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Science (New York, N.Y.) Oct 2022Microbiota-derived metabolites that elicit DNA damage can contribute to colorectal cancer (CRC). However, the full spectrum of genotoxic chemicals produced by indigenous...
Microbiota-derived metabolites that elicit DNA damage can contribute to colorectal cancer (CRC). However, the full spectrum of genotoxic chemicals produced by indigenous gut microbes remains to be defined. We established a pipeline to systematically evaluate the genotoxicity of an extensive collection of gut commensals from inflammatory bowel disease patients. We identified isolates from divergent phylogenies whose metabolites caused DNA damage and discovered a distinctive family of genotoxins-termed the indolimines-produced by the CRC-associated species A non-indolimine-producing mutant lacked genotoxicity and failed to exacerbate colon tumorigenesis in mice. These studies reveal the existence of a previously unexplored universe of genotoxic small molecules from the microbiome that may affect host biology in homeostasis and disease.
Topics: Animals; Mice; Colorectal Neoplasms; DNA Damage; Gastrointestinal Microbiome; Inflammatory Bowel Diseases; Morganella morganii; Indoles; Carcinogenesis; Humans; Mutagens; HeLa Cells
PubMed: 36302024
DOI: 10.1126/science.abm3233 -
Indian Journal of Medical Microbiology 2021Morganella morganii is a Gram-negative, rod-shaped, facultative anaerobic bacillus divided into two subspecies, morganii and sibonii. Previously classified as Proteus... (Review)
Review
BACKGROUND
Morganella morganii is a Gram-negative, rod-shaped, facultative anaerobic bacillus divided into two subspecies, morganii and sibonii. Previously classified as Proteus morganii, it belongs to human gut commensal microbiota. Nevertheless, on rare occasions, especially in nosocomial and postoperative environment as well as in patients with the impaired immune system and young children, it may cause potentially fatal systemic infection.
OBJECTIVES
The aim of our systematic review was to determine whether and what invasive infections in humans were caused by Morganella morganii and to estimate outcomes of administered antibiotic management.
DATA SOURCES
This systematic review was registered at the PROSPERO database of systematic reviews and meta-analyses before initiation of the research (registration number CRD42020171919). Study eligibility criteria and participants. patients of any age and both sex harbouring Morganella morganii as the only microorganism in bodily fluids or tissues, from where it was isolated and identified by one or more of the following diagnostic methods: conventional techniques including colony morphology, Vitek 2, API or BD Phoenix biochemical systems, as well as more sophisticated methods, such as Matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) and species-specific PCR for M. morganii.
METHODS AND INTERVENTIONS
We have systematically searched MEDLINE, EBSCO, SCOPUS, SCINDEX and GOOGLE SCHOLAR for case reports and case series with M. morganii invasive infections.
RESULTS
M. morganii can cause serious infections of different tissue in patients of any age. The most isolates were susceptible to ceftazidime, imipenem and amikacin. Majority of the patients completely recovered after antibiotic treatment. About 15% of the patients died despite of the therapy. Gentamicin was the most frequently used antibiotic in the treatment of infection caused by M. morganii.
CONCLUSION
M. morganii invasive infections should be taken into consideration by the clinicians, especially in hospital conditions, due to its high degree of mortality and high potential of this bacterium to develop multidrug resistance. Treatment of M. morganii infections should include gentamycin in combination with third generation cephalosporin or another antibiotic to which M. morganii is susceptible (after testing isolates for third cephalosporin generation for the production of AmpC β -lactamases).
Topics: Anti-Bacterial Agents; Cephalosporins; Enterobacteriaceae Infections; Humans; Morganella morganii
PubMed: 34193353
DOI: 10.1016/j.ijmmb.2021.06.005 -
Clinical Infectious Diseases : An... Jun 2021In vitro data support the use of combination of aztreonam (ATM) with ceftazidime-avibactam (CAZ-AVI), but clinical studies are lacking. The aim of our study was to... (Observational Study)
Observational Study
BACKGROUND
In vitro data support the use of combination of aztreonam (ATM) with ceftazidime-avibactam (CAZ-AVI), but clinical studies are lacking. The aim of our study was to compare the outcome of patients with bloodstream infections (BSIs) due to metallo-β-lactamase (MBL)-producing Enterobacterales treated either with CAZ-AVI plus ATM or other active antibiotics (OAAs).
METHODS
This was a prospective observational study including patients admitted to 3 hospitals in Italy and Greece. The primary outcome measure was 30-day all-cause mortality. Secondary outcomes were clinical failure at day 14 and length of stay after BSI diagnosis. Cox regression analysis including a propensity score (PS) for receiving CAZ-AVI + ATM was performed to evaluate primary and secondary outcomes. A PS-based matched analysis was also performed.
RESULTS
We enrolled 102 patients with BSI; 82 had infections caused by NDM-producing (79 Klebsiella pneumoniae and 3 Escherichia coli) and 20 by VIM-producing (14 K. pneumoniae, 5 Enterobacter species, 1 Morganella morganii) strains. The 30-day mortality rate was 19.2% in the CAZ-AVI + ATM group vs 44% in the OAA group (P = .007). The PS-adjusted analysis showed that the use of CAZ-AVI + ATM was associated with lower 30-day mortality (hazard ratio [HR], 0.37 [95% confidence interval {CI}, .13-.74]; P = .01), lower clinical failure at day 14 (HR, 0.30 [95% CI, .14-.65]; P = .002), and shorter length of stay (subdistributional HR, 0.49 [95% CI, .30-.82]; P = .007). The PS-matched analysis confirmed these findings.
CONCLUSIONS
The CAZ-AVI + ATM combination offers a therapeutic advantage compared to OAAs for patients with BSI due to MBL-producing Enterobacterales. Further studies are warranted.
Topics: Anti-Bacterial Agents; Azabicyclo Compounds; Aztreonam; Ceftazidime; Drug Combinations; Greece; Humans; Italy; Microbial Sensitivity Tests; Sepsis; beta-Lactamases
PubMed: 32427286
DOI: 10.1093/cid/ciaa586 -
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 -
European Journal of Case Reports in... 2022Purpura fulminans (PF) is a dermatological manifestation of a life-threatening condition characterized by disseminated intravascular coagulation and endovascular...
UNLABELLED
Purpura fulminans (PF) is a dermatological manifestation of a life-threatening condition characterized by disseminated intravascular coagulation and endovascular thrombosis. The idiopathic/infectious form is the most common and usually associated with infection by or . We describe a case of -induced bacteriaemia complicated with PF in an individual who had undergone a recent urinary tract infection intervention. The patient presented with purpuric skin lesions, fever and hypotension but had no alterations in coagulation parameters or disseminated intravascular coagulation. Aggressive early resuscitation, intravenous antibiotics and wound care were essential to a favourable response.
LEARNING POINTS
Purpura fulminans is a dermatological manifestation of an underlying life-threatening condition, and is characterized by disseminated intravascular coagulation and skin necrosis.It is a morbid and potentially fatal condition that can be a cutaneous manifestation of bacteraemia.Early identification and accurate diagnosis of the underlying cause can help minimize morbidity and mortality; management should be tailored to the individual, with the use of intravenous antibiotics, necrotic skin excision and aggressive early resuscitation.
PubMed: 36506741
DOI: 10.12890/2022_003670 -
Frontiers in Microbiology 2021Ongoing acquisition of antimicrobial resistance genes has made a new clinical treatment challenge. Understanding the molecular epidemiology of will contribute to...
Ongoing acquisition of antimicrobial resistance genes has made a new clinical treatment challenge. Understanding the molecular epidemiology of will contribute to clinical treatment and prevention. We undertook a 6-year clinical molecular epidemiological investigation of from three tertiary hospitals in China since 2014. Antimicrobial susceptibility testing was performed using a VITEK-2 system. All isolates were screened for β-lactam and plasmid-mediated quinolone resistance genes by PCR. Isolates carrying carbapenem-resistant genes were subjected to whole-genome sequencing (WGS). The variation and evolution of these mobile genetic elements (MGEs) were then systematically analyzed. Among all isolates ( = 335), forty (11.9%) were recognized as multidrug resistant strains. , , , and were the top four most prevalent resistance genes. Notably, phylogenomic and population structure analysis suggested clade 1 (rhierBAPS SC3 and SC5) associated with multiple resistance genes seemed to be widely spread. WGS showed a -carrying IncX3 plasmid and a genomic island 2 variant carrying , coexisted in the same multidrug resistant strain zy_m28. Additionally, a -carrying IncP-1β type plasmid was found in the strain nx_m63. This study indicates a clade of is prone to acquire resistance genes, and multidrug resistant are increasing by harboring a variety of MGEs including two newly discovered ones in the species. We should be vigilant that may bring more extensive and challenging antimicrobial resistance issue.
PubMed: 34650543
DOI: 10.3389/fmicb.2021.744291 -
Public Health May 2020The global increase in rare opportunistic microbial infections is alarming. The current review was undertaken to study the diversified disease spectrum, pathogenicity,... (Review)
Review
OBJECTIVES
The global increase in rare opportunistic microbial infections is alarming. The current review was undertaken to study the diversified disease spectrum, pathogenicity, and resistance patterns of Morganella morganii.
STUDY DESIGN
This study is a review of the diversified disease spectrum of M. morganii.
METHODS
The articles used in this review were all extracted from PubMed and Google Scholar, using the terms 'M. morganii', 'prevalence', 'virulence factors', 'infections', 'resistance pattern', and 'genomics'. This review includes original articles, reviews, and case reports focusing on M. morganii, hospital-based prevalence studies, and studies on resistance in M. morganii published between 1906 and April 2019. Articles published in English, French, Spanish, and Chinese were reviewed.
RESULTS
M. morganii has had a significant impact as a clinical pathogen and the pace of its occurrence and the increase in its resistance rates puts this bacterium on the path to becoming the next 'superbug'. These developments not only impact M. morganii, but as a result of gene and plasmid transfer evolution, other clinical pathogens have been able to acquire their diverse intrinsic and acquired virulence genes. Its vast host range raises concerns around its capacity to generate new infections through novel symbiotic relationships.
CONCLUSIONS
M. morganii opportunism is being increasingly reported across the globe. This bacterium is accumulating intrinsic and acquired multidrug resistance genes, resulting in increased morbidity and mortality rates for M. morganii infections and complicating its treatment. M. morganii should be recognized as a clinically significant pathogen, and clinicians should place this microorganism in the list of causative possibilities during patient care. It is important for both the infection control activities in hospitals and in public health sector.
Topics: Drug Resistance, Multiple, Bacterial; Enterobacteriaceae Infections; Humans; Morganella morganii; Virulence
PubMed: 32169625
DOI: 10.1016/j.puhe.2020.01.016 -
Science (New York, N.Y.) Oct 2022Unexpected members of the gut microbiota produce diverse host cell genotoxins.
Unexpected members of the gut microbiota produce diverse host cell genotoxins.
Topics: Colorectal Neoplasms; DNA Damage; Gastrointestinal Microbiome; Morganella morganii; Mutagens; Humans; Mice; Animals
PubMed: 36302018
DOI: 10.1126/science.ade6952 -
Frontiers in Microbiology 2021The bacterium can produce the biogenic amines (BA) cadaverine, putrescine, and histamine and is responsible for high histamine concentrations in fish products. These...
The bacterium can produce the biogenic amines (BA) cadaverine, putrescine, and histamine and is responsible for high histamine concentrations in fish products. These BA can have toxic effects upon ingestion and are undesired in food. The purpose of this study was to characterize the phenotype and genotype of 11 isolated from cheese in regard to the BA formation. In addition, we investigated the phylogeny, trehalose fermentation ability, and antibiotic resistance of the cheese isolates. To do so, we sequenced their genomes using both long and short read technologies. Due to the presence of the trehalose operon and the ability to ferment trehalose, the cheese isolates can be assigned to the subsp. . Comparative genomics with public available genomes shows that the genomes of the cheese isolates cluster together with other subsp. genomes. All genomes between subsp. and subsp. are separated by an average nucleotide identity (ANI) of less than 95.0%. Therefore, the subspecies could represent two distinct species. Nine of the strains decarboxylated lysine yielding cadaverine . This metabolic activity is linked to a previously unknown gene cluster comprising genes encoding a lysine-tRNA ligase (), an HTH-transcriptional regulator (), a cadaverine-lysine antiporter (), and a lysine decarboxylase (. The formation of putrescine is linked to the gene encoding an ornithine decarboxylase. The gene is disrupted in five strains by an insertion sequence, and these strains only exhibit a weak putrescine production. Antimicrobial susceptibility profiling revealed that all cheese strains are resistant to tetracycline, chloramphenicol, tigecycline, colistin, and ampicillin. These phenotypes, except for colistin which is intrinsic, could be linked to antimicrobial resistance genes located on the chromosome.
PubMed: 34867855
DOI: 10.3389/fmicb.2021.738492 -
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