- Publikační typ
- abstrakt z konference MeSH
BACKGROUND: Amikacin monotherapy is recommended for urinary tract infection (UTI) treatment with multi-resistant pathogens. Even though amikacin efficacy in the treatment of UTIs is dependent on its urinary concentration, there are no robust data proving that sufficiently high urinary concentration is reached in patients with reduced glomerular filtration rate (GFR). METHODS: A prospective study to monitor amikacin penetration into urine of 70 patients [40 males, median (interquartile range) age 70 (65-79) years] with different levels of glomerular filtration decline, including patients treated by dialysis, was conducted. The bactericidal efficacy of amikacin in urine samples has been evaluated. RESULTS: Patients with estimated GFR (eGFR) <30 mL/min had significantly lower median amikacin urinary concentration than patients with eGFR >30 mL/min (89.75 vs 186.0 mg/L, P < .0001; 200.5 vs 830.0 mg/L, P < .0001; and 126.0 vs 408.0 mg/L, P < .0001 for minimal, maximal and minimal together with maximal concentrations, respectively). The amount of amikacin eliminated in the first 10-13 h after dose administration was dependent on eGFR (r2 = 0.6144, P < .0001). The urinary concentration of amikacin in patients treated by dialysis was indirectly proportional to pH of urine. The plasma concentrations of amikacin did not correlate with urinary levels in patients in either of the GFR categories. Microbiological evaluation showed that the critical urinary concentration for efficacy of amikacin during UTI monotherapy in patients treated by dialysis is 100 mg/L. We found that 4 out of 11 patients treated by dialysis did not reach this level during the treatment. CONCLUSION: Systemic administration of amikacin monotherapy in patients treated by dialysis is questionable as the concentrations of amikacin in their urine are often below the threshold of effectivity. Amikacin plasma concentrations are not a major determinant of amikacin concentration in urine, therefore pulse dosing is neither necessary nor safe in patients treated by dialysis, and may cause undesirable toxicity.
- Publikační typ
- časopisecké články MeSH
In the microbiological diagnosis of bloodstream infections (BSI), blood culture (BC) is considered the gold standard test despite its limitations such as low sensitivity and slow turnaround time. A new FDA-cleared and CE-marked platform utilizing magnetic resonance to detect amplified DNA of the six most common and/or problematic BSI pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Escherichia coli; referred to as ESKAPEc) is available and may shorten the time to diagnosis and potentially improve antimicrobial utilization. Whole blood samples from hospitalized patients with clinical signs of sepsis were analyzed using the T2Bacteria Panel (T2Biosystems) and compared to simultaneously collected BC. Discrepant results were evaluated based on clinical infection criteria, combining supporting culture results and the opinion of treating physicians. A total of 55 samples from 53 patients were evaluated. The sensitivity and specificity of the T2Bacteria panel was 94% (16 out of 17 detections of T2Bacteria-targeted organisms) and 100%, respectively, with 36.4% (8 of 22) causes of BSI detected only by this method. The T2Bacteria Panel detected pathogens on average 55 hours faster than standard BC. In our study, 9 of 15 patients with positive T2Bacteria Panel results received early-targeted antibiotic therapy and/or modification of antimicrobial treatment based on T2Bacteria Panel findings. Given the high reliability, faster time to detection, and easy workflow, the technique qualifies as a point-of-care testing approach.
- MeSH
- Acinetobacter baumannii účinky léků genetika izolace a purifikace MeSH
- antibakteriální látky farmakologie MeSH
- antibiotická politika metody MeSH
- bakteriemie krev farmakoterapie mikrobiologie MeSH
- Enterococcus faecium účinky léků genetika izolace a purifikace MeSH
- Escherichia coli účinky léků genetika izolace a purifikace MeSH
- Klebsiella pneumoniae účinky léků genetika izolace a purifikace MeSH
- krev mikrobiologie MeSH
- kultivační vyšetření krve MeSH
- lidé MeSH
- prospektivní studie MeSH
- Pseudomonas aeruginosa účinky léků genetika izolace a purifikace MeSH
- Staphylococcus aureus účinky léků genetika izolace a purifikace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Fast and accurate detection of causative agents of bloodstream infections remains a challenge of today's microbiology. We compared the performance of cutting-edge technology based on polymerase chain reaction coupled with electrospray ionization-mass spectrometry (PCR/ESI-MS) with that of conventional broad-range 16S rRNA PCR and blood culture to address the current diagnostic possibilities for bloodstream infections. Of 160 blood samples tested, PCR/ESI-MS revealed clinically meaningful microbiological agents in 47 samples that were missed by conventional diagnostic approaches (29.4% of all analyzed samples). Notably, PCR/ESI-MS shortened the time to positivity of the blood culture-positive samples by an average of 34 hr. PCR/ESI-MS technology substantially improved current diagnostic tools and represented an opportunity to make bloodstream infections diagnostics sensitive, accurate, and timely with a broad spectrum of microorganisms covered.
As controversy persists regarding the benefits of mechanical circulatory support in septic shock with a predominantly vasoplegic phenotype, preclinical studies may provide a useful alternative to fill the actual knowledge gap. Here, we investigated the physiologic responses to venoarterial extracorporeal membrane oxygenation therapy (VA-ECMO) in a clinically relevant porcine peritonitis-induced model of refractory vasodilatory septic shock. In 12 anesthetized, mechanically ventilated, and instrumented domestic pigs, septic shock was induced by intraperitoneally inoculating autologous feces. After reaching the threshold for refractory vasodilatory shock (norepinephrine dose ≥1 μg/kg/min), the pigs were randomized into the conservative treatment group (control) or the VA-ECMO group (target flow 100 mL/kg/min). The time to develop refractory vasodilatory shock was similar in both groups (18.8 h in the ECMO group, 18.1 h in the control group). There was no difference between the groups in terms of time to death measured from the point of reaching the predefined vasopressor threshold (7.1 h for the ECMO group, 7.9 h for the control group). The initiation of ECMO resulted in a markedly increased fluid and vasopressor support. Although treatment with ECMO compromised neither renal nor carotid blood flow initially, both progressively decreased later during the experiment. The pattern of sepsis-induced multiorgan injury, alterations in energy metabolism, and the systemic inflammatory response were remarkably similar between both groups. In conclusion, the application of VA-ECMO in this model of peritonitis-induced refractory vasodilatory septic shock aggravated hemodynamic deterioration. Our findings contribute to increasing equipoise with respect to the clinical utility of VA-ECMO in refractory vasodilatory shock.
Background: Treatment with mesenchymal stem cells (MSCs) has elicited considerable interest as an adjunctive therapy in sepsis. However, the encouraging effects of experiments with MSC in rodents have not been adequately studied in large-animal models with better relevance to human sepsis. Objectives: Here, we aimed to assess safety and efficacy of bone marrow-derived MSCs in a clinically relevant porcine model of progressive peritonitis-induced sepsis. Methods: Thirty-two anesthetized, mechanically ventilated, and instrumented pigs were randomly assigned into four groups (n = 8 per group): (1) sham-operated group (CONTROL); (2) sham-operated group treated with MSCs (MSC-CONTROL); (3) sepsis group with standard supportive care (SEPSIS); and (4) sepsis group treated with MSCs (MSC-SEPSIS). Peritoneal sepsis was induced by inoculating cultivated autologous feces. MSCs (1 × 106/kg) were administered intravenously at 6 h after sepsis induction. Results: Before, 12, 18, and 24 h after the induction of peritonitis, we measured systemic, regional, and microvascular hemodynamics, multiple-organ functions, mitochondrial energy metabolism, systemic immune-inflammatory response, and oxidative stress. Administration of MSCs in the MSC-CONTROL group did not elicit any measurable acute effects. Treatment of septic animals with MSCs failed to mitigate sepsis-induced hemodynamic alterations or the gradual rise in Sepsis-related organ failure assessment scores. MSCs did not confer any protection against sepsis-mediated cellular myocardial depression and mitochondrial dysfunction. MSCs also failed to modulate the deregulated immune-inflammatory response. Conclusion: Intravenous administration of bone marrow-derived MSCs to healthy animals was well-tolerated. However, in this large-animal, clinically relevant peritonitis-induced sepsis model, MSCs were not capable of reversing any of the sepsis-induced disturbances in multiple biological, organ, and cellular systems.
Fast and accurate detection of causative agents of bloodstream infections remains a challenge of today's microbiology. We compared the performance of cutting-edge technology based on polymerase chain reaction coupled with electrospray ionization-mass spectrometry (PCR/ESI-MS) with that of conventional broad-range 16S rRNA PCR and blood culture to address the current diagnostic possibilities for bloodstream infections. Of 160 blood samples tested, PCR/ESI-MS revealed clinically meaningful microbiological agents in 47 samples that were missed by conventional diagnostic approaches (29.4% of all analyzed samples). Notably, PCR/ESI-MS shortened the time to positivity of the blood culture-positive samples by an average of 34 hr. PCR/ESI-MS technology substantially improved current diagnostic tools and represented an opportunity to make bloodstream infections diagnostics sensitive, accurate, and timely with a broad spectrum of microorganisms covered.
- MeSH
- bakteriemie diagnóza mikrobiologie MeSH
- diagnostické techniky molekulární metody MeSH
- dospělí MeSH
- hmotnostní spektrometrie s elektrosprejovou ionizací metody MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikrobiologické techniky MeSH
- mladý dospělý MeSH
- polymerázová řetězová reakce metody MeSH
- reprodukovatelnost výsledků MeSH
- RNA ribozomální 16S MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- sepse diagnóza mikrobiologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Patients with serious infections at risk of deterioration represent highly challenging clinical situations, and in particular for junior doctors. A comprehensive clinical examination that integrates the assessment of vital signs, hemodynamics, and peripheral perfusion into clinical decision making is key to responding promptly and effectively to evolving acute medical illnesses, such as sepsis or septic shock. Against this background, the new concept of sepsis definition may provide a useful link between junior doctors and consultant decision making. The purpose of this article is to introduce the updated definition of sepsis and suggest its practical implications, with particular emphasis on integrative clinical assessment, allowing for the rapid identification of patients who are at risk of further deterioration.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
OBJECTIVES: To investigate the potential benefits of vagus nerve stimulation in a clinically-relevant large animal model of progressive sepsis. DESIGN: Prospective, controlled, randomized trial. SETTING: University animal research laboratory. SUBJECTS: Twenty-five domestic pigs were divided into three groups: 1) sepsis group (eight pigs), 2) sepsis + vagus nerve stimulation group (nine pigs), and 3) control sham group (eight pigs). INTERVENTIONS: Sepsis was induced by cultivated autologous feces inoculation in anesthetized, mechanically ventilated, and surgically instrumented pigs and followed for 24 hours. Electrical stimulation of the cervical vagus nerve was initiated 6 hours after the induction of peritonitis and maintained throughout the experiment. MEASUREMENTS AND MAIN RESULTS: Measurements of hemodynamics, electrocardiography, biochemistry, blood gases, cytokines, and blood cells were collected at baseline (just before peritonitis induction) and at the end of the in vivo experiment (24 hr after peritonitis induction). Subsequent in vitro analyses addressed cardiac contractility and calcium handling in isolated tissues and myocytes and analyzed mitochondrial function by ultrasensitive oxygraphy. Vagus nerve stimulation partially or completely prevented the development of hyperlactatemia, hyperdynamic circulation, cellular myocardial depression, shift in sympathovagal balance toward sympathetic dominance, and cardiac mitochondrial dysfunction, and reduced the number of activated monocytes. Sequential Organ Failure Assessment scores and vasopressor requirements significantly decreased after vagus nerve stimulation. CONCLUSIONS: In a clinically-relevant large animal model of progressive sepsis, vagus nerve stimulation was associated with a number of beneficial effects that resulted in significantly attenuated multiple organ dysfunction and reduced vasopressor and fluid resuscitation requirements. This suggests that vagus nerve stimulation might provide a significant therapeutic potential that warrants further thorough investigation.
- MeSH
- elektrostimulační terapie MeSH
- hemodynamika MeSH
- hyperlaktatemie krev prevence a kontrola MeSH
- modely nemocí na zvířatech MeSH
- monocyty * MeSH
- multiorgánové selhání patofyziologie terapie MeSH
- myokard patologie MeSH
- náhodné rozdělení MeSH
- nervus vagus * MeSH
- počet leukocytů MeSH
- prasata MeSH
- progrese nemoci MeSH
- prospektivní studie MeSH
- sepse patofyziologie terapie MeSH
- srdce patofyziologie MeSH
- srdeční mitochondrie fyziologie MeSH
- vazokonstriktory terapeutické užití MeSH
- vyhodnocení orgánové dysfunkce MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Sepsis, newly defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection, is the most common cause of death in ICUs and one of the principal causes of death worldwide. Although substantial progress has been made in the understanding of fundamental mechanisms of sepsis, translation of these advances into clinically effective therapies has been disappointing. Given the extreme complexity of sepsis pathogenesis, the paradigm "one disease, one drug" is obviously flawed and combinations of multiple targets that involve early immunomodulation and cellular protection are needed. In this context, the immune-reprogramming properties of cell-based therapy using mesenchymal stem cells (MSC) represent an emerging therapeutic strategy in sepsis and associated organ dysfunction. This article provides an update of the current knowledge regarding MSC in preclinical models of sepsis and sepsis-induced acute kidney injury. Recommendations for further translational research in this field are discussed.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
