Wild strains of Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis were tested in an experimental hyperbaric chamber to determine the possible effect of hyperbaric oxygen on the susceptibility of these strains to the antibiotics ampicillin, ampicillin + sulbactam, cefazolin, cefuroxime, cefoxitin, gentamicin, sulfamethoxazole + trimethoprim, colistin, oxolinic acid, ofloxacin, tetracycline, and aztreonam during their cultivation at 23 °C and 36.5 °C. Ninety-six-well inoculated microplates with tested antibiotics in Mueller-Hinton broth were cultured under standard incubator conditions (normobaric normoxia) for 24 h or in an experimental hyperbaric chamber (HAUX, Germany) for 24 h at 2.8 ATA of 100% oxygen (hyperbaric hyperoxia). The hyperbaric chamber was pressurised with pure oxygen (100%). Both cultures (normoxic and hyperoxic) were carried out at 23 °C and 36.5 °C to study the possible effect of the cultivation temperature. No significant differences were observed between 23 and 36.5 °C cultivation with or without the 2-h lag phase in Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis. Cultivation in a hyperbaric chamber at 23 °C and 36.5 °C with or without a 2-h lag phase did not produce significant changes in the minimum inhibitory concentration (MIC) of Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis. For the tested strains of Pseudomonas aeruginosa, the possible effect of hyperbaric oxygen on their antibiotic sensitivity could not be detected because the growth of these bacteria was completely inhibited by 100% hyperbaric oxygen at 2.8 ATA under all hyperbaric conditions tested at 23 °C and 36.5 °C. Subsequent tests with wild strains of pseudomonads, burkholderias, and stenotrophomonads not only confirmed the fact that these bacteria stop growing under hyperbaric conditions at a pressure of 2.8 ATA of 100% oxygen but also indicated that inhibition of growth of these bacteria under hyperbaric conditions is reversible.
- MeSH
- ampicilin farmakologie MeSH
- anaerobní bakterie MeSH
- antibakteriální látky farmakologie MeSH
- Bacteria MeSH
- Escherichia coli MeSH
- hyperbarická oxygenace * MeSH
- Klebsiella pneumoniae MeSH
- kombinace léků trimethoprim a sulfamethoxazol farmakologie MeSH
- kyslík MeSH
- lidé MeSH
- mikrobiální testy citlivosti MeSH
- oxidační stres MeSH
- pseudomonádové infekce * MeSH
- Pseudomonas aeruginosa MeSH
- sulbaktam MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- 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
Pseudomonas aeruginosa, an opportunistic pathogen, has been found to cause several chronic and acute infections in human. Moreover, it often shows drug-tolerance and poses a severe threat to public healthcare through biofilm formation. In this scenario, two molecules, namely, cuminaldehyde and tobramycin, were used separately and in combination for the efficient management of biofilm challenge. The minimum inhibitory concentration (MIC) of cuminaldehyde and tobramycin was found to be 150 μg/mL and 1 μg/mL, respectively, against Pseudomonas aeruginosa. The checkerboard assay revealed that the fractional inhibitory concentration (FIC) index of cuminaldehyde and tobramycin was 0.36 suggesting a synergistic association between them. The sub-MIC dose of cuminaldehyde (60 μg/mL) or tobramycin (0.06 μg/mL) individually did not show any effect on the microbial growth curve. However, the same combinations could affect microbial growth curve of Pseudomonas aeruginosa efficiently. In connection to biofilm management, it was observed that the synergistic interaction between cuminaldehyde and tobramycin could inhibit biofilm formation more efficiently than their single use (p < 0.01). Further investigation revealed that the combinations of cuminaldehyde and tobramycin could generate reactive oxygen species (ROS) that resulted in the increase of membrane permeability of bacterial cells leading to the efficient inhibition of microbial biofilm formation. Besides, the synergistic interaction between cuminaldehyde (20 μg/mL) and tobramycin (0.03 μg/mL) also showed significant biofilm dispersal of the test microorganism (p < 0.01). Hence, the results suggested that synergistic action of cuminaldehyde and tobramycin could be applied for the efficient management of microbial biofilm.
Pseudomonas aeruginosa (PA) is considered the first causal agent of morbidity and mortality in people with cystic fibrosis (CF) disease. Multi-resistant strains have emerged due to prolonged treatment with specific antibiotics, so new alternatives have been sought for their control. In this context, there is a renewed interest in therapies based on bacteriophages (phages) supported by several studies suggesting that therapy based on lytic phages and biofilm degraders may be promising for the treatment of lung infections in CF patients. However, there is little clinical data about phage studies in CF and the effectiveness and safety in patients with this disease has not been clear. Therefore, studies regarding on phage characterization, selection, and evaluation in vitro and in vivo models will provide reliable information for designing effective cocktails, either using mixed phages or in combination with antibiotics, making a great progress in clinical research. Hence, this review focuses on the most relevant and recent findings on the activity of lytic phages against PA strains isolated from CF patients and hospital environments, and discusses perspectives on the use of phage therapy on the treatment of PA in CF patients.
- MeSH
- antibakteriální látky MeSH
- bakteriofágy * MeSH
- cystická fibróza * MeSH
- fágy pseudomonád * MeSH
- lidé MeSH
- pseudomonádové infekce * MeSH
- Pseudomonas aeruginosa MeSH
- Check Tag
- lidé 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
