Stenotrophomonas maltophilia pneumonia in critical COVID-19 patients.

Stenotrophomonas maltophilia, an environmental aerobic non-fermentative Gram-negative bacilli, has gained attention in many nosocomial outbreaks. COVID-19 patients in intensive care unit have extended hospital stay and are severely immunosuppressed. This study aimed to determine the prevalence and risk factors of S. maltophilia pneumonia in critical COVID-19 patients. A total of 123 COVID-19 patients in ICU admitted between March 2020 and March 2021 were identified from the authors' institutional database and assessed for nosocomial pneumonia. Demographic data and factors predisposing to S. maltophilia pneumonia were collected and analyzed. The mean age was 66 ± 13 years and 74% were males. Median APACHE and SOFA scores were 13 (IQR = 8-19) and 4 (3-6), respectively. The Median NEWS2 score was 6 (Q1 = 5; Q3 = 8). The Median ICU stay was 12 (Q1 = 7; Q3 = 22) days. S. maltophilia was found in 16.3% of pneumonia patients, leading to a lengthier hospital stay (34 vs. 20 days; p < 0.001). Risk factors for S. maltophilia pneumonia included previous treatment with meropenem (p < 0.01), thrombopenia (p = 0.034), endotracheal intubation (p < 0.001), foley catheter (p = 0.009) and central venous catheter insertion (p = 0.016). S. maltophilia nosocomial pneumonia is frequent in critical COVID-19 patients. Many significant risk factors should be addressed to reduce its prevalence and negative impact on outcomes.

Efficacy in Galleria mellonella Larvae and Application Potential Assessment of a New Bacteriophage BUCT700 Extensively Lyse Stenotrophomonas maltophilia.

In recent years, Stenotrophomonas maltophilia (S. maltophilia) has become an important pathogen of clinically acquired infections accompanied by high pathogenicity and high mortality. Moreover, infections caused by multidrug-resistant S. maltophilia have emerged as a serious challenge in clinical practice. Bacteriophages are considered a promising alternative for the treatment of S. maltophilia infections due to their unique antibacterial mechanism and superior bactericidal ability compared with traditional antibiotic agents. Here, we reported a new phage BUCT700 that has a double-stranded DNA genome of 43,214 bp with 70% GC content. A total of 55 ORFs and no virulence or antimicrobial resistance genes were annotated in the genome of phage BUCT700. Phage BUCT700 has a broad host range (28/43) and can lyse multiple ST types of clinical S. maltophilia (21/33). Furthermore, bacteriophage BUCT700 used the Type IV fimbrial biogenesis protein PilX as an adsorption receptor. In the stability test, phage BUCT700 showed excellent thermal stability (4 to 60°C) and pH tolerance (pH = 4 to 12). Moreover, phage BUCT700 was able to maintain a high titer during long-term storage. The adsorption curve and one-step growth curve showed that phage BUCT700 could rapidly adsorb to the surface of S. maltophilia and produce a significant number of phage virions. In vivo, BUCT700 significantly increased the survival rate of S. maltophilia-infected Galleria mellonella (G. mellonella) larvae from 0% to 100% within 72 h, especially in the prophylactic model. In conclusion, these findings indicate that phage BUCT700 has promising potential for clinical application either as a prophylactic or therapeutic agent. IMPORTANCE The risk of Stenotrophomonas maltophilia infections mediated by the medical devices is exacerbated with an increase in the number of ICU patients during the Corona Virus Disease 2019 (COVID-19) epidemic. Complications caused by S. maltophilia infections could complicate the state of an illness, greatly extending the length of hospitalization and increasing the financial burden. Phage therapy might be a potential and promising alternative for clinical treatment of multidrug-resistant bacterial infections. Here, we investigated the protective effects of phage BUCT700 as prophylactic and therapeutic agents in Galleria mellonella models of infection, respectively. This study demonstrates that phage therapy can provide protection in targeting S. maltophilia-related infection, especially as prophylaxis.

Analysis of biofilm formation in nosocomial Stenotrophomonas maltophilia isolates collected in Bulgaria: An 11-year study (2011-2022).

The present study aimed to explore the genotypic and phenotypic characteristics of biofilm formation in Bulgarian nosocomial Stenotrophomonas maltophilia isolates (n = 221) during the period 2011-2022, by screening for the presence of biofilm-associated genes (BAG) (spgM, rmlA and rpfF), their mutational variability, and assessment of the adherent growth on a polystyrene surface. The methodology included: PCR amplification, whole-genome sequencing (WGS) and crystal violet microtiter plate assay for biofilm quantification. The overall incidence of BAG was: spgM 98.6%, rmlA 86%, and rpfF 66.5%. The most prevalent genotype was spgM+/rmlA+/rpfF+ (56.1%), followed by spgM+/rmlA+/rpfF- (28.5%), and spgM+/rmlA-/rpfF+ (9.5%), with their significant predominance in lower respiratory tract isolates compared to those with other origin (P < 0.001). All strains examined were characterized as strong biofilm producers (OD550 from 0.224 ± 0.049 to 2.065 ± 0.023) with a single exception that showed a weak biofilm-forming ability (0.177 ± 0.024). No significant differences were observed in the biofilm formation according to the isolation source, as well as among COVID-19 and non-COVID-19 isolates (1.256 ± 0.028 vs. 1.348 ± 0.128, respectively). Also, no correlation was found between the biofilm amounts and the corresponding genotypes. WGS showed that the rmlA accumulated a larger number of variants (0.0086 per base) compared to the other BAG, suggesting no critical role of its product to the biofilm formation. Additionally, two of the isolates were found to harbour class 1 integrons (7-kb and 2.6-kb sized, respectively) containing sul1 in their 3' conservative ends, which confers sulfonamide resistance. To the best of our knowledge, this is the first study on S. maltophilia biofilm formation in Bulgaria, which also identifies novel sequence types (ST819, ST820 and ST826). It demonstrates the complex nature of this adaptive mechanism in the multifactorial pathogenesis of biofilm-associated infections.

Stenotrophomonas maltophilia Infection Associated with COVID-19: A Case Series and Literature Review.

BACKGROUND We aimed to identify the risk factors for Stenotrophomonas maltophilia infection in patients with COVID-19. CASE REPORT Case 1. A 52-year-old COVID-19-positive woman with systemic lupus erythematosus was administered remdesivir (RDV) and methylprednisolone (mPSL) 1000 mg/day for 3 days, and subsequently administered baricitinib and ceftriaxone. Following respiratory deterioration, she was transferred to the Intensive Care Unit (ICU) and the antibiotics were switched to meropenem (MEPM). Blood and sputum cultures were positive for S. maltophilia. Administration of trimethoprim-sulfamethoxazole (TMP-SMX) showed clinical improvement. Case 2. An 80-year-old COVID-19-positive man was treated with RDV, dexamethasone, and baricitinib. Owing to severe hypoxia, he was transferred to the ICU and MEPM was administered. Sputum culture was positive for S. maltophilia. TMP-SMX administration temporarily improved his symptoms; however, he died from COVID-19-associated invasive aspergillosis. Case 3. A 48-year-old COVID-19-positive man who was mechanically intubated was transferred to our hospital and treated with RDV, mPSL, and piperacillin/tazobactam. Sputum culture revealed S. maltophilia; treatment with TMP-SMX improved his respiratory status. Case 4. An 80-year-old COVID-19-positive man was treated with RDV and dexamethasone. Owing to severe hypoxemia, he was transferred to the ICU and the antibiotics were switched to MEPM. Sputum culture revealed S. maltophilia. Administration of TMX-SMX improved his respiratory status. CONCLUSIONS Isolation of S. maltophilia in respiratory specimens of patients with COVID-19 should prompt clinicians to administer treatment for S. maltophilia-associated pneumonia in ICU-admitted patients who have been intubated, have been administered broad-spectrum antibiotics, or have immunocompromised status.

Stenotrophomonas isolates in a tertiary care centre in South India.

PURPOSE: Stenotrophomonas maltophilia is an emerging multi-drug resistant pathogen increasingly isolated in India. This study aimed to identify patients from whom Stenotrophomonas maltophilia had been isolated and assess predictors of mortality in this population. METHODS: This was a retrospective cohort study of hospitalized patients with a positive culture for S. maltophilia over a 3-year period. Clinical details and laboratory results were assessed from hospital records. Bivariate and multivariate analysis was used to identify risk factors for mortality. RESULTS: One hundred and nineteen patients (mean age 48.6 years) were included in the study. Of these, 111 patients were hospitalized for at least 48 â€‹hours prior to culture and 98 were admitted in the intensive care unit. Bivariate analysis revealed multiple associations with mortality, including a background of renal, cardiac, autoimmune disease, recent carbapenam use and COVID-19 infection and increasing ventilatory requirement, lower PaO2/FiO2 (P/F) ratio, vasopressor use, thrombocytopenia, and hypoalbuminemia at the time of positive isolate. Multivariate analysis showed that autoimmune disease [OR 27.38; 95% CI (1.39-540)], a P/F ratio of less than 300 [OR 7.58; 95% CI (1.52-37.9)], vasopressor requirement [OR 39.50; 95% CI (5.49-284)] and thrombocytopenia [OR 11.5; 95% CI (2.04-65.0)] were statistically significantly associated with increased mortality, while recent surgery and receipt of antibiotics [OR 0.16; 95% CI (0.03-0.8)] targeted against S. maltophilia were associated with decreased mortality. CONCLUSION: Stenotrophomonas maltophilia is primarily isolated in patients in the intensive care unit. In our study the need for vasopressors, autoimmune disease, lower P/F ratios and thrombocytopenia were associated with higher mortality. The association of targeted antibiotics with reduced mortality suggests that the pathogenic role of S. maltophilia should not be underestimated. This finding needs to be confirmed with larger, prospective studies.

ENDOGENOUS ENDOPHTHALMITIS IN THE SETTING OF COVID-19 INFECTION: A Case Series.

PURPOSE: To describe endogenous endophthalmitis in the setting of COVID-19 pneumonia. METHODS: Patients recovering from COVID-19 pneumonia who presented to our department with any or all of the following complaints: pain, watering, redness, and decreased vision were identified. All relevant data were collected for analysis. RESULTS: Three patients with endogenous endophthalmitis were identified. All patients had been treated for COVID-19 pneumonia and therefore had received remdesivir and systemic steroids; 2 of the 3 patients received tocilizumab. All patients received vitreous biopsy, vitrectomy, and intraocular antibiotic injection. Patient 1 demonstrated Klebsiella pneumoniae in blood culture, K. pneumoniae and Escherichia coli in urine culture, and K. pneumoniae in vitreous fluid, whereas Patients 2 and 3 demonstrated Stenotrophomonas maltophilia and methicillin-resistant Staphylococcus aureus in the blood and nasopharyngeal culture, respectively. Correspondingly, the same organism was cultured from vitreous in Patients 2 and 3. The visual acuity at the last follow-up in Patients 1 to 3 was 20/100, 20/80, and 20/40, respectively. The probable source of infection was identified in each as renal calculi, dental caries, and the pharynx, respectively. Real-time polymerase chain reaction demonstrated the presence of Severe Acute Respiratory Syndrome Coronavirus 2 in the vitreous fluid of Patient 1. CONCLUSION: We report good outcomes of early intervention for endogenous endophthalmitis in the setting of COVID-19 infection. We also document the presence of SARS-CoV-2 in vitreous.

Effectors of the Stenotrophomonas maltophilia Type IV Secretion System Mediate Killing of Clinical Isolates of Pseudomonas aeruginosa.

Previously, we documented that Stenotrophomonas maltophilia encodes a type IV secretion system (T4SS) that allows the organism to kill, in contact-dependent fashion, heterologous bacteria, including wild-type Pseudomonas aeruginosa. Bioinformatic screens based largely on the presence of both a C-terminal consensus sequence and an adjacent gene encoding a cognate immunity protein identified 13 potential antibacterial effectors, most of which were highly conserved among sequenced strains of S. maltophilia. The immunity proteins of two of these proved especially capable of protecting P. aeruginosa and Escherichia coli against attack from the Stenotrophomonas T4SS. In turn, S. maltophilia mutants lacking the putative effectors RS14245 and RS14255 were impaired for killing not only laboratory E. coli but clinical isolates of P. aeruginosa, including ones isolated from the lungs of cystic fibrosis patients. That complemented mutants behaved as wild type did confirmed that RS14245 and RS14255 are required for the bactericidal activity of the S. maltophilia T4SS. Moreover, a mutant lacking both of these proteins was as impaired as a mutant lacking the T4SS apparatus, indicating that RS14245 and RS14255 account for (nearly) all of the bactericidal effects seen. Utilizing an interbacterial protein translocation assay, we determined that RS14245 and RS14255 are bona fide substrates of the T4SS, a result confirmed by examination of mutants lacking both the T4SS and the individual effectors. Delivery of the cloned 14245 protein (alone) into the periplasm resulted in the killing of target bacteria, indicating that this effector, a putative lipase, is both necessary and sufficient for bactericidal activity. IMPORTANCE S. maltophilia is an increasingly important opportunistic pathogen. Inherently resistant to many antibiotics, S. maltophilia is often associated with lung infection, being, among other things, a complicating factor in cystic fibrosis patients. Moreover, it is a common form of coinfection in COVID-19 patients. In these various clinical settings and in natural habitats, S. maltophilia coexists with other pathogens, including P. aeruginosa. Previously, we documented that S. maltophilia possesses a T4SS that kills other bacteria, a notable observation given that most prior work on interbacterial competition has highlighted bactericidal effects of type VI secretion systems. By utilizing approaches ranging from bioinformatics to mutant analysis to protein translocation assays, we have now identified two substrates of the Stenotrophomonas T4SS that largely mediate the killing of pathogenic P. aeruginosa. These results represent a major advance in understanding S. maltophilia, the roles of T4SSs, concepts regarding clinically relevant, interbacterial competition, and activities of bactericidal effectors.

Treatment refractory Stenotrophomonas maltophilia bacteraemia and pneumonia in a COVID-19-positive patient.

Stenotrophomonas maltophilia is an opportunistic pathogen that most often infects patients requiring mechanical ventilation, indwelling central venous catheters and broad-spectrum antibiotics. The reported incidence of S. maltophilia infection has increased over the past two decades, and many of its risk factors are commonly seen in patients with severe COVID-19 infection. Our case regards a patient with severe COVID-19 pneumonia, who subsequently developed disseminated S. maltophilia infection, refractory to first-line treatment and optimal medical management. This case highlights the high index of suspicion required for diagnosing secondary complications in patients with COVID-19 infection and highlights the difficulty in treating disseminated S. maltophilia infection in critically ill patients.

Co-morbidity of Covid-19 and Stenotrophomonas maltophilia in a Patient with Hodgkin's Lymphoma History from North of Iran.

INTRODUCTION: Immunocompromised patients, especially those hospitalized, are at a higher risk for infection with opportunistic pathogens such as Stenotrophomonas maltophilia (S. maltophilia) which is a multidrug-resistant gram-negative bacillus and can cause a challenge in the management of patients with concomitant COVID-19 and S. maltophilia pneumonia. CASE PRESENTATION: A 71-year-old man with Hodgkin's lymphoma presented with severe respiratory symptoms of COVID-19 was intubated upon admission and the initial standard treatment for COVID-19 was started for him. The patient subsequently developed superimposed bacterial pneumonia with S. maltophilia. According to that, the patient's intubation tube was removed and a tracheostomy was performed for him. Also, antibiotic treatment was replaced with Colistin and Co-trimoxazole drugs. Finally, after 31 days of hospitalization in the ICU and the appropriate drug treatment, he was discharged with reduced symptoms and partial recovery. CONCLUSION: It should be noted that the occurrence of co-infection with multidrug-resistant pathogens such as S. maltophilia requires proper management to select appropriate treatment methods and drugs, so that in addition to proper effectiveness, it does not lead to side effects and complications associated with COVID-19 disease.

Renal Transplant Recipient with Concurrent COVID-19 and Stenotrophomonas maltophilia Pneumonia Treated with Trimethoprim/Sulfamethoxazole Leading to Acute Kidney Injury: A Therapeutic Dilemma.

BACKGROUND Although coronavirus disease 2019 (COVID-19) manifests primarily as a lung infection, its involvement in acute kidney injury (AKI) is gaining recognition and is associated with increased morbidity and mortality. Concurrent infection, which may require administration of a potentially nephrotoxic agent, can worsen AKI and lead to poor outcomes. Stenotrophomonas maltophilia is a multidrug-resistant gram-negative bacillus associated with nosocomial infections, especially in severely immunocompromised and debilitated patients. Trimethoprim/sulfamethoxazole combination (TMP/SMX) is considered the treatment of choice but can itself lead to AKI, posing a significant challenge in the management of patients with concomitant COVID-19 and S. maltophilia pneumonia. CASE REPORT A 64-year-old male with end-stage renal disease and post renal transplant presented with severe respiratory symptoms of COVID-19 and was intubated upon admission. His renal functions were normal at the time of admission. The patient subsequently developed superimposed bacterial pneumonia with S. maltophilia requiring administration of TMP/SMX. However, TMP/SMX led to the development of AKI, which continued to worsen despite appropriate management including hemodialysis. This coincided with and most likely resulted in the patient's clinical deterioration and ultimate death. CONCLUSIONS The etiology of kidney disease involvement in patients with COVID-19 is still evolving and appears to be multifactorial. The condition can significantly worsen especially when nephrotoxic agents are given, probably due to a cumulative or synergistic effect. Great caution should be taken when administering nephrotoxic agents in the setting of COVID-19 as it can lead to adverse patient outcomes.