Microbial drug resistance最新文献

This study investigates two isolates of Salmonella enterica subspecies enterica serovar Enteritidis (S. Enteritidis), designated Sal B and Sal D, isolated from the blood and pleural fluid, respectively, of the same patient. Drug susceptibility testing revealed significant differences: Sal D exhibited greater resistance to ticarcillin/clavulanate, piperacillin/sulbactam, and ciprofloxacin compared with Sal B. Morphologically, Sal B formed rougher and drier colonies than Sal D at 37°C. Sal B demonstrated significantly stronger biofilm-forming ability and higher adhesion capacity to HaCaT cells than Sal D, whereas Sal D showed superior adaptation to acidic conditions (pH 3.0). Virulence assays indicated no significant differences between the isolates, suggesting comparable pathogenic potential. Comparative genomic analysis showed high gene content conservation but identified two nonsynonymous single-nucleotide polymorphisms (nsSNPs) and an insertion in the envZ and siiE genes. These genetic variations may account for the observed differences in drug susceptibility and biological characteristics. Collectively, these findings suggest that S. Enteritidis can undergo adaptive changes in response to distinct host environments, influencing drug resistance, adhesion, and acid resistance. This knowledge may inform future strategies for the treatment and prevention of Salmonella infections.

Antimicrobial resistance (AMR) poses a significant global health threat, with projections indicating it could surpass cancer in mortality rates by 2050 if left unaddressed. Optimizing antimicrobial dosing is critical to mitigate resistance and improve clinical outcomes. Traditional approaches, including population pharmacokinetics (PK) models and Bayesian estimation, are limited by mechanistic hypothesis requirements and complexity. Artificial intelligence (AI) and machine learning (ML) offer transformative solutions by leveraging large datasets to predict drug exposure accurately, refine sampling strategies, and enable real-time dose adjustments through therapeutic drug monitoring. This review highlights the role of ML models, in managing PK and pharmacodynamic variability across diverse patient populations. AI models often equal or outperform traditional methods in achieving therapeutic targets while minimizing toxicity, as demonstrated in some case studies involving ganciclovir, vancomycin, and daptomycin. Despite challenges such as data quality, interpretability, and integration with clinical workflows, AI's dynamic adaptability and precision underscore its potential. Future directions emphasize integrating multi-omics data, developing bedside decision-support tools, and expanding AI applications to broader drug categories and populations. Continued research and clinical validation are essential to harness AI's full potential in advancing precision medicine and combating AMR effectively.

Rapidly growing mycobacteria (RGM) have been causing diseases with an increasing incidence that require long and difficult treatment. In this regard, it is a priority to seek rapid and low-cost optimization of therapeutic alternatives. Thus, our objective is to explore the combined activity between verapamil (VP) and the antimicrobials clarithromycin, amikacin, and clofazimine (CFZ) against Mycobacterium smegmatis, Mycobacterium abscessus subsp. abscessus, Mycobacterium abscessus subsp. massiliense, Mycobacterium abscessus subsp. bolletii, Mycobacterium chelonae, and Mycobacterium fortuitum. According to the checkerboard assay, it was observed that the best combination was between VP and CFZ, with synergistic activity on all tested bacteria. The time-killing assay demonstrated that VP improved the killing of CFZ and extended its inhibitory activity 16 times. In this sense, VP has modulating activity with most of the tested antimicrobials, especially with CFZ, and thus may have potential activity in preventing bacterial resistance that could be pointed out as a model for synergism in attempts at screening molecules for RGM infection treatments.

Background: Emergence and the rising prevalence of extended-spectrum β-lactamases (ESBLs) producing multidrug-resistant Klebsiella spp. is a global concern. Methods: 391 samples were collected from environmental and people in an intensive vegetable cultivation area in eastern China in June 2019. ESBLs-producing Klebsiella spp. were obtained by PCR and strain identification. The resistance genotype and phenotype of the strain were determined by PCR and drug susceptibility test. The number and size of plasmids were determined by pulsed-field gel electrophoresis assays of plasmids. The plasmid of bla_CTX-M was determined by DNA imprinting hybridization, and the transferability of plasmid was understood by plasmid conjugation experiment. Whole-genome sequencing analysis (WGS) was used to obtain other antimicrobial resistance genes, virulence factors, mobile elements, and genetic environment. Results: Seventeen ESBL-producing Klebsiella spp. were multi-drug resistant. Sixteen ESBLs-producing Klebsiella spp. carried the bla_CTX-M, and the size of the plasmid containing the bla_CTX-M anged from ∼33.3 kb to ∼244.4 kb. Thirteen ESBLs-producing Klebsiella spp. carried the bla_CTX-M were successfully transferred to the recipient bacterium through plasmid mediation. Single nucleotide polymorphism analysis showed clonal transmission between river water (J4-J8) and river sediment (J9), in river water (J3) and human feces (J12). WGS showed that all bla_CTX-M were associated with the mobile element Tn3 and/or IS1380 family. All strains carried virulence factors related to adhesion, colonization, and pathogenicity. Conclusion: This study reminds us that antibiotic-resistant bacteria (ARB) from vegetable cultivation environments can spread to human. It is vital to enhance surveillance of the vegetable cultivation area and high vigilance for the risk of ARB movement from the vegetable plantation environment to humans.

Salmonella is a foodborne zoonotic pathogen and a hazard to public health. Surveillance of the prevalence of Salmonella is important. This study sought to understand the population structure, antimicrobial susceptibility, and virulence-associated gene profile of 100 Salmonella, which were randomly selected from clinical foodborne diarrhea fecal samples during 2015 and 2019 in the Jiangsu Province, China. After whole-genome sequencing and in silico analysis, we found that the prevalence of clinical foodborne Salmonella in Jiangsu Province was periodic and that the serotypes were diverse, covering 9 serogroups and 19 serotypes. S. Enteritidis was the most prevalent serotype, followed by S. Typhimurium. A high prevalence of antimicrobial resistance was also observed in this study, nearly half (47/100) of Salmonella isolates were determined to be multidrug-resistant (resistant to ≥3 antimicrobial agents), the antimicrobial resistance genotype and phenotype were associated but not closely related, and antimicrobial resistance differed between the major Salmonella sequence types. Additionally, we found that the virulence-associated gene profile is highly concordant with the serotype. Our work shows the association among serotype, antimicrobial resistance, and virulence gene profile, demonstrating the connection between genotype and phenotype and providing epidemiological data for Salmonella.

Purpose: The aim of the present study was to examine the clinical distribution and antibiotic susceptibility of the Burkholderia cepacia complex (BCC). Methods: The BCC clinical strains were obtained from the First Affiliated Hospital of Zhejiang University School of Medicine in China from January 2019 to January 2024, and hisA gene sequencing was employed for strain identification. The in vitro susceptibility of various antibacterials was measured through the disk diffusion method and the broth microdilution method. Results: A total of 386 strains of BCC were collected. Among them, the most common strains were B. cenocepacia (45.9%), B. multivorans (45.1%), and B. contaminans (7.0%). B. multivorans was the main one in respiratory specimens, whereas B. cenocepacia dominated in blood specimens. B. cenocepacia, B. multivorans, and B. contaminans exhibited a susceptibility over 95% to meropenem and sulfamethoxazole-trimethoprim, whereas varying sensitivities were displayed to levofloxacin, ceftazidime, and minocycline (p < 0.05). Among tetracyclines, eravacycline exhibited the lowest minimum inhibitory concentration 90 (MIC90) values 1 µg/mL for B. cenocepacia, 1 µg/mL for B. multivorans, and 2 µg/mL for B. contaminans. This was followed by tigecycline (MIC90: 2 µg/mL, 2 µg/mL, and 4 µg/mL, respectively), minocycline (MIC90: 8 µg/mL, 2 µg/mL, and 8 µg/mL, respectively), and omadacycline (MIC90: 8 µg/mL, 4 µg/mL, and 16 µg/mL, respectively). Compared with the broth microdilution method, the category agreement (CA) of sulfamethoxazole-trimethoprim and ceftazidime was >95%, and the very major error was <1%, whereas the CA of minocycline and meropenem was <90%. Conclusions: Thus, there are differences in the in vitro antimicrobial susceptibility of different BCC strains, with eravacycline demonstrating lower MIC values compared with tigecycline, minocycline, and omadacycline.

Increasing prevalence of multidrug-resistant infections has rendered the healthcare systems ineffective in managing infectious diseases. Drugs of "last resort" like carbapenems and polymyxins are becoming less effective in the management of antibiotic-resistant Gram-negative bacterial infections, leaving the clinicians with limited choices. Evaluation of the efficacy of other available broad-spectrum antibiotics (belonging to a different class) is warranted as a treatment alternative. The current study was undertaken to evaluate the in vitro antibacterial activity of minocycline and a new drug, omadacycline among carbapenem-resistant Gram-negative bacteria (GNB), isolated from clinical samples (pus and sputum) and to genotypically analyze them. A prospective cross-sectional study was conducted in a 3,200-bedded tertiary care medical center, located in Lucknow in the northern part of India. All the clinical isolates recovered from pus and sputum samples of patients admitted in intensive care units were processed according to the standard protocols. Identification and antibiotic susceptibility testing were performed, and carbapenem-resistant Gram-negative bacteria (CRGNB) showing resistance to minocycline were included in the study. Molecular screening of β-lactamase and tetracycline resistance genes was done by the conventional polymerase chain reaction method. Minimum inhibitory concentration analysis was performed using the broth microdilution technique. Among 700 CRGNB, 15.29% (n = 107/700) were minocycline resistant by disk diffusion method. Genetic analysis demonstrated the presence of tetracycline-resistant genes in about one-third isolates, among which the tet(B) gene was present in 41.12% (n = 44/107). Upon broth microdilution analysis, the overall minimum inhibitory concentration for minocycline was raised, wherein 4.76% (n = 5/107) of our clinical Gram-negative isolates were inhibited at ≤8 mg/L and 15.23% (n = 28/107) were inhibited at ≤16 mg/L. Omadacycline was able to inhibit 13.08% (n = 14/107) of the minocycline-resistant isolates at ≤4 mg/L (susceptible breakpoint for Enterobacterales). Based on the cut-off value proposed, 15.09% (n = 16/107) isolates resistant to minocycline were inhibited by omadacycline. High prevalence of multidrug-resistant bugs entails judicious use of minocycline and omadacycline. The presence of tet genes coexisting with bla_NDM and bla_OXA in our bacterial isolates shows that the resistance pattern in Gram-negative bacilli is regularly evolving, and a fully functional surveillance program across the health care system is needed to prevent the emergence and spread of antimicrobial resistance.

Urinary tract infections (UTIs) are common in small animals, posing significant clinical challenges due to their recurrence and discomfort. This study investigated the bacterial causes and antimicrobial resistance patterns of UTIs in dogs and cats presented to an important Veterinary Teaching Hospital in São Paulo, Brazil, the largest city in Latin America. Samples were collected from 31 dogs and 9 cats via ultrasound-guided cystocentesis. Bacterial cultures were performed, species identification was accomplished with matrix-assisted laser desorption ionization-time of flight mass spectrometry, and antimicrobial susceptibility testing was done using the Kirby-Bauer method. Escherichia coli was the most frequently isolated pathogen, accounting for 27.9% of cases, followed by Staphylococcus pseudintermedius, Proteus mirabilis, and Klebsiella pneumoniae. Ampicillin resistance was observed in 70.4% of enterobacteria, with many E. coli strains exhibiting multidrug resistance. Whole-genome sequencing of an extended-spectrum beta-lactamase-producing uropathogenic Escherichia coli strain from a feline patient was performed; it was identified as ST354, a leading cause of UTIs worldwide in humans and animals, carrying the bla_CTX-M-14 gene and other resistance determinants. Phylogenetic analysis indicated genetic proximity between this strain and others from Brazilian poultry and environmental sources. These findings emphasize the need for antimicrobial resistance surveillance in veterinary UTIs and advocate for stricter antibiotic stewardship to inform diagnostic and therapeutic approaches within a One Health perspective.

Introduction: Infections due to carbapenem-resistant Enterobacteriaceae (CRE) in intensive care units (ICUs) pose a significant threat. Colonization with CRE is a prerequisite for bacterial translocation/infections. This work aimed to determine risk factors for CRE colonization in ICU patients. Methods: To find relevant works, PubMed, EMBASE, and references of eligible studies were systematically searched using appropriate keywords up to September 2023. Odds ratios (ORs) and 95% confidence intervals were used to compare risk factor between CRE colonized cases and CRE noncolonized controls. Results: Twelve studies were included. Previous hospitalization (OR: 2.26), previous ICU stay (OR: 10.33), higher acute physiology and chronic health evaluation (APACHE) II score (mean difference [MD]: 4.38), central venous catheter (OR: 4.07), long-term gastric tube (OR: 3.01), hemodialysis catheter (OR: 3.38), urinary catheter (OR: 2.59), mechanical ventilation (OR: 3.41), endoscopy (OR: 3.37), tracheostomy (OR: 3.46), and exposure to antibiotics such as glycopeptide (OR: 10.68), aminoglycosides (OR: 6.53), tigecycline (OR: 6.87), vancomycin (OR: 5.32), carbapenems (OR: 5.23), cephalosporins (OR: 4.96), metronidazole (OR: 4.82), penicillin (OR: 4.41), and β-lactams/β-lactamase inhibitor (OR: 4.28) are highly associated with CRE colonization. Conclusions: ICU-admitted patients with prior hospitalization, ICU stay, previous antibiotic use, and invasive devices/procedures exposures should be prioritized in the screening strategy for CRE colonization to prevent nosocomial infections.

Aeromonas dhakensis is prevalent in aquatic environments in Taiwan and known for its notable antimicrobial resistance. However, comprehensive pan-genomic studies for this species in Taiwan are limited. This study analyzed 28 clinical A. dhakensis isolates using single-molecule real-time sequencing technology, coupled with diverse databases, to elucidate the whole genomes. The focus was on phylogenetic relatedness, antimicrobial resistance genes, and mobile genetic elements. Genomic analysis and multilocus sequence typing were utilized to identify A. dhakensis strains of heterogeneous origins. The detection of various β-lactamase genes (bla_cphA, bla_imiH, bla_AQU, bla_OXA, bla_TEM-1, bla_TRU-1, and bla_VEB) in clinical A. dhakensis isolates raises concern, especially considering the use of carbapenems and third-generation cephalosporins in patients with severe infections. Notably, most A. dhakensis strains carry chromosome-encoded β-lactamases, including AmpC, metallo-β-lactamase, and oxacillinase, and were susceptible to cefepime in drug susceptibility tests. A. dhakensis strains were also susceptible to aminoglycosides, fluoroquinolones, tigecycline, and trimethoprim/sulfamethoxazole. Three of the 28 A. dhakensis isolates carried plasmids containing an array of drug resistance genes, suggesting this species is likely a recipient or donor of drug resistance genes through horizontal gene transfer. Our findings provide valuable insights into the antimicrobial resistance of A. dhakensis, highlighting the medical implications of its β-lactamase diversity and its potential role in the horizontal gene transfer of drug resistance genes.