INTRODUCTION: It is hypothesized that systemically administered antibiotics penetrate wound sites more effectively during negative pressure wound therapy (NPWT). However, there is a lack of clinical data from patients who receive NPWT for deep sternal wound infection (DSWI) after open-heart surgery. Here, we evaluated vancomycin penetration into exudate in this patient group. PATIENTS AND METHODS: For this prospective observational study, we enrolled 10 consecutive patients treated with NPWT for post-sternotomy DSWI. On the first sampling day, serum and exudate samples were synchronously collected at 0 (pre-dose), 0.5, 1, 2, 3 and 6 h after vancomycin administration. On the following three consecutive days, additional samples were collected, only before vancomycin administration. RESULTS: The ratio of average vancomycin concentration in wound exudate to in serum was higher for free (unbound) (1.51 ± 0.53) than for total (bound + unbound) (0.91 ± 0.29) concentration (p = 0.049). The percentage of free vancomycin was higher in wound exudate than serum (0.79 ± 0.19 vs. 0.46 ± 0.16; p = 0.04). Good vancomycin wound penetration was maintained on the following three days (vancomycin trough exudate-to-serum concentration ratio > 1). The total hospital stay was significantly longer in patients with DSWI (46 ± 11.6 days) versus without DSWI (14 ± 11.7 days) (p < 0.001). There was no in-hospital or 90-day mortality. Two patients experienced late DSWI recurrence. All-cause mortality was 4.8% during a median follow-up of 2.5 years. CONCLUSION: Vancomycin effectively penetrates wound exudate in patients receiving NPWT for DSWI after open-heart surgery.The protocol for this study was registered at ClinicalTrials.gov on July 16, 2024 (NCT06506032).
- MeSH
- antibakteriální látky * farmakokinetika aplikace a dávkování MeSH
- exsudáty a transsudáty metabolismus mikrobiologie MeSH
- infekce chirurgické rány * MeSH
- kardiochirurgické výkony * škodlivé účinky MeSH
- lidé středního věku MeSH
- lidé MeSH
- prospektivní studie MeSH
- senioři MeSH
- sternotomie * škodlivé účinky MeSH
- sternum chirurgie MeSH
- terapie ran pomocí řízeného podtlaku * metody MeSH
- vankomycin * aplikace a dávkování farmakokinetika MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
BACKGROUND: Exposure of critically ill patients to antibiotics lead to intestinal dysbiosis, which often manifests as antibiotic-associated diarrhoea. Faecal microbiota transplantation restores gut microbiota and may lead to faster resolution of diarrhoea. METHODS: Into this prospective, multi-centre, randomized controlled trial we will enrol 36 critically ill patients with antibiotic-associated diarrhoea. We will exclude patients with ongoing sepsis, need of systemic antibiotics, or those after recent bowel surgery or any other reason that prevents the FMT. Randomisation will be in 1:1 ratio. Patients in the control group will receive standard treatment based on oral diosmectite. In the intervention group, patients will receive, in addition to the standard of care, faecal microbiota transplantation via rectal tube, in the form of a preparation mixed from 7 thawed aliquots (50 mL) made from fresh stool of 7 healthy unrelated donors and quarantined deep frozen for 3 to 12 months. Primary outcome is treatment failure defined as intervention not delivered or diarrhoea persisting at day 7 after randomisation. Secondary outcomes include safety measures such as systemic inflammatory response, adverse events, and also diarrhoea recurrence within 28 days. Exploratory outcomes focus on gut barrier function and composition of intestinal microbiota. DISCUSSION: Faecal microbiota transplantation has been effective for dysbiosis in non-critically ill patients with recurrent C. difficile infections and it is plausible to hypothesize that it will be equally effective for symptoms of dysbiosis in the critically ill patients. In addition, animal experiments and observational data suggest other benefits such as reduced colonization with multi-drug resistant bacteria and improved gut barrier and immune function. The frozen faeces from unrelated donors are immediately available when needed, unlike those from the relatives, who require lengthy investigation. Using multiple donors maximises graft microbiota diversity. Nonetheless, in vulnerable critically ill patients, Faecal microbiota transplantation might lead to bacterial translocation and unforeseen complications. From growing number of case series it is clear that its off label use in the critically ill patients is increasing and that there is a burning need to objectively assess its efficacy and safety, which this trial aims. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT05430269).
- MeSH
- antibakteriální látky * škodlivé účinky terapeutické užití MeSH
- dysbióza terapie mikrobiologie MeSH
- feces mikrobiologie MeSH
- fekální transplantace * metody škodlivé účinky MeSH
- klinické zkoušky, fáze II jako téma MeSH
- kritický stav * MeSH
- lidé MeSH
- multicentrické studie jako téma MeSH
- prospektivní studie MeSH
- průjem * terapie mikrobiologie MeSH
- randomizované kontrolované studie jako téma MeSH
- střevní mikroflóra * účinky léků MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- protokol klinické studie MeSH
3,5-Dinitrobenzylsulfanyl tetrazoles and 1,3,4-oxadiazoles, previously identified as having high in vitro activities against both replicating and nonreplicating mycobacteria and favorable cytotoxicity and genotoxicity profiles were investigated. First we demonstrated that these compounds act in a deazaflavin-dependent nitroreduction pathway and thus require a nitro group for their activity. Second, we confirmed the necessity of both nitro groups for antimycobacterial activity through extensive structure-activity relationship studies using 32 structural types of analogues, each in a five-membered series. Only the analogues with shifted nitro groups, namely, 2,5-dinitrobenzylsulfanyl oxadiazoles and tetrazoles, maintained high antimycobacterial activity but in this case mainly as a result of DprE1 inhibition. However, these analogues also showed increased toxicity to the mammalian cell line. Thus, both nitro groups in 3,5-dinitrobenzylsulfanyl-containing antimycobacterial agents remain essential for their high efficacy, and further efforts should be directed at finding ways to address the possible toxicity and solubility issues, for example, by targeted delivery.
- MeSH
- antituberkulotika farmakologie chemie MeSH
- mikrobiální testy citlivosti MeSH
- Mycobacterium tuberculosis * MeSH
- nitroreduktasy MeSH
- oxadiazoly farmakologie chemie MeSH
- savci MeSH
- tetrazoly farmakologie chemie MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Bacterial biofilms pose significant challenges, from healthcare-associated infections to biofouling in industrial systems, resulting in significant health impacts and financial losses globally. Classic antimicrobial methods often fail to eradicate sessile microbial communities within biofilms, requiring innovative approaches. This review explores the structure, formation, and role of biofilms, highlighting the critical importance of exopolysaccharides in biofilm stability and resistance mechanisms. We emphasize the potential of microbial enzymatic approaches, particularly focusing on glycosidases, proteases, and deoxyribonucleases, which can disrupt biofilm matrices effectively. We also delve into the importance of enzymes such as cellobiose dehydrogenase, which disrupts biofilms by degrading polysaccharides. This enzyme is mainly sourced from Aspergillus niger and Sclerotium rolfsii, with optimized production strategies enhancing its efficacy. Additionally, we explore levan hydrolase, alginate lyase, α-amylase, protease, and lysostaphin as potent antibiofilm agents, discussing their microbial origins and production optimization strategies. These enzymes offer promising avenues for combating biofilm-related challenges in healthcare, environmental, and industrial settings. Ultimately, enzymatic strategies present environmentally friendly solutions with high potential for biofilm management and infection control.
The emergence of biofilm-induced drug tolerance poses a critical challenge to public healthcare management. Pseudomonas aeruginosa, a gram-negative opportunistic bacterium, is involved in various biofilm-associated infections in human hosts. Towards this direction, in the present study, a combinatorial approach has been explored as it is a demonstrably effective strategy for managing microbial infections. Thus, P. aeruginosa has been treated with cuminaldehyde (a naturally occurring phytochemical) and gentamicin (an aminoglycoside antibiotic) in connection to the effective management of the biofilm challenges. It was also observed that the test molecules could show increased antimicrobial activity against P. aeruginosa. A fractional inhibitory concentration index (FICI) of 0.65 suggested an additive interaction between cuminaldehyde and gentamicin. Besides, a series of experiments such as crystal violet assay, estimation of extracellular polymeric substance (EPS), and microscopic images indicated that an enhanced antibiofilm activity was obtained when the selected compounds were applied together on P. aeruginosa. Furthermore, the combination of the selected compounds was found to reduce the secretion of virulence factors from P. aeruginosa. Taken together, this study suggested that the combinatorial application of cuminaldehyde and gentamicin could be considered an effective approach towards the control of biofilm-linked infections caused by P. aeruginosa.
- MeSH
- antibakteriální látky * farmakologie MeSH
- benzaldehydy * farmakologie MeSH
- biofilmy * účinky léků MeSH
- cymeny farmakologie MeSH
- faktory virulence MeSH
- gentamiciny * farmakologie MeSH
- lidé MeSH
- mikrobiální testy citlivosti * MeSH
- Pseudomonas aeruginosa * účinky léků fyziologie MeSH
- synergismus léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
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
Horizontal gene transfer (HGT) is a key driver in the evolution of bacterial genomes. The acquisition of genes mediated by HGT may enable bacteria to adapt to ever-changing environmental conditions. Long-term application of antibiotics in intensive agriculture is associated with the dissemination of antibiotic resistance genes among bacteria with the consequences causing public health concern. Commensal farm-animal-associated gut microbiota are considered the reservoir of the resistance genes. Therefore, in this study, we identified known and not-yet characterized mobilized genes originating from chicken and porcine fecal samples using our innovative pipeline followed by network analysis to provide appropriate visualization to support proper interpretation.
- MeSH
- antibakteriální látky MeSH
- Bacteria genetika MeSH
- bakteriální geny MeSH
- genom bakteriální MeSH
- mikrobiota * MeSH
- prasata MeSH
- přenos genů horizontální * MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Environmental pollution is a serious problem that can cause sicknesses, fatality, and biological contaminants such as bacteria, which can trigger allergic reactions and infectious illnesses. There is also evidence that environmental pollutants can have an impact on the gut microbiome and contribute to the development of various mental health and metabolic disorders. This study aimed to study the antibiotic resistance and virulence potential of environmental Pseudomonas aeruginosa (P. aeruginosa) isolates in slaughterhouses. A total of 100 samples were collected from different slaughterhouse tools. The samples were identified by cultural and biochemical tests and confirmed by the VITEK 2 system. P. aeruginosa isolates were further confirmed by CHROMagarTM Pseudomonas and genetically by rpsL gene analysis. Molecular screening of virulence genes (fimH, papC, lasB, rhlI, lasI, csgA, toxA, and hly) and antibiotic resistance genes (blaCTX-M, blaAmpC, blaSHV, blaNDM, IMP-1, aac(6')-Ib-, ant(4')IIb, mexY, TEM, tetA, and qnrB) by PCR and testing the antibiotic sensitivity, biofilm formation, and production of pigments, and hemolysin were carried out in all isolated strains. A total of 62 isolates were identified as P. aeruginosa. All P. aeruginosa isolates were multidrug-resistant and most of them have multiple resistant genes. blaCTX-M gene was detected in all strains; 23 (37.1%) strains have the ability for biofilm formation, 33 strains had virulence genes, and 26 isolates from them have more than one virulence genes. There should be probably 60 (96.8%) P. aeruginosa strains that produce pyocyanin pigment. Slaughterhouse tools are sources for multidrug-resistant and virulent pathogenic microorganisms which are a serious health problem. Low-hygienic slaughterhouses could be a reservoir for resistance and virulence genes which could then be transferred to other pathogens.
- MeSH
- antibakteriální látky * farmakologie MeSH
- bakteriální léková rezistence genetika MeSH
- biofilmy účinky léků růst a vývoj MeSH
- faktory virulence * genetika MeSH
- jatka * MeSH
- mikrobiální testy citlivosti * MeSH
- mikrobiologie životního prostředí MeSH
- Pseudomonas aeruginosa * genetika účinky léků patogenita izolace a purifikace MeSH
- virulence genetika MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Bismuth quadruple therapies (BQTs) including bismuth, a proton pump inhibitor (PPI) and two antibiotics have been shown to be highly effective for treating Helicobacter pylori infection even in areas of high bacterial antibiotic resistance. OBJECTIVE: To describe the time trends of use, effectiveness and safety of BQT in Europe using the European Registry on Helicobacter pylori Management (Hp-EuReg). DESIGN: Patients registered in the Hp-EuReg from 2013 to 2021 who had received BQT were included. The regimens prescribed, the number of eradication attempts, effectiveness, adherence and safety were analysed. The effectiveness was assessed by modified intention to treat (mITT). Time-trend and multivariate analyses were performed to determine variables that predicted treatment success. RESULTS: Of the 49 690 patients included in the Hp-EuReg, 15 582 (31%) had received BQT. BQT use increased from 8.6% of all treatments in 2013 to 39% in 2021. Single-capsule BQT-containing bismuth, metronidazole and tetracycline-plus a PPI (single-capsule BQT, ScBQT) was the most frequent treatment mode (43%). Schemes that obtained an effectiveness above 90% were the 10-day ScBQT and 14-day BQT using tetracycline plus metronidazole, or amoxicillin plus either clarithromycin or metronidazole. Only ScBQT achieved above 90% cure rates in all the geographical areas studied. Using the ScBQT scheme, adherence, the use of standard or high-dose PPIs, 14-day prescriptions and the use of BQT as first-line treatment were significantly associated with higher mITT effectiveness. CONCLUSION: The use of BQT increased notably in Europe over the study period. A 10-day ScBQT was the scheme that most consistently achieved optimal effectiveness. TRIAL REGISTRATION NUMBER: NCT02328131.
- MeSH
- amoxicilin terapeutické užití aplikace a dávkování MeSH
- antibakteriální látky * terapeutické užití škodlivé účinky aplikace a dávkování MeSH
- bismut * terapeutické užití aplikace a dávkování MeSH
- dospělí MeSH
- Helicobacter pylori * účinky léků MeSH
- infekce vyvolané Helicobacter pylori * farmakoterapie MeSH
- inhibitory protonové pumpy * terapeutické užití aplikace a dávkování škodlivé účinky MeSH
- klarithromycin terapeutické užití aplikace a dávkování MeSH
- kombinovaná farmakoterapie * MeSH
- lidé středního věku MeSH
- lidé MeSH
- metronidazol terapeutické užití aplikace a dávkování MeSH
- registrace * MeSH
- senioři MeSH
- tetracyklin terapeutické užití aplikace a dávkování MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
- Geografické názvy
- Evropa MeSH
The antibiotic resistance genes (ARGs) limit the susceptibility of bacteria to antimicrobials, representing a problem of high importance. Current research on the presence of ARGs in microorganisms focuses mainly on humans, livestock, hospitals, or wastewater. However, the spectrum of ARGs in the dust resistome in workplaces and households has gone relatively unexplored. This pilot study aimed to analyze resistome in indoor dust samples from participants' workplaces (a pediatric hospital, a maternity hospital, and a research center) and households and compare two different approaches to the ARGs analysis; high-throughput quantitative PCR (HT-qPCR) and whole metagenome shotgun sequencing (WMGS). In total, 143 ARGs were detected using HT-qPCR, with ARGs associated with the macrolides, lincosamides, and streptogramin B (MLSB) phenotype being the most abundant, followed by MDR (multi-drug resistance) genes, and genes conferring resistance to aminoglycosides. A higher overall relative quantity of ARGs was observed in indoor dust samples from workplaces than from households, with the pediatric hospital being associated with the highest relative quantity of ARGs. WMGS analysis revealed 36 ARGs, of which five were detected by both HT-qPCR and WMGS techniques. Accordingly, the efficacy of the WMGS approach to detect ARGs was lower than that of HT-qPCR. In summary, our pilot data revealed that indoor dust in buildings where people spend most of their time (workplaces, households) can be a significant source of antimicrobial-resistant microorganisms, which may potentially pose a health risk to both humans and animals.
- MeSH
- antibakteriální látky farmakologie MeSH
- Bacteria genetika izolace a purifikace účinky léků klasifikace MeSH
- bakteriální geny genetika MeSH
- bakteriální léková rezistence genetika MeSH
- charakteristiky rodiny MeSH
- kvantitativní polymerázová řetězová reakce MeSH
- lidé MeSH
- metagenom MeSH
- mikrobiologie vzduchu MeSH
- pilotní projekty MeSH
- prach * analýza MeSH
- pracoviště * MeSH
- vysoce účinné nukleotidové sekvenování MeSH
- znečištění vzduchu ve vnitřním prostředí MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
