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1.
Annu Rev Microbiol ; 74: 787-813, 2020 09 08.
Article in English | MEDLINE | ID: mdl-32692613

ABSTRACT

Food has a major impact on all aspects of health. Recent data suggest that food composition can also affect susceptibility to infections by enteropathogenic bacteria. Here, we discuss how food may alter the microbiota as well as mucosal defenses and how this can affect infection. Salmonella Typhimurium diarrhea serves as a paradigm, and complementary evidence comes from other pathogens. We discuss the effects of food composition on colonization resistance, host defenses, and the infection process as well as the merits and limitations of mouse models and experimental foods, which are available to decipher the underlying mechanisms.


Subject(s)
Diet , Enterobacteriaceae/pathogenicity , Gastrointestinal Microbiome , Host-Pathogen Interactions , Salmonella Infections/prevention & control , Animals , Diarrhea/microbiology , Diarrhea/prevention & control , Disease Models, Animal , Food Analysis , Humans , Mice , Salmonella Infections/microbiology , Salmonella typhimurium/pathogenicity
2.
Mol Biol Evol ; 40(11)2023 Nov 03.
Article in English | MEDLINE | ID: mdl-37931146

ABSTRACT

Genes that undergo horizontal gene transfer (HGT) evolve in different genomic backgrounds. Despite the ubiquity of cross-species HGT, the effects of switching hosts on gene evolution remains understudied. Here, we present a framework to examine the evolutionary consequences of host-switching and apply this framework to an antibiotic resistance gene commonly found on conjugative plasmids. Specifically, we determined the adaptive landscape of this gene for a small set of mutationally connected genotypes in 3 enteric species. We uncovered that the landscape topographies were largely aligned with minimal host-dependent mutational effects. By simulating gene evolution over the experimentally gauged landscapes, we found that the adaptive evolution of the mobile gene in one species translated to adaptation in another. By simulating gene evolution over artificial landscapes, we found that sufficient alignment between landscapes ensures such "adaptive equivalency" across species. Thus, given adequate landscape alignment within a bacterial community, vehicles of HGT such as plasmids may enable a distributed form of genetic evolution across community members, where species can "crowdsource" adaptation.


Subject(s)
Anti-Bacterial Agents , Evolution, Molecular , Genotype , Gene Transfer, Horizontal , Genomics
3.
Antimicrob Agents Chemother ; 68(1): e0069523, 2024 Jan 10.
Article in English | MEDLINE | ID: mdl-38084954

ABSTRACT

Carbapenem-resistant Enterobacteriaceae (CREs) are described by the Centers for Disease Control as an urgent threat, and there is a critical need for new therapeutic agents able to treat infections caused by these pathogens. Herein, we describe the microbiological profile, the mechanism f action, and the in vitro safety as well as the pharmacokinetic (PK)/PD profile of SMT-738, a small molecule belonging to a new chemical class. SMT-738 is active against Enterobacterales [including multi-drug-resistant Escherichia coli with 90% of isolates having a minimum inhibitory concentration (MIC90) of 1 µg/mL and Klebsiella pneumoniae 2 µg/mL] and inactive against a broad panel of Gram-negative and Gram-positive pathogens. SMT-738 displays rapid bactericidal activity (2-4 h) and has a low propensity for resistance development (less than ~10-9). Characterization of resistant mutants following exposure to SMT-738 identified mutations within the lipoprotein transport complex (LolCDE), a clinically unexploited and essential bacterial molecular target in Gram-negative bacteria. SMT-738 has a promising in vitro toxicology profile. Furthermore, PK studies demonstrated that when dosed intravenously, SMT-738 maintained exposure levels across infection sites (bloodstream/urinary tract/lung). Proof-of-concept studies across multiple murine in vivo infection models (bloodstream/pneumonia/urinary tract) demonstrated that SMT-738 significantly reduced the bacterial burden compared to baseline and vehicle control. SMT-738 represents a promising novel drug candidate being developed to address clinically challenging serious life-threatening infections caused by highly resistant Enterobacteriaceae including CRE.


Subject(s)
Anti-Bacterial Agents , Enterobacteriaceae Infections , Mice , Animals , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Enterobacteriaceae/genetics , Gram-Negative Bacteria , Klebsiella pneumoniae/genetics , Lipoproteins , Microbial Sensitivity Tests , Enterobacteriaceae Infections/drug therapy
4.
Antimicrob Agents Chemother ; 68(4): e0140423, 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38411995

ABSTRACT

Piperacillin/tazobactam (TZP) is administered intravenously in a fixed ratio (8:1) with the potential for inadequate tazobactam exposure to ensure piperacillin activity against Enterobacterales. Adult patients receiving continuous infusion (CI) of TZP and therapeutic drug monitoring (TDM) of both agents were evaluated. Demographic variables and other pertinent laboratory data were collected retrospectively. A population pharmacokinetic approach was used to select the best kidney function model predictive of TZP clearance (CL). The probability of target attainment (PTA), cumulative fraction of response (CFR) and the ratio between piperacillin and tazobactam were computed to identify optimal dosage regimens by continuous infusion across kidney function. This study included 257 critically ill patients (79.3% male) with intra-abdominal, bloodstream, and hospital-acquired pneumonia infections in 89.5% as the primary indication. The median (min-max range) age, body weight, and estimated glomerular filtration rate (eGFR) were 66 (23-93) years, 75 (39-310) kg, and 79.2 (6.4-234) mL/min, respectively. Doses of up to 22.5 g/day were used to optimize TZP based on TDM. The 2021 chronic kidney disease epidemiology equation in mL/min best modeled TZP CL. The ratio of piperacillin:tazobactam increased from 6:1 to 10:1 between an eGFR of <20 mL/min and >120 mL/min. At conventional doses, the PTA is below 90% when eGFR is ≥100 mL/min. Daily doses of 18 g/day and 22.5 g/day by CI are expected to achieve a >80% CFR when eGFR is 100-120 mL/min and >120-160 mL/min, respectively. Inadequate piperacillin and tazobactam exposure is likely in patients with eGFR ≥ 100 mL/min. Dose regimen adjustments informed by TDM should be evaluated in this specific population.


Subject(s)
Gammaproteobacteria , beta-Lactamase Inhibitors , Adult , Humans , Male , Aged , Aged, 80 and over , Female , beta-Lactamase Inhibitors/pharmacokinetics , Anti-Bacterial Agents/pharmacokinetics , beta-Lactams , Retrospective Studies , Penicillanic Acid/therapeutic use , Penicillanic Acid/pharmacokinetics , Piperacillin, Tazobactam Drug Combination/pharmacokinetics , Piperacillin/pharmacokinetics , Tazobactam , beta-Lactamases , Microbial Sensitivity Tests
5.
Antimicrob Agents Chemother ; 68(10): e0069324, 2024 Oct 08.
Article in English | MEDLINE | ID: mdl-39158279

ABSTRACT

Treatment options for carbapenem-resistant gram-negative bacilli (CR-GNB), especially metallo-ß-lactamase (MBL)-producing CR-GNB, are limited. Aztreonam (ATM) in combination with avibactam (AVI) has shown potential for treating MBL-producing carbapenem-resistant Enterobacterales (CREs) and Stenotrophomonas maltophilia. However, data on ATM in combination with other ß-lactamase inhibitors (BLIs) are limited. We performed a multicenter study to evaluate the in vitro activities of ATM in combination with AVI, vaborbactam (VAB), relebactam (REL), tazobactam (TAZ) as well as with their commercially available formulations against CREs and S. maltophilia using broth microdilution. AVI restored ATM activity for MBL-producing CREs (ATM: 9.8% vs ATM-AVI: 78.0%) and S. maltophilia (ATM: 0% vs ATM-AVI: 93.3%). REL also moderately restored activity of ATM in MBL-producing CREs (ATM: 9.8% vs ATM-REL: 42.7%) and S. maltophilia (ATM: 0% vs ATM-REL: 68.9%). VAB and TAZ demonstrated very limited effect on the activity of ATM against CR-GNB evaluated. The combination of ATM with ceftazidime-AVI (CAZ-AVI) demonstrated maximum activity against CREs. Although ATM-CAZ-AVI is the most potent regimen available for CREs and S. maltophilia, ATM-IMI-REL might be a reasonable alternative.


Subject(s)
Anti-Bacterial Agents , Azabicyclo Compounds , Aztreonam , Boronic Acids , Microbial Sensitivity Tests , beta-Lactamase Inhibitors , beta-Lactamases , Aztreonam/pharmacology , Azabicyclo Compounds/pharmacology , Anti-Bacterial Agents/pharmacology , beta-Lactamases/metabolism , beta-Lactamase Inhibitors/pharmacology , Boronic Acids/pharmacology , Carbapenems/pharmacology , Humans , Gram-Negative Bacteria/drug effects , Stenotrophomonas maltophilia/drug effects , Tazobactam/pharmacology
6.
BMC Microbiol ; 24(1): 361, 2024 Sep 21.
Article in English | MEDLINE | ID: mdl-39306658

ABSTRACT

BACKGROUND: Epidemiological investigations have revealed an important association between infection, inflammation and prostate cancer. Certain bacterial species, such as Klebsiella spp, Escherichia coli, Pseudomonas spp, Proteus mirabilis, Chlamydia trachomatis have been linked to prostate cancer. This study aimed to examine the microbiota; specifically bacterial species that have been linked to prostate infections in the urine of individuals diagnosed with prostate cancer. RESULTS: Sixty-six prostate cancer patients and forty controls provided midstream urine samples. The urine samples were grown on suitable medium, and bacterial isolates were detected by standard microbiological methods. Additionally, the antibiotic sensitivity pattern of the bacterial isolates was analysed. A total of number of 72 bacterial isolates were obtained from the urine of study participants. The results showed the presence of Escherichia coli (50.0%), Pseudomonas aeruginosa (18.1%), Klebsiella spp (15.3%), Staphylococcus aureus (8.3%), Enterobacter spp (4.2%), and Proteus mirabilis (2.8%) in the urine. The most common bacterial species isolated from prostate cancer patients was Escherichia coli, which was susceptible to levofloxacin (100%), tobramycin (91.7%), and amikacin (62.5%). CONCLUSIONS: This study's findings established the presence of bacteria previously linked to prostatitis. This report indicates a high prevalence of pro-inflammatory bacteria and uropathogens in the urinary tract of men diagnosed with prostate cancer.


Subject(s)
Anti-Bacterial Agents , Bacteria , Microbial Sensitivity Tests , Prostatic Hyperplasia , Prostatic Neoplasms , Humans , Male , Prostatic Neoplasms/microbiology , Anti-Bacterial Agents/pharmacology , Prostatic Hyperplasia/microbiology , Middle Aged , Prevalence , Aged , Nigeria/epidemiology , Bacteria/drug effects , Bacteria/isolation & purification , Bacteria/classification , Urinary Tract Infections/microbiology , Urinary Tract Infections/epidemiology , Escherichia coli/drug effects , Escherichia coli/isolation & purification , Klebsiella/drug effects , Klebsiella/isolation & purification , Proteus mirabilis/drug effects , Proteus mirabilis/isolation & purification , Pseudomonas aeruginosa/drug effects , Pseudomonas aeruginosa/isolation & purification
7.
BMC Microbiol ; 24(1): 360, 2024 Sep 21.
Article in English | MEDLINE | ID: mdl-39306662

ABSTRACT

BACKGROUND: Urinary tract infections (UTIs) are the second most common infection, affecting 150 million people each year worldwide. Enterobacteriaceae species expressing extended-spectrum ß-lactamases (ESBLs) are on the rise across the globe and are becoming a severe problem in the therapeutic management of clinical cases of urinary tract infection. Knowledge of the prevalence and antibiogram profile of such isolates is essential to develop an appropriate treatment methodology. This study aimed to investigate the prevalence of Enterobacteriaceae isolates exhibiting ESBL and their selective oral antibiogram profile at the district general hospital, Polonnaruwa. RESULTS: A total of 4386 urine specimens received to the Microbiology Laboratory during the study period. Among them, 1081 (24.6%) showed positive results for urine culture while 200/1081 specimens showed ESBL isolates. Out of the selected 200 specimen's majority (67.5%) of samples received from the In-Patient Department. There were 200 patients and reported that 115 (57.5%) were females and 85 (42.5%) were males. The majority (51%) of the patients belong to the age group of 55-74 years. Among the ESBLs positive specimens, the majority 74.5% (n = 149) identified organisms were E. coli followed by Klebsiella spp.17.5% (n = 35), Enterobacteriaceae 7% (n = 14) and only1% (n = 2) isolate of Proteus spp. Mecillinam (87.92%) and Nitrofurantoin (83.2%) showed higher effectiveness against E. coli. Nitrofurantoin showed the highest effectiveness against Klebsiella spp. (40%), other Enterobacteriaceae spp. (100%). Proteus spp. showed 100% effectiveness and resistance respectively against Ciprofloxacin, Cotrimoxazole and Nitrofurantoin. CONCLUSION: The most predominant ESBLs producing uro-pathogen was the E. coli in the study setting and E. coli had higher sensitivity rate against Mecillinam. Among currently used oral antibiotics Nitrofurantoin was the best choice for UTIs caused by ESBL producers.


Subject(s)
Anti-Bacterial Agents , Enterobacteriaceae Infections , Enterobacteriaceae , Microbial Sensitivity Tests , Urinary Tract Infections , beta-Lactamases , Humans , Urinary Tract Infections/microbiology , Urinary Tract Infections/drug therapy , Female , Middle Aged , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/pharmacology , Male , beta-Lactamases/metabolism , Aged , Enterobacteriaceae/drug effects , Enterobacteriaceae/enzymology , Enterobacteriaceae/isolation & purification , Enterobacteriaceae Infections/microbiology , Enterobacteriaceae Infections/drug therapy , Adult , Young Adult , Aged, 80 and over , Adolescent , Nitrofurantoin/pharmacology , Nitrofurantoin/therapeutic use , Prevalence , Escherichia coli/drug effects , Escherichia coli/isolation & purification , Escherichia coli/enzymology
8.
BMC Microbiol ; 24(1): 216, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38890647

ABSTRACT

OBJECTIVE: This study aims to conduct an in-depth genomic analysis of a carbapenem-resistant Proteus mirabilis strain to uncover the distribution and mechanisms of its resistance genes. METHODS: The research primarily utilized whole-genome sequencing to analyze the genome of the Proteus mirabilis strain. Additionally, antibiotic susceptibility tests were conducted to evaluate the strain's sensitivity to various antibiotics, and related case information was collected to analyze the clinical distribution characteristics of the resistant strain. RESULTS: Study on bacterial strain WF3430 from a tetanus and pneumonia patient reveals resistance to multiple antibiotics due to extensive use. Whole-genome sequencing exposes a 4,045,480 bp chromosome carrying 29 antibiotic resistance genes. Two multidrug-resistant (MDR) gene regions, resembling Tn6577 and Tn6589, were identified (MDR Region 1: 64.83 Kb, MDR Region 2: 85.64 Kbp). These regions, consist of integrative and conjugative elements (ICE) structures, highlight the intricate multidrug resistance in clinical settings. CONCLUSION: This study found that a CR-PMI strain exhibits a unique mechanism for acquiring antimicrobial resistance genes, such as blaNDM-1, located on the chromosome instead of plasmids. According to the results, there is increasing complexity in the mechanisms of horizontal transmission of resistance, necessitating a comprehensive understanding and implementation of targeted control measures in both hospital and community settings.


Subject(s)
Anti-Bacterial Agents , Bacterial Proteins , Drug Resistance, Multiple, Bacterial , Microbial Sensitivity Tests , Proteus Infections , Proteus mirabilis , Whole Genome Sequencing , beta-Lactamases , Proteus mirabilis/genetics , Proteus mirabilis/drug effects , Proteus mirabilis/enzymology , Proteus mirabilis/isolation & purification , beta-Lactamases/genetics , Humans , Drug Resistance, Multiple, Bacterial/genetics , Anti-Bacterial Agents/pharmacology , Proteus Infections/microbiology , Bacterial Proteins/genetics , Chromosomes, Bacterial/genetics , Genome, Bacterial/genetics , Carbapenems/pharmacology
9.
Microb Pathog ; 193: 106778, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38972366

ABSTRACT

Antimicrobial resistance and biofilm formation by microbial pathogens pose a significant challenge to poultry production systems due to the persistent risk of dissemination and compromise of bird health and productivity. In this context, the study aimed to investigate the occurrence of different multiresistance phenotypes and the biofilm-forming ability of Enterobacteriaceae isolated from broiler chicken excreta in poultry production units in Ceará, Brazil. Samples were collected from three distinct broiler breeding facilities and subjected to isolation, identification, antibiotic susceptibility testing, phenotypic screening for ß-lactamases enzymes, and biofilm formation evaluation. Seventy-one strains were identified, being Escherichia coli (37 %) and Proteus mirabilis (32 %), followed by Klebsiella pneumoniae (11 %), Providencia stuartii (9 %), Klebsiella aerogenes (6 %), Alcaligenes faecalis (4 %), and Salmonella sp. (1 %). A significant proportion (87 %) of multiresistant strains were detected. For the phenotypic evaluation of ß-lactamases production, strains with resistance to second and third-generation cephalosporins and carbapenems were tested. About 4 of 6 and 10 of 26 were positive for inducible chromosomal AmpC ß-lactamase and extended-spectrum ß-lactamase (ESBL), respectively. Regarding biofilm formation, it was observed that all MDR strains were capable of forming biofilm. In this sense the potential of these MDR bacteria to develop biofilms becomes a significant concern, representing a real threat to both human and animal health, as biofilms offer stability, antimicrobial protection, and facilitate genetic transfer.


Subject(s)
Anti-Bacterial Agents , Biofilms , Chickens , Drug Resistance, Multiple, Bacterial , Enterobacteriaceae , Farms , Feces , Microbial Sensitivity Tests , beta-Lactamases , Animals , Biofilms/growth & development , Biofilms/drug effects , Brazil , beta-Lactamases/genetics , beta-Lactamases/metabolism , Feces/microbiology , Enterobacteriaceae/drug effects , Enterobacteriaceae/isolation & purification , Enterobacteriaceae/genetics , Anti-Bacterial Agents/pharmacology , Chickens/microbiology , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Poultry/microbiology , Enterobacteriaceae Infections/microbiology , Enterobacteriaceae Infections/veterinary
10.
Microb Pathog ; : 106728, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38906492

ABSTRACT

OBJECTIVES: Severe infection caused by Carbapenem-resistant Enterobacteriaceae (CRE) is a challenge for clinical anti-infective therapy, and clinical intervention to improve control of CRE is of great significance. The study aims to determine the molecular epidemiology and risk factors of CRE infections to provide evidence for effective control of nosocomial infection in patients with CRE. METHODS: A total of 192 non-repetitive CRE strains were collected from January 2020 to December 2021 in Northwest China. To explore the risk factors of CRE infection by univariate and Logistic regression analysis, 1:1 case-control study was used to select Carbapenem sensitive Enterobacteriaceae (CSE) infection patients at the same period as the control group. RESULTS: Among the 192 CRE strains, the most common isolates included Klebsiella pneumoniae (Kpn) and Enterobacter cloacae (Ecl). The CRE strain showed the lowest rate of resistance to amikacin at 58.3. 185 CRE strains carried carbapenemase resistance genes of concern in this study. KPC-2 (n=94) was the most common carbapenemase, followed by NDM-1 (n=69), NDM-5 (n=22) and IMP-4 (n=5). OXA-48 and VIM were not detected. And KPC-2 was the most common in all strains. Logistic regression analysis implicated days of invasive ventilator-assisted ventilation (OR=1.452; 95 % CI 1.250~1.686), antibiotic combination therapy (OR=2.149; 95 % CI 1.128~4.094), hypoalbuminemia (OR=6.137; 95 % CI 3.161~11.913), history of immunosuppressant use (OR=25.815; 95 % CI 6.821~97.706) and days of hospitalization (OR=1.020; 95 % CI 1.006~1.035) as independent risk factors associated with CRE infection. Age (OR=0.963; 95% CI 0.943~0.984) and history of hormone use (OR=0.119; 95 % CI 0.028~0.504) were protective factors for CRE infection (P < 0.05). CONCLUSIONS: The resistance of commonly used antibiotics in clinical is severe, and CRE strains mainly carry KPC-2 and NDM-1. Multiple risk factors for CRE infection and their control can effectively prevent the spread of CRE.

11.
Article in English | MEDLINE | ID: mdl-38652096

ABSTRACT

A Gram-negative, motile, rod-shaped bacterial strain, CA-0114T, was isolated from the midgut of a western honey bee, Apis mellifera. The isolate exhibited ≤96.43 % 16S rRNA gene sequence identity (1540 bp) to members of the families Enterobacteriaceae and Erwiniaceae. Phylogenetic trees based on genome blast distance phylogeny and concatenated protein sequences encoded by conserved genes atpD, fusA, gyrB, infB, leuS, pyrG and rpoB separated the isolate from other genera forming a distinct lineage in the Enterobacteriaceae. In both trees, the closest relatives were Tenebrionicola larvae YMB-R21T and Tenebrionibacter intestinalis BIT-L3T, which were isolated previously from Tenebrio molitor L., a plastic-eating mealworm. Digital DNA-DNA hybridization, orthologous average nucleotide identity and average amino acid identity values between strain CA-0114T and the closest related members within the Enterobacteriaceae were ≤23.1, 75.45 and 76.04 %, respectively. The complete genome of strain CA-0114T was 4 451669 bp with a G+C content of 52.12 mol%. Notably, the apparent inability of strain CA-0114T to ferment d-glucose, inositol and l-rhamnose in the API 20E system is unique among closely related members of the Enterobacteriaceae. Based on the results obtained through genotypic and phenotypic analysis, we propose that strain CA-0114T represents a novel species and genus within the family Enterobacteriaceae, for which we propose the name Apirhabdus apintestini gen. nov., sp. nov. (type strain CA-0114T=ATCC TSD-396T=DSM 116385T).


Subject(s)
Bacterial Typing Techniques , Base Composition , DNA, Bacterial , Enterobacteriaceae , Fatty Acids , Nucleic Acid Hybridization , Phylogeny , RNA, Ribosomal, 16S , Sequence Analysis, DNA , Animals , Bees/microbiology , RNA, Ribosomal, 16S/genetics , Enterobacteriaceae/classification , Enterobacteriaceae/isolation & purification , Enterobacteriaceae/genetics , DNA, Bacterial/genetics , Fatty Acids/analysis , Genome, Bacterial
12.
Int Microbiol ; 2024 Mar 22.
Article in English | MEDLINE | ID: mdl-38517580

ABSTRACT

Phage therapy has recently been revitalized in the West with many successful applications against multi-drug-resistant bacterial infections. However, the lack of geographically diverse bacteriophage (phage) genomes has constrained our understanding of phage diversity and its genetics underpinning host specificity, lytic capability, and phage-bacteria co-evolution. This study aims to locally isolate virulent phages against uropathogenic Escherichia coli (E. coli) and study its phenotypic and genomic features. Three obligately virulent Escherichia phages (øEc_Makalu_001, øEc_Makalu_002, and øEc_Makalu_003) that could infect uropathogenic E. coli were isolated and characterized. All three phages belonged to Krischvirus genus. One-step growth curve showed that the latent period of the phages ranged from 15 to 20 min, the outbreak period ~ 50 min, and the burst size ranged between 74 and 127 PFU/bacterium. Moreover, the phages could tolerate a pH range of 6 to 9 and a temperature range of 25-37 °C for up to 180 min without significant loss of phage viability. All phages showed a broad host spectrum and could lyse up to 30% of the 35 tested E. coli isolates. Genomes of all phages were approximately ~ 163 kb with a gene density of 1.73 gene/kbp and an average gene length of ~ 951 bp. The coding density in all phages was approximately 95%. Putative lysin, holin, endolysin, and spanin genes were found in the genomes of all three phages. All phages were strictly virulent with functional lysis modules and lacked any known virulence or toxin genes and antimicrobial resistance genes. Pre-clinical experimental and genomic analysis suggest these phages may be suitable candidates for therapeutic applications.

13.
Infection ; 52(1): 19-28, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37878197

ABSTRACT

OBJECTIVE: Carbapenem-resistant Enterobacteriaceae (CRE) pose a significant threat to human health and have emerged as a major public health concern. We aimed to compare the efficacy and the safety of ceftazidime-avibactam (CAZ-AVI) and polymyxin in the treatment of CRE infections. METHODS: A systematic review and meta-analysis was performed by searching the databases of EMBASE, PubMed, and the Cochrane Library. Published studies on the use of CAZ-AVI and polymyxin in the treatment of CRE infections were collected from the inception of the database until March 2023. Two investigators independently screened the literature according to the inclusion and exclusion criteria, evaluated the methodological quality of the included studies and extracted the data. The meta-analysis was performed using RevMan 5.4 software. RESULTS: Ten articles with 833 patients were included (CAZ-AVI 325 patients vs Polymyxin 508 patients). Compared with the patients who received polymyxin-based therapy, the patients who received CAZ-AVI therapy had significantly lower 30-days mortality (RR = 0.49; 95% CI 0.01-2.34; I2 = 22%; P < 0.00001), higher clinical cure rate (RR = 2.70; 95% CI 1.67-4.38; I2 = 40%; P < 0.00001), and higher microbial clearance rate (RR = 2.70; 95% CI 2.09-3.49; I2 = 0%; P < 0.00001). However, there was no statistically difference in the incidence of acute kidney injury between patients who received CAZ-AVI and polymyxin therapy (RR = 1.38; 95% CI 0.69-2.77; I2 = 22%; P = 0.36). In addition, among patients with CRE bloodstream infection, those who received CAZ-AVI therapy had significantly lower mortality than those who received polymyxin therapy (RR = 0.44; 95% CI 0.27-0.69, I2 = 26%, P < 0.00004). CONCLUSIONS: Compared to polymyxin, CAZ-AVI demonstrated superior clinical efficacy in the treatment of CRE infections, suggesting that CAZ-AVI may be a superior option for CRE infections.


Subject(s)
Azabicyclo Compounds , Carbapenem-Resistant Enterobacteriaceae , Enterobacteriaceae Infections , Humans , Anti-Bacterial Agents/therapeutic use , Polymyxins/therapeutic use , Enterobacteriaceae Infections/drug therapy , Microbial Sensitivity Tests , Ceftazidime/therapeutic use , Drug Combinations
14.
Infection ; 52(1): 155-163, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37608043

ABSTRACT

PURPOSE: Enterobacteriaceae (EB) bloodstream infections (BSI) are frequent and serious in older patients. Physicians are faced with the dilemma of prescribing early appropriate empirical antibiotics to limit the risk of death, and sparing broad-spectrum antibiotic prescription. The aim of the study was to assess the rate of appropriate empirical antibiotics prescription to treat EB BSI in older patients and its impact on survival. METHODS: This study conducted in 49 centres enrolled retrospectively up to the 10 last consecutive patients aged 75 years and over and treated for EB BSI. Factors related to in-hospital death were investigated using logistic regression. RESULTS: Among the 487 enrolled patients (mean age 86 ± 5.9 years), 70% had at least one risk factor of being infected by third-generation cephalosporins (3GC)-resistant strain; however, only 13.8% of EB strains were resistant to 3GC. An empirical antimicrobial treatment was initiated for 418 patients (85.8%), and for 86% (n = 360/418) of them, it was considered appropriate. In-hospital mortality was 12.7% (n = 62) and was related to the severity of infection (OR 3.17, CI 95% 1.75-5.75), while a urinary portal of entry was protective (OR 0.34, CI 95% 0.19-0.60). Neither the absence of nor inappropriate empirical antibiotics prescription was associated with increased mortality. CONCLUSION: While patients enrolled in this study were at risk of being infected by multidrug-resistant bacteria, yet mainly treated with 3GC, empirical antibiotics prescription was appropriate in most cases and did not influence mortality.


Subject(s)
Bacteremia , Enterobacteriaceae Infections , Sepsis , Humans , Aged , Aged, 80 and over , Enterobacteriaceae , Retrospective Studies , Hospital Mortality , Enterobacteriaceae Infections/drug therapy , Enterobacteriaceae Infections/microbiology , Anti-Bacterial Agents/therapeutic use , Sepsis/microbiology , Bacteremia/microbiology
15.
Avian Pathol ; 53(2): 115-123, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38096268

ABSTRACT

RESEARCH HIGHLIGHTS: Large number of bacteria isolated from femoral heads of clinically healthy broilers.The prevailing taxa in femoral heads were Escherichia/Shigella and Enterococcus spp.Continuous presence of bacteria in blood and liver of clinically healthy broilers.Enterobacteriaceae, Enterococcaceae, and Staphylococcaceae prevail in blood and liver.


Subject(s)
Femur Head , Poultry Diseases , Humans , Animals , Enterobacteriaceae , Chickens , Enterococcaceae , Bacteria , Poultry Diseases/microbiology
16.
Anal Bioanal Chem ; 416(10): 2465-2478, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38383664

ABSTRACT

Carbapenem-resistant Enterobacteriaceae (CRE) is a major pathogen that poses a serious threat to human health. Unfortunately, currently, there are no effective measures to curb its rapid development. To address this, an in-depth study on the surface-enhanced Raman spectroscopy (SERS) of 22 strains of 7 categories of CRE using a gold silver composite SERS substrate was conducted. The residual networks with an attention mechanism to classify the SERS spectrum from three perspectives (pathogenic bacteria type, enzyme-producing subtype, and sensitive antibiotic type) were performed. The results show that the SERS spectrum measured by the composite SERS substrate was repeatable and consistent. The SERS spectrum of CRE showed varying degrees of species differences, and the strain difference in the SERS spectrum of CRE was closely related to the type of enzyme-producing subtype. The introduced attention mechanism improved the classification accuracy of the residual network (ResNet) model. The accuracy of CRE classification for different strains and enzyme-producing subtypes reached 94.0% and 96.13%, respectively. The accuracy of CRE classification by pathogen sensitive antibiotic combination reached 93.9%. This study is significant for guiding antibiotic use in CRE infection, as the sensitive antibiotic used in treatment can be predicted directly by measuring CRE spectra. Our study demonstrates the potential of combining SERS with deep learning algorithms to identify CRE without culture labels and classify its sensitive antibiotics. This approach provides a new idea for rapid and accurate clinical detection of CRE and has important significance for alleviating the rapid development of resistance to CRE.


Subject(s)
Carbapenem-Resistant Enterobacteriaceae , Deep Learning , Humans , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Silver/chemistry , Spectrum Analysis, Raman/methods
17.
Crit Care ; 28(1): 66, 2024 03 01.
Article in English | MEDLINE | ID: mdl-38429791

ABSTRACT

Molecular oxygen is typically delivered to patients via oxygen inhalation or extracorporeal membrane oxygenation (ECMO), potentially resulting in systemic hyperoxia from liberal oxygen inhalation or localized hyperoxia in the lower body from peripheral venoarterial (VA) ECMO. Consequently, this exposes the gastrointestinal tract to excessive oxygen levels. Hyperoxia can trigger organ damage due to the overproduction of reactive oxygen species and is associated with increased mortality. The gut and gut microbiome play pivotal roles in critical illnesses and even small variations in oxygen levels can have a dramatic influence on the physiology and ecology of gut microbes. Here, we reviewed the emerging preclinical evidence which highlights how excessive inhaled oxygen can provoke diffuse villous damage, barrier dysfunction in the gut, and gut dysbiosis. The hallmark of this dysbiosis includes the expansion of oxygen-tolerant pathogens (e.g., Enterobacteriaceae) and the depletion of beneficial oxygen-intolerant microbes (e.g., Muribaculaceae). Furthermore, we discussed potential impact of oxygen on the gut in various underlying critical illnesses involving inspiratory oxygen and peripheral VA-ECMO. Currently, the available findings in this area are somewhat controversial, and a consensus has not yet to be reached. It appears that targeting near-physiological oxygenation levels may offer a means to avoid hyperoxia-induced gut injury and hypoxia-induced mesenteric ischemia. However, the optimal oxygenation target may vary depending on special clinical conditions, including acute hypoxia in adults and neonates, as well as particular patients undergoing gastrointestinal surgery or VA-ECMO support. Last, we outlined the current challenges and the need for future studies in this area. Insights into this vital ongoing research can assist clinicians in optimizing oxygenation for critically ill patients.


Subject(s)
Hyperoxia , Adult , Infant, Newborn , Humans , Hyperoxia/complications , Critical Illness/therapy , Dysbiosis , Oxygen/adverse effects , Hypoxia
18.
J Appl Microbiol ; 135(10)2024 Oct 03.
Article in English | MEDLINE | ID: mdl-39327002

ABSTRACT

AIMS: Plant-based alternatives to meat and dairy products have become increasingly popular in the UK. Despite a public perception that they have a relatively low microbiological risk, outbreaks of illness have been linked with these foods. This study aimed to assess the microbiological safety and quality of vegan alternatives to dairy and meat products available in England. METHODS AND RESULTS: Samples were collected between September 2022 and March 2023 from retail, production, and catering premises, and tested for a range of bacterial pathogens and hygiene indicators using standard procedures. A total of 937 samples were tested, of which 92% were of a satisfactory microbiological quality, 3% were borderline, and 5% were unsatisfactory. Those interpreted as unsatisfactory were due to elevated counts of Enterobacteriaceae and Escherichia coli (indicators of poor hygiene) rather than pathogenic microorganisms. Listeria monocytogenes was present in five samples of tofu, all from the same producer (all at counts of <100 CFU g-1), while other Listeria species were detected at counts of <20 CFU g-1 in two burgers and two 'vegan chicken' products. The majority of samples did not have pH and water activity values that would significantly contribute to preventing microbial growth: 62.4% had pH > 5.0 and 82.4% had Aw > 0.94. CONCLUSIONS: The majority of vegan products examined were of a satisfactory quality, but results demonstrate that microbiological control must be maintained using appropriate processing and storage temperatures, and application of a safe length of shelf life.


Subject(s)
Food Microbiology , Meat Products , England , Meat Products/microbiology , Enterobacteriaceae/isolation & purification , Dairy Products/microbiology , Escherichia coli/isolation & purification , Listeria monocytogenes/isolation & purification , Animals , Food Contamination/analysis , Food Safety , Diet, Vegetarian , Colony Count, Microbial
19.
Can J Microbiol ; 70(2): 63-69, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38063167

ABSTRACT

This study shows how wild fishes from urbanized rivers could be involved in the spread of antibiotic-resistant Enterobacterales. Antibiotic resistance profiles and molecular detection of clinical integron (IntI1) were carried out on 105 Enterobacterales isolated from 89 wildfish (skin or gut) belonging to 8 species. The proportion of isolates resistant to at least one antibiotic was independent of fish species and reached 28.3% within the Escherichia coli (E. coli) population and 84.7% in the non-E.coli Enterobacterales. Bacteria involved in nosocomial infections were isolated, such as E. coli, Klebsiella, and Enterobacter, as well as the environmental bacteria (Lelliottia, Butiauxella, and Kluyvera).


Subject(s)
Anti-Bacterial Agents , Escherichia coli , Animals , Anti-Bacterial Agents/pharmacology , Escherichia coli/genetics , Rivers/microbiology , Enterobacteriaceae/genetics , Bacteria , Fishes , Microbial Sensitivity Tests , beta-Lactamases
20.
Lett Appl Microbiol ; 77(9)2024 Sep 02.
Article in English | MEDLINE | ID: mdl-39227173

ABSTRACT

Colistin resistance poses a major therapeutic challenge and resistant strains have now been reported worldwide. However, the occurrence of such bacteria in aquatic environments is considerably less understood. This study aimed to isolate and characterize colistin-resistant strains from water and plastic litter collected in an urban recreational estuary. Altogether, 64 strains with acquired colistin resistance were identified, mainly Acinetobacter spp. and Enterobacter spp. From these, 40.6% were positive for at least one mcr variant (1-9), 26.5% harbored, extended-spectrum beta-lactamases, 23.4% harbored, sulfonamide resistance genes, and 9.3% harbored, quinolone resistance genes. merA, encoding mercury resistance, was detected in 10.5% of these strains, most of which were also strong biofilm producers. The minimum inhibitory concentration toward colistin was determined for the mcr-positive strains and ranged from 2 to ≥512 µg ml-1. Our findings suggest that Gram-negative bacteria highly resistant to a last-resort antimicrobial can be found in recreational waters and plastic litter, thereby evidencing the urgency of the One Health approach to mitigate the antimicrobial resistance crisis.


Subject(s)
Anti-Bacterial Agents , Colistin , Drug Resistance, Bacterial , Estuaries , Microbial Sensitivity Tests , Plastics , Colistin/pharmacology , Anti-Bacterial Agents/pharmacology , Water Microbiology , Bacteria/genetics , Bacteria/drug effects , Bacteria/isolation & purification , Bacteria/classification , Gram-Negative Bacteria/drug effects , Gram-Negative Bacteria/genetics , Gram-Negative Bacteria/isolation & purification
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