Microbial drug resistance最新文献

Background: Antimicrobial resistance (AMR) is a growing global threat that complicates the treatment of infectious diseases, including plague. Yersinia pestis, the causative agent of plague, remains a serious public health concern in natural foci, such as those in Kazakhstan, where approximately 40% of the territory is plague-endemic. Despite the last reported human case in 2003, data on antibiotic resistance among Y. pestis isolates from these foci, especially historical ones, remain limited. Materials and Methods: A total of 75 Y. pestis strains were examined, including 61 isolates obtained from patients and deceased individuals during epidemic outbreaks (1926-2003) and 14 isolates from carriers and vectors in natural plague foci. Taxonomic identification was conducted using the Vitek 2 Compact 30 system. Antibiotic susceptibility was assessed by Kirby-Bauer disk diffusion and E-test methods. Extended-spectrum β-lactam (ESBL) activity was evaluated phenotypically, and resistance genes to glycopeptides and β-lactams were screened by real-time polymerase chain reaction (RT-PCR) using the BacResista GLA Detection Kit. Results: All isolates showed complete susceptibility (100%) to β-lactams, tetracyclines, aminoglycosides, amphenicols, glycopeptides, lincosamides, and quinolones. The overall susceptibility rate across antibiotic classes was 97.5%. Macrolides exhibited low activity (0.0-58.0%), consistent with known limitations against Gram-negative bacteria. No ESBL production was detected phenotypically, and RT-PCR screening found no resistance genes (vanA/B, mecA, tem, ctx-M-1, shv, oxa, imp, kpc, ndm, etc.). Conclusions: These findings confirm a lack of resistance to key antibiotic classes in historical Y. pestis isolates from Kazakhstan. Despite the absence of recent human cases, ongoing epizootics among wild animals highlight a persistent risk of transmission. This study, conducted for the first time in Kazakhstan, has important implications for public health preparedness and clinical management during plague outbreaks.

A notable increase in the incidence of vancomycin-resistant Enterococcus faecium (VREfm) was observed at a hospital in Guangzhou, China, during 2022-2023. We conducted a retrospective cross-sectional study from January 1, 2022, to August 31, 2023, to investigate the clinical and genomic characteristics of VREfm. Clinical data were extracted from electronic medical records, and infection control measures were reviewed from the relevant department. VREfm confirmation was performed using antimicrobial susceptibility testing. Genomic characteristics were analyzed via the whole-genome sequencing. The prevalence of VREfm among E. faecium isolates rose significantly from 13.3% (10/75) in 2022 to 26.4% (40/151) by August 2023 (p < 0.001). Concurrently, usage of third-generation cephalosporins increased by 8.4% (22.47 to 24.36 defined daily doses per 100 patient days), carbapenems by 34% (51.47-68.97), and vancomycin by 18% (21.15-24.97) (all p ≤ 0.001). Molecular analysis revealed ST80/CC17 (78%, 39/50) as the dominant clone, carrying vanA and virulence genes (scm, acm, and fss3), suggesting clonal expansion of a lineage rarely reported in Guangzhou. Our study documented an outbreak of ST80/CC17 vanA-positive VREfm, characterized by virulence genes (scm, acm, and fss3) and clonal dominance (78%, 39/50). The temporal association between reduced sodium hypochlorite disinfection (2.7-fold decline, p = 0.002), increased antibiotic selective pressure, and pathogen transmission highlights multifactorial drivers of this epidemic. These findings underscore the complex multifactorial nature of pathogen transmission, including the role of antibiotic use, infection control measures, and environmental factors in the spread of multidrug-resistant clones. Strengthened infection control strategies-integrating targeted disinfection, antibiotic stewardship, and genomic surveillance-are imperative to curb the spread of such multidrug-resistant clones.

Carbapenem-resistant Enterobacterales (CRE) pose a critical threat in intensive care units (ICUs) due to rapid transmission potential and limited treatment options. The study aimed to determine the incidence of intestinal CRE colonization among ICU patients, characterize the isolates phenotypically and genotypically and identify associated risk factors. This cross-sectional study was conducted in a tertiary care hospital in North India and included 236 ICU patients. Clinical, demographic, lifestyle, and dietary data were collected through standardizedv questionnaires and medical records. CRE isolates were identified using standard microbiological techniques and characterized for resistance genes. CRE colonization was detected in 69.07% of patients. Escherichia coli (74.15%) and Klebsiella pneumoniae (21.61%) were the predominant species, with a significant rise in K. pneumoniae colonization during ICU stays (p = 0.049), suggesting nosocomial transmission. Asthma emerged as a novel independent risk factor (p = 0.023, 100% colonization). Other significant associations included non-vegetarian diet (p = 0.02), prolonged ICU stay (p = 0.010), and prior broad-spectrum antibiotic use (p = 0.028). Molecular analysis showed 84% of CRE isolates harbored the bla_NDM-1 gene, while bla_IMP was absent. CRE colonization was significantly associated with higher mortality (38.0% vs. 23.3%, p = 0.026). The study reveals a high prevalence of intestinal CRE colonization among ICU patients and highlights key modifiable risk factors and regional resistance patterns. Routine rectal screening, stringent infection control, and robust antimicrobial stewardship are urgently needed to limit CRE spread. A deeper understanding of colonization dynamics is essential to improving outcomes in critically ill patients.

Sulfamethoxazole-trimethoprim (SXT) is an important empirical treatment agent against various bacterial infections. In this study, we aimed to elucidate the mechanisms underlying SXT resistance in Haemophilus influenzae clinical isolates from Japan, as information on such resistance remains limited. A total of 79 H. influenzae clinical isolates collected in 2018 and 2022 were analyzed. The SXT resistance rates were 38.7% in 2018 and 35.3% in 2022. Multilocus sequence typing analysis revealed that ST422 was the most common sequence type (36.7%), followed by ST107 (26.7%). Horizontal transfer assays using the genomic DNA or PCR-amplified fragments revealed that SXT resistance was transferred to the susceptible isolates via genomic DNA and PCR-amplified folA fragments, indicating that FolA mediates SXT resistance in H. influenzae. Site-directed mutagenesis revealed that the substitution of isoleucine at position 95 in FolA was associated with SXT resistance. All SXT-resistant isolates had an amino acid substitution at position 95 in FolA: leucine in 26 of the 30 strains, valine in 3 strains, and glycine in 1 strain. Our findings demonstrate that SXT resistance in H. influenzae was prevalent and can spread via horizontal transfer. Furthermore, an amino acid substitution at position 95 of FolA played a key role in conferring resistance.

Stenotrophomonas maltophilia is an opportunistic, multidrug-resistant pathogen emerging in pediatric infections. Its intrinsic resistance to multiple antibiotics and genetic diversity complicates both the identification of this species and treatment strategies. We conducted genomic and phenotypic analyses of isolates of Stenotrophomonas spp. from pediatric patients to assess species diversity through multilocus sequence typing and average nucleotide identity analyses. Antimicrobial susceptibility and resistance mechanisms, particularly the sul1 gene linked to sulfonamide resistance, were investigated. Our findings revealed multiple genomospecies. Of the isolates initially identified as S. maltophilia using matrix-assisted laser desorption ionization-time-of-flight mass spectrometry, only 58.5% were identified as such through molecular analyses. These other Stenotrophomonas species may not be standardized for antimicrobial susceptibility testing by the Clinical and Laboratory Standards Institute and the European Committee on Antimicrobial Susceptibility and Testing. The sul1 gene, carried on a mobilized class 1 integron, emerged as the primary driver of trimethoprim-sulfamethoxazole resistance, raising concerns about the rapid dissemination of resistance traits. Our findings underscore the diagnostic and therapeutic challenges posed by Stenotrophomonas spp. infections, highlighting the urgent need for enhanced molecular diagnostics for accurate species identification and resistance profiling. Continuous surveillance and updates to clinical guidelines are essential for improving infection management in pediatric patients.

Mupirocin (MUP) is a topical antibiotic derived from Pseudomonas fluorescens, widely used for the treatment of superficial skin infections and decolonization of methicillin-resistant Staphylococcus aureus (MRSA). Its unique mechanism of action, selective inhibition of bacterial isoleucyl-transfer RNA synthetase, confers high specificity with minimal risk of cross-resistance to other antibiotic classes. This narrative review provides an updated overview of MUP's chemical structure, mechanism of action, clinical efficacy, resistance mechanisms, and global resistance trends based on literature published from 2017 to 2024. Recent clinical studies confirm MUP's continued effectiveness, particularly in the decolonization of MRSA nasal infections. However, resistance, including high-level MUP resistance mediated by the mupA and mupB genes, is increasingly reported worldwide. A better understanding of resistance patterns and judicious use of MUP is essential to preserving its clinical utility in the context of rising antimicrobial resistance.

We investigated fecal colonization with third-generation cephalosporin-resistant (3GC-r) Enterobacterales and carbapenem-resistant Enterobacterales among food animals and their handlers in Ghana. A total of 252 fecal samples were collected from 211 animals and 41 human handlers across 20 farms between May and August 2023. Enterobacterales were isolated using standard methods and identified using Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry fingerprints and 16SrRNA sequencing. Antibiotic susceptibility testing was done using standard methods. Extended spectrum beta-lactamase (ESBL) and carbapenemase genes were identified by PCR and sequencing. A total of 264 Enterobacterales were isolated, comprising 44 from human handlers and 220 from food animals. Among human isolates, 31 (70.5%) were 3GC-r, with 9 (20.5%) expressing the ESBL phenotype and 2 (4.5%) producing carbapenemases. The most common ESBL genes detected were bla_CTX-M-15 (n = 5/9) and bla_CTX-M-14 (n = 2/9), while carbapenemase-producing isolates harbored bla_NDM-1 (n = 1/2) or bla_IMP-1 (n = 1/2). In food animals, 94 (42.7%) of Enterobacterales isolates were 3GC-r, with 11 (5.0%) carrying ESBL genes, predominantly bla_CTX-M-15 (n = 5/11). One E. coli isolate exhibited carbapenemase production (bla_NDM-1) with an ESBL gene (bla_CTX-M-1). Meropenem was the most effective antibiotic agent against the study isolates (≤5% resistance). Concordance of isolate/resistance gene combinations was observed at three farms where at least one human handler and at least one farm animal carried the same 3GC-r Escherichia coli with the same resistance genes, including bla_CTX-M-15, bla_TEM-10, and bla_NDM-1. The findings indicate a potential for zoonotic transmission of resistance genes between food animals and their human handlers.

Twenty-six genetically diverse Escherichia coli isolated from poultry and pigs in Cuba and harboring the extended-spectrum-β-lactamase (ESBL) gene bla_CTX-M-32 were sequenced using short- and long-read technologies to identify and characterize the ESBL-containing genetic elements, and their transferability was determined by conjugation. The bla_CTX-M-32 gene was located on plasmids in 15 E. coli (4 from pigs, 11 from poultry), on the chromosome in five porcine and four poultry E. coli, and on both the chromosome and plasmids in two poultry E. coli strains. The bla_CTX-M-32 plasmids of incompatibility groups IncF (n = 6) and IncX (n = 3) were detected in strains from chickens and pigs, and those of IncN (n = 4) and IncH (n = 4) were only present in poultry E. coli. The plasmids were conjugative except for the IncX1 and one of the IncFII and IncFIA plasmids that had truncations in the tra and trh regions. ISEc9-ISKpn26-bla_CTX-M-32-wbuC was the most common ESBL-carrying genetic context in both plasmids and chromosomes, and two other structures (ISKpn26-bla_CTX-M-32-wbuC, IS26-bla_CTX-M-32-wbuC) were less frequent. This study provides new insights into the genetic backgrounds of bla_CTX-M-32 and its spread through plasmids between genetically different E. coli from different animals and geographically distant farms.

The bacteria Klebsiella pneumoniae is encapsulated, rod-shaped, nonmotile, and Gram-negative bacilli. K. pneumoniae causes a variety of illnesses. They express various virulence factors such as capsules, which are primary virulence factors responsible for the pathogenicity and protection of bacteria from phagocytosis, lipopolysaccharide, which act as external membranes of the bacteria; and fimbriae-І and ІІІ which promote the binding to biological surfaces like medical devices such as ventilators. K. pneumoniae's resistance to cephalosporins (3^rd and 4^th generation), quinolones, carbapenem, and colistin is increasing. Colistin is the last trait to treat multidrug-resistant K. pneumoniae. The monotherapy is becoming ineffective to treat infections. Plasmid-borne genes called mcr-1 mediate colistin resistance, which is more prevalent. Colistin resistance and gene detection were done by using Epsilometry-test and conventional PCR, respectively. Amikacin was tested for synergism with colistin. Colistin with zinc oxide nanoparticle (NP) synergism was also tested. The properties of zinc oxide NPs are assessed by Fourier-transform infrared (FTIR), scanning electron microscope (SEM), and ultraviolet (UV) visible spectroscopy. Antibacterial activity of zinc oxide NPs was determined using the agar well diffusion method. In our study, we encourage combination drug therapy to treat the colistin-resistant K. pneumoniae. The synergistic activity of combined drugs was tested using checker-board technique. The results revealed that the synergistic activity of colistin combined with zinc oxide NPs and amikacin against colistin-resistant K. pneumoniae was found to be effective and can be further developed against the colistin resistant K. pneumoniae.