Phage cocktail amikacin combination as a potential therapy for bacteremia associated with carbapenemase producing colistin resistant Klebsiella pneumoniae DOI Creative Commons

Aye Mya Sithu Shein,

Dhammika Leshan Wannigama, Cameron Hurst

и другие.

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Ноя. 22, 2024

The increasing occurrence of hospital-associated infections, particularly bacteremia, caused by extensively drug-resistant (XDR) carbapenemase-producing colistin-resistant Klebsiella pneumoniae highlights a critical requirement to discover new therapeutic alternatives. Bacteriophages having host-specific bacteriolytic effects are promising alternatives for combating these pathogens. Among 12 phages isolated from public wastewater in Thailand, two phages-vB_kpnM_05 (myovirus) and vB_kpnP_08 (podovirus) showed broad-host range, producing activities against 81.3% (n = 26) 78.1% 25) 32 XDR K. pneumoniae, with capsular types—K15, K17, K50, K51, K52/wzi-50 K2/wzi-2. Both short replication times, large burst sizes rapid adsorptions. They exhibited significant stability under various environmental conditions. Genomic analysis revealed that both genetically distinct Myoviridae Podoviridae family, the lack toxin, virulence, lysogeny antibiotic resistance genes. These characteristics highlighted their potential utilizing phage therapy pneumoniae. Although cocktail combining vB_kpnM_05 provided bacteriolysis longer duration (8 h) than its monophage (6 h), bacterial regrowth was observed which suggested an evitable development phages' selection pressures. Future study will be undertaken elucidate precise mechanisms developed associated fitness cost. Remarkably, amikacin at sub-inhibitory concentrations produced potent synergy completely suppressing vitro. Our demonstrated prophylactic effectiveness cocktail-amikacin combination as alternative strategy overcoming bacteremia carbapenemase colistin vivo.

Язык: Английский

tesG expression as a potential clinical biomarker for chronic Pseudomonas aeruginosa pulmonary biofilm infections DOI Creative Commons
Dhammika Leshan Wannigama, Cameron Hurst, Peter N. Monk

и другие.

BMC Medicine, Год журнала: 2025, Номер 23(1)

Опубликована: Март 31, 2025

Pseudomonas aeruginosa infections in the lungs affect millions of children and adults worldwide. To our knowledge, no clinically validated prognostic biomarkers for chronic pulmonary P. exist. Therefore, this study aims to identify potential markers biofilm lung infections. Here, we screened expression 11 regulatory genes (tesG, algD, lasR, lasA, lasB, pelB, phzF, rhlA, rsmY, rsmZ, sagS) associations between clinical status infection. RNA was extracted from 210 sputum samples patients (n = 70) with (mean age; 29.3–56.2 years; 33 female). Strong formation correlated prolonged hospital stays (212.2 days vs. 44.4 days) increased mortality (46.2% (18)). is associated tesG (P 0.001), influencing extended intensive care unit 0.002) or hospitalisation pneumonia risk 0.006), 0.001). Notably, linked modulation systemic inflammatory responses predicts biomass. This provides first dataset levels as a predictive biomarker

Язык: Английский

Процитировано

2
Phage cocktail amikacin combination as a potential therapy for bacteremia associated with carbapenemase producing colistin resistant Klebsiella pneumoniae DOI Creative Commons

Aye Mya Sithu Shein,

Dhammika Leshan Wannigama, Cameron Hurst

и другие.

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Ноя. 22, 2024

The increasing occurrence of hospital-associated infections, particularly bacteremia, caused by extensively drug-resistant (XDR) carbapenemase-producing colistin-resistant Klebsiella pneumoniae highlights a critical requirement to discover new therapeutic alternatives. Bacteriophages having host-specific bacteriolytic effects are promising alternatives for combating these pathogens. Among 12 phages isolated from public wastewater in Thailand, two phages-vB_kpnM_05 (myovirus) and vB_kpnP_08 (podovirus) showed broad-host range, producing activities against 81.3% (n = 26) 78.1% 25) 32 XDR K. pneumoniae, with capsular types—K15, K17, K50, K51, K52/wzi-50 K2/wzi-2. Both short replication times, large burst sizes rapid adsorptions. They exhibited significant stability under various environmental conditions. Genomic analysis revealed that both genetically distinct Myoviridae Podoviridae family, the lack toxin, virulence, lysogeny antibiotic resistance genes. These characteristics highlighted their potential utilizing phage therapy pneumoniae. Although cocktail combining vB_kpnM_05 provided bacteriolysis longer duration (8 h) than its monophage (6 h), bacterial regrowth was observed which suggested an evitable development phages' selection pressures. Future study will be undertaken elucidate precise mechanisms developed associated fitness cost. Remarkably, amikacin at sub-inhibitory concentrations produced potent synergy completely suppressing vitro. Our demonstrated prophylactic effectiveness cocktail-amikacin combination as alternative strategy overcoming bacteremia carbapenemase colistin vivo.

Язык: Английский

Процитировано

4