this study was to better understand the clinical and demographic characteristics of the 13 case-patients identified during this investigation. Methods: A retrospective case series was conducted by reviewing medical records for case-patients with culture-confirmed S. maltophilia admitted between July and November. The CDC Healthcare-Associated Infection Outbreak Investigation Abstraction Form was used to systematically collect details about each case-patient’s hospitalization and course of illness. A Gantt chart was developed in Microsoft Excel to illustrate key events during their hospitalization. Results: Of the 13 case-patients, 69% were male and the median age was 69 years (range: 30 to 77). All S. maltophilia infections were hospital-acquired (>3 days after admission) with 92% being respiratory and 46% resistant to more than one class of antibiotics. All case-patients were admitted to the ICU and had known risk factors associated with developing S. maltophilia infection, including intubation (100%) and receiving antibiotic therapy prior to infection (77%). Other major risk factors included invasive surgery (77%), co-infections (77%), chronic respiratory disease (62%), hypertension (54%), and renal failure (31%). All were severely immunocompromised. Forty-six percent of the case-patients died from complications associated with their illness. Conclusion: This is the first S. maltophilia outbreak reported in Alabama. The findings of this case series underscored the importance of employing strict infection prevention measures to reduce poor health outcomes and how strong antibiotic stewardship programs are needed to limit transmission among vulnerable patient populations in these settings. It is recommended that hospitals conduct routine environmental sampling and have a WMP that is effective in limiting S. maltophilia.

Gram-negative bacterial infections in surgical intensive care unit patients following abdominal surgery: high mortality associated with Stenotrophomonas maltophilia infection

BackgroundStenotrophomonas maltophilia, a multidrug-resistant gram-negative bacteria (GNB), is an emerging nosocomial pathogen. This study assessed the clinical outcomes of GNB infections in surgical intensive care unit (SICU) patients post-abdominal surgery, focusing on the differences between S. maltophilia and other GNBs, including Pseudomonas aeruginosa.MethodsA retrospective study was conducted on SICU patients at Kaohsiung Chang Gung Memorial Hospital from 2010 to 2020, who developed GNB infections following abdominal surgery.ResultsOf 442 patients, 237 had S. maltophilia and 205 had non-S. maltophilia GNB infections (including 81 with P. aeruginosa). The overall mortality rate was 44.5%, and S. maltophilia infection emerged as a significant contributor to the mortality rate in patients with GNB infections. S. maltophilia patients had longer mechanical ventilation and SICU stays, with a 30-day mortality rate of 35.4%, higher than the non-S. maltophilia GNB (22.9%) and P. aeruginosa (21%) groups. In-hospital mortality was also higher in the S. maltophilia group (53.2%) compared to the non-S. maltophilia GNB (34.6%) and P. aeruginosa groups (29.6%). Risk factors for acquiring S. maltophilia included a higher Sequential Organ Failure Assessment score and prior broad-spectrum antibiotics use. Older age, polymicrobial infections, and elevated bilirubin were associated with increased 30-day mortality in S. maltophilia patients.ConclusionS. maltophilia infections in post-abdominal surgery patients are linked to higher mortality than non-S. maltophilia GNB and P. aeruginosa infections, emphasizing the need for early diagnosis and treatment to improve outcomes.

Optimizing Antibiotic Therapy for Stenotrophomonas maltophilia Infections in Critically Ill Patients: A Pharmacokinetic/Pharmacodynamic Approach.

Stenotrophomonas maltophilia is an opportunistic, multidrug-resistant non-fermentative Gram-negative bacillus, posing a significant challenge in clinical treatment due to its numerous intrinsic and acquired resistance mechanisms. This study aimed to evaluate the adequacy of antibiotics used for the treatment of S. maltophilia infections in critically ill patients using a pharmacokinetic/pharmacodynamic (PK/PD) approach. The antibiotics studied included cotrimoxazole, levofloxacin, minocycline, tigecycline, cefiderocol, and the new combination aztreonam/avibactam, which is not yet approved. By Monte Carlo simulations, the probability of target attainment (PTA), the PK/PD breakpoints, and the cumulative fraction of response (CFR) were estimated. PK parameters and MIC distributions were sourced from the literature, the European Committee on Antimicrobial Susceptibility Testing (EUCAST), and the SENTRY Antimicrobial Surveillance Program collection. Cefiderocol 2 g q8h, minocycline 200 mg q12h, tigecycline 100 mg q12h, and aztreonam/avibactam 1500/500 mg q6h were the best options to treat empirically infections due to S. maltophilia. Cotrimoxazole provided a higher probability of treatment success for the U.S. isolates than for European isolates. For all antibiotics, discrepancies between the PK/PD breakpoints and the clinical breakpoints defined by EUCAST (or the ECOFF) and CLSI were detected.

Pathogenic spectrum and drug resistance of bloodstream infection in patients with acute myeloid leukaemia: a single centre retrospective study.

Bloodstream infection (BSI) represent a prevalent complication in haematological malignancies (HMs). Typically, Patients with BSI usually undergo empirical treatment pending pathogen identification. The timely and effective management of BSIs significantly influences patient prognosis. However, pathogen distribution in BSIs exhibits regional variation. In this study, we investigated the clinical characteristics, pathogen spectrum, drug resistance, risk factors of short-term prognosis and long-term prognostic factors of acute myeloid leukemia (AML) patients with BSI at Zhejiang Provincal People's Hospital. From 2019 to 2021, a total of 56 AML patients with BSI were treated in the Department of Haematology at Zhejiang Province People's Hospital. Data regarding pathogen spectrum and drug resistance were collected for analysis. The patients were stratified into non-survivor cohort and survivor cohort within 30 days after BSI, and the predictors of 30-days mortality were identified through both univariate and multivariate Logistic regression analyses. Furthermore, Kaplan-Meier survival analysis and Cox regression analysis were employed to ascertain the risk factors associated with poor prognosis in AML patients complicated by BSI. A total of 70 strains of pathogenic bacteria were isolated from 56 AML patients with BSI. Gram-negative bacteria constituted the predominant pathogens (71.4%), with Klebsiella pneumoniae being the most prevalent (22.9%). Gram-positive bacteria and fungi accounted for 22.9% and 5.7%, respectively. Univariate and multivariate analyses revealed significant differences in total protein, albumin levels, and the presence of septic shock between the non-survivor cohort and the survior cohort 30 days post-BSI. COX regression analysis showed that agranulocytosis duration exceeding 20 days (HR:3.854; 95% CI: 1.451-10.242) and septic shock (HR:3.788; 95% CI: 1.729-8.299) were independent risk factors for poor prognosis in AML patients complicated by BSI. Notably, the mortality rate within 30 days after Stenotrophomonas maltophilia infection was up to 71.4%. In this study, Gram-negative bacteria, predominantly Klebsiella pneumoniae, constituted the primary pathogens among AML patients with BSIs. Serum albumin levels and the presence of septic shock emerged as independent risk factors for mortality within 30 days among AML patients with BSI. In terms of long-term prognosis, extended agranulocytosis duration exceeding 20 days and septic shock were associated with elevated mortality rates in AML patients with BSI. Additionally, in our centre, Stenotrophomonas maltophilia infection was found to be associated with a poor prognosis. Early intervention for Stenotrophomonas maltophilia infection in our centre could potentially improve patient outcomes.

Bactericidal effectors of the Stenotrophomonas maltophilia type IV secretion system: functional definition of the nuclease TfdA and structural determination of TfcB.

Stenotrophomonas maltophilia expresses a type IV protein secretion system (T4SS) that promotes contact-dependent killing of other bacteria and does so partly by secreting the effector TfcB. Here, we report the structure of TfcB, comprising an N-terminal domain similar to the catalytic domain of glycosyl hydrolase (GH-19) chitinases and a C-terminal domain for recognition and translocation by the T4SS. Utilizing a two-hybrid assay to measure effector interactions with the T4SS coupling protein VirD4, we documented the existence of five more T4SS substrates. One of these was protein 20845, an annotated nuclease. A S. maltophilia mutant lacking the gene for 20845 was impaired for killing Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Moreover, the cloned 20845 gene conferred robust toxicity, with the recombinant E. coli being rescued when 20845 was co-expressed with its cognate immunity protein. The 20845 effector was an 899 amino-acid protein, comprised of a GHH-nuclease domain in its N-terminus, a large central region of indeterminant function, and a C-terminus for secretion. Engineered variants of the 20845 gene that had mutations in the predicted catalytic site did not impede E. coli, indicating that the antibacterial effect of 20845 involves its nuclease activity. Using flow cytometry with DNA staining, we determined that 20845, but not its mutant variants, confers a loss in DNA content of target bacteria. Database searches revealed that uncharacterized homologs of 20845 occur within a range of bacteria. These data indicate that the S. maltophilia T4SS promotes interbacterial competition through the action of multiple toxic effectors, including a potent, novel DNase.IMPORTANCEStenotrophomonas maltophilia is a multi-drug-resistant, Gram-negative bacterium that is an emerging pathogen of humans. Patients with cystic fibrosis are particularly susceptible to S. maltophilia infection. In hospital water systems and various types of infections, S. maltophilia co-exists with other bacteria, including other pathogens such as Pseudomonas aeruginosa. We previously demonstrated that S. maltophilia has a functional VirB/D4 type VI protein secretion system (T4SS) that promotes contact-dependent killing of other bacteria. Since most work on antibacterial systems involves the type VI secretion system, this observation remains noteworthy. Moreover, S. maltophilia currently stands alone as a model for a human pathogen expressing an antibacterial T4SS. Using biochemical, genetic, and cell biological approaches, we now report both the discovery of a novel antibacterial nuclease (TfdA) and the first structural determination of a bactericidal T4SS effector (TfcB).

Trimethoprim-sulfamethoxazole versus levofloxacin for the treatment of Stenotrophomonas maltophilia infections: A multicentre cohort study

BackgroundTrimethoprim-sulfamethoxazole (TMP-SMX) has long been considered the treatment of choice for infections caused by Stenotrophomonas maltophilia. Levofloxacin has emerged as a potential option for treating these infections. This study aimed to evaluate the clinical outcomes in patients who received TMP-SMX versus levofloxacin for treating S. maltophilia infections. MethodsA retrospective, cohort study was conducted in 4 tertiary centres and included patients who were treated with either TMP-SMX or levofloxacin for infections caused by S. maltophilia. The main study outcomes were overall in-hospital mortality, 30-d mortality, and clinical cure. Safety outcomes were also evaluated. Multivariate analysis using logistic regression was used to control for the effect of the covariables. ResultsWe included 371 patients in this study, 316 received TMP-SMX and 55 patients received levofloxacin. A total of 70% were in the intensive care unit and 21% presented with bacteraemia. No statistically significant differences were observed in overall in-hospital mortality (52% vs. 40%; P = 0.113; odd ratio [OR], 1.59; 95% confidence interval [CI], 0.89–2.86), 30-d mortality (28% vs. 25%; P = 0.712; OR, 1.13; 95% CI, 0.59–2.18), or clinical cure (55% vs. 64%; P = 0.237; OR, 0.70; 95% CI, 0.37–1.31). Rates of acute kidney injury were comparable between the two groups (11% vs. 7%; P = 0.413). ConclusionPatients receiving levofloxacin for the treatment of infections caused by S. maltophilia demonstrated clinical outcomes similar to those receiving TMP-SMX. Our study suggests that levofloxacin can be a reasonable alternative to TMP-SMX to treat these infections.

The Importance of Nonpharmacological Applications in the Management of Infections Caused by Stenotrophomonas maltophilia in Pediatric Patients: A Single-Center Experience

Abstract Objective This study aimed to contribute to the literature by evaluating the clinical characteristics of children with Stenotrophomonas maltophilia infection, predisposing factors, and implementation of additional measures for disease control, with the goal of improving survival and reducing mortality in pediatric patients. Methods Clinical data and microbiological test results of patients with S. maltophilia growth in cultures of samples from any biological site and clinical symptoms of systemic infection referred to the pediatric clinic of a tertiary university hospital between January 2021 and August 2023 were reviewed. Results The study included 40 patients with a median age of 2.5 years (range 1–16 years). Medical devices were present in 26 patients (65%). Polymicrobial growth occurred in 16 patients (40%). Prior to the detection of S. maltophilia infection, 35 patients (87.5%) received broad-spectrum antimicrobial therapy. Death occurred in 11 patients (27.5%). In 2022, there were 23 cases of S. maltophilia infection, with the highest number occurring in March 2022 (9 cases per month). After that date, various nonpharmacological measures were implemented for all patients with confirmed infection, including strict contact isolation in single-occupancy, high-efficiency particulate air-filtered rooms. Conclusion There were multiple risk factors for increased mortality in our study population. Despite these unfavorable factors, the mortality rate was low. Disease control was achieved through nonpharmacological interventions implemented alongside antimicrobial therapy, resulting in effective prevention of potential outbreaks. Implementation of nonpharmacological interventions alongside medical treatment can reduce mortality and improve survival in pediatric patients with S. maltophilia infection.

The airway microbiome of persons with cystic fibrosis correlates with acquisition and microbiological outcomes of incident Stenotrophomonas maltophilia infection.

Chronic infection with Stenotrophomonas maltophilia in persons with cystic fibrosis (pwCF) has been linked to an increased risk of pulmonary exacerbations and lung function decline. We sought to establish whether baseline sputum microbiome associates with risk of S. maltophilia incident infection and persistence in pwCF. pwCF experiencing incident S. maltophilia infections attending the Calgary Adult CF Clinic from 2010-2018 were compared with S. maltophilia-negative sex, age (+/-2 years), and birth-cohort-matched controls. Infection outcomes were classified as persistent (when the pathogen was recovered in ≥50% of cultures in the subsequent year) or transient. We assessed microbial communities from prospectively biobanked sputum using V3-V4 16S ribosomal RNA (rRNA) gene sequencing, in the year preceding (Pre) (n = 57), at (At) (n = 22), and after (Post) (n = 31) incident infection. We verified relative abundance data using S. maltophilia-specific qPCR and 16S rRNA-targeted qPCR to assess bioburden. Strains were typed using pulse-field gel electrophoresis. Twenty-five pwCF with incident S. maltophilia (56% female, median 29 years, median FEV1 61%) with 33 total episodes were compared with 56 uninfected pwCF controls. Demographics and clinical characteristics were similar between cohorts. Among those with incident S. maltophilia infection, sputum communities did not cluster based on infection timeline (Pre, At, Post). Communities differed between the infection cohort and controls (n = 56) based on Shannon Diversity Index (SDI, p = 0.04) and clustered based on Aitchison distance (PERMANOVA, p = 0.01) prior to infection. At the time of incident S. maltophilia isolation, communities did not differ in SDI but clustered based on Aitchison distance (PERMANOVA, p = 0.03) in those that ultimately developed persistent infection versus those that were transient. S. maltophilia abundance within sputum was increased in samples from patients (Pre) relative to controls, measuring both relative (p = 0.004) and absolute (p = 0.001). Furthermore, S. maltophilia abundance was increased in sputum at incident infection in those who ultimately developed persistent infection relative to those with transient infection, measured relatively (p = 0.04) or absolute (p = 0.04), respectively. Microbial community composition of CF sputum associates with S. maltophilia infection acquisition as well as infection outcome. Our study suggests sputum microbiome may serve as a surrogate for identifying infection risk and persistence risk.

Clinical Outcomes of Trimethoprim/Sulfamethoxazole in Critically Ill Patients with Stenotrophomonas maltophilia Bacteremia and Pneumonia Utilizing Renal Replacement Therapies.

Background: The clinical outcomes of usual doses of Trimethoprim-sulfamethoxazole (TMP/SMZ) for treating S. maltophilia in critically ill patients on renal replacement therapies (RRT) have not been established. We sought to assess the clinical outcomes of TMP/SMZ in patients with sepsis utilizing RRT. Methods: A retrospective study was performed on all critically ill adult patients with S. maltophilia infections who received RRT between May 2015 and January 2022. The primary endpoint was clinical cure while the secondary endpoints were microbiologic cure, 30-day infection recurrence, and mortality. Results: Forty-five subjects met the inclusion criteria. The median age was 70.0 [interquartile range (IQR): 63.5-77] years, 57.8% were males, and the median body mass index was 25.7 [IQR: 22-30.2] kg/m2. Clinical success and failure were reported in 18 (40%) and 27 (60%) cases, respectively. There was no significant difference between the 30-day reinfection rates of both groups; however, mortality was significantly higher in the clinical failure group, involving 12 patients (44.4%), versus none in the clinical success group (p = 0.001). The median daily dose of TMP/SMZ upon continuous veno-venous hemofiltration was 1064 [IQR: 776-1380] mg in the clinical cure group vs. 768 [IQR:540-1200] mg in the clinical failure group (p = 0.035). Meanwhile, the median dose for those who received intermittent hemodialysis was 500 [IQR: 320-928] mg in the clinical success group compared to 640 [IQR: 360-1005] mg in the clinical failure group (p = 0.372). A total of 55% experienced thrombocytopenia, 42% hyperkalemia, and 2.2% neutropenia. The multivariable logistic regression analysis showed that the total daily dose at therapy initiation was the only independent factor associated with clinical success after adjusting for different variables including the body mass index [Odds ratio 1.004; 95% confidence interval: (1-1.007), p = 0.044]. Conclusions: Although the S. maltophilia isolates were reported as susceptible, TMP/SMZ with conventional doses to treat bacteremia and pneumonia in critically ill patients utilizing RRT was associated with high rates of clinical and microbiologic failure as well as with mortality. Larger outcomes and pharmacokinetics studies are needed to confirm our findings.

Evolution of Resistance against Ciprofloxacin, Tobramycin, and Trimethoprim/Sulfamethoxazole in the Environmental Opportunistic Pathogen Stenotrophomonas maltophilia.

Stenotrophomonas maltophilia is an opportunistic pathogen that produces respiratory infections in immunosuppressed and cystic fibrosis patients. The therapeutic options to treat S. maltophilia infections are limited since it exhibits resistance to a wide variety of antibiotics such as β-lactams, aminoglycosides, tetracyclines, cephalosporins, macrolides, fluoroquinolones, or carbapenems. The antibiotic combination trimethoprim/sulfamethoxazole (SXT) is the treatment of choice to combat infections caused by S. maltophilia, while ceftazidime, ciprofloxacin, or tobramycin are used in most SXT-resistant infections. In the current study, experimental evolution and whole-genome sequencing (WGS) were used to examine the evolutionary trajectories of S. maltophilia towards resistance against tobramycin, ciprofloxacin, and SXT. The genetic changes underlying antibiotic resistance, as well as the evolutionary trajectories toward that resistance, were determined. Our results determine that genomic changes in the efflux pump regulatory genes smeT and soxR are essential to confer resistance to ciprofloxacin, and the mutation in the rplA gene is significant in the resistance to tobramycin. We identified mutations in folP and the efflux pump regulator smeRV as the basis of SXT resistance. Detailed and reliable knowledge of ciprofloxacin, tobramycin, and SXT resistance is essential for safe and effective use in clinical settings. Herein, we were able to prove once again the extraordinary ability that S. maltophilia has to acquire resistance and the importance of looking for alternatives to combat this resistance.