Decrease of ESKAPE virulence with a cationic heme-mimetic gallium porphyrin photosensitizer: The Trojan horse strategy that could help address antimicrobial resistance.

INTRODUCTION: Emerging antibiotic resistance among bacterial pathogens has forced an urgent need for alternative non-antibiotic strategies development that could combat drug resistant-associated infections. Suppression of virulence of ESKAPE pathogens' by targeting multiple virulence traits provides a promising approach. OBJECTIVES: Here we propose an iron-blocking antibacterial therapy based on a cationic heme-mimetic gallium porphyrin (GaCHP), which antibacterial efficacy could be further enhanced by photodynamic inactivation. METHODS: We used gallium heme mimetic porphyrin (GaCHP) excited with light to significantly reduce microbial viability and suppress both the expression and biological activity of several virulence traits of both Gram-positive and Gram-negative ESKAPE representatives, i.e., S. aureus and P. aeruginosa. Moreover, further improvement of the proposed strategy by combining it with routinely used antimicrobials to resensitize the microbes to antibiotics and provide enhanced bactericidal efficacy was investigated. RESULTS: The proposed strategy led to substantial inactivation of critical priority pathogens and has been evidenced to suppress the expression and biological activity of multiple virulence factors in S. aureus and P. aeruginosa. Finally, the combination of GaCHP phototreatment and antibiotics resulted in promising strategy to overcome antibiotic resistance of the studied microbes and to enhance disinfection of drug resistant pathogens. CONCLUSION: Lastly, considering high safety aspects of the proposed treatment toward host cells, i.e., lack of mutagenicity, no dark toxicity and mild phototoxicity, we describe an efficient alternative that simultaneously suppresses the functionality of multiple virulence factors in ESKAPE pathogens.

Priming effect with photoinactivation against extensively drug-resistant Enterobacter cloacae and Klebsiella pneumoniae.

In this study, we present antimicrobial blue light (aBL) and antimicrobial photoinactivation with green light in the presence of Rose Bengal (aPDI) to modulate the susceptibility of extensively drug-resistant (XDR) Enterobacter cloacae and Klebsiella pneumoniae clinical isolates to antimicrobials. This process can be considered a photodynamic priming tool that influences other therapeutic options, such as antibiotics. The current study evaluated the different environments to estimate the most effective priming conditions by testing a broad spectrum of antimicrobials (including antimicrobials with different targets and mechanisms of action). The susceptibility of the E. cloacae and K. pneumoniae clinical isolates to various antibiotics after aBL and green light (with rose bengal) as aPDI treatment was examined with multiple methods of synergy testing (e.g., diffusion methods, checkerboard assay, postantibiotic effect), and most effective photoinactivation conditions were implemented for each environment. When Enterobacteriaceae were exposed to aBL, the most efficient reduction in survival rate under TSB conditions was observed. Similar results were observed when rose bengal, as a photosensitizer, was present during the exposure to green light in PBS. aBL and aPDI led to an increased susceptibility of K. pneumoniae and E. cloacae isolates to chloramphenicol and colistin or fosfomycin and colistin antibiotics, respectively. However, among the 4 tested isolates, we observed synergies between different antimicrobial agents and photoinactivation conditions. Thus, it may suggest that the sensitization process may be considered a strain dependent priming tool.

Open lung biopsy performed in idiopathic pulmonary fibrosis is a safe procedure.

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease with a fatal prognosis. The diagnosis is made on the basis of high-resolution computed tomography and histological examination in selected cases. AIM: To determine the risk of complications of open lung biopsy performed in patients with IPF. MATERIAL AND METHODS: We performed a retrospective analysis of 51 patients who underwent diagnostic excision of pulmonary parenchyma due to IPF in the period 1995-2014. We assessed the complication rate, length of drainage, postoperative period and 30-day mortality. We compared the results of treatment in the groups of patients operated on with thoracotomy and videothoracoscopy. RESULTS: The mean age of patients was 58 (47% female, 53% male) forced vital capacity (FVC) was 81%, forced expiratory volume in 1 s (FEV1) was 80% and body mass index (BMI) was 27 kg/m2. Thoracotomies (lateral, muscle sparing or anterior) were performed in 20 patients between 1995 and 2012 and videothoracoscopy in 31 patients operated on in the years 2009-2014. Patients in study groups did not differ considering age (p = 0.40), gender (p = 0.81), FVC (p = 0.08), FEV1 (p = 0.13) or BMI (p = 0.75). Postoperative complications occurred in 3.9% of patients (atrial arrhythmia 1.9% and recurrent pneumothorax 1.9%) with equal incidence in both study groups (p = 0.75). Median stay after thoracotomy was 4 days while after videothoracoscopy it was 3 days (p = 0.04). CONCLUSIONS: Open lung biopsy performed on patients with IPF is a safe procedure. Open lung biopsy performed through thoracotomy could be as safe as through VATS, however is characterized by longer postoperative stay.