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2.
Heliyon ; 10(16): e35816, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39253247

RESUMO

Objectives: To evaluate the accuracy of beta-lactamase gene detection directly from urine samples by Nanopore sequencing. Methods: DNA was extracted from bacterial pellets in spun urine. The purified DNA was then sequenced in native form by a Nanopore sequencer (MinION) to identify the organisms and beta-lactamase genes. Results were compared to routine urine cultures and standard antimicrobial susceptibility tests (AST). Results: We processed 60 urine samples of which routine cultures grew Enterobacteriaceae, including 28 carbapenem-resistant (CRE), 17 extended-spectrum beta-lactamase (ESBL) or AmpC producing, and 15 non-ESBL/AmpC phenotypes. We excluded 7 samples with extremely low DNA amounts (<1 ng/µl) for a final case of 53 in total. The sensitivity of antimicrobial resistance gene detection within 6 h, the optimal duration from real-time simulation, of Nanopore sequencing for the diagnosis of carbapenem-resistant and ceftriaxone-resistant phenotypes was 73.9 % (95%CI 56.0-91.9 %) and 81.1 % (95%CI 68.5-93.7 %), while the specificity was 96.7 % (95%CI 90.2-100.0 %) and 56.3 % (95%CI 31.9-80.6 %), respectively. The median times for MinION to generate DNA reads containing carbapenemase and ESBL/AmpC genes were 93 min (IQR 17-245.5) and 99 min (IQR 31.25-269.75) after sequencing commencement, respectively. Conclusions: Nanopore sequencing can identify bacterial genotypic resistance in urine and may enable clinicians to adjust antimicrobial therapy earlier than routine AST.

3.
Int J Mol Sci ; 25(17)2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39273526

RESUMO

Antimicrobial resistance is increasingly concerning, causing millions of deaths and a high cost burden. Given that carbapenemase-producing Enterobacterales are particularly concerning due to their ability to develop structural modifications and produce antibiotic-degrading enzymes, leading to high resistance levels, we sought to summarize the available data on the efficacy and safety regarding the combination of meropenem-vaborbactam (MV) versus the best available therapy (BAT). Articles related to our objective were searched in the PubMed and Scopus databases inception to July 2024. To assess the quality of the studies, we used the Cochrane risk-of-bias tool, RoB2. The outcomes were pooled as a risk ratio (RR) and a 95% confidence interval (95%CI). A total of four published studies were involved: one retrospective cohort study and three phase 3 trials, including 432 patients treated with MV and 426 patients treated with BAT (mono/combination therapy with polymyxins, carbapenems, aminoglycosides, colistin, and tigecycline; or ceftazidime-avibactam; or piperacillin-tazobactam). No significant difference in the clinical response rate was observed between MV and the comparators at the TOC (RR = 1.29, 95%CI [0.92, 1.80], p = 0.14) and EOT (RR = 1.66, 95%CI [0.58, 4.76], p = 0.34) visits. MV was associated with a similar microbiological response as the comparators at TOC (RR = 1.63, 95%CI [0.85, 3.11], p = 0.14) and EOT assessment (RR = 1.16, 95%CI [0.88, 1.54], p = 0.14). In the pooled analysis of the four studies, 28-day all-cause mortality was lower for MV than the control groups (RR = 0.47, 95%CI [0.24, 0.92], p = 0.03). MV was associated with a similar risk of adverse events (AEs) as comparators (RR = 0.79, 95%CI [0.53, 1.17], p = 0.23). Additionally, MV was associated with fewer renal-related AEs than the comparators (RR = 0.32, 95%CI [0.15, 0.66], p = 0.002). MV was associated with a similar risk of treatment discontinuation due to AEs (RR = 0.76, 95%CI [0.38, 1.49], p = 0.42) or drug-related AEs (RR = 0.56, 95%CI [0.28, 1.10], p = 0.09) as the comparators. In conclusion, MV presents a promising therapeutic option for treating CRE infections, demonstrating similar clinical and microbiological responses as other comparators, with potential advantages in mortality outcomes and renal-related AEs.


Assuntos
Antibacterianos , Ácidos Borônicos , Enterobacteriáceas Resistentes a Carbapenêmicos , Combinação de Medicamentos , Infecções por Enterobacteriaceae , Meropeném , Humanos , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Meropeném/uso terapêutico , Meropeném/farmacologia , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Antibacterianos/efeitos adversos , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Enterobacteriaceae/microbiologia , Ácidos Borônicos/uso terapêutico , Resultado do Tratamento , Carbapenêmicos/uso terapêutico , Carbapenêmicos/farmacologia , Compostos Heterocíclicos com 1 Anel
4.
IJID Reg ; 12: 100407, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39220204

RESUMO

Objectives: This study aims to provide lacking data on antibiotics and treatment strategies used in the management of carbapenem-resistant Enterobacteriaceae (CRE) infections in Nigeria. Methods: A cross-sectional study was carried out at the University College Hospital in Ibadan. CRE isolated from routine culture of specimens from hospitalized patients from December 2021 to September 2022 was identified. Treatment information and other data were collected from the patients' medical records. Results: The hospital laboratory isolated CRE from 55 patients during the study period and 27 (49.1%) of them had data available for the study. The most frequently isolated CRE was Klebsiella spp. (13 of 27, 48.1%). Of the 24 patients who received empiric antibiotics, only two (8.3%) of their CRE isolates were susceptible. After receiving culture results, 18 (66.7%) patients were treated with at least one antibiotic, to which resistance was documented. Only three (11.1%) patients overall commenced or remained on an antibiotic, to which their CRE isolate was susceptible. Conclusions: Despite culture data, we found a high prevalence of drug-pathogen mismatch in CRE treatment, including new or persistent use of antibiotics, to which resistance was documented. Antimicrobial stewardship efforts need to be strengthened to specifically address CRE treatment and effective antibiotics need to be made accessible.

5.
J Biosci Bioeng ; 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39244484

RESUMO

Plasmids are molecular genetic tools used for trans-complementation and gene expression in bacteria. Challenges faced by researchers include limited repertoire of antibiotic resistance of plasmids, issues related to plasmid compatibility and restricted or incompatible multiple cloning sites when needing to change plasmid copy number to tune production of their protein of interest. In this study, a series of plasmids were generated with compatible multiple cloning sites and homologous DNA regions to allow for modular cloning for rapid exchange of antibiotic resistance and plasmid origin. Plasmids generated in this series have options for high, mid, and low plasmid copy number, and have either an integrated FLAG epitope in the multiple cloning site or possess an uninterrupted multiple cloning site with the option of using the common LacZ-based blue/white screening method. Low copy plasmids also have one of five antibiotic selection markers. To demonstrate functionality of these plasmids, a representative FLAG tagged protein and mCherry were cloned into the low copy plasmids and expressed in various bacteria belonging to the Enterobacteriaceae family. In conclusion, by creating a new plasmid series, we have expanded the toolkit of available molecular biology tools for bacterial work.

6.
BMC Microbiol ; 24(1): 361, 2024 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-39306658

RESUMO

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.


Assuntos
Antibacterianos , Bactérias , Testes de Sensibilidade Microbiana , Hiperplasia Prostática , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/microbiologia , Antibacterianos/farmacologia , Hiperplasia Prostática/microbiologia , Pessoa de Meia-Idade , Prevalência , Idoso , Nigéria/epidemiologia , Bactérias/efeitos dos fármacos , Bactérias/isolamento & purificação , Bactérias/classificação , Infecções Urinárias/microbiologia , Infecções Urinárias/epidemiologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/isolamento & purificação , Klebsiella/efeitos dos fármacos , Klebsiella/isolamento & purificação , Proteus mirabilis/efeitos dos fármacos , Proteus mirabilis/isolamento & purificação , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/isolamento & purificação
7.
BMC Microbiol ; 24(1): 360, 2024 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-39306662

RESUMO

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.


Assuntos
Antibacterianos , Infecções por Enterobacteriaceae , Enterobacteriaceae , Testes de Sensibilidade Microbiana , Infecções Urinárias , beta-Lactamases , Humanos , Infecções Urinárias/microbiologia , Infecções Urinárias/tratamento farmacológico , Feminino , Pessoa de Meia-Idade , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Masculino , beta-Lactamases/metabolismo , Idoso , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/enzimologia , Enterobacteriaceae/isolamento & purificação , Infecções por Enterobacteriaceae/microbiologia , Infecções por Enterobacteriaceae/tratamento farmacológico , Adulto , Adulto Jovem , Idoso de 80 Anos ou mais , Adolescente , Nitrofurantoína/farmacologia , Nitrofurantoína/uso terapêutico , Prevalência , Escherichia coli/efeitos dos fármacos , Escherichia coli/isolamento & purificação , Escherichia coli/enzimologia
9.
Lett Appl Microbiol ; 77(9)2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39227173

RESUMO

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.


Assuntos
Antibacterianos , Colistina , Farmacorresistência Bacteriana , Estuários , Testes de Sensibilidade Microbiana , Plásticos , Colistina/farmacologia , Antibacterianos/farmacologia , Microbiologia da Água , Bactérias/genética , Bactérias/efeitos dos fármacos , Bactérias/isolamento & purificação , Bactérias/classificação , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/genética , Bactérias Gram-Negativas/isolamento & purificação
10.
Microbiol Spectr ; : e0036124, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39287384

RESUMO

In this study, the genomes of 22 Enterobacteriaceae isolates from fresh produce and herbs obtained from retail markets in northern Germany were completely sequenced with MiSeq short-read and MinION long-read sequencing and assembled using a Unicycler hybrid assembly. The data showed that 17 of the strains harbored between one and five plasmids, whereas in five strains, only the circular chromosomal DNA was detected. In total, 38 plasmids were identified. The size of the plasmids detected varied between ca. 2,000 and 326,000 bp, and heavy metal resistance genes were found on seven (18.4%) of the plasmids. Eleven plasmids (28.9%) showed the presence of antibiotic resistance genes. Among large plasmids (>32,000 bp), IncF plasmids (specifically, IncFIB and IncFII) were the most abundant replicon types, while all small plasmids were Col-replicons. Six plasmids harbored unit and composite transposons carrying antibiotic resistance genes, with IS26 identified as the primary insertion sequence. Class 1 integrons carrying antibiotic resistance genes were also detected on chromosomes of two Citrobacter isolates and on four plasmids. Mob-suite analysis revealed that 36.8% of plasmids in this study were found to be conjugative, while 28.9% were identified as mobilizable. Overall, our study showed that Enterobacteriaceae from fresh produce possess antibiotic resistance genes on both chromosome and plasmid, some of which are considered to be transferable. This indicates the potential for Enterobacteriaceae from fresh produce that is usually eaten in the raw state to contribute to the transfer of resistance genes to bacteria of the human gastrointestinal system. IMPORTANCE: This study showed that Enterobacteriaceae from raw vegetables carried plasmids ranging in size from 2,715 to 326,286 bp, of which about less than one-third carried antibiotic resistance genes encoding resistance toward antibiotics such as tetracyclines, aminoglycosides, fosfomycins, sulfonamides, quinolones, and ß-lactam antibiotics. Some strains encoded multiple resistances, and some encoded extended-spectrum ß-lactamases. The study highlights the potential of produce, which may be eaten raw, as a potential vehicle for the transfer of antibiotic-resistant bacteria.

11.
J Appl Microbiol ; 2024 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-39327002

RESUMO

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 E. coli (indicators of poor hygiene) rather than pathogenic micro-organisms. 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.

12.
Chin Med ; 19(1): 130, 2024 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-39327592

RESUMO

BACKGROUND: Qin-Yu-Qing-Chang decoction (QYQC), an herbal formula from China, is extensively employed to manage ulcerative colitis (UC) and exhibits potential benefits for colonic function. Nevertheless, the fundamental molecular mechanisms of QYQC remain largely uncharted. METHODS: The primary constituents of QYQC were determined utilizing UHPLC-MS/MS analysis and the effectiveness of QYQC was assessed in a mouse model of colitis induced by dextran sulfate sodium. Evaluations of colon inflammatory responses and mucosal barrier function were thoroughly assessed. RNA sequencing, molecular docking, colonic energy metabolism, and 16S rRNA sequencing analysis were applied to uncover the complex mechanisms of QYQC in treating UC. Detect the signal transduction of the peroxisome proliferator-activated receptor-γ (PPAR-γ) both in the nucleus and cytoplasm. Furthermore, a PPAR-γ antagonist was strategically utilized to confirm the functional targets that QYQC exerts. RESULTS: Utilizing UHPLC-MS/MS, the principal constituents of the nine traditional Chinese medicinal herbs comprising QYQC were systematically identified. QYQC treatment substantially ameliorated colitis in mice, as evidenced by the improvement in symptoms and the reduction in colonic pathological injuries. Besides, QYQC treatment mitigated the inflammatory response and improved mucosal barrier function. Furthermore, QYQC enhanced the mitochondria citrate cycle (TCA cycle) by triggering PPAR-γ signaling and increasing the proportion of PPAR-γ entering the nucleus. This prevented the unconstrained expansion of facultative anaerobes, particularly pathogenic Escherichia coli (E. coli, family Enterobacteriaceae) and thus improved colitis. Results of molecular docking indicated that the representative chemical components of QYQC including Baicalin, Paeoniflorin, Mollugin, and Imperatorin bound well with PPAR-γ. The impact of QYQC on colitis was diminished in the presence of a PPAR-γ antagonist. CONCLUSIONS: In summary, QYQC ameliorates UC by activating PPAR-γ signaling and increasing the proportion of PPAR-γ entering the nucleus, which enhances the energy metabolism of intestinal epithelial cells and thereby preventing the uncontrolled proliferation of facultative anaerobes.

13.
Cureus ; 16(8): e67885, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39328654

RESUMO

Background Ear infections encompass otitis media (OM) which is a significant cause of hearing loss and otitis externa (OE) which may affect the surrounding tissues leading to serious complications. This study reports the common pathogens causing ear infections. Methods Microbiological, clinical, and demographic data of ear-infected patients who visited King Fahad Hospital in Al-Baha, Saudi Arabia, during the period from January 2019 to June 2023 were enrolled in this study. Result  This study enrolled 307 patients aged 1-94 years, with a median age of 40 years (IQR=22-57). Overall, the detectable infection rate was 81.1% (n=249), while 18.9% (n=58) had no identified aetiology. Of all isolates, 178 (58%) were bacterial, while 71 (23.1%) were fungal. Staphylococcus aureus (S. aureus) followed by Pseudomonas aeruginosa (P. aeruginosa), Enterobacteriaceae, andcoagulase-negative Staphylococcus (CoNS) were the main bacterial isolates. Of the total 63 S. aureus isolates, 21 (33%) were methicillin-resistant (MRSA). A cohort of 227 subjects were diagnosed with either OM (n=178; 79.5%), OE (n=46; 20.5%), or both OM and OE (n=3; 1%). Of those with OM, children constituted 89.1% (41/46) as compared to 75.3% (134/178) of adults (p=0.041). The main isolates from OM patients were S. aureus followed by P. aeruginosa and fungi. Of 49 OE patients, 16 (32.7%) had no identified pathogen, while 15 (30.6%) had fungi, and 13 (29.5%) had P. aeruginosa. Conclusions Ear infections in general were mainly bacterial followed by fungal with a considerable proportion of unidentified aetiology. A significant proportion of S. aureus isolates were MRSA. S. aureus followed by P. aeruginosa and fungi were the main causes of OM, while fungi followed by P. aeruginosa were the main causes of OE.

14.
Indian J Microbiol ; 64(3): 1215-1221, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39282205

RESUMO

The Cepheid Xpert Carba-R assay has been demonstrated to be reliable for rapid detection of carbapenemase-producing orgnisms (CPO) directly from rectal swabs but the performance of which remains unclear in Asia.We searched PubMed, EMBASE and Cochrane Library databases to identify studies according to predetermined criteria. STATA 13.0 software was used to analyze the tests for sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), area under the summary receiver operating characteristic curves (AUC). QUADAS-2 was used to assess the quality of included studies with RevMan 5.2. A total of 5 unique studies involving 10807 samples met the inclusion criteria. The pooled sensitivity, specificity, PLR, NLR, and the AUC with 95% CIs of Xpert Carba-R were 0.91 (0.72-0.97), 0.99 (0.96-1.00), 71.24 (25.41-199.73), 0.09 (0.03-0.32), 0.99 (0.98-1.00), respectively. Deeks'funnel plot showed no publication bias.The present meta-analysis showed the Xpert Carba-R assay had good sensitivity and perfect specificity for detecting CPOs on rectal swabs.

15.
Cell Host Microbe ; 32(9): 1469-1487.e9, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39197455

RESUMO

Cytotoxic chemotherapies have devastating side effects, particularly within the gastrointestinal tract. Gastrointestinal toxicity includes the death and damage of the epithelium and an imbalance in the intestinal microbiota, otherwise known as dysbiosis. Whether dysbiosis is a direct contributor to tissue toxicity is a key area of focus. Here, from both mammalian and bacterial perspectives, we uncover an intestinal epithelial cell death-Enterobacteriaceae signaling axis that fuels dysbiosis. Specifically, our data demonstrate that chemotherapy-induced epithelial cell apoptosis and the purine-containing metabolites released from dying cells drive the inter-kingdom transcriptional re-wiring of the Enterobacteriaceae, including fundamental shifts in bacterial respiration and promotion of purine utilization-dependent expansion, which in turn delays the recovery of the intestinal tract. Inhibition of epithelial cell death or restriction of the Enterobacteriaceae to homeostatic levels reverses dysbiosis and improves intestinal recovery. These findings suggest that supportive therapies that maintain homeostatic levels of Enterobacteriaceae may be useful in resolving intestinal disease.


Assuntos
Disbiose , Enterobacteriaceae , Microbioma Gastrointestinal , Mucosa Intestinal , Disbiose/induzido quimicamente , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Camundongos , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/metabolismo , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Mucosa Intestinal/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/microbiologia , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacologia , Intestinos/efeitos dos fármacos , Intestinos/microbiologia , Transdução de Sinais , Purinas/metabolismo , Purinas/farmacologia
16.
Microbiol Spectr ; : e0387623, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39162554

RESUMO

Metallo-beta-lactamase (MBL)-producing carbapenem-resistant Enterobacteriaceae (CRE) infections continue to pose a serious threat to healthcare. Due to their unique active site, MBLs evade the activity of many novel beta-lactam/beta-lactamase inhibitor combinations, which have been specifically targeted toward those carbapenemases with serine active sites. Furthermore, resistance to most, if not all, other clinically relevant antimicrobial classes leaves few reliable therapeutic options. Combination therapy has thus played a vital role in the treatment of MBL-producing CRE infections. In this study, we utilized the static time-kill assay to investigate clinically relevant concentrations of cefepime, piperacillin-tazobactam, and meropenem alone and in combination with either amikacin or the novel plazomicin to determine if combinations of routinely used beta-lactam therapy with an aminoglycoside would achieve bactericidal activity against eight clinically isolated Verona integron-encoded MBL (VIM)-producing CRE. Furthermore, we compared this activity to the combination of aztreonam/avibactam, which has shown potent activity against MBL-producing CRE. Both aztreonam/avibactam and meropenem with either aminoglycoside were rapidly bactericidal within 4 hours and remained bactericidal through 24 hours against all isolates with few exceptions. Combinations including cefepime and piperacillin-tazobactam were also rapidly bactericidal, but activity after 24 hours was inconsistent depending upon the partner aminoglycoside and isolate. Further investigation is warranted to elucidate optimal antibiotic exposures against MBL-producing CRE, including novel agents in the pipeline.IMPORTANCECarbapenem-resistant Enterobacterales (CRE) are one of the most pressing antimicrobial-resistant threats at present. In addition to exhibiting resistance to many, if not all, commonly used antimicrobial agents, CRE achieves these resistant phenotypes through a variety of mechanisms, each of which can uniquely affect available treatment options. The present study is an in vitro investigation of several Verona integron-encoded metallo-beta-lactamase (VIM)-producing CRE isolated from patients at our academic medical center. Because metallo-beta-lactamases (MBLs) are inherently resistant to many of the novel treatments designed to treat CRE due to their different active site composition, we tested several antimicrobial combinations containing routinely utilized broad-spectrum beta-lactams and aminoglycosides. Our results further our understanding of combination therapy options against VIM-producing CRE, including with non-carbapenem-beta-lactams cefepime and piperacillin. By optimizing combinations of existing antimicrobial agents, we hope to expand the available armamentarium against these resistant pathogens.

17.
Antimicrob Agents Chemother ; : e0069324, 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39158279

RESUMO

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.

18.
Infect Genet Evol ; 124: 105658, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39168275

RESUMO

The rapid emergence of Extended-spectrum ß-lactamase producing Enterobacteriaceae (ESBL-E) is a major global public health concern. Previous studies have identified that intensive medical care of dogs and cats in veterinary hospitals have accelerated the infections and spread of ESBL-E. To investigate the spread of ESBL-E in a veterinary hospital, a total of 202 samples including hospitalized animals, veterinary healthcare workers and environment were collected from a veterinary hospital in Chengdu, China. ESBL-E were identified by antimicrobial susceptibility testing and 16 s rRNA sequencing and were further conducted on ESBL gene detection and multilocus sequence typing (MLST). At last, strains with transmission potential were analyzed by whole genome sequencing (WGS). Our results showed that the overall prevalence of ESBL-positive isolates was 34.7% (70/202), with 55.3% (26/47) in animals, 29.3% (12/41) in healthcare workers and 28.1% (32/114) in environment swabs. Twenty diverse MLST types were detected, with ST744, ST231 as the most prevalent ones. Transmission chains of two ESBL-E.coli (ST744 blaCTX-M-18, blaTEM-1) from cat_21 to cat_14, and two ESBL-Kp (ST231 blaCTX-M-27, blaTEM-1, blaSHV-1) from cat_20 to cat_37 were further confirmed by WGS. Furthermore, interdisciplinary investigation and cooperation of AMR are needed to better limit the transmissions of high-risk strains and to implement effective public health interventions.


Assuntos
Infecções por Enterobacteriaceae , Enterobacteriaceae , Hospitais Veterinários , Tipagem de Sequências Multilocus , beta-Lactamases , China/epidemiologia , Animais , beta-Lactamases/genética , beta-Lactamases/metabolismo , Enterobacteriaceae/genética , Enterobacteriaceae/enzimologia , Enterobacteriaceae/efeitos dos fármacos , Infecções por Enterobacteriaceae/microbiologia , Infecções por Enterobacteriaceae/epidemiologia , Infecções por Enterobacteriaceae/transmissão , Infecções por Enterobacteriaceae/veterinária , Gatos , Cães , Humanos , Sequenciamento Completo do Genoma , Filogenia , Antibacterianos/farmacologia , Testes de Sensibilidade Microbiana
19.
J Infect Public Health ; 17(10): 102535, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39216133

RESUMO

BACKGROUND: The gut microbiome is made up of a diverse range of bacteria, especially gram-negative bacteria, and is crucial for human health and illness. There is a great deal of interest in the dynamic interactions between gram-negative bacteria and their host environment, especially considering antibiotic resistance. This work aims to isolate gram-negative bacteria that exist in the gut, identify their species, and use resistance-associated gene analysis to define their resistance mechanisms. METHODS: Samples were collected from all patients who had a stool culture at a tertiary care center in Lebanon. Each type of bacteria that was identified from the stool samples was subjected to critical evaluations, and all discovered strains underwent antimicrobial susceptibility testing. Polymerase chain reaction was used to profile the genes for Carbapenem-resistant Enterobacteriaceae (CRE), Extended-spectrum beta-lactamase (ESBL), and that of Pseudomonas aeruginosa strains. RESULTS: Escherichia coli, Klebsiella species, and Pseudomonas aeruginosa turned out to be the predominant microbiota members. Escherichia coli strains had a high frequency of extended-spectrum beta-lactamase genes, with the most discovered gene being bla CTX-M. Additionally, a considerable percentage of isolates had carbapenemase-resistant Enterobacteriaceae genes, suggesting the rise of multidrug-resistant strains. Multidrug resistance genes, such as bla mexR, bla mexB, and bla mexA, were found in strains of Pseudomonas aeruginosa, highlighting the possible difficulties in treating infections brought on by these bacteria. CONCLUSION: The findings highlight the critical importance of effective surveillance and response measures to maintain the effectiveness of antibiotics considering the introduction of multidrug resistance genes in Pseudomonas aeruginosa and ESBL and CRE genes in Escherichia coli.


Assuntos
Antibacterianos , Fezes , Bactérias Gram-Negativas , Testes de Sensibilidade Microbiana , beta-Lactamases , Humanos , Fezes/microbiologia , Líbano , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/isolamento & purificação , Bactérias Gram-Negativas/genética , Antibacterianos/farmacologia , beta-Lactamases/genética , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/isolamento & purificação , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/genética , Farmacorresistência Bacteriana Múltipla/genética , Infecções por Bactérias Gram-Negativas/microbiologia , Feminino , Masculino , Escherichia coli/genética , Escherichia coli/efeitos dos fármacos , Escherichia coli/isolamento & purificação , Adulto , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Enterobacteriáceas Resistentes a Carbapenêmicos/isolamento & purificação , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Farmacorresistência Bacteriana/genética , Centros de Atenção Terciária , Proteínas de Bactérias/genética
20.
J Econ Entomol ; 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39121386

RESUMO

Sterile insect technique (SIT) is a useful strategy for preventing and mitigative establishment of invasive insect species. SIT of the pest tephritid Mediterranean fruit fly, Ceratitis capitata (Wiedemann, 1824)WiedemannWiedemann, has been effective in preventing population establishment in vulnerable agricultural areas of the United States. However, irradiation-induced sterilization can have detrimental impacts resulting in reduced performance metrics. Mediterranean fruit fly males reared for SIT have been shown to have differences in their microbiomes relative to other population sources, which has been postulated to be a factor in how well flies compete with wild conspecifics. To identify baseline performance metrics on the effects of irradiation on the gut microbiome of mass-reared flies in Hawai'i, a study was performed to assess performance metrics and microbiome (bacterial 16S rRNA) variation across multiple timepoints. Mediterranean fruit fly pupae were selected from mass-reared trays intended for release, and paired samples were either irradiated or remained as controls and transported to the laboratory for evaluation. Irradiated flies exhibited fewer successful fliers, more rapid mortality rates, and were less active relative to control nonirradiated flies. Contrary to initial expectations, irradiation did not exert substantial impacts on the composition or diversity of bacterial reads. Samples were primarily comprised of sequences classified as Klebsiella and there were low levels of both read and taxonomic diversity relative to other 16S surveys of medfly. Although this study does not demonstrate a strong effect of irradiation alone on the Mediterranean fruit fly microbiome, there are several explanations for this discrepancy.

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