Microbial drug resistance最新文献

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.

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.

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.

Supplements with their own beneficial effect on hosts are consumed by us. N-acetyl cysteine (NAC) and Vitamin C (Vit C) are antioxidants and supplements, consumed for their beneficial properties. The present investigation evaluates the effect of their antioxidant property on antibiotic efficacy against Escherichia coli cells from different physiological states, including exponential and stationary-phase, cell aggregates, and in-vitro stress-induced persister cells. Survival was measured in cfu/mL by cfu (colony-forming unit) counting, with efficacy determined by log-fold change in survival by comparing CFUs in antibiotics alone and antibiotic + antioxidant combinations. Fluoroquinolones in the presence of NAC reduced ∼1 log CFUs of log-phase and persister cells, while Vit C reduced CFUs (∼1-3-log increase) of cells from all physiological states. Aminoglycosides results were inconclusive; streptomycin's activity declined (∼1-3-log increase in survival), whereas amikacin's activity potentiated (∼1-log reduction in cfu/mL). Rifampicin's showed reduced activity (∼2-3 log increase in survival) with Vit C in all the states and a ∼1-2 log increase with NAC, especially in cell aggregates and persisters. Beta-lactams activity showed variability, with amoxicillin and ampicillin not being influenced, but ceftriaxone showed significant reduction of efficacy (∼2-3-log increase in survival) in all the treatments. The findings suggest that the overall impact of antioxidants on antibiotic efficacy varies depending on the antibiotic class.

CRISPR-Cas (clustered regularly interspaced short palindromic repeats-CRISPR associated) systems are common among enterococci and may prevent the acquisition of mobile genetic elements carrying antimicrobial resistance genes. In this study, we correlate the presence of CRISPR with genes associated with macrolide resistance and high-level resistance to aminoglycosides (HLR-A) among 216 Enterococcus faecalis and 82 Enterococcus faecium isolates. We used PCR to detect genes associated with macrolide resistance, HLR-A, and type II-A CRISPR elements. We used two-tailed Fisher's exact test to evaluate correlation between CRISPR and resistance genes. One hundred and seven (35.9%) isolates had at least one HLR-A gene; the prevalent genes were aac(6')-Ie-aph(2″)-Ia and ant(6)-Ia found in 61 (57%) and 46 (43%) isolates, respectively. The macrolide resistance genes erm(A) and erm(B) were found in 116 (38.9%) isolates. Overall, 174 (58.4%) isolates had at least one CRISPR element; the predominant one was CRISPR3-Cas (n = 117; 39.2%). The presence of three genes, two related to HLR-A [aph(2″)-Ic and ant(6)-Ia] and one macrolide resistance gene [erm(B)], was associated with the absence of CRISPR (p < 0.05), mainly in E. faecalis lacking CRISPR3-Cas. We observed the association between the absence of CRISPR and the presence of major aminoglycoside and macrolide resistance determinants, contributing to the understanding of the evolution of resistance in enterococci.

This study evaluated the antimicrobial efficacy of electrolyzed water (EW) and chlorine-based disinfectant (CLD) over time, focusing on the impact of pH, free chlorine (FCL), and oxidation-reduction potential (ORP). EW and CLD are commonly used for wound care and surgical instrument disinfection, but their chemical instability limits their use. The study was conducted in the Microbiology Laboratory of the University of Guanajuato, using Escherichia coli ATCC 25922 as the test organism. Disinfectants were maintained at 40°C, with systematic monitoring of pH, FCL, and ORP. Minimum bactericidal concentration was used to assess antimicrobial activity before and after thermal exposure. Statistical analyses included Kruskal-Wallis one-way ANOVA, and the Friedman test. Results showed that the antimicrobial activity of EW depended on FCL concentration, with a significant correlation between the absence of FCL and increased minimum bactericidal concentration (p < 0.01). Disinfectants with alkaline pH demonstrated greater stability over time (p < 0.01). The findings highlight the importance of FCL, pH, and ORP in the effectiveness of these disinfectants and underscore their limitations due to chemical instability in clinical settings.

Methicillin-resistant Staphylococcus aureus (MRSA) infections pose serious treatment challenges, particularly in peritoneal dialysis patients due to their increased susceptibility to infections and antibiotic resistance. Vancomycin, a standard antibiotic treatment for MRSA, is currently being compromised due to the evolution of multidrug-resistant microorganisms. Therefore, there is an urgent need for alternative therapeutic strategies to obstruct the increasing antibiotic resistance and bacterial biofilm formation. The present study explores curcumin, a natural bioactive compound possessing antimicrobial and anti-inflammatory properties, as a potential therapeutic for MRSA. The standard optical density method confirmed the antibacterial activity of curcumin against Staphylococcus aureus (MTCC-3160). Furthermore, we investigated the impact of curcumin on bacterial metabolism. Metabolic analysis of S. aureus culture media over a 20-h period revealed that curcumin exerts bacteriostatic effects by inhibiting specific metabolic pathways, potentially linked to energy and sugar metabolism. Furthermore, the synergistic effect of curcumin combined with vancomycin was assessed against 20 clinical MRSA strains using the broth microdilution method. The results demonstrated that curcumin enhanced the antibacterial activity of vancomycin in 17 strains by reducing its minimum inhibitory concentration (MIC) significantly. The MIC of curcumin and vancomycin has been found to decrease significantly when used in combination, with curcumin's MIC decreased to as low as 0.5 µg/mL and vancomycin's MIC to 0.5 µg/mL for all strains. Synergistic effects were seen in 17 out of 20 strains, having fractional inhibitory concentration index values between 0.04 and 0.56. These findings suggest that curcumin-vancomycin combination therapy could offer an effective treatment strategy for MRSA infections which may combat antibiotic resistance and reduce treatment-related toxicity.

Multidrug-resistant bacterial infections are a rising threat to human health and currently account for 1.3 million deaths annually. Notably, 70% of these deaths are due to gram-negative pathogens, and no new classes of gram-negative-active antibiotics have been approved by the US Food and Drug Administration in the past 55 years. The challenges of converting compounds with in vitro biochemical activity to whole cell gram-negative antibacterial activity are significant, as the outer membrane and promiscuous efflux pumps thwart the potential of most antibiotic candidates. Significant strides have been made toward understanding compound penetration and accumulation in gram-negative bacteria, but efflux remains a major obstacle for antibiotic drug discovery. Recent advances in machine learning (ML) algorithms and increased accessibility of code and programs for the nonexpert suggest artificial intelligence could help address the efflux problem. Here, we discuss work toward understanding efflux and cast a vision for how ML can be utilized to address compound efflux from gram-negative bacteria.