Emergence of multidrug-resistant Klebsiella pneumoniae in hospitalised young children

Patil, Sandip; Dong, Shaowei; Francisco, Ngiambudulu M.; Liu, Sixi; Wen, Fu Qiang

doi:10.1016/s2666-5247(23)00094-0

Cited by 2 publications

(1 citation statement)

References 5 publications

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“…The emergence of multidrug-resistant Klebsiella pneumoniae strains associated with hospital-and community-acquired infections, such as bacteremia, meningitis, pneumonia, and urinary tract infections (UTIs) [1][2][3], is a major concern for choosing the appropriate medical treatment [4]. The multidrug resistance of K. pneumoniae occurs mainly through the horizontal transfer of resistance genes through mobile genetic elements, such as plasmids, transposons, and integrons [5,6].…”

Section: Introductionmentioning

confidence: 99%

Extensive Expression of the Virulome Related to Antibiotic Genotyping in Nosocomial Strains of Klebsiella pneumoniae

Paniagua-Contreras,

Bautista-Cerón,

Morales-Espinosa

et al. 2023

IJMS

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The emergence of hyper-virulent and multidrug-resistant (MDR) strains of Klebsiella pneumoniae isolated from patients with hospital- and community-acquired infections is a serious health problem that increases mortality. The molecular analysis of virulome expression related to antimicrobial-resistant genotype and infection type in K. pneumoniae strains isolated from patients with hospital- and community-acquired infections has been poorly studied. In this study, we analyzed the overall expression of the virulence genotype associated with the antimicrobial resistance genotype and pulse field gel electrophoresis (PFGE) type (PFtype) in K. pneumoniae. We studied 25 strains of K. pneumoniae isolated from patients who developed bacteremia and pneumonia during their hospital stay and 125 strains from outpatients who acquired community-acquired infections. Susceptibility to 12 antimicrobials was determined by Kirby–Bauer. The identification of K. pneumoniae and antibiotic-resistance genes was performed using polymerase chain reaction (PCR). To promote the expression of the virulence genes of K. pneumoniae, an in vitro infection model was used in human epithelial cell lines A549 and A431. Bacterial RNA was extracted with the QIAcube robotic workstation, and reverse transcription to cDNA was performed with the Reverse Transcription QuantiTect kit (Qiagen). The determination of the expression of the virulence genes was performed by real-time PCR. In addition, 57.3% (n = 86) of the strains isolated from patients with hospital- and community-acquired infections were multidrug-resistant (MDR), mainly to beta-lactam antibiotics (CB, AM, CFX, and CF), aminoglycosides (GE), quinolones (CPF and NOF), nitrofurantoin (NF), and sulfamethoxazole/trimethoprim (SXT). The most frequently expressed genes among strains isolated from hospital- and community-acquired infections were adhesion-type, ycfm (80%), mrkD (51.3%), and fimH (30.7%); iron uptake, irp2 (84%), fyuA (68.7%), entB (64.7%), and irp1 (56.7%); and protectins, rpmA (26%), which were related to antibiotic-resistance genes, blaTEM (96%), blaSHV (64%), blaCITM (52.6%), blaCTXM-1 (44.7%), tetA (74%), sul1 (57.3%), aac(3)-IV (40.7%), and aadA1 (36%). The results showed the existence of different patterns of expression of virulome related to the genotype of resistance to antimicrobials and to the PFtypes in the strains of K. pneumoniae that cause hospital- and community-acquired infections. These findings are important and may contribute to improving medical treatment strategies against infections caused by K. pneumoniae.

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Section: Introductionmentioning

confidence: 99%

Extensive Expression of the Virulome Related to Antibiotic Genotyping in Nosocomial Strains of Klebsiella pneumoniae

Paniagua-Contreras,

Bautista-Cerón,

Morales-Espinosa

et al. 2023

IJMS

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Advancing Phage Therapy: A Comprehensive Review of the Safety, Efficacy, and Future Prospects for the Targeted Treatment of Bacterial Infections

Palma,

2024

Infectious Disease Reports

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Background: Phage therapy, a treatment utilizing bacteriophages to combat bacterial infections, is gaining attention as a promising alternative to antibiotics, particularly for managing antibiotic-resistant bacteria. This study aims to provide a comprehensive review of phage therapy by examining its safety, efficacy, influencing factors, future prospects, and regulatory considerations. The study also seeks to identify strategies for optimizing its application and to propose a systematic framework for its clinical implementation. Methods: A comprehensive analysis of preclinical studies, clinical trials, and regulatory frameworks was undertaken to evaluate the therapeutic potential of phage therapy. This included an in-depth assessment of key factors influencing clinical outcomes, such as infection site, phage–host specificity, bacterial burden, and immune response. Additionally, innovative strategies—such as combination therapies, bioengineered phages, and phage cocktails—were explored to enhance efficacy. Critical considerations related to dosing, including inoculum size, multiplicity of infection, therapeutic windows, and personalized medicine approaches, were also examined to optimize treatment outcomes. Results: Phage therapy has demonstrated a favorable safety profile in both preclinical and clinical settings, with minimal adverse effects. Its ability to specifically target harmful bacteria while preserving beneficial microbiota underpins its efficacy in treating a range of infections. However, variable outcomes in some studies highlight the importance of addressing critical factors that influence therapeutic success. Innovative approaches, including combination therapies, bioengineered phages, expanded access to diverse phage banks, phage cocktails, and personalized medicine, hold significant promise for improving efficacy. Optimizing dosing strategies remains a key area for enhancement, with critical considerations including inoculum size, multiplicity of infection, phage kinetics, resistance potential, therapeutic windows, dosing frequency, and patient-specific factors. To support the clinical application of phage therapy, a streamlined four-step guideline has been developed, providing a systematic framework for effective treatment planning and implementation. Conclusion: Phage therapy offers a highly adaptable, targeted, and cost-effective approach to addressing antibiotic-resistant infections. While several critical factors must be thoroughly evaluated to optimize treatment efficacy, there remains significant potential for improvement through innovative strategies and refined methodologies. Although phage therapy has yet to achieve widespread approval in the U.S. and Europe, its accessibility through Expanded Access programs and FDA authorizations for food pathogen control underscores its promise. Established practices in countries such as Poland and Georgia further demonstrate its clinical feasibility. To enable broader adoption, regulatory harmonization and advancements in production, delivery, and quality control will be essential. Notably, the affordability and scalability of phage therapy position it as an especially valuable solution for developing regions grappling with escalating rates of antibiotic resistance.

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Emergence of multidrug-resistant Klebsiella pneumoniae in hospitalised young children

Cited by 2 publications

References 5 publications

Extensive Expression of the Virulome Related to Antibiotic Genotyping in Nosocomial Strains of Klebsiella pneumoniae

Extensive Expression of the Virulome Related to Antibiotic Genotyping in Nosocomial Strains of Klebsiella pneumoniae

Advancing Phage Therapy: A Comprehensive Review of the Safety, Efficacy, and Future Prospects for the Targeted Treatment of Bacterial Infections

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