Microbial drug resistance最新文献

Objective: To characterize the clinical and genomic features of vancomycin-resistant enterococci (VRE) in a tertiary hospital in Huizhou and identify risk factors to inform local infection control.

Methods: A retrospective study included 58 VRE and 25 vancomycin-susceptible Enterococci (VSE) strains (August 2023-May 2025). Clinical data and antimicrobial susceptibility were analyzed; whole-genome sequencing (WGS) was performed on 54 VRE strains.

Results: Midstream urine was the primary VRE-positive specimen. ICU admission, polyantibiotic use (≥3 agents), and urinary catheterization were key risk factors for VRE. All VRE isolates were Enterococcus faecium and showed a predominantly clonal population structure, dominated by CC17/ST80 (68.8%) and CC2/ST106 (64.6%) under the two multilocus sequence typing schemes; five novel STs were ultimately identified in the latter scheme. VRE was universally resistant to ampicillin, with high resistance to penicillin, levofloxacin, and teicoplanin, while linezolid and tigecycline remained effective. Genotypically, 94.8% carried vanA, 100% carried virulence gene esp, and aminoglycoside and macrolide resistance genes were prevalent. A unique VRE strain (VRE48) showed resistance without canonical van genes, harboring a Ddl Ser210Tyr mutation.

Background: This study aimed to determine the prevalence of carbapenem-resistant Enterobacterales (CRE), to characterize their molecular resistance mechanisms, and to assess associated clinical outcomes among intensive care unit (ICU) patients in Tunisia.

Methods: A cross-sectional study was conducted from January to March 2025 in the ICU of Habib Thameur Hospital and included all patients with clinically significant CRE infections. Resistance determinants were identified using multiplex polymerase chain reaction with reverse dot blot hybridization.

Results: Among 95 ICU admissions, 17 patients developed CRE infections, corresponding to an incidence density of 21.6 cases per 1,000 patient-days. All infections were hospital-acquired. The most frequent risk factors were the presence of central venous and urinary catheters (16 patients each) and mechanical ventilation (15 patients). Klebsiella pneumoniae predominated, accounting for 26 of 27 isolates, all of which were multidrug-resistant (MDR), with a median antibiotic resistance index of 1.00. The bla_NDM and bla_OXA-48 genes were detected in 81.5% and 77.8% of isolates, respectively, with 70.4% co-producing both carbapenemases. All K. pneumoniae isolates harbored bla_SHV and/or bla_CTX-M, while a single Escherichia coli isolate carried bla_OXA-48. Cluster analysis revealed strong associations between β-lactamase production and resistance to aminoglycosides and fluoroquinolones, suggesting co-selection of MDR strains. Empirical antimicrobial therapy was appropriate in only 47% of cases, and ICU mortality reached 82.4%.

Conclusion: These findings highlight an alarmingly high burden of CRE infections in this ICU, driven mainly by K. pneumoniae co-producing NDM and OXA-48, and underscore the urgent need for strengthened infection control and antimicrobial stewardship strategies.

Methicillin-resistant Staphylococcus aureus (MRSA), a critical pathogen according to the World Health Organization, requires new treatments and resistance surveillance. This study compared the antibiotic susceptibility of clinical methicillin-susceptible S. aureus (MSSA) and MRSA isolates to last-line agents, including teicoplanin, linezolid, and daptomycin. A total of 134 S. aureus strains isolated from skin and soft tissue infections (SSTIs) were confirmed by detecting the nuc gene via PCR. MRSA and MSSA were identified by cefoxitin disk diffusion and confirmed by mecA gene amplification. Antibiotic susceptibility was initially screened by the Kirby-Bauer disk diffusion method, with minimum inhibitory concentrations (MICs) of last-resort antibiotics (teicoplanin, linezolid, and daptomycin) precisely determined by broth microdilution. Multidrug-resistant (MDR) phenotypes were defined as resistance to ≥2 non-β-lactam antimicrobial classes for MRSA and ≥3 for MSSA. Statistical analyses were conducted with chi-square and Fisher's exact tests. MRSA isolates exhibited significantly greater resistance than MSSA to cefazolin, gentamicin, amikacin, azithromycin, tetracycline, clindamycin, ciprofloxacin, and teicoplanin (p < 0.05). While daptomycin remained highly effective (96.3% susceptibility), concerning rates of non-susceptibility were observed for linezolid (41%) and teicoplanin (15.7%), primarily among MRSA isolates. Overall, MDR was prevalent in 41.7% of the S. aureus isolates. Daptomycin and cefazolin remain effective against MRSA and MSSA SSTIs, respectively. However, emerging resistance to last-line agents such as teicoplanin and linezolid is alarming and necessitates enhanced surveillance, prudent antibiotic use, and increased antimicrobial research to counter the growing threat of antibiotic resistance.

Background: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) and multidrug-resistant (MDR) P. aeruginosa limit therapeutic options but have been sparsely documented in Ghana.

Methods: From November 2023 to December 2024, we conducted a prospective cross-sectional study of P. aeruginosa isolates from acute-care hospitals in Greater Accra, Ghana. Isolates were identified by matrix-assisted laser desorption ionization-time of flight, and antimicrobial susceptibility was assessed by disk diffusion as per Clinical Laboratory Standard Institute guidelines. Meropenem-resistant isolates with positive carbapenemase phenotype were subjected to whole-genome sequencing. Multivariable logistic regression models identified risk factors for infections caused by MDR and carbapenemase-producing Pseudomonas aeruginosa (CRPA).

Results: P. aeruginosa accounted for 0.32% (n = 267/83,589) of all bacterial infections identified from submitted clinical specimens and 2.82% (n = 267/12,236) of culture-positive infections. Of the 267 P. aeruginosa isolates, 20.2% (n = 54/267) were MDR and 13.5% (n = 36/267) were CRPA. Amikacin retained the highest activity against P. aeruginosa. The mean multiple antibiotic resistance index among MDR isolates (0.51 ± 0.26) was significantly higher than that among non-MDR P.aeruginosa isolates (0.02 ± 0.07; p < 0.001), with a large between-group difference (Hedges' g = 3.70). Only one isolate (2.7%) harbored a single carbapenemase gene, blaNDM-1. The remaining 35 carried a blaOXA-50-type backbone that co-occurred with either class A carbapenemases (blaKPC [n = 7], blaSME-1 [n = 4], blaGES-5 [n = 1]) or class B metallo-β-lactamases (blaNDM-1 [n = 19], blaVIM-5 [n = 3], blaIMP-15 [n = 1]). blaNDM-1 was the most dominant carbapenemase gene (n = 20/36) . Wound infection was the strongest predictor of MDR infections (adjusted odds ratio [aOR] = 3.01; 95% confidence interval (CI) = 1.43-4.47; p = 0.001], whereas inpatient status was the strongest predictor of CRPA infection (aOR = 3.32; 95% CI = 0.98-4.09; p = 0.001).

Conclusions: MDR P. aeruginosa and carbapenem Resistant P.aeruginosa (CRPA), mostly blaNDM-1 producers, are major causes of infection in our setting. Restricting carbapenem use through stewardship and strengthening infection control is essential to limit CRPA spread.

This study analyzed factors associated with mortality in Klebsiella pneumoniae bacteremia, particularly the role of combination therapy. Medical records of 109 patients (2012-2018) were reviewed to assess risk factors for carbapenem-resistant K. pneumoniae (CRKP) bacteremia. The total 30-day mortality was 41.3%. Excess mortality was calculated for the following groups: multidrug-resistant (MDR) K. pneumoniae, CRKP, and carbapenem-susceptible K. pneumoniae. Of 109 isolates, 64.2% were CRKP. All patients received empirical therapy; 20.2% received monotherapy, while the remainder received combination therapy, which was linked to longer intensive care unit stays and higher primary bacteremia rates. Overall, inappropriate empirical treatment occurred in 62.4% of patients. Both monotherapy (40.9%) and combination therapy (36.8%) groups showed similarly high rates of inappropriate treatment. Hemodialysis catheter use was a risk factor (p = 0.0238). Third- and fourth-generation cephalosporins had the highest mortality (45.9%), whereas MDR strains showed the lowest (4.51%). Although combination therapy alone did not significantly reduce mortality, Kaplan-Meier analysis revealed no survival benefit. However, monotherapy increased mortality, suggesting that combination therapy may still play a role in mitigating outcomes. Carbapenem resistance in K. pneumoniae bacteremia remains alarmingly high and correlates with excess mortality and inappropriate empirical treatment.

The misuse of broad-spectrum antibiotics has facilitated the emergence of carbapenem-resistant Salmonella enterica subsp. enterica (CRSE). This study aims to investigate the genomic characteristics and epidemiological patterns of two strains isolated from pediatric patients, along with 21 CRSE strains collected from humans worldwide. The antimicrobial susceptibility tests were detected by the agar microdilution method. Whole-genome sequence of the two CRSE strains was sequenced using the Illumina platform. Acquisition and analysis of WGS data were performed by the NCBI Pathogen Detection Portal, BacWGSTdb 2.0, Salmonella In Silico Typing Resource, and the Center for Genomic Epidemiology. Two S. Typhimurium isolates from children carried the carbapenemase gene bla_NDM-5 and belonged to ST34. The CRSE isolates predominantly contained the carbapenem resistance gene bla_OXA-48 in the United Kingdom and bla_NDM in China. The virulence gene profiles of these isolates were consistent across different regions. Carbapenem-resistant S. Typhimurium and S. Kentucky were predominantly found in China and the United Kingdom, respectively. ST198 strains were prevalent in the United Kingdom, whereas all ST34 strains were identified in China. This investigation underscores the global dissemination of carbapenem-resistant Salmonella in humans, revealing variations in drug resistance, serotypes, and sequence types across different regions. Therefore, the global detection of carbapenem resistance has important guiding significance for controlling its transmission, preventing infection, and clinical treatment.

The global rise of multidrug-resistant (MDR) bacteria has renewed interest in bacteriophage-derived enzymes as alternative antibacterials. Phage-encoded lytic proteins-including holins, endolysins, polysaccharide depolymerases, and virion-associated lysins (VALs)-act via distinct mechanisms to disrupt bacterial cells or their protective polysaccharide barriers. Holins accumulate in the bacterial membrane and suddenly form pores, enabling endolysins to access and cleave peptidoglycan bonds. Endolysins are peptidoglycan hydrolases (glycosidases, amidases, endopeptidases, etc.) that cause rapid osmotic lysis of Gram-positive pathogens and, if engineered (e.g., fused to membrane-penetrating peptides), can kill Gram-negative bacteria from without. Polysaccharide depolymerases degrade bacterial capsules, biofilm exopolysaccharides and LPS O-antigens, stripping away virulence factors and exposing underlying cells to phage or host defenses. VALs (or VAPGHs) are phage tail enzymes that locally cleave peptidoglycan at infection onset to permit viral DNA entry. Each class has been studied in natural and engineered forms (e.g., "artilysins" and "chimeolysins" with optimized activity or spectrum). These proteins exhibit rapid, specific bacteriolysis (often synergistic with antibiotics) and low resistance propensity, but challenges remain in delivery, stability, and immunogenicity. Here, we review the molecular actions, advantages and limitations, and the therapeutic applications of holins, endolysins, depolymerases, and VALs (natural and engineered) against MDR infections.

β-Lactams are an important class of antibiotics that target penicillin-binding proteins (PBPs) essential to bacterial cell wall synthesis. They are used to treat serious bacterial infections, including those caused by the versatile pathogen Staphylococcus aureus. Some strains carry the resistance gene, mecA, encoding a β-lactam-insensitive PBP2A that allows for peptidoglycan synthesis in the presence of β-lactams such as methicillin, limiting treatment options. We previously identified BAY 11-7082 as having antibacterial activity against methicillin-resistant S. aureus (MRSA) and showed that it re-sensitizes MRSA to β-lactams such as penicillin G, making BAY 11-7082 and its analogs promising candidates for the development of an antibiotic adjuvant. Although the direct antibacterial mechanism of BAY 11-7082 remains undefined, here we aimed to better understand how it potentiates β-lactam activity. We tested BAY 11-7082 in combination with a variety of β-lactams and identified a subset that were synergistic in MRSA but not methicillin-susceptible S. aureus, suggesting that they may directly or indirectly impact the function of PBP2A. Electron and fluorescence microscopy studies revealed that unlike other β-lactam adjuvants, such as those that target the biosynthesis of wall teichoic acids (WTAs), BAY 11-7082 failed to impact cell division, disrupt PBP2 localization, or activate a sensitive reporter of cell wall damage. However, the production of WTA was necessary for BAY 11-7082-β-lactam synergy. Together, these data suggest its mechanism of β-lactam potentiation is distinct from known compounds, making BAY 11-7082 a useful tool to better understand the complexity of resistance in MRSA.

Background and objectives: Staphylococcus aureus infection and its antibiotic resistance (ABR) situation are topical concerns. To formulate an effective response strategy tailored to our hospital and provide clinicians with a reliable basis for empirical antimicrobial use in the early phases of treatment.

Method: Between 2014 and 2023, a total of 11,886 S. aureus isolates and 3,417 methicillin-resistant S. aureus (MRSA) isolates were enrolled. The distribution of these isolates over the 10-year period was analyzed, along with trends in ABR among all S. aureus isolates, those from respiratory tract specimens, those from pediatric patients, and MRSA isolates.

Results: The detection number of S. aureus and MRSA strains showed an increasing trend over the 10-year period. However, while the proportion of S. aureus among Gram-positive strains (G+) remained stable, its proportion among all bacterial pathogens (BPS) decreased. S. aureus and MRSA strains were primarily isolated from respiratory tract specimens, wound pus, and blood specimens. The top three departments with the highest detection rates of S. aureus were Pediatrics, Pediatric Surgery, and Orthopedics, in order. Resistance rates to oxacillin and penicillin G were nearly universal, approaching 100%. In contrast, resistance to gentamicin, rifampicin, ciprofloxacin, levofloxacin, moxifloxacin, cotrimoxazole, clindamycin, erythromycin, and tetracycline showed different downward trends across the four study groups.

Conclusion: In conclusion, the prevalence of S. aureus infections within our hospital remains a significant concern. It is imperative to closely monitor the epidemiological distribution and ABR patterns of this pathogen to facilitate early intervention and guide appropriate therapeutic strategies.

Antimicrobial resistance remains a major threat to global public health, with increasing reports of the spread of β-lactamase genes posing significant risks. The number of Enterobacteriaceae harboring plasmid-mediated AmpC enzymes has been rising worldwide, with prevalence rates varying across regions. These β-lactamases are of particular epidemiological concern because they confer resistance to several β-lactam antibiotics, including penicillins, second and third-generation cephalosporins, and monobactams, while isolates typically remain susceptible to cefepime and carbapenems. This study reports, for the first time in Brazil, the detection of the bla_ACT-5 gene in a Klebsiella pneumoniae isolate recovered from a community-acquired infection clinical sample in Rio de Janeiro, which notably exhibited resistance to both cefepime and carbapenems.