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Background Stenotrophomonas maltophilia causes opportunistic infections in immunocompromised and patients in intensive care units (ICUs). An outbreak of S. maltophilia in ICU is described which highlights the importance of the risk of infection from contaminated medical devices and suction fluids in ventilated patients. Methods The investigation of the outbreak was carried out. Environmental sampling was done. This was followed by MALDI-TOF MS typing and recA gene-based-phylogeny. Results In February, S. maltophilia was reported from the central line blood of six patients from ICU within a span of two weeks. The peripheral line blood cultures were sterile in all patients. Relevant environmental sampling of the high-touch surface and fluids revealed S. maltophilia strains in normal saline used for suction and in the inspiratory circuit of two patients. The isolated strains from patients and environment (inspiratory fluid) showed a minimum of 95.41% recA gene sequence identity between each other. Strict cleaning and disinfection procedures were followed. Continuous surveillance was done and no further case of S. maltophilia was detected. Timely diagnosis and removal of central line prevented development of central-line associated blood stream infection. Conclusion This outbreak report illustrates that environmental sources like suction fluid and normal saline could be the source of S. maltophilia in ICU patients.

Background To depict ecthyma gangrenosum (EG) clinical presentation and evolution in a large multicenter pediatric retrospective collection of children with malignancies or bone marrow failure syndromes, to facilitate early diagnosis. Methods EG episodes diagnosed in the period 2009-2019 were identified by a retrospective review of clinical charts at centers belonging to the Italian Pediatric Hematology Oncology Association. Results Thirty-eight cases of EG occurring in children (male/female 16/22; median age 5.2 years) with hematologic malignancy (29), allogeneic stem cell transplantation (2) or relapsed/refractory solid tumor (3) were collected. The involved sites were: perineal region (19), limbs (10), trunk (6), head and the iliac crest (3). Bacteremia was present in 22 patients. Overall, the germs isolated were Pseudomonas aeruginosa (30), Stenotrophomonas maltophilia (3) and Escherichia coli (1); 31% of them were multidrug-resistant. All patients received antibacterial treatment, while surgery was performed in 24 patients (63.1%). Predisposing underlying conditions for EG were severe neutropenia (97.3%), corticosteroid treatment (71%) and iatrogenic diabetes (23.7%). All patients recovered, but EG recurred in 5 patients. Nine patients (24%) showed sequelae (deep scars, with muscle atrophy in 2). Four patients (10.5%) died, 1 due to relapse of EG with Carbapenem-resistant Enterobacteriaceae co-infection and 3 due to the progression of the underlying disease. Conclusions EG requires early recognition and a proper and timely treatment to obtain the recovery and to avoid larger necrotic lesions, eventually evolving in scarring sequelae.

Background The emergence of concurrent levofloxacin- and trimethoprim/sulfamethoxazole (TMP/SMX)-resistant Stenotrophomonas maltophilia (LTSRSM) in Taiwan is becoming a serious problem, but clinical data analysis on this has not been reported. Methods A matched case-control-control study was conducted to investigate risk factors for LTSRSM occurrence in hospitalized patients. For patients with LTSRSM infection/colonization (the case group), two matched control groups were used: control group A with levofloxacin- and TMP/SMX-susceptible S. maltophilia (LTSSSM) and control group B without S. maltophilia. Besides, tigecycline, ceftazidime, cefepime, ciprofloxacin, gentamicin, amikacin, and colistin susceptibilities in collected LTSRSM and levofloxacin- and TMP/SMX-susceptible S. maltophilia (LTSSSM) isolates were compared. Results From January 2014 to June 2016, 129 LTSRSM from cultured 1213 S. maltophilia isolates (10.6%) were identified. A total of 107 LTSRSM infected patients paired with 107 LTSSSM-, and 107 non-S. maltophilia-infected ones were included. When compared with control group A, previous fluoroquinolone and TMP/SMX use was found to be independently associated with LTSRSM occurrence. When compared with control group B, mechanical ventilation, cerebrovascular disease, and previous fluoroquinolone use were risk factors for LTSRSM occurrence. Eighty-five LTSRSM and 85 LTSSSM isolates were compared for antibiotic susceptibilities; the resistance rates and minimum inhibitory concentrations of tigecycline and ceftazidime were significantly higher for LTSRSM than for LTSSSM isolates. Conclusion The emergence of LTSRSM showing cross resistance to tigecycline and ceftazidime would further limit current therapeutic options. Cautious fluoroquinolone and TMP/SMX use may be helpful to limit such high-level resistant strains of S. maltophilia occurrence.

Objectives: The prevalence of Gram-negative bacteria (GNB) demonstrating extensive, multiple antimicrobial resistance is increasing in England, leaving few treatment choices. Cefiderocol is a novel siderophore cephalosporin approved in Europe for the treatment of aerobic GNB infections in adults with limited treatment options. We report pooled data for a clinical isolate set collected in England between 2014–2018. Methods: MICs were determined by broth microdilution according to International Organization for Standardization guidelines. Cefiderocol susceptibility was tested using iron-depleted cation-adjusted Muller–Hinton broth. Susceptibility rates were based on EUCAST breakpoints. In the absence of a species-specific breakpoint, pharmacokinetic/pharmacodynamic breakpoints were used. Results: Of 1886 isolates from England [74.1% Enterobacterales (18.7% Escherichia coli, 17.2% Klebsiella pneumoniae), 25.9% non-fermenters (18.4% Pseudomonas aeruginosa, 3.7% Acinetobacter baumannii)], 98.7% were cefiderocol-susceptible. Cefiderocol susceptibility in Enterobacterales (99.0%) was significantly (P < 0.01) greater than ceftolozane/tazobactam (94.3%), but similar to meropenem (99.3%) and ceftazidime/avibactam (99.4%). Overall, cefiderocol susceptibility (98.0%) in non-fermenters was significantly (P < 0.01) higher than comparators (range, 84.5–92.4%). Susceptibility to cefiderocol was 98.3–99.6% by infection source and was significantly (P < 0.01) greater than comparators for isolates from patients with nosocomial pneumonia (cefiderocol, 98.3%; comparators range, 79.8–93.8%). Excluding intrinsically meropenem-resistant Stenotrophomonas maltophilia, 47/1846 isolates (2.5%) were meropenem-resistant. A high proportion of meropenem-resistant P. aeruginosa were susceptible to cefiderocol (95.0%). All S. maltophilia isolates (40/40) were cefiderocol-susceptible. Conclusion: A substantial proportion of clinical isolates from England, representing a wide range of pathogens across multiple infection sources, was cefiderocol-susceptible. Cefiderocol retained activity against meropenem-resistant strains.

Purpose Stenotrophomonas maltophilia has emerged as a critical opportunistic pathogen associated with significant morbidity and mortality. Tetracycline derivatives have been recognized as alternative treatment options, but they have varied pharmacokinetic properties. An integrated approach to different tetracycline derivatives for formulary decisions is reported. Methods The minimum inhibitory concentration (MIC) data from clonally diverse bloodstream S. maltophilia isolates were examined, along with the pharmacokinetic profiles of 4 tetracycline derivatives, to predict achievable pharmacodynamic exposures with standard intravenous dosing regimens. Antimicrobial therapy was assessed using the ratio of daily drug acquisition cost relative to the ratio of the free-drug area under the time-concentration curve (fAUC) to minimum inhibitory concentration (MIC) for 90% of isolates (fAUC/MIC90). Results In our analysis, minocycline had the greatest fAUC/MIC90. Doxycycline was the most financially preferred agent, as calculated using 2020 average wholesale price for base-case estimates of drug acquisition cost. Conclusion An integrated evaluation for antimicrobial formulary decision-making addressed local susceptibility data, pharmacokinetics, pharmacodynamics, dosing regimens, and drug acquisition costs. This comprehensive method is more objective than the conventional approach and warrants validation.

ObjectivesComplicated urinary tract infections (cUTIs) are frequently encountered in hospitals and ICUs. Increasingly, the causative pathogens harbour enzymatic resistance mechanisms. Taniborbactam is a novel β-lactamase inhibitor with activity against Ambler class A, B, C and D β-lactamases. Herein, we assessed the efficacy of cefepime alone and the combination cefepime/taniborbactam in a neutropenic murine cUTI model.MethodsEighteen cefepime-resistant clinical isolates (9 Enterobacterales, 3 Pseudomonas aeruginosa and 6 Stenotrophomonas maltophilia; cefepime MIC = 32 to >512 mg/L) were assessed. Cefepime/taniborbactam MICs ranged from 0.06 to 128 mg/L. Human-simulated plasma regimens (HSRs) of cefepime alone and in combination with taniborbactam were developed in the murine cUTI model. The efficacy of cefepime HSR and cefepime/taniborbactam HSR was determined as the change in log10 cfu/kidney at 48 h compared with 48 h controls.ResultsMean ± SD initial bacterial burden was 5.66 ± 0.56 log10 cfu/kidney, which increased to 9.05 ± 0.39 log10 cfu/kidney at 48 h. The cefepime HSR was ineffective, as bacterial burden was similar to untreated controls (−0.14 ± 0.40 change in log10 cfu/kidney). In contrast, cefepime/taniborbactam exhibited substantial killing, with log10 cfu/kidney changes of −5.48 ± 1.3, −4.79 ± 0.3 and −5.04 ± 0.7 for ESBL/AmpC-, KPC- and OXA-48-harbouring Enterobacterales, respectively. Cefepime/taniborbactam also exhibited robust killing of P. aeruginosa (−6.5 ± 0.26) and S. maltophilia (−5.66 ± 0.71).ConclusionsHumanized exposures of cefepime/taniborbactam achieved robust killing of Enterobacterales, P. aeruginosa and S. maltophilia harbouring ESBL, AmpC, KPC and/or OXA-48. These data support the role of cefepime/taniborbactam for cUTI treatment for cefepime/taniborbactam MICs up to 32 mg/L.

Candida utilis and Stenotrophomonas maltophilia co-infections connected to meningitis are uncommon. We describe a patient who developed C. utilis and S. maltophilia after undergoing neurosurgery and received effective nosocomial meningitis treatment. Multiple neurosurgeries were required for a 16-year-old girl due to complications. For probable nosocomial meningitis, she was treated with cefepime with vancomycin. Meropenem and liposomal amphotericin B were prescribed after her seizure and positive CSF culture for Candida utilis. Consequently, S. maltophilia was discovered in the CSF, and ceftazidime and trimethoprim-sulfamethoxazole were prescribed. The patient has been hemodynamically stable for the past two months, and consecutive CSF cultures have been negative. To the best of our knowledge, this is the first case of C. utilis and S. maltophilia co-infection that has been successfully handled.

Thibaud Soumagne, Florence Levesque, Julie Milot, Krystelle Godbout, Yves Lacasse, François Maltais Service de pneumologie, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec, QC, CanadaCorrespondence: Thibaud SoumagneService de pneumologie, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec, QC, CanadaEmail thibaud_soumagne@live.frIntroduction: Stenotrophomonas maltophilia is an emerging Gram-negative MDR bacteria. In patients with chronic obstructive pulmonary disease (COPD), it is mostly found in those with severe exacerbation of COPD requiring mechanical ventilation. The significance of S. maltophilia when detected in the sputum of ambulatory patients with COPD is uncertain.Objective: To access the prevalence and the risk factors of the presence of S. maltophilia in the sputum of ambulatory patients with COPD and to determine whether it was associated with prognosis.Methods: All consecutive unselected ambulatory patients with GOLD 2– 4 COPD were recruited between January 2017 and September 2019 from the COPD clinic of a tertiary care hospital. Presence of S. maltophilia was defined by a positive sputum culture for S. maltophilia. Demographics, COPD characteristics, comorbidities and known predisposing risk factors associated with S. maltophilia were collected from medical records.Results: S. maltophilia was detected in the sputum of 41/393 (10%) of study participants. Comorbidities, exacerbation, use of oral steroids and carbapenems in the previous year were risk factors for the presence of S. maltophilia. After adjusting on confounding factors associated with mortality including age, Charlson comorbidity index and FEV1, S. maltophilia was significantly associated with mortality (adjusted hazard ratio 2.3; 95% CI 1.1– 4.9).Conclusion: In the current study, we found that 10% of ambulatory patients with GOLD 2– 4 COPD had S. maltophilia detected in their sputum. In addition, S. maltophilia may represent a marker of overall morbidity in patients with COPD.Keywords: Stenotrophomonas maltophilia, pulmonary disease, chronic obstructive, risk factors, prognosis

Background Antimicrobial resistance (AMR) of non-fermenting Gram-negative bacteria (NFGNB) is increasingly recognized as urgent healthcare threat. Trend data on AMR of NFGNB in Saudi Arabia are either old or limited. The objective was to estimate the prevalence and resistance trends of isolated NFGNB in Saudi Arabia. Methods A retrospective multicenter study involving seven tertiary care hospitals in Saudi Arabia was conducted between 2011 and 2016. Susceptibility testing for non-duplicate isolates was performed according to the Clinical and Laboratory Standards Institute (CLSI) guidelines in College of American Pathologists accredited diagnostic microbiology laboratories in the participating hospitals. Results Out of 461,274 isolates, 100,132 (21.7%) were NFGNB which represented 30% of gram-negative pathogens. Pseudomonas aeruginosa was the most common (73.6%), followed by Acinetobacter baumannii (21.0%) and Stenotrophomonas maltophilia (5.3%). Resistance trends of P. aeruginosa were increasing for aztreonam (absolute increase during the study was 17.3%), imipenem (12.3%), and meropenem (11.6%). A. baumannii was fully resistant to several beta lactam drugs, and resistance trends were increasing for potential treatments such as tigecycline (25.1%) and tobramycin (15.5%). S. maltophilia was >90% resistant to trimethoprim/ sulfamethoxazole and ciprofloxacin by the end of the study. Conclusion We are reporting high and/or increasing resistance of NFGNB to common treatment options. The current findings call for urgent actions to combat the increasing resistance of NFGNB. Large scale sharing of AMR data collected at different hospitals with the Saudi AMR committee would be critical to set priorities and monitor progress.

Aim: To focus on the frequency of ICU-acquired infections in Sars Co-V2 Corona Virus disease (COVID 19) patients. Method: A retrospective observational study carried out in two tertiary care hospitals treating COVID 19 cases, Services Institute of Medical Sciences and Bahria International Hospital, Lahore. Data was collected from the medical records of the COVID 19 ICUs of both hospitals from May 1, 2020 to April30, 2021. All charts were reviewed for the evidence of positive cultures. The treatment given prior to positive cultures, after the availability of culture results and outcomes were also recorded. Results: A total of 432 records were reviewed and 400 cases were included while 32 cases were excluded because of incomplete data. The frequency of infections per 1,000 days of ICU stay was calculated in 90 (22.5%) patients. Gram-negative bacteria accounted for 68 cases (75.5%) with Pseudomonas in 44 cases (48.8%), Acinetobacter in 23/90 (25.5%) while 17 cases (18.8%) had gram positive infection with Enterococcus in 14/18 (77.77%) or 14/90 (15.55%), MRSA in 4/18 (22.22%) 4/90 (4.44%), while 5/90 (5.5%) had more than 2 isolates at same time. Among these 3 had both pseudomonas and Acinetobacter while 2 patients had Pseudomonas and Stenotrophomonas Maltophilia. Conclusion: There seems to be an increase in the infection rate among critically sick COVID 19 patients admitted in ICU. Use of steroids and Tocilizumab seems to play a role through their immunomodulatory effects. Keywords: Tocilizumab, Secondary infections

BACKGROUND Stenotrophomonas maltophilia is an opportunistic pathogen and a dreaded cause of bacteraemia with 30-day mortality rates ranging from 14 to 69%. The purpose of this cohort study was to evaluate outcomes of S. maltophilia bacteraemia, at Rigshospitalet, a tertiary hospital in Copenhagen, Denmark. METHODS We included all patients with a blood culture positive for S. maltophilia, from January 1, 2015 to April 1, 2020. We extracted data on antimicrobial susceptibility, treatment, central venous catheter intervention and severe haematological disease. RESULTS Sixty-one cases of S. maltophilia bacteraemia were identified. The overall 90-day mortality was 18%. Sixty percent of patients had a central venous catheter intervention performed. Seventy-nine percent of patients were treated with trimethoprim/sulfamethoxazole (TMP/SMX). Patients with central venous catheter intervention had significantly better survival than those without (HR: 0.16 [95% CI: 0.03-0.73]). Severe haematological disease and patients, who received intensive care unit (ICU) care, were at higher risk of death than other patients (HR: 5.93 [95% CI: 1.18 - 29.94] and HR: 8.37 [95% CI: 1.79 - 39.20], respectively). We found no evidence that any antibiotic regime was superior with regard to 90-day mortality. CONCLUSIONS We did not find evidence to support a change in the current standard-of-care regimen of TMP/SMX and CVC removal. Larger clinical trials are needed to guide such recommendations.

Introduction Tigecycline is a potential alternative to trimethoprim–sulfamethoxazole in treating Stenotrophomonas maltophilia infections due to its potent in vitro antimicrobial activity. Clinical evidence regarding the use of tigecycline in the treatment of S. maltophilia infections is scarce. In this study, we assessed the efficacy of tigecycline treating ventilator-associated pneumonia (VAP) due to S. maltophilia in comparison with fluoroquinolones. Methods This is a multicenter retrospective cohort study of patients admitted between January 2017 and December 2020 with the diagnosis of VAP caused by S. maltophilia receiving either tigecycline or fluoroquinolones as the definitive therapy ≥ 48 h. Clinical outcomes including 28-day mortality, clinical cure and microbiological cure were analyzed. Results Of 82 patients with S. maltophilia VAP included, 46 received tigecycline, and 36 received fluoroquinolones; 70.7% of patients had polymicrobial pneumonia, and the appropriate empiric therapy was applied to only 14.6% of patients. The overall 28-day mortality was 39%. Compared with patients receiving fluoroquinolones, tigecycline therapy resulted in worse clinical cure (32.6% vs. 63.9%, p = 0.009) and microbiological cure (28.6% vs. 59.1%, p = 0.045), while there was no statistical difference between 28-day mortality (47.8% vs. 27.8%, p = 0.105) in the two groups. Similar results were also shown in the inverse probability of treatment weighted univariable regression model and multivariable regression model. Conclusions The standard dose of tigecycline therapy was associated with a lower clinical and microbiological cure rate but not associated with an increased 28-day mortality in patients with S. maltophilia VAP compared with fluoroquinolones. Considering the unfavorable clinical outcomes, we therefore recommend against using the standard dose of tigecycline in treating S. maltophilia VAP unless new clinical evidence emerges. Supplementary Information The online version contains supplementary material available at 10.1007/s40121-021-00516-5.

Bacterial endophthalmitis is a rare intraocular infection, and prompt administration of intravitreal antibiotics is crucial for preventing severe vision loss. The retrospective study is to investigate the in vitro susceptibility to the antibiotics vancomycin, amikacin, and ceftazidime of bacterial endophthalmitis isolates in specimens at a tertiary referral center from January 1996 to April 2019 in Taiwan. Overall, 450 (49.9%) isolates were gram positive, 447 (49.6%) were gram negative, and 4 (0.4%) were gram variable. In gram-positive isolates, coagulase-negative staphylococci were the most commonly cultured bacteria (158, 35.1%), followed by streptococci (100, 22.2%), enterococci (75, 16.7%), and Staphylococcus aureus (70, 15.6%). In gram-negative isolates, they were Klebsiella pneumoniae (166, 37.1%) and Pseudomonas aeruginosa (131, 29.3%). All gram-positive organisms were susceptible to vancomycin, with the exception of one Enterococcus faecium isolate (1/450, 0.2%). Of the gram-negative isolates, 96.9% and 93.7% were susceptible to ceftazidime and amikacin, respectively. Nine isolates (9/447, 2.0%) were multidrug-resistant gram-negative bacteria, comprising Klebsiella pneumoniae (4/164, 2.4%), Acinetobacter baumannii (2/3, 67%), and Stenotrophomonas maltophilia (3/18, 17%). In conclusion, in vitro susceptibility testing revealed that vancomycin remains the suitable antibiotic treatment for gram-positive endophthalmitis. Ceftazidime and amikacin provide approximately the same degree of gram-negative coverage. Multidrug-resistant bacterial endophthalmitis was uncommon.

To describe endogenous endophthalmitis in the setting of COVID-19 pneumonia.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.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.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.

Background. Since 2020 COVID-19 pandemic became an emergent public sanitary incident. The epidemiology data and the impact on prognosis of secondary infection in severe and critical COVID-19 patients in China remained largely unclear.Methods. We retrospectively reviewed medical records of all adult patients with laboratory-confirmed COVID-19 who were admitted to ICUs from January 18th 2020 to April 26th 2020 at two hospitals in Wuhan, China and one hospital in Guangzhou, China. We measured the frequency of bacteria and fungi cultured from respiratory tract, blood and other body fluid specimens. The risk factors for and impact of secondary infection on clinical outcomes were also assessed. Results. Secondary infections were very common (86.6%) when patients were admitted to ICU for >72 hours. The majority of infections were respiratory, with the most common organisms being Klebsiella pneumoniae (24.5%), Acinetobacter baumannii (21.8%), Stenotrophomonas maltophilia (9.9%), Candida albicans (6.8%), and Pseudomonas spp. (4.8%). Furthermore, the proportions of multidrug resistant (MDR) bacteria and carbapenem resistant Enterobacteriaceae (CRE) were high. We also found that age ≥60 years and mechanical ventilation ≥13days independently increased the likelihood of secondary infection. Finally, patients with positive cultures had reduced ventilator free days in 28 days and patients with CRE and/or MDR bacteria positivity showed lower 28 day survival rate.Conclusions. In a retrospective cohort of severe and critical COVID-19 patients admitted to ICUs in China, the prevalence of secondary infection was high, especially with CRE and MDR bacteria, resulting in poor clinical outcomes.

Bacteria have long been considered drivers in the development of cutaneous lymphoma, as bacterial antigens may encourage reactive, dysregulated lymphocytic proliferation.1,2 For example, Staphylococcus aureus infection has been implicated in the pathogenesis of mycosis fungoides and Sezary syndrome, whereas Borrelia burgdorferi is clinically associated with primary cutaneous B-cell lymphoma.3, 4, 5, 6, 7 Stenotrophomonas maltophilia is an opportunist gram-negative bacterium, primarily recognized as a cause of nosocomial infection among immunocompromised individuals.8 Ste maltophilia, specifically, has been associated with breast implant–associated anaplastic large-cell lymphoma (BIA-ALCL),9,10 and it has also been reported to be an antigenic driver in cutaneous pseudolymphoma.11 We report a new association of primary cutaneous anaplastic large-cell lymphoma (PC-ALCL) with Ste maltophilia in otherwise immunocompetent men.

Background Fatal hemorrhagic pneumonia is one of the most severe manifestations of Stenotrophomonas maltophilia (SM) infections. Here, we aimed to investigate the clinical characteristics of SM bacteremia and to identify the risk factors of hemorrhagic pneumonia caused by SM in patients with hematologic diseases. Methods The clinical records of 55 patients diagnosed with hematologic diseases and SM bacteremia were retrospectively reviewed. We compared patients’ clinical characteristics and outcomes between the hemorrhagic pneumonia group and non-hemorrhagic pneumonia group. Results Twenty-seven (49.1%) patients developed hemorrhagic pneumonia. The overall mortality rate of SM bacteremia was 67.3%. Hemorrhagic pneumonia (adjusted HR 2.316, 95% CI 1.140–4.705; P = 0.020) was an independent risk factor of 30-day mortality in hematological patients with SM bacteremia. Compared with the non-hemorrhagic pneumonia group, patients in the hemorrhagic pneumonia group were older and showed clinical manifestations as higher proportions of isolated SM in sputum culture, neutropenia and elevated procalcitonin (PCT). Multivariate analysis showed that neutropenia, high levels of PCT, prior tigecycline therapy within 1 month were independent risk factors associated with hemorrhagic pneumonia. Conclusions Neutropenia, high level of PCT and prior tigecycline therapy within 1 month were significant independent predictors of hemorrhagic pneumonia in hematologic patients with SM bacteremia. Due to no effective antibiotics to prevent hemorrhagic pneumonia, prophylaxis of SM infection and its progression to hemorrhagic pneumonia is particularly important.

Background Trimodality therapy is a treatment option for patients with locally advanced non-small cell lung cancer (LA-NSCLC). Thoracic radiation has both early (radiation pneumonitis) and late (chronic lung injury [CLI]) adverse effects on the lung. While CLI is expected to result in various problems in long-term survivors, these manifestations have not been precisely investigated. Methods We enrolled 112 LA-NSCLC patients who had received induction chemoradiotherapy followed by surgery, and then undergone follow-up computed tomography (CT) every 6 months for greater than 1 year. All chest CT images were reviewed to evaluate any injury of the pulmonary parenchyma. Results CLI at 1 year after surgery and its progression were observed in 94 (84%) and 38 (34%) patients, respectively. Progressive lung fibrosis as the first manifestation of CLI progression was most frequent after right middle and lower lobectomy. Cavity formation was the subsequent manifestation after progressive lung fibrosis , and chronic infection was the final stage of CLI. The cumulative rate of chronic infection was 76.4% at 10 years in patients with cavity formation. Ten patients with chronic infection included 7 cases of pulmonary aspergillosis and 2 cases of cavity infections with methicillin-resistant Staphylococcus aureus or Stenotrophomonas maltophilia. Among them, 4 patients required surgical interventions including completion pneumonectomy or fenestration. Conclusions CLI is a common incidence after trimodality therapy for LA-NSCLC. CLI frequently results in cavity formation, which is a precursor of highly refractory chronic infections requiring surgical intervention. Appropriate management needs to be established for CLI developing after trimodality therapy.

BACKGROUND Stenotrophomonas maltophilia is a gram-negative bacillus, multidrug resistant (MDR) opportunistic pathogen, which is normally present in hospital surroundings. It has been one of the leading causes of nosocomial infections due to risk factors such as extended intensive care unit (ICU) stays and multiple invasive procedures. In this study we wanted to assess the antibiotic sensitivity pattern with various antimicrobial agents i.e. levofloxacin, minocycline, ceftazidime, chloramphenicol, & ticarcillin-clavulanic acid with special focus on trimethoprim-sulfamethoxazole (TMP-SMX). METHODS In vitro analysis was conducted on 164 Stenotrophomonas maltophilia strains isolated from blood and respiratory tract from January 2016 to November 2020. Antibiotic susceptibility and minimum inhibitory concentration (MIC) testing for trimethoprim-sulfamethoxazole (TMP-SMX), levofloxacin (LVX), ticarcillin - clavulanic acid (TIM), and minocycline (MIN) were performed using Vitek 2, as per clinical and laboratory standards institute (CLSI) guideline. RESULTS A total of 164 S. maltophilia were isolated. Out of the 164 S. maltophilia isolates, 26 (16 %) were isolated from blood, 114 (70 %) were isolated from respiratory samples, 20 (12 %) from pus & tissue, and 4 (2 %) from urine. Out of the 164 patients, 130 (80 %) were males and 32 (20 %) were females. Maximum patients were above 50 years of age 93 (56 %) followed by 20 - 50 years 55 (34 %). Out of the 164 patients, 67 (40 %) were admitted to wards, 92 (56 %) were in ICU and 5 (3 %) were seen in out-patient department (OPD). A total of 90 % strains were sensitive to trimethoprim-sulfamethoxazole (TMP-SMX). Total 91 % strains were sensitive to levofloxacin. CONCLUSIONS S. maltophilia is emerging as a significant nosocomial pathogen, with a growing rate of isolation. Trimethoprim- sulfamethoxazole (TMP-SMX) is still the drug of choice, but resistance to it has been reported. KEYWORDS Minimum Inhibitory Concentration, Trimethoprim-Sulfamethoxazole (TMP-SMX), Levofloxacin

Introduction Stenotrophomonas maltophilia keratitis is an uncommon infectious disease of the cornea. The clinical features, antibiotic susceptibility, and clinical outcomes of S. maltophilia keratitis were investigated in this study. Methods Between January 2015 and February 2020, the medical records of 16 patients with culture-proven S. maltophilia-associated infectious keratitis were retrospectively reviewed. Clinical data were analyzed regarding risk factors, clinical presentation, antibiotic susceptibility, and clinical outcomes. Results The average age of the patients was 56.24 ± 24.84 years. The most common risk factors for S. maltophilia keratitis were trauma (6/16, 37.5%), use of contact lenses (6/16, 37.5%), and herpes simplex virus keratitis (3/16, 18.8%), which caused ocular instability. Regarding the antibiotic sensitivities, most isolates (15/16, 93.8%) were susceptible to fluoroquinolones, 87.5% (14/16) of them to aminoglycosides, and 81.3% (13/16) of them to beta-lactams. Patients were classified into two groups according to the initial antibiotic eye drops, and there were significant differences in the final visual acuity between two groups: mixed fluoroquinolone, beta-lactam, aminoglycoside group, and mixed beta-lactam and aminoglycoside groups (p = 0.039). Conclusion Ocular infection due to S. maltophilia is an opportunistic infection followed by instability of the ocular surface. In cases of S. maltophilia infection, mixed use of fluoroquinolone, beta-lactam, and aminoglycoside should be considered for treatment of choice.

Introduction: Non-fermentative Gram-negative bacterias (NFGNBs) are a major cause of life threatening infections in hospitalized children. in this study, we aimed to evaluate the demographic and clinical characteristics of NFGNBs infections and identify the risk factors and outcomes of bloodstream infections (BSIs) caused by carbapenem-resistant (CR) NFGNBs infections. Methods: A retrospective cohort was designed to evaluate the patients with a BSI caused by NFGNBs between in January 2014 and December 2017. Results: A total of 131 episodes from 115 patients were evaluated. The mean age of the patients was 4.79 +/-(4.74) year. The most commonly isolated NFGNBs species was Acinetobacter spp. (35.9%), Pseudomonas spp. (34.4%), and Stenotrophomonas maltophilia (13%). The rate of carbapenem-resistance was 38.2% in Acinetobacter spp. and 26.6% in Pseudomonas spp. The comparison of CR group with carbapenem-susceptible (CS) group showed statistical significance for the length of hospital stay prior to onset of infection and total hospital stay (P values were 0.001, 0.008). Based on the univariate analysis, requirement of mechanical ventilation, central venous catheter, nasogastric tube, Foley catheter, severe neutropenia (14 days), prior intensive care unit admission and prior antimicrobial treatment (carbapenems, colistin, glycopeptide) were more common in carbapenemresistant NFGNBs infections (P values are 0.001, 0.012, 0.000, 0.005, 0.042, 0.027, 0.007, 0.007). in patients with NFGNBs infections 14-day and 30-day mortality rates were %16.8 and 21.4%. Conclusion: CR infections were more common in children with prolonged and severe neutropenia. Prior antimicrobial use and intensive care unit admission were more common in CR infections. (c) 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Relevance. Infectious septic complications caused by polyresistant gram-negative micro-organisms are a pressing issue in the treatment of patients after polychemotherapy (PCT) and hematopoietic stem cell transplantation at the high risk of the fulminant current and high lethality against the background of hematopoesis aplasia. One of the therapeutic strategies of antimicrobial treatment is the systematic use of 0.5 % hydroxymethylquinoxaline dioxide (dioxidine) solution in the complex antibacterial therapy of patients with severe infectious-septic complications. The preparation has a bactericidal type of action, a wide spectrum of antibacterial activity. Experience in adult clinical practice has demonstrated the effectiveness of dioxidine in the treatment of the most severe forms of aerobic and anaerobic infection. Strict dose enforcement and injection technique to avoid the appearance of side effects. Data on the intravenous use of dioxin in children are presented in a limited number of scientific literature.The aim of the study was to demonstrate the efficacy of systemic use of hydroxymethylquinoxaline dioxide (0.5 % dioxidine solution) in children with infectious complications progressing against the background of aplasia of hematopoiesis caused by multidrug-resistant pathogens Pseudomonas aeruginosa, Klebsiella pneumoniae, Enterobacter cloacae, Stenotrophomonas maltophilia.Materials and methods. 16 patients with a verified gram-negative infection were prescribed 0.5 % hydroxymethylquinoxaline dioxide solution as part of a combination antimicrobial therapy were included in the retrospective study. The median age of patients was 5 years (6 months – 16 years), 11 (69 %) were boys and 5 (31 %) girls.All children included in the study has infectious-septic complications at the PCT-induced hematopoietic aplasia, obtained according to the protocols of the main disease: severe combined immune deficiency (n = 2), idiopathic aplastic anaemia (n = 3), solid tumor (n = 2), acute myeloblastic leukemia (n = 7), acute lymphoblastic leukemia (n = 2). The main criterion for adding to the study was the existence at the least one site with a verified gram-negative infection (Pseudomonas aeruginosa, Klebsiella pneumoniae, Enterobacter cloacae, Stenotrophomonas maltophilia): bacteriemia (n = 11), oral mucosa (n = 6), ulcerative necrotic damage of perineum (n = 6), enterocolite (n = 6), infectionseptic compartments in the subcutaneous fat (n = 4), pleuropneumonia (n = 4), abscesses and inflammatory infiltration of the liver, spleen, pancreas, kidneys, lymph nodes (n = 1), infection of soft tissues in the area of the ventricular bypass with inflammatory changes of the brain membranes (n = 1).All patients received 0.5 % of the solution of dioxin by injection according of vital importance, as they had pathogens with confirmed laboratory resistance or clinical progression of the infectious process against the background of combined antibacterial therapy.Discussion. There is a complete control of fulminant developing infectious-septic processes caused by polyresistant micro-organisms against the background of hydroxymethylquinoxaline dioxide therapy in all 16 patients. The eradication of the pathogen, according to the microbiological study, has been confirmed in almost all observed patients, the efficacy of the drug has been preserved throughout the period of treatment, and the resistance of micro-organisms has not been observed. Strict adherence to the dosing and infusion technique of hydroxymethylquinoxaline dioxide has helped to achieve the full resolution of the infection process in all children without side-effects.Conclusion. On the basis of the experience presented, in immunocomputed patients of young age, 0.5 % dioxidine solution can be used as a necessary reserve preparation for the treatment of the most severe forms of infections of different localization, caused by polyresistant strains of gram-negative micro-organisms.

Objectives: Stenotrophomonas maltophilia, a Gram-negative non-fermentative bacillus, has emerged as an important nosocomial pathogen in recent years. It is intrinsically resistant to many antibiotics and has the ability to acquire antibiotic resistance by multiple mechanisms. Treating Stenotrophomonas infections, therefore, is a serious challenge for physicians. This study aimed to investigate the antibiotic susceptibility patterns and risk factors contributing to S. maltophilia infections. Methods: A retrospective cross-sectional study was conducted at Sohar Hospital in Sohar, Oman. The demographic, clinical and microbiological data of individuals from whom S. maltophilia was isolated between September 2016 and August 2019 were reviewed. Descriptive statistics were presented as frequencies and percentages. Results: A total of 41 S. maltophilia isolates from clinical specimens of 41 patients were studied. Infection occurred predominantly in males (73%) and the majority of patients (88%) were either ≤5 years old or >60 years old. All inpatients had at least one comorbidity while 50% had more than one. All inpatients were exposed to various medical interventions such as intensive care (44%), mechanical ventilation (41%), haemodialysis (25%), Foley’s catheterisation (13%) and central venous lines (6%). Most patients (81%) were in hospital longer than two weeks. The susceptibility rates of S. maltophilia to minocycline (97%), trimethoprimsulfamethoxazole (93%) and levofloxacin (92%) were high; the rate was lowest for ceftazidime (50%). Conclusion: S. maltophilia was found to be an important nosocomial opportunistic pathogen. Prolonged hospital stay and exposure to various medical interventions were key factors contributing to the development of infection. Minocycline and ceftazidime were found to be the most and least susceptible drugs, respectively. KEYWORDS Nosocomial Infection; Opportunistic Infections; Fluoroquinolones; Hemodialysis; Ventilation; Oman.

Background The incidence of secondary pulmonary infections is not well described in hospitalized COVID-19 patients. Understanding the incidence of secondary pulmonary infections and the associated bacterial and fungal microorganisms identified can improve patient outcomes. Objective This narrative review aims to determine the incidence of secondary bacterial and fungal pulmonary infections in hospitalized COVID-19 patients, and describe the bacterial and fungal microorganisms identified. Method We perform a literature search and select articles with confirmed diagnoses of secondary bacterial and fungal pulmonary infections that occur 48 h after admission, using respiratory tract cultures in hospitalized adult COVID-19 patients. We exclude articles involving co-infections defined as infections diagnosed at the time of admission by non-SARS-CoV-2 viruses, bacteria, and fungal microorganisms. Results The incidence of secondary pulmonary infections is low at 16% (4.8–42.8%) for bacterial infections and lower for fungal infections at 6.3% (0.9–33.3%) in hospitalized COVID-19 patients. Secondary pulmonary infections are predominantly seen in critically ill hospitalized COVID-19 patients. The most common bacterial microorganisms identified in the respiratory tract cultures are Pseudomonas aeruginosa, Klebsiella species, Staphylococcus aureus, Escherichia coli, and Stenotrophomonas maltophilia. Aspergillus fumigatus is the most common microorganism identified to cause secondary fungal pulmonary infections. Other rare opportunistic infection reported such as PJP is mostly confined to small case series and case reports. The overall time to diagnose secondary bacterial and fungal pulmonary infections is 10 days (2–21 days) from initial hospitalization and 9 days (4–18 days) after ICU admission. The use of antibiotics is high at 60–100% involving the studies included in our review. Conclusion The widespread use of empirical antibiotics during the current pandemic may contribute to the development of multidrug-resistant microorganisms, and antimicrobial stewardship programs are required for minimizing and de-escalating antibiotics. Due to the variation in definition across most studies, a large, well-designed study is required to determine the incidence, risk factors, and outcomes of secondary pulmonary infections in hospitalized COVID-19 patients.

Non-fermenting Gram-negative bacilli (NFGNB) are emerging as important cause of blood stream infections. We aimed to determine the prevalence and antibiotic susceptibility pattern of NFGNB isolated from blood of patients with sepsis. We found, in 176 patients, the most common to be Pseudomonas aeruginosa (74) and Acinetobacter baumanii complex (39) followed by Stenotrophomonas maltophilia (16), Sphingomonas paucimobilis (6), Burkholderia cepacia (5) and Ochrobactrum anthropic (1). Generally, organisms showed a good sensitivity towards colistin, carbapenems and fluoroquinolones, whereas cephalosporins were ineffective.

In multidisciplinary hospitals, there are conditions conducive to the emergence of healthcare-associated infections: high concentration of people with reduced immunity in a limited area, the presence of a significant number of sources of contagion (patients and carriers), a change in the biocenosis of the mucous membranes and skin of patients and medical personnel under the influence of widespread use of antibiotics and cytostatics. The aim of the research was in the intercomparison of the standardized bacteriological algorithms and the MALDI Biotyper system in the microbiological diagnosis of pathogens as illustrated by the healthcare-associated diseases. Materials and methods . Seventy-eight patients of a multidisciplinary hospital of a regional level (Irkutsk) in 2018–2019 were examined. The age of patients ranged from 1 to 15 years. The material for the study was blood, sputum, swabs from the tracheobronchial tree, throat, nose, wound, abdominal fluid, cerebrospinal fluid, and swabs from environmental objects. Identification of the isolated cultures (78 bacterial strains) was carried out using generally accepted bacteriological methods, as well as using the MALDI Biotyper system. Results and discussions. In the structure of healthcare-associated infections, Pseudomonas aeruginosa occupied a leading position. Not all isolates of microorganisms were identified by standardized bacteriological methods. The identification of strains with characteristic manifestations of physiological and biochemical characteristics was more reliable. Identification difficulties arose in the presence of atypical properties of microorganisms when the use of MALDI Biotyper would be crucial. Conclusion . It is necessary to apply an integrated approach to conduct reliable diagnostics of pathogens. It includes standardized bacteriological methods and methods for identifying microorganisms using mass spectrometry in the subsequent stages.

Objectives We analyzed the clinical aspects and treatment outcomes of Stenotrophomonas maltophilia (SM) keratitis and Pseudomonas aeruginosa (PA) keratitis. Methods Medical records of 55 inpatients with culture-proven SM (n=21) and PA (n=34) keratitis were retrospectively reviewed. Predisposing factors, clinical characteristics, and treatment outcomes were compared between the SM and PA groups. Results The mean symptom duration was longer in the SM group than in the PA group (10.4:4.3 days; P=0.012). The most common predisposing factor was corneal trauma (47.6%) in the SM group and contact-lens wear (38.2%) in the PA group. There were no differences in the mean epithelial defect size (12.7:11.9 mm2; P=0.861), hypopyon (33.3%:44.1%; P=0.428), surgical treatment (4.8%:14.7%; P=0.390), or poor clinical outcomes (26.8%:30.3%; P=0.760) between the SM and PA groups. In multivariate logistic regression, risk factors for poor clinical outcomes were hypopyon (odds ratio [OR], 52.00; P=0.010) in the SM group and symptom duration≥7 days (OR, 44.32; P=0.015), age≥60 years (OR, 21.13; P=0.019), and hypopyon (OR, 15.20; P=0.038) in the PA group. Conclusion Compared with PA keratitis, SM keratitis had slower progression, and its clinical characteristics and treatment results were not worse. In both groups, hypopyon was the risk factor for a poor clinical outcome.

Background: Bloodstream infection (BSI) is a common and serious complication after patients with hematologic malignancies (HM) receiving chemotherapy. This study examined real-world data seeking to characterize HM BSI and identify risk factors for BSI emergence and mortality. Methods: We retrospectively analyzed the pathogenic epidemiology, antibiotic resistance, and BSI risk factors in a single-center cohort including 3014 consecutive patients with HM receiving chemotherapy between 2013 and 2016. Results of the pathogenic epidemiology were validated via comparison to available reported data. Results: We found that 725 patients (24.1%) had BSIs. Gram-negative (G-) bacteria represented 64.7% of the 744 isolated pathogenic strains, while Gram-positive (G+) bacteria and fungi accounted for 27.7% and 7.7% of the BSIs, respectively. The most common isolates were Klebsiella pneumoniae (19.2%), and 95.1% of the multidrug-resistant strains (MDR) were extended-spectrum beta-lactamase producing strains. G- bacteria were the main microflora responsible for BSI in our cohort of Chinese HM patients compared to studies in developed countries or in neutropenic children with HM or solid tumors. Multivariate analysis revealed that male sex, age ≥ 45 and < 65 yr, hospital length of stay ≥ 9d, neutropenia ≥ 7d before cultures, ≥ 2 antibiotics, and infections (gastrointestinal, perirectal, or urinary tract) independently predicted BSI emergence. Furthermore, age ≥ 65 yr, neutropenia ≥ 7d before blood cultures, no HM remission, lower white blood cell count, ≥ 3 antibiotics, respiratory infections, and Acinetobacter baumannii and Stenotrophomonas maltophilia BSI were independent predictors of 30-day mortality. Conclusions: G- bacteria were the predominant microflora during the study period and antibiotic resistance levels of the pathogens detected were high, especially for MDR strains. The mortality of BSI patients was high in this large cohort. Close attention should be paid to the risk factors identified here to facilitate timely and effective clinical management of such patients.

Introduction: Carbapenem resistant organisms (CRO) constitute a large group of bacteria with different mechanisms of resistance and recently increasing global incidence. This rise has ambiguous dynamics and essential local epidemiologic data is lacking. Materials and methods: In this retrospective study at the 400-bed Saint George Hospital (SGH) in Beirut, Lebanon, we retrieved electronic laboratory records of all intrinsic and acquired CRO isolates from January 1, 2010 until June 30, 2018. Isolation density was calculated as: number of isolates/1000PD. Analysis carried out using WHOnet with a trend time series analysis. Results: During the study period, a total of 2150 non-duplicate CRO were isolated. While Acinetobacter baumanii (AB), Pseudomonas aeruginosa (CRPa), and Stenotrophomonas maltophilia (Sm) constituted 85% of total CRO in the study period, the carbapenem resistant enterobacteriaceae (CRE) rose from few sporadic cases before 2016 to a solid 32% of total CRO in 2018. Our most concrete trends were as follows. The rate of AB bacteremia was at an average of 0.114/1000 PD from 2011 to 2014. In 2015, a sudden doubling of AB bacteremia to 0.23/1000 PD. In 2017, there was a significant decrease to 0.113/1,000PD (p

Objective: The purpose of this study was to identify the potential of resveratrol in inhibiting the growth and production of two enzymes, hyaluronidase and protease, in Stenotrophomonas maltophilia, which has become a burn wound pathogen of great significance. Method: Stenotrophomonas maltophilia (ATCC 17666) was cultured in nutrient broth and the microbial load was standardised to 0.5 McFarland standard at 600nm. The study included antimicrobial assays (well diffusion and resazurin dye binding method), hyaluronidase expression regulation assay (hyaluronic acid hydrolysis assay and turbidity assay) and protease expression regulation assay (casein hydrolysis assay and determination of specific activity of protease using tyrosine standard). Results: The minimum inhibitory concentration (MIC) of resveratrol against Stenotrophomonas maltophilia was found to be 125µg/ml. Hyaluronidase production in the organism treated with resveratrol was found to be half that in the untreated organism. The specific activity of protease produced by the organism treated with resveratrol was found to be one-quarter that in the untreated organism, as analysed by the tyrosine standard estimation protocol. Conclusion: Resveratrol was found to be a potent compound to treat Stenotrophomonas maltophilia infections. In addition to the antimicrobial and enzyme-regulatory properties of resveratrol, it also shows anti-oxidant and anti-inflammatory properties. This finding has great scope clinically as resveratrol may prove to be an ideal drug to treat burn wound infections.

Objectif : Dans un contexte de ressources limitées, la connaissance du profil des germes contaminant les blocs opératoires et leur résistance aux antibiotiques constitue un maillon de la prévention des infections associées aux soins. Ainsi, l'objectif de notre étude était de déterminer la sensibilité aux antibiotiques des bactéries isolées de l'environnement du bloc opératoire de l'Hôpital National de Zinder. Matériels et Méthodes : Nous avions mené une étude prospective, transversale et descriptive de Janvier à Mars 2020. Les prélèvements avaient été réalisés par écouvillonnage le matin avant le début des activités et avaient concerné les mains et blouses des chirurgiens, le matériel de chirurgie et les équipements du bloc opératoire. Nous avions effectué l'isolement, l'identification et l'antibiogramme des souches bactériennes au niveau du laboratoire de biologie par des techniques conventionnelles classiques. Résultats : Au total, 74 prélèvements avaient été effectués. La culture était positive dans 58,10% des cas (43/74). Les bactéries isolées étaient constituées de 25 souches de Bacillus spp (58,13%), 10 souches de bactéries Gram négatif non fermentaires avec Acinetobacter bamanii (14,0%), Pseudomonas aeruginosa (7,0%) et Stenotrophomonas maltophilia (2,3%) et 8 souches d'entérobactéries représentées par Serratia marcescens (4,7%), Enterobacter cloacae (4,7%), Enterobacter aerogenes (4,7%), Escherichia coli (2,3%) et Klebsiella pneumoniae (2,3%).Concernant la sensibilité des souches aux antibiotiques, une seule souche d'Enterobacter aerogenes était résistante à l'Imipenème et 3 des 9 entérobactéries isolées étaient productrices de bétalactamase à spectre élargi. Conclusion : Au vu de résultats de cette étude, il convient de mettre en place des procédures adaptées en vue d'une meilleure surveillance microbiologique des blocs opératoires. Cela contribuera sans doute à la prévention des infections associées aux soins.

Cefiderocol (CFDC), (formerly S-649266), is a novel injectable siderophore cephalosporin developed by Shionogi & Co., Ltd., with potent in vitro activity against Gram-negative pathogens including multidrug-resistant (MDR) Enterobacteriaceae and non-fermenting organisms, such as Pseudomonas aeruginosa, Acinetobacter baumannii, Burkholderia cepacia, and Stenotrophomonas maltophilia. Characterized by its siderophore catechol-moiety, CFDC uses a "trojan-horse approach" to navigate through the bacterial periplasmic space, thus evading various beta-lactam degrading enzymes and other mechanisms of resistance present in Gram-negative bacteria. More specifically in carbapenem-resistant Enterobacteriaceae, CFDC has been shown to have activity against extended spectrum beta-lactamases (ESBLs), such as CTX-type, SHV-type, and TEM-type, as well as the Ambler classes of beta-lactamases, including class A (KPC), class B (NDM, IMP, and VIM), class C (AmpC), and class D (OXA, OXA-24, OXA-48, and OXA-48-like). In addition to the strong activity that CFDC has been shown to have against MDR P. aeruginosa, it has also displayed activity against the OXA-23, OXA-24, and OXA-51, beta-lactamases commonly found in MDR A. baumannii. Cefiderocol was recently approved by the US Food and Drug Administration (FDA) for use in complicated urinary tract infections (cUTI), including pyelonephritis, for use in patients 18 years or older with limited or no alternative options for treatment, and is currently being evaluated in a phase III trial for use in nosocomial pneumonia caused by Gram-negative pathogens. The unique features and enhanced activity of CFDC suggest that it is likely to serve as a viable therapeutic option in the treatment of MDR Gram-negative infections. The purpose of this review is to provide an overview of previously published literature explaining CFDC's pharmacology, pharmacokinetic / pharmacodynamic (PK / PD) properties, microbiologic activity, resistance mechanisms, safety parameters, dosing and administration, clinical data, and potential place in therapy.

The best-known cutaneous manifestations of septicemia in the skin are the so-called "septic vasculitis" and "septic vasculopathy," which represent two sides of the same pathogenetic process. The spectrum of cutaneous presentations of septicemia is, however, more complex, extending beyond septic vasculitis/vasculopathy. We describe the exceptional histopathological findings of skin lesions associated with Stenotrophomonas maltophilia septicemia, featuring a lymphohistiocytic infiltrate characterized by predominance of foamy macrophages containing granular basophilic material negative for PAS, Gram, Fite, and Grocott. Albeit an uncommon occurrence, S. maltophilia septicemia should be included in the broad differential diagnosis of cutaneous lesions occurring in immunocompromised individuals with worsening general conditions. Awareness of these histopathological findings may facilitate the identification of this insidious infectious agent as a source of nosocomial septicemia.

Background: Stenotrophomonas maltophilia is a Gram-negative bacillus and opportunistic emergent pathogen causing hospi- tal-acquired infections (HAIs). Due to risk factors such as prolonged intensive care unit stay and invasive procedures, it has become one of the leading causes of HAIs. Objective: The aim of this study was to evaluate the epidemiology of S.maltophilia infections over a six-year period at Düzce University Hospital, Turkey. Methods: The incidence, clinical characteristics, antimicrobial susceptibility and outcomes of nosocomial S. maltophilia in- fections during this period were retrospectively analyzed. Results: During the study period, 67 samples obtained from 61 patients were identified. Pneumonias (82%) were the most common HAIs, followed by bloodstream infections (10.5%), urinary tract infections (3%), skin and soft tissue infections (3%) and surgical site infection (1.5%). Admission to intensive care, hospitalization exceeding 30 days, and previous use of broad-spectrum antibiotics constituted risk factors. Resistance to cotrimoxazole (6%) was lower than that to levofloxacin (18%). Conclusion: The most important risk factors for S.maltophilia infection in patients are previous exposure to antibiotics, pro- longed hospitalization and invasive procedures such as mechanic ventilation. Discharging patients as early as possible with the rational use of antibiotics may be effective in reducing S. maltophilia infections and resistance rates. Keywords: Stenotrophomonas maltophilia; hospital-acquired infections; epidemiology; risk factors.

We present Stenotrophomonas maltophilia infections in 317 hospitalized patients in a large health network over a 3-year period. The majority of patients were elderly. Most infections were polymicrobial: respiratory 95.2%, wound 91%, urinary 80.8% and blood 64.3%. Younger patients were small in number and were more common in those with otitis externa, infections from injection drug use and those with line infections. Most deaths were in patients with terminal conditions and polymicrobial infections and mortality could not be directly attributed to Stenotrophomonas maltophilia. None of the sputum, bronchial, urinary or wound culture positive patients had positive blood cultures. Only blood (14/317) or ear (7/317) culture positive patients had significant numbers of younger individuals with only 3 out of 14 over age 50 in blood culture positive patients and 1/7 in those with otitis externa. Those with bacteremia included patients with injection drug use, chronic pain syndromes and vascular catheter infections. 94% of urinary infections, 91.7% wound infections and 85.8% respiratory isolates were in those above age 50. Overwhelming majority of urinary infections were in males with drainage devices present in 75%. Recurrent infections were uncommon. Respiratory specimens were frequently associated with tracheostomies and endotracheal tubes. Most wound infections were in chronic lower extremity ulcers. Prior carbapenem use was not significant in this study. Isolates from all sites were over 98% susceptible to Trimethoprim/sulphamethoxazole. Limitations: The study group only had 1 organ transplant and 2 cystic fibrosis patients and no burn wound infections.

BACKGROUND To better understand the mechanisms of infection with nontuberculous mycobacteria (NTM) in patients with cystic fibrosis (CF), we explore different risk factors associated with NTM positivity in a meta-analysis. METHODS Studies published before 31 July 2019 were selected from MEDLINE. Combined odds ratios (ORs) were calculated by pooling the ORs of each study. The weighted mean difference (WMD) was used for continuous numerical measurements. Summary data were pooled using fixed- or random-effects models according to the presence of heterogeneity (P 50%). RESULTS Nineteen studies with a total of 23 418 patients, of whom 1421 (6%) were diagnosed as NTM positive, were included. Older age was significantly associated with NTM positivity (WMD = 2.12, 95% confidence interval [CI]: 1.11-3.13; P

To the editor, Stenotrophomonas maltophilia is globally recognized as an emerging multidrug-resistant (MDR) pathogen in healthcare facilities, especially in the intensive care units (ICUs) where it...

Objective The study aimed to evaluate the association between microbes in the lower respiratory tract (LRT) and the srisk for severe bronchopulmonary dysplasia (sBPD) in premature infants. Methods We conducted a retrospective, single-center study of preterm infants who were admitted to the neonatal intensive care unit (NICU) of Southern Medical University Affiliated Maternal & Child Health Hospital of Foshan, China, between January 2015 and December 2017. The microbes in the LRT were screened by using tracheobronchial aspirate fluid (TAF) culture. Results One hundred and fifty-five infants were included in the analysis. Among 155 infants, 41 were diagnosed with sBPD, and 114 were diagnosed without sBPD. There were significant differences between infants with and without sBPD in regard to birth weight (BW), gestational age (GA), the duration of endotracheal ventilation and supplemental oxygen. The incidence of retinopathy (ROP) and sepsis was higher in the sBPD infants than in the infants without sBPD. There was a difference in the detection rate of Gram-negative bacteria (GNB) between the two groups. Stenotrophomonas maltophilia and Klebsiella pneumoniae were mainly detected in TAF. Conclusions The LRT microbes were different between infants with and without sBPD, and GNB is more frequently detected in sBPD infants.

Stenotrophomonas maltophilia is an aerobic, oxidase-negative and catalase-positive bacillus. S. maltophilia is a recognized opportunistic pathogen. Due to the advancements in invasive medical procedures, organ transplantation and chemotherapy of malignant illnesses, the relevance of this pathogen increased significantly. The therapy of S. maltophilia infections is challenging, as these bacteria show intrinsic resistance to multiple classes of antibiotics, the first-choice drug is sulfamethoxazole/trimethoprim. Our aim was to assess the epidemiology of S. maltophilia from various clinical samples and the characterization of resistance-levels and resistotyping of these samples over a long surveillance period. The study included S. maltophilia bacterial isolates from blood culture samples, respiratory samples and urine samples and the data for the samples, received between January 2008 until December 2017, a total of 817 S. maltophilia isolates were identified (respiratory samples n = 579, 70.9%, blood culture samples n = 175, 21.4% and urine samples n = 63, 7.7%). Levofloxacin and colistin-susceptibility rates were the highest (92.2%; n = 753), followed by tigecycline (90.5%, n = 739), the first-line agent sulfamethoxazole/trimethoprim (87.4%, n = 714), while phenotypic resistance rate was highest for amikacin (72.5% of isolates were resistant, n = 592). The clinical problem of sulfamethoxazole/trimethoprim-resistance is a complex issue, because there is no guideline available for the therapy of these infections.

What is known and objective Stenotrophomonas maltophilia is an intrinsically multidrug-resistant (MDR) organism which commonly presents as a respiratory tract infection. S. maltophilia is typically treated with high-dose sulfamethoxazole/trimethoprim (SMX/TMP). However, SMX/TMP and other treatment options for S. maltophilia can be limited because of resistance, allergy, adverse events or unavailability of the drug; use of novel agents may be necessary to adequately treat this MDR infection and overcome these limitations. Case description This small case series describes two patients who underwent treatment with tigecycline for ventilator-associated pneumonia (VAP) caused by S. maltophilia after admission to a trauma intensive care unit. At the time of admission for the two reported patients, a national drug shortage of intravenous (IV) SMX/TMP prevented its use. Tigecycline was chosen as a novel agent to treat S. maltophilia VAP based on culture and susceptibility data, and it was used successfully. Both patients showed clinical signs of improvement with eventual cure and discharge from the hospital after treatment with tigecycline, and one patient demonstrated confirmed microbiological cure with a negative repeat bronchoscopic bronchoalveolar lavage (BAL). What is new and conclusion To our knowledge, this small case series is the first documentation of utilizing tigecycline to treat S. maltophilia VAP in the United States. Although it likely should not be considered as a first-line agent, tigecycline proved to be an effective treatment option in the two cases described in the setting of a national drug shortage of the drug of choice.

Purpose To study the clinical characteristics and factors associated with mortality of patients who had Stenotrophomonas maltophilia infections. Patients and Methods We conducted a retrospective study to determine the clinical characteristics and factors associated with mortality for S. maltophilia infections among hospitalized adult patients at Siriraj Hospital. The clinical and microbiological data were collected from medical records December 2013-December 2016. Results Of 1221 subjects whose clinical samples grew S. maltophilia, 213 were randomly selected for chart review. One hundred patients with a true infection were analyzed. Their median age was 66 years; 47 were males; 46 were critically ill with a median APACHE II score of 18 (2-32); and 91 received antibiotic treatment, mainly with carbapenems (56%), before being diagnosed with a S. maltophilia infection. Pulmonary (53%) and bloodstream infections (25%) were the most common infections. The median length of hospitalization was 19 days before infection onset. The in-hospital mortality rate was 54%. The following factors were associated with mortality: a pre-existing respiratory infection (OR 6.28, 1.33-29.78; p.021); critical illness (OR 3.33, 1.45-7.62; p.005); multi-organ dysfunction (OR 2.44, 1.05-5.70; p.039); being on mechanical ventilation (OR 4.44, 1.90-10.39; p.001); concurrent immunosuppressive therapy (OR 2.67, 1.10-6.47; p.029); intravascular (OR 4.43, 1.79-10.92; p.001) and urinary catheterization (OR 4.83, 1.87-12.47; p.001); and serum albumin

Aim: To investigate if the prior use of nontargeted antibiotics induces cross-tolerance in Stenotrophomonas maltophilia. Methods: Antibiotic induction was performed to evaluate daptomycin and vancomycin as possible tolerance-inducing drugs measured by minimum bactericidal concentration/minimum inhibitory concentration (MIC) ratio, adapted disk-diffusion tests and time–kill curves. Results: After antibiotic exposure, three potentially tolerant strains were isolated, maintaining the same MIC value of levofloxacin, with minimum bactericidal concentration/MIC ratio slightly higher than the parental. In the adapted disk-diffusion test, one strain (D25) showed high tolerance level for levofloxacin, ceftazidime and ticarcillin-clavulanate. In time–kill activity of levofloxacin, D25 presented a subpopulation of persisters with survival rate higher (1.6-fold) than the parental. Conclusion: Previous exposure of S. maltophilia to daptomycin can induce cross-tolerance to ceftazidime and ticarcillin-clavulanate and cross-persistence to levofloxacin.

Purpose of review The increase in skin and soft tissue infections (SSTI) because of multidrug-resistant (MDR) pathogens is a global concern. Although MDR Gram-negative bacteria (GNB) are often overlooked as a cause of SSTIs, their burden on the morbidity of many subgroups of patients is high. There is a paucity in the available treatment options and guidelines on how to treat these pathogens. This manuscript reviews the management of SSTIs caused by carbapenem-resistant Enterobacteriaceae (CRE), Pseudomonas aeruginosa (CRPA), Acinetobacter baumannii (CRAB), and Stenotrophomonas maltophilia. We also highlight a few novel antibiotics that show promise in the future management of MDR-GNB SSTIs. Recent findings Studies on treatment options of MDR-GNB SSTIs are scarce. Most clinical trials investigating new antibiotics have addressed conditions such as complicated intraabdominal infections, complicated urinary infections, and respiratory infections. CREs are a heterogenous group of pathogens with various mechanisms of resistance dictating susceptibility to different antimicrobial agents. Ceftazidime--avibactam, and meropenem--vaborbactam have potent activity against some of the CREs, especially Klebsiella pneumoniae carbapenemase (KPC) producers. Several novel antibiotics have potent activity against CRPA SSTIs, such as ceftazidime--avibactam, ceftolozane--tazobactam, cefiderocol, delafloxacin, finafloxacin, and murepavadin. Cefiderocol may also play an important role in the management of CRAB SSTIs, along with plazomicin and eravacycline. Summary MDR-GNB play a major role in SSTIs in patients with underlying immunodeficiency, as well as burn or trauma-related injuries. With the alarming global rise in MDR-GNB resistance, antibiotic therapy for SSTIs is challenging and must be guided by in-vitro susceptibility results. Currently, data extrapolated from other indications and combination therapy can be used empirically pending microbiological data and susceptibilities. Novel antibiotics are currently under development. It is hoped that future clinical trials will be designed to address MDR-GNB SSTIs.

Stenotrophomonas maltophilia es una bacteria oportunista que causa diversos tipos de infecciones asociadas a la atención sanitaria en pacientes debilitados, especialmente en aquellos que previamente han recibido antimicrobianos de amplio espectro. Stenotrophomonas maltophilia se posiciona hoy en día como un patógeno nosocomial de ámbito general, añadiéndose a otros multirresistentes como Staphylococcus aureus, Acinetobacter spp. y Pseudomonas aeruginosa. Presentamos este caso dado que es el primero que encontramos en nuestro servicio, simulando una infección recurrente por micobacterias, con el objetivo de demostrar el protocolo utilizado para diagnóstico y tratamiento; Este germen es poco frecuentemente reportado, siendo todos en inmunosuprimidos o con tratamiento antibiótico prolongado. Este agente infeccioso debe considerarse e incluirse entre los diagnósticos diferenciales de conglomerados ganglionares abscedados. En pacientes con inmunosupresión sospechada o conocida es necesario descartar la presencia de microorganismos oportunistas, para poder proveerle un adecuado diagnóstico y tratamiento específico

Severe bacterial infections are a serious problem after cord blood transplantation (CBT). Colonization with multidrug-resistant Gram-negative rods (MRGNR) is associated with increased morbidity and mortality after allogeneic hematopoietic cell transplantation. However, its impact on outcomes after CBT is unclear. We aim to explore the impact of colonization with MRGNRs in adult patients undergoing CBT. We retrospectively analyzed 145 adult patients who received single-unit CBT in our institute. As a standard practice in our institute, all patients were screened for colonization with MRGNR by oral cavity swabs, urine, and stool specimens between the day of admission for CBT and the day of discharge or day 100 after CBT. There were 62 incidents of colonization with MRGNR in 52 patients, of which 25 involved Stenotrophomonas maltophilia, 19 multidrug-resistant Pseudomonas spp., and 18 extended-spectrum beta-lactamase-producing Enterobacteriaceae. On multivariate analysis, MRGNR persistence significantly affected increase in non-relapse mortality (NRM) (hazard ratio [HR], 8.96; 95% CI 1.85-43.46; P = 0.006) and the subsequent development of bloodstream infection due to MRGNR (HR 11.82; 95% CI 2.15-64.87; P = 0.004), but not MRGNR clearance, compared with non-colonized patients. These data suggest that persistent colonization with MRGNR is significantly associated with higher NRM in CBT for adults.

This study investigated the epidemiology of adult patients with bacteremia caused by seven major gram-negative bacteria during a year at four university hospitals in Japan. Of the 438 cases included, Escherichia coli (247 patients) was the most frequently isolated pathogen, followed by Klebsiella species (89 patients), Enterobacter species (31 patients), Pseudomonas aeruginosa (29 patients), Bacteroides species (19 patients), Acinetobacter species (12 patients) and Stenotrophomonas maltophilia (11 patients). The overall, crude in-hospital mortality was 16.4%, ranging from 9.7% with Enterobacter species to 54.5% with S. maltophilia. Community- and hospital-acquired bacteremia accounted for 52.5% and 47.5%, respectively. Enterobacteriaceae were isolated from 93.0% of patients with community-acquired bacteremia, whereas non-fermenting bacteria were isolated from 21.6% of patients with hospital-acquired bacteremia. Of the 423 patients analyzed, 86.8% and 13.2% were monomicrobial and polymicrobial infections, respectively, and their in-hospital mortalities were 13.9% and 30.4%, respectively. Although carbapenem-resistant Enterobacteriaceae were not detected, extended-spectrum β-lactamase (ESBL) production was seen in 24.3% of E. coli and 6.7% of Klebsiella species, respectively. E. coli producing ESBL showed high resistance rates to fluoroquinolones (approximately 90%), in contrast to non-producing-E. coli (approximately 21%). The susceptibilities to carbapenems and fluoroquinolones were approximately 80% for P. aeruginosa, whereas all Acinetobacter species were susceptible to these antibiotics. Bacteroides species showed 100% susceptibility to piperacillin/tazobactam and carbapenems, but only 47.4% were susceptible to clindamycin. Further studies, as well as continued surveillance, are required to determine the appropriate therapeutic strategy for gram-negative bacteremia.