- Klíčová slova
- záměrná kompenzovaná vazoplegie, steatotické jaterní onemocnění spojené s metabolickou dysfunkcí, DCV, MASLD,
- MeSH
- beta-laktamová antibiotika terapeutické užití MeSH
- cévy MeSH
- endokrinní chirurgické výkony MeSH
- enterobakteriální infekce farmakoterapie MeSH
- feochromocytom chirurgie MeSH
- klinická studie jako téma * MeSH
- lidé MeSH
- měření krevního tlaku metody MeSH
- metabolický syndrom komplikace MeSH
- peroperační péče metody MeSH
- přerušované hladovění MeSH
- pseudomonádové infekce farmakoterapie MeSH
- ztučnělá játra dietoterapie etiologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- souhrny MeSH
The major cause of mortality in people with cystic fibrosis (pwCF) is progressive lung disease characterised by acute and chronic infections, the accumulation of mucus, airway inflammation, structural damage and pulmonary exacerbations. The prevalence of Pseudomonas aeruginosa rises rapidly in the teenage years, and this organism is the most common cause of chronic lung infection in adults with cystic fibrosis (CF). It is associated with an accelerated decline in lung function and premature death. New P. aeruginosa infections are treated with antibiotics to eradicate the organism, while chronic infections require long-term inhaled antibiotic therapy. The prevalence of P. aeruginosa infections has decreased in CF registries since the introduction of CF transmembrane conductance regulator modulators (CFTRm), but clinical observations suggest that chronic P. aeruginosa infections usually persist in patients receiving CFTRm. This indicates that pwCF may still need inhaled antibiotics in the CFTRm era to maintain long-term control of P. aeruginosa infections. Here, we provide an overview of the changing perceptions of P. aeruginosa infection management, including considerations on detection and treatment, the therapy burden associated with inhaled antibiotics and the potential effects of CFTRm on the lung microbiome. We conclude that updated guidance is required on the diagnosis and management of P. aeruginosa infection. In particular, we highlight a need for prospective studies to evaluate the consequences of stopping inhaled antibiotic therapy in pwCF who have chronic P. aeruginosa infection and are receiving CFTRm. This will help inform new guidelines on the use of antibiotics alongside CFTRm.
- MeSH
- antibakteriální látky * aplikace a dávkování terapeutické užití MeSH
- aplikace inhalační MeSH
- cystická fibróza * komplikace mikrobiologie farmakoterapie MeSH
- lidé MeSH
- protein CFTR * genetika MeSH
- pseudomonádové infekce * farmakoterapie MeSH
- Pseudomonas aeruginosa * účinky léků izolace a purifikace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Tato práce poskytuje krátký přehled kožních bakteriálních onemocnění, které vyvolávají gramnegativní bakterie. Jedná se o méně častá onemocnění, která mohou mít bohatý klinický obraz a diferenciální diagnostiku. Mezi nejčastější kožní infekce vyvolané gramnegativními bakteriemie patří infekce Pseudomonas aeruginosa. Z dalších infekcí lze zmínit projevy při závažných akutních, ale i chronických meningokových infekcích, nebo kožní postižení vyvolané bakterií Bartonella henselae.
This review provides a brief overview of skin bacterial infections caused by gram-negative bacteria. These infections are less common and can have a rich clinical picture and differential diagnosis. Pseudomonas aeruginosa infection is among the most common skin infections caused by gram-negative bacteria. Among other infections, we can mention manifestations in severe acute, but also chronic, meningococcal infections, or skin lesions caused by the bacterium Bartonella henselae.
- MeSH
- antibakteriální látky terapeutické užití MeSH
- bakteriální nemoci kůže * diagnóza klasifikace MeSH
- gramnegativní bakterie patogenita účinky léků MeSH
- infekce bakteriemi rodu Bartonella diagnóza etiologie farmakoterapie MeSH
- lidé MeSH
- meningokokové infekce diagnóza etiologie farmakoterapie MeSH
- pseudomonádové infekce etiologie farmakoterapie patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy 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
AIM: The objective of this study was to evaluate off-label high-dose ceftazidime population pharmacokinetics in cancer patients with suspected or proven extensively drug-resistant (XDR) Pseudomonas aeruginosa infections and then to compare the achievement of the pharmacokinetic/pharmacodynamic (PK/PD) target after standard and off-label high-dose regimens using population model-based simulations. A further aim was to clinically observe the occurrence of adverse effects during the off-label high-dose ceftazidime treatment. METHODS: In patients treated with off-label high-dose ceftazidime (3 g every 6 h), blood samples were collected and ceftazidime serum levels measured using LC-MS/MS. A pharmacokinetic population model was developed using a nonlinear mixed-effects modelling approach and Monte Carlo simulations were then used to compare standard and high-dose regimens for PK/PD target attainment. RESULTS: A total of 14 cancer patients with serious infection suspected of XDR P. aeruginosa aetiology were eligible for PK analysis. XDR P. aeruginosa was confirmed in 10 patients as the causative pathogen. Population ceftazidime volume of distribution was 13.23 L, while clearance started at the baseline of 1.48 L/h and increased by 0.0076 L/h with each 1 mL/min/1.73 m2 of eGFR. High-dose regimen showed significantly higher probability of target attainment (i.e., 86% vs. 56% at MIC of 32 mg/L). This was translated into a very low mortality rate of 20%. Only one case of reversible neurological impairment was observed. CONCLUSION: We proved the superiority of the ceftazidime off-label high-dose regimen in PK/PD target attainment with very low occurrence of adverse effects. The off-label high-dose regimen should be used to optimize treatment of XDR P. aeruginosa infections.
- MeSH
- antibakteriální látky škodlivé účinky farmakokinetika MeSH
- ceftazidim škodlivé účinky farmakokinetika MeSH
- chromatografie kapalinová MeSH
- lidé MeSH
- metoda Monte Carlo MeSH
- mikrobiální testy citlivosti MeSH
- nádory * komplikace farmakoterapie MeSH
- off-label použití léčivého přípravku MeSH
- pseudomonádové infekce * farmakoterapie MeSH
- Pseudomonas aeruginosa MeSH
- tandemová hmotnostní spektrometrie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem 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
In this review, we summarize the main points that were raised and highlighted during the pre-conference meeting to the 17th European Cystic Fibrosis Society Basic Science Conference, held from 30 March to 2 April, 2022 in Albufeira, Portugal. Keynote lectures provided an update on the latest information regarding the phenomenon of antimicrobial resistance (AMR) in cystic fibrosis (CF). Traditional themes such as in vitro antibiotic susceptibility testing and its clinical value, AMR evolution in persistent Pseudomonas aeruginosa infection and the impact of biofilm on AMR were discussed. In addition, the report gives an overview on very recent AMR-related topics that include an ecological view of AMR in CF lung, referred to as resistome, and novel anti-infective approaches in preclinical or early clinical research such as antibiofilm drugs and bacteriophages.
- MeSH
- antibakteriální látky farmakologie terapeutické užití MeSH
- bakteriální léková rezistence MeSH
- cystická fibróza * komplikace farmakoterapie MeSH
- infekce dýchací soustavy * farmakoterapie MeSH
- lidé MeSH
- mikrobiální testy citlivosti MeSH
- pseudomonádové infekce * diagnóza farmakoterapie MeSH
- Pseudomonas aeruginosa MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Research Support, N.I.H., Extramural 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
Pseudomonas aeruginosa is a gram-negative bacterium capable of forming persistent biofilms that are extremely difficult to eradicate. The species is most infamously known due to complications in cystic fibrosis patients. The high mortality of cystic fibrosis is caused by P. aeruginosa biofilms occurring in pathologically overly mucous lungs, which are the major cause facilitating the organ failure. Due to Pseudomonas biofilm-associated infections, remarkably high doses of antibiotics must be administered, eventually contributing to the development of antibiotic resistance. Nowadays, multidrug resistant P. aeruginosa is one of the most terrible threats in medicine, and the search for novel antimicrobial drugs is of the utmost importance. We have studied the effect of low molecular weight chitosan (LMWCH) on various stages of P. aeruginosa ATCC 10145 biofilm formation and eradication, as well as on production of other virulence factors. LMWCH is a well-known naturally occurring agent with a vast antimicrobial spectrum, which has already found application in various fields of medicine and industry. LMWCH at a concentration of 40 mg/L was able to completely prevent biofilm formation. At a concentration of 60 mg/L, this agent was capable to eradicate already formed biofilm in most studied times of addition (2-12 h of cultivation). LMWCH (50 mg/L) was also able to suppress pyocyanin production when added 2 and 4 h after cultivation. The treatment resulted in reduced formation of cell clusters. LMWCH was proved to be an effective antibiofilm agent worth further clinical research with the potential to become a novel drug for the treatment of P. aeruginosa infections.
