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Medicina Aug 2022Spinal muscular atrophy (SMA) has been known as a clinical entity for 130 yearsis still recognized today as the most severe autosomal recessive neuromuscular disease... (Review)
Review
Spinal muscular atrophy (SMA) has been known as a clinical entity for 130 yearsis still recognized today as the most severe autosomal recessive neuromuscular disease (5q,13,2) in pediatrics. Until 2015, SMA treatment was limited to ventilatory, nutritional, and physical therapy support. Currently, the existence of genetic treatments: gene modification by inclusion of exon 7 to the SMN2 gene (nusinersen and risdiplam) or insertion of the SMN1 gene through the adeno-associated viral transporter (onasemnogene) have radically modified the clinical evolution of children with SMA,especially if they are treated early. This review details the effects of the 3 treatments currently in use worldwide.
Topics: Child; Humans; Muscular Atrophy, Spinal
PubMed: 36054863
DOI: No ID Found -
Nature Jul 2020Animals coexist in commensal, pathogenic or mutualistic relationships with complex communities of diverse organisms, including microorganisms. Some bacteria produce...
Animals coexist in commensal, pathogenic or mutualistic relationships with complex communities of diverse organisms, including microorganisms. Some bacteria produce bioactive neurotransmitters that have previously been proposed to modulate nervous system activity and behaviours of their hosts. However, the mechanistic basis of this microbiota-brain signalling and its physiological relevance are largely unknown. Here we show that in Caenorhabditis elegans, the neuromodulator tyramine produced by commensal Providencia bacteria, which colonize the gut, bypasses the requirement for host tyramine biosynthesis and manipulates a host sensory decision. Bacterially produced tyramine is probably converted to octopamine by the host tyramine β-hydroxylase enzyme. Octopamine, in turn, targets the OCTR-1 octopamine receptor on ASH nociceptive neurons to modulate an aversive olfactory response. We identify the genes that are required for tyramine biosynthesis in Providencia, and show that these genes are necessary for the modulation of host behaviour. We further find that C. elegans colonized by Providencia preferentially select these bacteria in food choice assays, and that this selection bias requires bacterially produced tyramine and host octopamine signalling. Our results demonstrate that a neurotransmitter produced by gut bacteria mimics the functions of the cognate host molecule to override host control of a sensory decision, and thereby promotes fitness of both the host and the microorganism.
Topics: Animals; Avoidance Learning; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Feeding Behavior; Gastrointestinal Microbiome; Intestines; Metabolomics; Mutation; Neurotransmitter Agents; Octanols; Octopamine; Providencia; Receptors, Biogenic Amine; Receptors, G-Protein-Coupled; Sensory Receptor Cells; Smell; Tyramine; Tyrosine Decarboxylase
PubMed: 32555456
DOI: 10.1038/s41586-020-2395-5 -
Open Forum Infectious Diseases Aug 2021Carbapenems are recommended treatment for serious infections caused by AmpC-producing gram-negative bacteria but can select for carbapenem resistance....
Meropenem Versus Piperacillin-Tazobactam for Definitive Treatment of Bloodstream Infections Caused by AmpC β-Lactamase-Producing spp, , , spp, or : A Pilot Multicenter Randomized Controlled Trial (MERINO-2).
BACKGROUND
Carbapenems are recommended treatment for serious infections caused by AmpC-producing gram-negative bacteria but can select for carbapenem resistance. Piperacillin-tazobactam may be a suitable alternative.
METHODS
We enrolled adult patients with bloodstream infection due to chromosomal AmpC producers in a multicenter randomized controlled trial. Patients were assigned 1:1 to receive piperacillin-tazobactam 4.5 g every 6 hours or meropenem 1 g every 8 hours. The primary efficacy outcome was a composite of death, clinical failure, microbiological failure, and microbiological relapse at 30 days.
RESULTS
Seventy-two patients underwent randomization and were included in the primary analysis population. Eleven of 38 patients (29%) randomized to piperacillin-tazobactam met the primary outcome compared with 7 of 34 patients (21%) in the meropenem group (risk difference, 8% [95% confidence interval {CI}, -12% to 28%]). Effects were consistent in an analysis of the per-protocol population. Within the subcomponents of the primary outcome, 5 of 38 (13%) experienced microbiological failure in the piperacillin-tazobactam group compared to 0 of 34 patients (0%) in the meropenem group (risk difference, 13% [95% CI, 2% to 24%]). In contrast, 0% vs 9% of microbiological relapses were seen in the piperacillin-tazobactam and meropenem arms, respectively. Susceptibility to piperacillin-tazobactam and meropenem using broth microdilution was found in 96.5% and 100% of isolates, respectively. The most common AmpC β-lactamase genes identified were , , , and . No ESBL, OXA, or other carbapenemase genes were identified.
CONCLUSIONS
Among patients with bloodstream infection due to AmpC producers, piperacillin-tazobactam may lead to more microbiological failures, although fewer microbiological relapses were seen.
CLINICAL TRIALS REGISTRATION
NCT02437045.
PubMed: 34395716
DOI: 10.1093/ofid/ofab387 -
International Journal of Molecular... Nov 2022Nowadays, antimicrobial resistance (AMR) represents a challenge for antibiotic therapy, mostly involving Gram-negative bacteria. Among the strategies activated to... (Review)
Review
Nowadays, antimicrobial resistance (AMR) represents a challenge for antibiotic therapy, mostly involving Gram-negative bacteria. Among the strategies activated to overcome AMR, the repurposing of already available antimicrobial molecules by encapsulating them in drug delivery systems, such as nanoparticles (NPs) and also engineered NPs, seems to be promising. Tobramycin is a powerful and effective aminoglycoside, approved for complicated infections and reinfections and indicated mainly against Gram-negative bacteria, such as , , , , , , , and species. However, the drug presents several side effects, mostly due to dose frequency, and for this reason, it is a good candidate for nanomedicine formulation. This review paper is focused on what has been conducted in the last 20 years for the development of Tobramycin nanosized delivery systems (nanoantibiotics), with critical discussion and comparison. Tobramycin was selected as the antimicrobial drug because it is a wide-spectrum antibiotic that is effective against both Gram-positive and Gram-negative aerobic bacteria, and it is characterized by a fast bactericidal effect, even against multidrug-resistant microorganisms (MDR).
Topics: Tobramycin; Gentamicins; Drug Resistance, Microbial; Aminoglycosides; Anti-Bacterial Agents
PubMed: 36430555
DOI: 10.3390/ijms232214080 -
Emerging Microbes & Infections Dec 2023as an opportunistic pathogen can cause serious infection, and moreover the emergence of multi-drug-resistant strains poses a potentially life-threatening risk to...
as an opportunistic pathogen can cause serious infection, and moreover the emergence of multi-drug-resistant strains poses a potentially life-threatening risk to public health. However, a comprehensive genomic study to reveal the population structure and dissemination of is still lacking. In this study, we conducted a genomic epidemiology analysis on the 580 global sequenced isolates, including 257 ones sequenced in this study (42 ones were fully sequenced). We established a genome sequence-based species classification scheme for , redefining the conventional 11 species into seven genocomplexes that were further divided into 18 genospecies, providing an extensively updated reference for species discrimination based on the largest genome dataset to date. We then dissected the profile of antimicrobial resistance genes and the prevalence of multi-drug-resistant strains among these genocomplexes/genospecies, disclosing the presence of diverse and abundant antimicrobial resistance genes and high resistance ratios against multiple classes of drugs in . We further dissected the genetic basis for the spread of in . genes were mainly carried by five incompatible (Inc) groups of plasmids: IncC, IncW, Inc, Inc, and Inc, and the last three were newly designated in this study. By tracking the spread of -carrying plasmids, IncC, Inc, Inc, and Inc plasmids were found to be highly involved in parallel horizontal transfer or vertical clonal expansion of among . Overall, our study provided a comprehensive genomic view of species differentiation, antimicrobial resistance prevalence, and plasmid-mediated dissemination in .
Topics: Providencia; Anti-Bacterial Agents; Plasmids; beta-Lactamases; Genomics; Microbial Sensitivity Tests
PubMed: 37874004
DOI: 10.1080/22221751.2023.2275596 -
Trials Apr 2021Extended-spectrum beta-lactamase (ESBL) and AmpC-producing Enterobacterales are common causes of bloodstream infection. ESBL-producing bacteria are typically resistant...
Ceftolozane-tazobactam versus meropenem for definitive treatment of bloodstream infection due to extended-spectrum beta-lactamase (ESBL) and AmpC-producing Enterobacterales ("MERINO-3"): study protocol for a multicentre, open-label randomised non-inferiority trial.
BACKGROUND
Extended-spectrum beta-lactamase (ESBL) and AmpC-producing Enterobacterales are common causes of bloodstream infection. ESBL-producing bacteria are typically resistant to third-generation cephalosporins and result in a sizeable economic and public health burden. AmpC-producing Enterobacterales may develop third-generation cephalosporin resistance through enzyme hyper-expression. In no observational study has the outcome of treatment of these infections been surpassed by carbapenems. Widespread use of carbapenems may drive the development of carbapenem-resistant Gram-negative bacilli.
METHODS
This study will use a multicentre, parallel group open-label non-inferiority trial design comparing ceftolozane-tazobactam and meropenem in adult patients with bloodstream infection caused by ESBL or AmpC-producing Enterobacterales. Trial recruitment will occur in up to 40 sites in six countries (Australia, Singapore, Italy, Spain, Saudi Arabia and Lebanon). The sample size is determined by a predefined quantity of ceftolozane-tazobactam to be supplied by Merck, Sharpe and Dohme (MSD). We anticipate that a trial with 600 patients contributing to the primary outcome analysis would have 80% power to declare non-inferiority with a 5% non-inferiority margin, assuming a 30-day mortality of 5% in both randomised groups. Once randomised, definitive treatment will be for a minimum of 5 days and a maximum of 14 days with the total duration determined by treating clinicians. Data describing demographic information, risk factors, concomitant antibiotics, illness scores, microbiology, multidrug-resistant organism screening, discharge and mortality will be collected.
DISCUSSION
Participants will have bloodstream infection due to third-generation cephalosporin non-susceptible E. coli and Klebsiella spp. or Enterobacter spp., Citrobacter freundii, Morganella morganii, Providencia spp. or Serratia marcescens. They will be randomised 1:1 to ceftolozane-tazobactam 3 g versus meropenem 1 g, both every 8 h. Secondary outcomes will be a comparison of 14-day all-cause mortality, clinical and microbiological success at day 5, functional bacteraemia score, microbiological relapse, new bloodstream infection, length of hospital stay, serious adverse events, C. difficile infection, multidrug-resistant organism colonisation. The estimated trial completion date is December 2024.
TRIAL REGISTRATION
The MERINO-3 trial is registered under the US National Institute of Health ClinicalTrials.gov register, reference number: NCT04238390 . Registered on 23 January 2020.
Topics: Adult; Humans; Anti-Bacterial Agents; Australia; beta-Lactamases; Cephalosporins; Clostridioides difficile; Escherichia coli; Italy; Lebanon; Meropenem; Microbial Sensitivity Tests; Multicenter Studies as Topic; Saudi Arabia; Sepsis; Singapore; Spain; Tazobactam; Equivalence Trials as Topic
PubMed: 33888139
DOI: 10.1186/s13063-021-05206-8 -
The American Journal of Tropical... Aug 2019is a member of the family Enterobacteriaceae that has been commonly implicated as a causative agent of diarrheal infection in humans and animals. Recent outbreaks of... (Review)
Review
is a member of the family Enterobacteriaceae that has been commonly implicated as a causative agent of diarrheal infection in humans and animals. Recent outbreaks of in both developing and developed countries have raised public health concerns. Several studies have suggested that can cause diarrhea by invading the intestinal mucosa, although its pathogenicity has not been well established. Often routine laboratory investigations that seek etiological agents of diarrhea do not actively pursue detection. Therefore, routine laboratory diagnosis should be given more attention for better understanding the epidemiology and pathogenicity of .
Topics: Animals; Diarrhea; Disease Outbreaks; Enterobacteriaceae Infections; Feces; Foodborne Diseases; Providencia
PubMed: 31218997
DOI: 10.4269/ajtmh.18-0376 -
Environmental Science and Pollution... Apr 2022
Topics: Chile; Environmental Exposure; Environmental Monitoring; Pesticides
PubMed: 35099697
DOI: 10.1007/s11356-022-18843-6 -
Insects May 2022(Diptera: Tephritidae) is responsible for extensive damage in agriculture with important economic losses. Several strategies have been proposed to control this insect...
(Diptera: Tephritidae) is responsible for extensive damage in agriculture with important economic losses. Several strategies have been proposed to control this insect pest including insecticides and the Sterile Insect Technique. Traditional control methods should be implemented by innovative tools, among which those based on insect symbionts seem very promising. Our study aimed to investigate, through the 16S Miseq analysis, the microbial communities associated with selected organs in three different medfly populations to identify possible candidates to develop symbiont-based control approaches. Our results confirm that and are the dominant bacteria in guts, while a more diversified microbial community has been detected in reproductive organs. Concertedly, we revealed for the first time the presence of and as stable components of the medfly's microbiota. Additionally, in the reproductive organs, we detected , a bacterium already proposed as a tool in the Symbiotic Control of Vector-Borne Diseases. A strain of , genetically modified to produce a green fluorescent protein, was used to ascertain the ability of to colonize specific organs of . Our study lays the foundation for the development of control methods for based on the use of symbiont bacteria.
PubMed: 35621808
DOI: 10.3390/insects13050474 -
Diagnostics (Basel, Switzerland) Mar 2023Microbiota are ecological communities of commensal, symbiotic, and pathogenic microorganisms. The microbiome could be involved in kidney stone formation through... (Review)
Review
Microbiota are ecological communities of commensal, symbiotic, and pathogenic microorganisms. The microbiome could be involved in kidney stone formation through hyperoxaluria and calcium oxalate supersaturation, biofilm formation and aggregation, and urothelial injury. Bacteria bind to calcium oxalate crystals, which causes pyelonephritis and leads to changes in nephrons to form Randall's plaque. The urinary tract microbiome, but not the gut microbiome, can be distinguished between cohorts with urinary stone disease (USD) and those without a history of the disease. In the urine microbiome, the role is known of urease-producing bacteria (, , , , , , and ) in stone formation. Calcium oxalate crystals were generated in the presence of two uropathogenic bacteria ( and . Non-uropathogenic bacteria ( and ) exhibit calcium oxalate lithogenic effects. The taxa and best distinguished the healthy cohort from the USD cohort, respectively. Standardization is needed in urine microbiome research for urolithiasis. Inadequate standardization and design of urinary microbiome research on urolithiasis have hampered the generalizability of results and diminished their impact on clinical practice.
PubMed: 36900094
DOI: 10.3390/diagnostics13050951