OBJECTIVES: Pseudomonas aeruginosa (PA) is a common causative pathogen of pneumonia acquired in the intensive care unit (ICU). The aim of this study was to determine the incidence of PA ICU pneumonia (PAIP) and to quantify its independent association with PA colonization at different body sites. METHODS: Adult patients on mechanical ventilation at ICU admission were prospectively enrolled across 30 European ICUs. PA colonization in the perianal area and in the lower respiratory tract was assessed within 72 hours after ICU admission and twice weekly until ICU discharge. PAIP development was evaluated daily. Competing risk models with colonization as a time-varying exposure and ICU death and discharge as competing events were fitted and adjusted for confounders to investigate the association between PA carriage and PAIP. RESULTS: A total of 1971 subjects were enrolled. The colonization prevalence with PA in the first 72 hours of ICU admission was 10.4% (179 perianal and 51 respiratory), whereas the acquisition incidence during the ICU stay was 7.0% (158 perianal and 47 respiratory). Of the 43 (1.8%) patients who developed PAIP, 11 (25.6%) were PA colonized on admission and 9 (20.9%) acquired colonization before PAIP onset. Both perianal (adjusted subdistribution hazard ratio, 4.4; 95% CI, 1.7-11.6) and respiratory colonization (adjusted subdistribution hazard ratio: 4.6, 95% CI, 1.9-11.1) were independently associated with PAIP development. DISCUSSION: PAIP incidence was higher in PA colonized vs. non-colonized patients. Colonization of both the rectum and of the respiratory tract was associated with development of PAIP. The increased risk of PA colonization for subsequent infection provides an opportunity for targeted preventive interventions.

• MeSH
• dospělí MeSH
• incidence MeSH
• infekce spojené se zdravotní péčí epidemiologie   mikrobiologie   MeSH
• jednotky intenzivní péče * statistika a číselné údaje   MeSH
• lidé středního věku MeSH
• lidé MeSH
• přenašečství epidemiologie   mikrobiologie   MeSH
• prevalence MeSH
• prospektivní studie MeSH
• pseudomonádové infekce * epidemiologie   mikrobiologie   MeSH
• Pseudomonas aeruginosa * izolace a purifikace   MeSH
• senioři MeSH
• ventilátorová pneumonie epidemiologie   mikrobiologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• Geografické názvy
• Evropa MeSH

BACKGROUND: Pseudomonas aeruginosa can proliferate in immunocompromised individuals, forming biofilms that increase antibiotic resistance. This bacterium poses a significant global health risk due to its resistance to human defenses, antibiotics, and various environmental stresses. The objective of this study was to evaluate the antibacterial, anti-biofilm, and anti-quorum sensing activities of galloylquinic acid compounds (GQAs) extracted from Copaifera lucens leaves against clinical isolates of multidrug-resistant (MDR) P. aeruginosa. We have investigated the optimal concentration of GQAs needed to eradicate preexisting biofilms and manage wound infections caused by P. aeruginosa, in vitro and in vivo. RESULTS: Our results revealed that GQAs exhibited 25-40 mm inhibition zone diameters, with 1-4 μg/mL MIC and 2-16 μg/mL MBC values. GQAs interfered with the planktonic mode of P. aeruginosa isolates, and significantly inhibited their growth in the pre-formed biofilm architecture, with MBIC80 and MBEC80 values of 64 μg/mL and 128 μg/mL, respectively. The anti-biofilm effect was confirmed by fluorescence staining and confocal microscopy which showed a dramatic reduction in the cell viability and the biofilm thickness (62.5%), after exposure to 128 μg/mL of GQAs in particular. The scanning electron micrographs showed that GQAs impaired biofilm and bacterial structures by interfering with the biomass and the exopolysaccharides forming the matrix. GQAs also interfered with virulence factors and bacterial motility, where 128 μg/mL of GQAs significantly (p < 0.05) reduced rhamnolipid, pyocyanin, and the swarming motility of the organism which play a vital role in the biofilm formation. GQAs downregulated 89% of the quorum-sensing genes (lasI and lasR, pqsA and pqsR) involved in the biofilm formation. CONCLUSION: GQAs demonstrate significant promise as novel and potent antibiofilm and antivirulence agents against clinical isolates of MDR P. aeruginosa, with substantial potential to enhance wound healing in biofilm-associated infections. This promising antibacterial action positions GQAs as a superior alternative for the treatment of biofilm-associated wound infections, with substantial potential to improve wound healing and mitigate the impact of persistent bacterial infections. CLINICAL TRIAL NUMBER: not applicable.

• MeSH
• antibakteriální látky * farmakologie   MeSH
• biofilmy * účinky léků   růst a vývoj   MeSH
• infekce v ráně * mikrobiologie   farmakoterapie   MeSH
• lidé MeSH
• listy rostlin chemie   MeSH
• mikrobiální testy citlivosti MeSH
• mnohočetná bakteriální léková rezistence účinky léků   MeSH
• myši MeSH
• pseudomonádové infekce * mikrobiologie   farmakoterapie   MeSH
• Pseudomonas aeruginosa * účinky léků   fyziologie   izolace a purifikace   MeSH
• quorum sensing * účinky léků   MeSH
• rostlinné extrakty farmakologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Antibiotic resistance (ATBR) is increasing every year as the overuse of antibiotics (ATBs) and the lack of newly emerging antimicrobial agents lead to an efficient pathogen escape from ATBs action. This trend is alarming and the World Health Organization warned in 2021 that ATBR could become the leading cause of death worldwide by 2050. The development of novel ATBs is not fast enough considering the situation, and alternative strategies are therefore urgently required. One such alternative may be the use of non-thermal plasma (NTP), a well-established antimicrobial agent actively used in a growing number of medical fields. Despite its efficiency, NTP alone is not always sufficient to completely eliminate pathogens. However, NTP combined with ATBs is more potent and evidence has been emerging over the last few years proving this is a robust and highly effective strategy to fight resistant pathogens. This minireview summarizes experimental research addressing the potential of the NTP-ATBs combination, particularly for inhibiting planktonic and biofilm growth and treating infections in mouse models caused by methicillin-resistant Staphylococcus aureus or Pseudomonas aeruginosa. The published studies highlight this combination as a promising solution to emerging ATBR, and further research is therefore highly desirable.

• MeSH
• antibakteriální látky * farmakologie   terapeutické užití   MeSH
• antibiotická rezistence MeSH
• bakteriální léková rezistence MeSH
• biofilmy * účinky léků   MeSH
• lidé MeSH
• methicilin rezistentní Staphylococcus aureus účinky léků   MeSH
• modely nemocí na zvířatech MeSH
• myši MeSH
• plazmové plyny * farmakologie   MeSH
• pseudomonádové infekce mikrobiologie   farmakoterapie   MeSH
• Pseudomonas aeruginosa účinky léků   MeSH
• stafylokokové infekce mikrobiologie   farmakoterapie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Antimicrobial susceptibility was determined for clinical gram-negative isolates from Czech Republic, Hungary, and Poland, where published data for ceftolozane/tazobactam (C/T) and imipenem/relebactam (IMI/REL) is scarce. C/T was active against 94.3% of Enterobacterales, 10-18% higher than the tested cephalosporins and piperacillin/tazobactam. IMI/REL was the most active tested agent against non-Morganellaceae Enterobacterales (99.7% susceptible). C/T was the most active among all studied agents except colistin against Pseudomonas aeruginosa (96.0% susceptible); susceptibility to IMI/REL was 90.7%. C/T maintained activity against 73.7-85.3% of β-lactam-resistant or multidrug-resistant P. aeruginosa subsets. C/T and IMI/REL could represent important treatment options for patients from these countries.

• MeSH
• antibakteriální látky farmakologie   terapeutické užití   MeSH
• cefalosporiny terapeutické užití   MeSH
• imipenem farmakologie   terapeutické užití   MeSH
• lidé MeSH
• mikrobiální testy citlivosti MeSH
• pseudomonádové infekce * farmakoterapie   mikrobiologie   MeSH
• Pseudomonas aeruginosa MeSH
• tazobaktam farmakologie   terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH
• Maďarsko MeSH
• Polsko MeSH

The Pseudomonas aeruginosa population has a nonclonal epidemic structure. It is generally composed of a limited number of widespread clones selected from a background of many rare and unrelated genotypes recombining at high frequency. Due to the increasing prevalence of nosocomial infections caused by multidrug-resistant/extensively drug-resistant (MDR/XDR) strains, it is advisable to implement infection control measures. Pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) are considered the gold standard methods in bacterial typing, despite being limited by cost, staff, and instrumental demands. Here, we present a novel mini-MLST scheme for P. aeruginosa rapid genotyping based on high-resolution melting analysis. Using the proposed mini-MLST scheme, 3,955 existing sequence types (STs) were converted into 701 melting types (MelTs), resulting in a discriminatory power of D = 0.993 (95% confidence interval [CI], 0.992 to 0.994). Whole-genome sequencing of 18 clinical isolates was performed to support the newly designed mini-MLST scheme. The clonal analysis of STs belonging to MelTs associated with international high-risk clones (HRCs) performed by goeBURST software revealed that a high proportion of the included STs are highly related to HRCs and have also been witnessed as responsible for serious infections. Therefore, mini-MLST provides a clear warning for the potential spread of P. aeruginosa clones recognized as MDR/XDR strains with possible serious outcomes. IMPORTANCE In this study, we designed a novel mini-MLST typing scheme for Pseudomonas aeruginosa. Its great discriminatory power, together with ease of performance and short processing time, makes this approach attractive for prospective typing of large isolate sets. Integrating the novel P. aeruginosa molecular typing scheme enables the development and spread of MDR/XDR high-risk clones to be investigated.

• MeSH
• buněčné klony MeSH
• genotyp MeSH
• lidé MeSH
• molekulární epidemiologie metody   MeSH
• multilokusová sekvenční typizace MeSH
• prospektivní studie MeSH
• pseudomonádové infekce * epidemiologie   mikrobiologie   MeSH
• Pseudomonas aeruginosa * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Resistant bacteria may leave the hospital environment through wastewater. The opportunistic pathogen Pseudomonas aeruginosa, due to its intrinsic resistance to many antibiotics and its ability to easily acquire antibiotic resistance determinants, poses a significant threat to public health. The aim of this study was to evaluate the antibiotic resistance profiles of cultivated P. aeruginosa in untreated hospital effluents in the Czech Republic. Fifty-nine P. aeruginosa strains isolated from six hospital wastewaters were tested for antimicrobial susceptibility through the disc diffusion method against seven antimicrobial agents. Resistance was found in all antibiotics tested. The highest resistance values were observed for ciprofloxacin (30.5%), gentamicin (28.8%), and meropenem (27.2%). The P. aeruginosa isolates also exhibited resistance to ceftazidime (11.5%), amikacin (11.5%), piperacillin-tazobactam (11.5%), and aztreonam (8.5%). Seventeen strains of P. aeruginosa (28.8%) were classified as multidrug-resistant (MDR). The results of this study revealed that antibiotic-resistant strains are commonly present in hospital wastewater and are resistant to clinically relevant antipseudomonal drugs. In the absence of an appropriate treatment process for hospital wastewater, resistant bacteria are released directly into public sewer networks, where they can serve as potential vectors for the spread of antibiotic resistance.

• MeSH
• antibakteriální látky farmakologie   terapeutické užití   MeSH
• antibiotická rezistence MeSH
• lidé MeSH
• mikrobiální testy citlivosti MeSH
• nemocnice MeSH
• odpadní voda mikrobiologie   MeSH
• pseudomonádové infekce * farmakoterapie   mikrobiologie   MeSH
• Pseudomonas aeruginosa * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

Conversion to mucoid form is a crucial step in the pathogenesis of P. aeruginosa in burns and cystic fibrosis (CF) patients. Alginate is considered the major component of biofilm and is highly associated with the formation of mucoid biofilm in this species. Nonsteroid anti-inflammatory drugs (NSAIDs), including ibuprofen, have shown promising antibacterial and antibiofilm potential for bacterial pathogens. In this study, we aimed to evaluate the effect of ibuprofen on the expression of alginate synthetase (alg8), GDP-mannose dehydrogenase (algD), and alginate lyase (algL) genes in multiple drug-resistant (MDR) P. aeruginosa strains. The biofilm formation potential and the expression of alg8, algD, and algL among the bacteria treated with ibuprofen (at sub-inhibitory concentration) were investigated using the crystal violet staining and real-time PCR assays, respectively. The minimum inhibitory concentration of ibuprofen for the studied strains was determined 1024-2048 μg/mL. We observed that ibuprofen was able to reduce bacterial biofilm by 51-77%. Also, the expression of alg8, algD, and algL decreased by 32, 52, and 48%, respectively. The reduction of the genes responsible for alginate synthesis indicates promising antivirulece potential of ibuprofen to combat P. aeruginosa infection, especially in burns and CF patients. Our findings suggest that ibuprofen could be used to reduce the pathogenicity of P. aeruginosa that could be used in combination with antibiotics to treat drug-resistant infections.

• MeSH
• algináty MeSH
• antibakteriální látky metabolismus   farmakologie   MeSH
• biofilmy MeSH
• cystická fibróza * mikrobiologie   MeSH
• ibuprofen metabolismus   farmakologie   MeSH
• lidé MeSH
• pseudomonádové infekce * farmakoterapie   mikrobiologie   MeSH
• Pseudomonas aeruginosa MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Between 2014 and 2017, 6,662 Enterobacterales and 1,953 P. aeruginosa isolates were collected by 19 centers in four central European countries and Israel. A further 2,585 Enterobacterales and 707 P. aeruginosa isolates were collected in 2018 by 28 centers in seven European countries and Israel as part of the Antimicrobial Testing Leadership and Surveillance (ATLAS) study. A central laboratory performed antimicrobial susceptibility testing using broth microdilution panels according to Clinical Laboratory Standards Institute (CLSI) guidelines. Susceptibility rates among Enterobacterales were highest to ceftazidime-avibactam (≥98.5%), colistin (≥97.3%), and meropenem (≥95.8%). Ceftazidime-resistant and multidrug-resistant (MDR) Enterobacterales subsets were highly susceptible to ceftazidime-avibactam (≥94.9%) and colistin (≥94.7%). Susceptibility rates to colistin among all P. aeruginosa were ≥97.4% and were ≥96.3% among ceftazidime-resistant and MDR subsets. Susceptibility rates to ceftazidime-avibactam were 91.9% (2014-2017), 86.3% (2018) and, in common with comparator agents, were lower among ceftazidime-resistant (≥51.7%) and MDR isolates (≥57.1%).

• MeSH
• antibakteriální látky farmakologie   MeSH
• azabicyklické sloučeniny farmakologie   MeSH
• bakteriální léková rezistence účinky léků   MeSH
• ceftazidim farmakologie   MeSH
• Enterobacteriaceae účinky léků   izolace a purifikace   MeSH
• enterobakteriální infekce mikrobiologie   MeSH
• fixní kombinace léků MeSH
• inhibitory beta-laktamasy farmakologie   MeSH
• lidé MeSH
• mikrobiální testy citlivosti MeSH
• pseudomonádové infekce mikrobiologie   MeSH
• Pseudomonas aeruginosa účinky léků   izolace a purifikace   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Evropa MeSH
• Izrael MeSH

Cystic fibrosis (CF) is the most common genetic disease in Caucasians. CF is manifested by abnormal accumulation of mucus in the lungs, which serves as fertile ground for the growth of microorganisms leading to recurrent infections and ultimately, lung failure. Mucus in CF patients consists of DNA from dead neutrophils as well as mucins produced by goblet cells. MUC5AC mucin leads to pathological plugging of the airways whereas MUC5B has a protective role against bacterial infection. Therefore, decreasing the level of MUC5AC while maintaining MUC5B intact would in principle be a desirable mucoregulatory treatment outcome. Fenretinide prevented the lipopolysaccharide-induced increase of MUC5AC gene expression, without affecting the level of MUC5B, in a lung goblet cell line. Additionally, fenretinide treatment reversed the pro-inflammatory imbalance of fatty acids by increasing docosahexaenoic acid and decreasing the levels of arachidonic acid in a lung epithelial cell line and primary leukocytes derived from CF patients. Furthermore, for the first time we also demonstrate the effect of fenretinide on multiple unsaturated fatty acids, as well as differential effects on the levels of long- compared to very-long-chain saturated fatty acids which are important substrates of complex phospholipids. Finally, we demonstrate that pre-treating mice with fenretinide in a chronic model of P. aeruginosa lung infection efficiently decreases the accumulation of mucus. These findings suggest that fenretinide may offer a new approach to therapeutic modulation of pathological mucus production in CF.

• MeSH
• aplikace orální MeSH
• buněčné linie MeSH
• cystická fibróza komplikace   genetika   patologie   MeSH
• fenretinid aplikace a dávkování   MeSH
• fosfolipidy metabolismus   MeSH
• hlen metabolismus   MeSH
• krysa rodu rattus MeSH
• kyselina arachidonová metabolismus   MeSH
• kyseliny dokosahexaenové metabolismus   MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• mucin 5AC metabolismus   MeSH
• mucin 5B metabolismus   MeSH
• myši inbrední CFTR MeSH
• myši MeSH
• plíce účinky léků   metabolismus   patologie   MeSH
• pneumonie mikrobiologie   patologie   prevence a kontrola   MeSH
• pseudomonádové infekce mikrobiologie   patologie   prevence a kontrola   MeSH
• Pseudomonas aeruginosa patogenita   MeSH
• respirační sliznice cytologie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Lower respiratory tract infection due to Pseudomonas aeruginosa has become increasingly challenging, resulting in a worse morbidity and mortality. Airway remodeling is a common phenomenon in this process, to which epithelial-mesenchymal transition (EMT) may contribute as an important promoter. Previous studies showed that epithelium-specific integrin αvβ6-mediated EMT was involved in pulmonary fibrosis via transforming growth factor-β1 (TGF-β1) signaling, but whether integrin αvβ6 plays a role in the P. aeruginosa-associated airway remodeling remains unknown. BEAS-2B cells were incubated with lipopolysaccharide (LPS) from P. aeruginosa in the presence or the absence of integrin αvβ6-blocking antibodies. Morphologic changes were observed by an inverted microscopy. The EMT markers were detected using Western blotting and immunofluorescence. The activation of TGF-β1-Smad2/3 signaling pathway was assessed. Furthermore, matrix metalloproteinase (MMP)-2 and -9 in the medium were measured using ELISA. P. aeruginosa's LPS decreased the expression of the epithelial marker E-cadherin and promoted the mesenchymal markers, vimentin and α-smooth muscle actin in BEAS-2B cells. The expression of integrin αvβ6 was significantly increased during EMT process. Blocking integrin αvβ6 could attenuate P. aeruginosa's LPS-induced EMT markers' expression via TGF-β1-Smad2/3 signaling pathway. Furthermore, blocking integrin αvβ6 could prevent morphologic changes and oversecretion of MMP-2 and -9. Integrin αvβ6 mediates epithelial-mesenchymal transition in human bronchial epithelial cells induced by lipopolysaccharides of P. aeruginosa via TGF-β1-Smad2/3 signaling pathway and might be a promising therapeutic target for P. aeruginosa-associated airway remodeling.

• MeSH
• antigeny nádorové genetika   metabolismus   MeSH
• epitelo-mezenchymální tranzice * MeSH
• epitelové buňky cytologie   účinky léků   metabolismus   MeSH
• integriny genetika   metabolismus   MeSH
• lidé MeSH
• lipopolysacharidy metabolismus   MeSH
• matrixové metaloproteinasy genetika   metabolismus   MeSH
• protein Smad2 genetika   metabolismus   MeSH
• protein Smad3 genetika   metabolismus   MeSH
• pseudomonádové infekce genetika   metabolismus   mikrobiologie   patofyziologie   MeSH
• Pseudomonas aeruginosa metabolismus   MeSH
• signální transdukce MeSH
• transformující růstový faktor beta1 genetika   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH