BACKGROUND: The effect of dual systemic antibiotic therapy against Pseudomonas aeruginosa in patients with pre-existing lung disease is unknown. To assess whether dual systemic antibiotics against P. aeruginosa in outpatients with COPD, non-cystic fibrosis (non-CF) bronchiectasis, or asthma can improve outcomes.
METHODS: Multicenter, randomised, open-label trial conducted at seven respiratory outpatient clinics in Denmark. Outpatients with COPD, non-CF bronchiectasis, or asthma with a current P. aeruginosa-positive lower respiratory tract culture (clinical routine samples obtained based on symptoms of exacerbation not requiring hospitalisation), regardless of prior P. aeruginosa-status, no current need for hospitalisation, and at least two moderate or one hospitalisation-requiring exacerbation within the last year were eligible. Patients were assigned 1:1 to 14 days of dual systemic anti-pseudomonal antibiotics or no antibiotic treatment. Primary outcome was time to prednisolone or antibiotic-requiring exacerbation or death from day 20 to day 365.
RESULTS: The trial was stopped prematurely based in lack of recruitment during the COVID-19 pandemic, this decision was endorsed by the Data and Safety Monitoring Board. Forty-nine outpatients were included in the study. There was a reduction in risk of the primary outcome in the antibiotic group compared to the control group (HR 0.51 (95%CI 0.27-0.96), p = 0.037). The incidence of admissions with exacerbation within one year was 1.1 (95%CI 0.6-1.7) in the dual antibiotic group vs. 2.9 (95%CI 1.3-4.5) in the control group, p = 0.037.
CONCLUSIONS: Use of dual systemic antibiotics for 14 days against P. aeruginosa in outpatients with chronic lung diseases and no judged need for hospitalisation, improved clinical outcomes markedly. The main limitation was the premature closure of the trial.
BACKGROUND: ClinicalTrials.gov, NCT03262142, registration date 2017-08-25.

Due to over-prescription of antibiotics, antimicrobial resistance has emerged to be a critical concern globally. Many countries have tightened the control of antibiotic usage, which, in turn, promotes the search for alternatives to antibiotics. Quite a few phytochemicals have been investigated. Benzyl isothiocyanate (BITC) is an important secondary metabolite in cruciferous species and exhibited potent antimicrobial activity under in vitro conditions. In this research, we undertook a comparative mouse model study of BITC with gentamycin sulfate (positive antibiotic control) and ceftiofur hydrochloride (negative antibiotic control) against Pseudomonas aeruginosa infection. Our results showed that BITC exhibited comparable or better antimicrobial activity and lower infiltration of mouse immune cells upon comparing to gentamycin sulfate. Furthermore, BITC did not impose any toxicity to the air pouch skin tissues. In summary, our current study suggests that BITC could be an alternative to antibiotics and deserves further in vivo and clinical trial studies.

We describe four cases of a novel carbapenem-resistant Pseudomonas aeruginosa ST179 clone carrying the blaKPC-2 or blaKPC-35 gene together with blaIMP-16, imported from Peru to Spain and isolated from leukemia patients. All isolates were multidrug-resistant but remained susceptible to fosfomycin, cefiderocol, and colistin. Whole-genome sequencing revealed that blaKPC-2 and blaKPC-35 were located in an IncP6 plasmid, whereas blaIMP-16 was in a chromosomal type 1 integron. This study highlights the global threat of multidrug-resistant P. aeruginosa clones and underscores the importance of monitoring and early detection of emerging resistance mechanisms to guide appropriate treatment strategies. The importation and spread of such clones emphasize the urgent need to implement strict infection control measures to prevent the dissemination of carbapenem-resistant bacteria.
OBJECTIVE: This is the first documented case of a Pseudomonas aeruginosa ST179 strain carrying the blaKPC-35 gene, and it represents the first report of a P. aeruginosa co-harboring blaIMP-16 and either blaKPC-2 or blaKPC-35, which wre imported from Peru to Spain, highlighting a threat due to the capacity of spreading carbapenem-resistance via plasmid conjugation.

BACKGROUND: This study interrogates infection related data in the Burns Registry of Australia and New Zealand (BRANZ), to examine associations of multi-drug resistant organisms (MDROs) and blood stream infection (BSI).
METHODS: Data between July 2016 and June 2021 were analysed to determine prevalence, risk factors and outcomes associated with BSIs and MDROs: Methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), carbapenem-resistant Pseudomonas spp. (CRP), and carbapenem-resistant Enterobacter (CRE). Data completeness and value for quality improvement activity were assessed.
RESULTS: We found a low incidence (3.4%) of the resistant organisms of interest, and no change over the study period. Fequency varied between services and increased with age and size of burn. MRSA was the commonest organism in all age groups. A positive BSI result occurred in 1.6% of patients (12.1% of cultures taken) at a median time of 10.2 days post injury. Free text identification of organisms was inconsistently documented.
CONCLUSIONS: The low rate and patterns of acquisition of MDROs of interest and BSIs is comparable with reports from countries with low incidence of massive burns. Wider adoption of a standardized laboratory reporting framework would help realise the potential of clinical quality registries to provide data which supports evidence based infection prevention initiatives.

BACKGROUND: Pseudomonas aeruginosa is a common cause of nosocomial infections. However, the emergence of multidrug-resistant strains has complicated the treatment of P. aeruginosa infections. While polymyxins have been the mainstay for treatment, there is a global increase in resistance to these antibiotics. Therefore, our study aimed to determine the prevalence and molecular details of colistin resistance in P. aeruginosa clinical isolates collected between June 2019 and May 2023, as well as the genetic linkage of colistin-resistant P. aeruginosa isolates.
RESULTS: The resistance rate to colistin was 9% (n = 18) among P. aeruginosa isolates. All 18 colistin-resistant isolates were biofilm producers and carried genes associated with biofilm formation. Furthermore, the presence of genes encoding efflux pumps, TCSs, and outer membrane porin was observed in all colistin-resistant P. aeruginosa strains, while the mcr-1 gene was not detected. Amino acid substitutions were identified only in the PmrB protein of multidrug- and colistin-resistant strains. The expression levels of mexA, mexC, mexE, mexY, phoP, and pmrA genes in the 18 colistin-resistant P. aeruginosa strains were as follows: 88.8%, 94.4%, 11.1%, 83.3%, 83.3%, and 38.8%, respectively. Additionally, down-regulation of the oprD gene was observed in 44.4% of colistin-resistant P. aeruginosa strains.
CONCLUSIONS: This study reports the emergence of colistin resistance with various mechanisms among P. aeruginosa strains in Ardabil hospitals. We recommend avoiding unnecessary use of colistin to prevent potential future increases in colistin resistance.

Antimicrobial de-escalation refers to reducing the spectrum of antibiotics used in treating bacterial infections. This strategy is widely recommended in many antimicrobial stewardship programs and is believed to reduce patients\' exposure to broad-spectrum antibiotics and prevent resistance. However, the ecological benefits of de-escalation have not been universally observed in clinical studies. This paper conducts computer simulations to assess the ecological effects of de-escalation on the resistance prevalence of Pseudomonas aeruginosa-a frequent pathogen causing nosocomial infections. Synthetic data produced by the models are then used to estimate the sample size and study period needed to observe the predicted effects in clinical trials. Our results show that de-escalation can reduce colonization and infections caused by bacterial strains resistant to the empiric antibiotic, limit the use of broad-spectrum antibiotics, and avoid inappropriate empiric therapies. Further, we show that de-escalation could reduce the overall super-infection incidence, and this benefit becomes more evident under good compliance with hand hygiene protocols among health care workers. Finally, we find that any clinical study aiming to observe the essential effects of de-escalation should involve at least ten arms and last for four years-a size never attained in prior studies. This study explains the controversial findings of de-escalation in previous clinical studies and illustrates how mathematical models can inform outcome expectations and guide the design of clinical studies.

OBJECTIVE: This study aims to investigate the risk factors for carbapenem-resistant Pseudomonas aeruginosa bloodstream infection (CRPA-BSI) and identify predictors of outcomes among patients with P. aeruginosa bloodstream infection (PA-BSI).
METHODS: A retrospective cohort study was conducted on patients with PA-BSI at Henan Cancer Hospital from 2013 to 2022.
RESULTS: Among the 503 incidences analysed, 15.1% of them were CRPA strains. Age, ANC < 100/mmc, receiving antifungal prophylaxis, exposure to carbapenems within the previous 90 days to onset of BSI, and allogeneic HSCT (allo-HSCT) were associated with the development of CRPA-BSI. CRPA-BSI patients experienced significantly higher 28-day mortality rates compared to those with carbapenem-susceptible P. aeruginosa bloodstream infection. Multivariate logistic regression analysis identified age at BSI, active stage of haematological disease, procalcitonin levels, prior corticosteroid treatment, isolation of CRPA, and septic shock as independent predictors of 28-day mortality.
CONCLUSIONS: Risk factors for CRPA-BSI include age, ANC < 100/mmc, antifungal prophylaxis, exposure to carbapenems, and allo-HSCT. Additionally, age at BSI, active haematological disease, procalcitonin levels, prior corticosteroid treatment, CRPA isolation, and septic shock contribute to increased mortality rates among patients with PA-BSI.

OBJECTIVE: Pseudomonas aeruginosa-induced keratitis is one of the most severe and challenging forms of corneal infection, owing to its associated intense inflammatory reactions leading to corneal necrosis and dense corneal scar with loss of vision. Since mesenchymal stem cells (MSCs) are reported to possess antimicrobial and immunomodulatory properties, they can be tested as an adjuvant treatment along with the antibiotics which are the current standard of care. This study aims to investigate the anti-bacterial and immunomodulatory roles of human bone marrow MSC-derived conditioned medium (MSC-CM) in P. aeruginosa-infected human corneal epithelial cells (HCECs) in vitro.
METHODS: The effect of MSC-CM on the growth of clinical isolates of P. aeruginosa was evaluated by colony-forming unit assay. The expression of inflammatory cytokines (IL-6 and TNF-α) and an antimicrobial peptide (Lipocalin 2) in lipopolysaccharide-treated MSCs and HCECs was analyzed through ELISA. Corneal epithelial repair following infection with P. aeruginosa was studied through scratch assay.
RESULTS: Compared to control (P. aeruginosa (5*105) incubated in DMEM (1 ml) at 37 °C for 16 h), MSC-CM significantly: i) inhibits the growth of P. aeruginosa (159*109 vs. 104*109 CFU/ml), ii) accelerates corneal epithelial repair following infection with P. aeruginosa (9% vs. 24% closure of the wounded area after 12 h of infection), and iii) downregulates the lipopolysaccharide-induced expression of IL-6, TNF-α and Lipocalin 2 in HCECs. A combination of MSC-CM with an antibiotic, Ciprofloxacin moderately regulated the expression of IL-6, TNF-α, and Lipocalin 2.
CONCLUSIONS: MSC-CM holds promise as an adjunctive therapeutic approach for P. aeruginosa-induced corneal epithelial damage.

BACKGROUND: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) infection has become a major public health concern. The recommendations for monotherapy and combination therapy in the current guidelines lack sufficient evidence to support them. The primary objective of this study is to determine the effectiveness of anti-Infective combination therapy compared to monotherapy in achieving clinical success in patients with CRPA infection and risk factors of clinical failure of monotherapy.
METHODS: A retrospective study from Medical Information Mart for Intensive Care IV (MIMIC-IV) was conducted. We included adults with infections caused by CRPA. The outcomes of this study were clinical success, complete clinical success, and 28-day all-cause mortality.
RESULTS: A total of 279 subjects were finally enrolled. The rate of clinical success for combination therapy was higher than that for monotherapy (73.1% versus 60.4%, p=0.028). Compared to clinical failure patients, patients in the clinical success group were more likely to die within 28 days after CRPA was found (48.3% versus 3.6%, p<0.001). In a multivariate logistic regression analysis, monotherapy was found to be significantly correlated with clinical success (OR, 0.559, 95% CI, 0.321-0.976; p = 0.041).
CONCLUSIONS: Combination therapy is more effective for CRPA infection patients, especially those whose SOFA score is ≥ 2 or whose Charlson comorbidity index is ≥ 6.

Pseudomonas aeruginosa (PA) is a prevalent opportunistic pathogen that has close associations with both acute and chronic infections. However, there exists an insufficiency of accurate and comprehensive data pertaining to the antimicrobial susceptibility patterns and clinical characteristics of both mucoid and non-mucoid strains of PA (mPA and non-mPA, respectively).
From January 1, 2021 to December 31, 2022, a thorough retrospective study was carried out to examine and compare the antibiotic susceptibility test outcomes and clinical characteristics of hospitalized patients with mPA and non-mPA infections.
This study investigated a cohort of 111 patients who were diagnosed with mPA infections, as well as 792 patients diagnosed with non-mPA infections. Significant demographic disparities, including gender (p < 0.001), age (p < 0.001), length of hospital stay (p < 0.001), diabetes (p = 0.043), and hypertension (p < 0.001), are evident between the mPA and non-mPA groups. The mPA group commonly necessitates hospitalization for respiratory system diseases, whereas the non-mPA group is associated with concomitant cardiovascular and cerebrovascular diseases. The mPA group demonstrates lower utilization rates of medical devices, such as Foley catheter (p < 0.001), nasogastric tube (p < 0.001), mechanical ventilation (p < 0.001), tracheostomy (p < 0.001), arterial and venous catheterization (p < 0.001), and exhibits superior organ function status, including lower incidences of hypoalbuminemia (p < 0.001), septic shock (p < 0.001), liver dysfunction (p < 0.001), renal failure (p < 0.001), and respiratory failure (p < 0.001). The non-mPA group is more vulnerable to infection with two or more bacterial pathogens compared to the mPA group, with the non-mPA group frequently resulting in Enterobacteriaceae infections and the mPA group being associated with fungal infections. Variations in antibiotic sensitivity are noted for Amikacin (p < 0.001), Ciprofloxacin (p < 0.001), Cefepime (p = 0.003), and Levofloxacin (p < 0.001) in antibiotic susceptibility testing, with resistance patterns closely tied to specific antibiotic usage.
There are significant demographic characteristics, clinical manifestations and antibiotic susceptibility between mPA and non-mPA infections. It is crucial to emphasize these characteristics due to their significant role in preventing and treating PA infections.