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International Journal of Infectious... Sep 2016Morganella morganii belongs to the tribe Proteeae of the Enterobacteriaceae family. This species is considered as an unusual opportunistic pathogen that mainly causes... (Review)
Review
Morganella morganii belongs to the tribe Proteeae of the Enterobacteriaceae family. This species is considered as an unusual opportunistic pathogen that mainly causes post-operative wound and urinary tract infections. However, certain clinical M. morganii isolates present resistance to multiple antibiotics by carrying various resistant genes (such as blaNDM-1, and qnrD1), thereby posing a serious challenge for clinical infection control. Moreover, virulence evolution makes M. morganii an important pathogen. Accumulated data have demonstrated that M. morganii can cause various infections, such as sepsis, abscess, purple urine bag syndrome, chorioamnionitis, and cellulitis. This bacterium often results in a high mortality rate in patients with some infections. M. morganii is considered as a non-negligent opportunistic pathogen because of the increased levels of resistance and virulence. In this review, we summarized the epidemiology of M. morganii, particularly on its resistance profile and resistant genes, as well as the disease spectrum and risk factors for its infection.
Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Enterobacteriaceae Infections; Humans; Morganella morganii; Urinary Tract Infections
PubMed: 27421818
DOI: 10.1016/j.ijid.2016.07.006 -
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 -
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 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 -
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 -
Microbiology Spectrum Jun 2022Although recent reports of extensively antibiotic-resistant strains have highlighted the importance of Morganella morganii as an emerging pathogen, the epidemiology of...
Although recent reports of extensively antibiotic-resistant strains have highlighted the importance of Morganella morganii as an emerging pathogen, the epidemiology of serious infections due to this organism is not well defined. The objective of this study was to determine the incidence, determinants, and outcomes of Morganella morganii bloodstream infections (BSIs). Retrospective, population-based surveillance for Morganella morganii BSIs was conducted in Queensland, Australia, in 2000 to 2019; 709 cases were identified, for an annual incidence of 9.2 cases per million population. Most cases were of community onset, with 280 (39.5%) community-associated cases and 226 (31.9%) health care-associated cases. Morganella morganii BSIs were rare in children and young adults, and the incidence increased markedly with advancing age. The most common foci of infection were skin and soft tissue (131 cases [18.5%]), genitourinary (97 cases [13.7%]), and intraabdominal (90 cases [12.7%]). Most patients (580 cases [81.8%]) had at least one comorbid medical illness, with diabetes mellitus (250 cases [35.3%]), renal disease (208 cases [29.3%]), and congestive heart failure (167 cases [23.6%]) being most prevalent. Resistance to one or more of quinolones, co-trimoxazole, aminoglycosides, or carbapenems was observed in 67 cases (9.5%), and this did not change significantly over the study. The 30-day all-cause case fatality rate was 21.2%, and increasing age, nonfocal infection, heart failure, dementia, and cancer were independently associated with increased risk of death. Morganella morganii BSIs are increasing in our population, and elderly male subjects and individuals with comorbidities are at highest risk. Although antibiotic resistance is not a major contributor to the current burden in Queensland, ongoing surveillance is warranted. Recent reports of extensively antibiotic-resistant strains have highlighted the importance of Morganella morganii as an emerging pathogen. Despite its present and evolving importance as an agent of human disease, there is a limited body of literature detailing the epidemiology of serious infections due to Morganella morganii. Therefore, the objectives of this study were to examine the incidence and determinants of Morganella morganii BSIs and to examine risk factors for death in a large Australian population in 2000 to 2019.
Topics: Aged; Anti-Bacterial Agents; Australia; Child; Enterobacteriaceae Infections; Humans; Male; Morganella morganii; Retrospective Studies; Sepsis
PubMed: 35467403
DOI: 10.1128/spectrum.00569-22 -
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 -
Frontiers in Cellular and Infection... 2022Catheter-associated urinary tract infections (CAUTIs) are one of the most common healthcare-associated infections in the US, accounting for over 1 million cases annually...
Catheter-associated urinary tract infections (CAUTIs) are one of the most common healthcare-associated infections in the US, accounting for over 1 million cases annually and totaling 450 million USD. CAUTIs have high morbidity and mortality rates and can be caused by a wide range of pathogens, making empiric treatment difficult. Furthermore, when urease-producing uropathogens cause symptomatic CAUTI or asymptomatic catheter colonization, the risk of catheter failure due to blockage increases. The enzyme urease promotes catheter blockage by hydrolyzing urea in urine into ammonia and carbon dioxide, which results in the formation of crystals that coat the catheter surface. If CAUTI is left untreated, the crystals can grow until they block the urinary catheter. Catheter blockage and subsequent failure reduces the quality of life for the chronically catheterized, as it requires frequent catheter exchanges and can promote more severe disease, including dissemination of the infection to the kidneys or bloodstream. Thus, understanding how urease contributes to catheter blockages and/or more severe disease among the broad range of urease-producing microbes may provide insights into better prevention or treatment strategies. However, clinical assays that detect urease production among clinical isolates are qualitative and prioritize the detection of urease from , the most well-studied uropathogenic urease producer. While urease from other known urease producers, such as , can also be detected with these methods, other uropathogens, including and , are harder to detect. In this study, we developed a high throughput, semiquantitative assay capable of testing multiple uropathogens in a rapid and efficient way. We validated the assay using Jack Bean urease, the urease producing species spp., and strains, and the non-urease producer: . This modified assay more rapidly detected urease-producing strains compared to the current clinical test, Christensen Urea Agar, and provided semiquantitative values that may be used to further investigate different aspects of urease regulation, production, or activity in these diverse species. Furthermore, this assay can be easily adapted to account for different environmental stimuli affecting urease production, including bacterial concentration, aeration, or addition of anti-urease compounds.
Topics: Escherichia coli; Humans; Quality of Life; Staphylococcus aureus; Urea; Urease; Urinary Catheters; Urinary Tract Infections
PubMed: 35392611
DOI: 10.3389/fcimb.2022.859093 -
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