scholarly journals Piscidin is Highly Active against Carbapenem-Resistant Acinetobacter baumannii and NDM-1-Producing Klebsiella pneumonia in a Systemic Septicaemia Infection Mouse Model

Marine Drugs ◽  
2015 ◽  
Vol 13 (4) ◽  
pp. 2287-2305 ◽  
Author(s):  
Chieh-Yu Pan ◽  
Jian-Chyi Chen ◽  
Te-Li Chen ◽  
Jen-Leih Wu ◽  
Cho-Fat Hui ◽  
...  
Keyword(s):  
Mouse Model ◽  
Acinetobacter Baumannii ◽  
Klebsiella Pneumonia ◽  
Highly Active ◽  
Carbapenem Resistant

scholarly journals In vivo efficacy of combination of colistin with fosfomycin or minocycline in a mouse model of multidrug-resistant Acinetobacter baumannii pneumonia

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Nam Su Ku ◽  
Su-Hyung Lee ◽  
Young- soun Lim ◽  
Heun Choi ◽  
Jin Young Ahn ◽  
...  
Keyword(s):  
Mouse Model ◽  
Acinetobacter Baumannii ◽  
Synergistic Effects ◽  
Bacterial Load ◽  
Multidrug Resistant ◽  
Therapeutic Options ◽  
Severance Hospital ◽  
Carbapenem Resistant ◽  
Combination Regimens

AbstractUnfortunately, the options for treating multidrug-resistant (MDR) Acinetobacter baumannii (A. baumannii) infections are extremely limited. Recently, fosfomycin and minocycline were newly introduced as a treatment option for MDR A. baumannii infection. Therefore, we investigated the efficacy of the combination of colistin with fosfomycin and minocycline, respectively, as therapeutic options in MDR A. baumannii pneumonia. We examined a carbapenem-resistant A. baumannii isolated from clinical specimens at Severance Hospital, Seoul, Korea. The effect of colistin with fosfomycin, and colistin with minocycline on the bacterial counts in lung tissue was investigated in a mouse model of pneumonia caused by MDR A. baumannii. In vivo, colistin with fosfomycin or minocycline significantly (p < 0.05) reduced the bacterial load in the lungs compared with the controls at 24 and 48 h. In the combination groups, the bacterial loads differed significantly (p < 0.05) from that with the more active antimicrobial alone. Moreover, the combination regimens of colistin with fosfomycin and colistin with minocycline showed bactericidal and synergistic effects compared with the more active antimicrobial alone at 24 and 48 h. This study demonstrated the synergistic effects of combination regimens of colistin with fosfomycin and minocycline, respectively, as therapeutic options in pneumonia caused by MDR A. baumannii.

scholarly journals Lyb-2-4, a unique genomic region of hypervirulent carbapenem-resistant Acinetobacter baumannii

2019 ◽  
Author(s):  
Chao Zheng ◽  
Jinyong Zhang ◽  
Min Zhang ◽  
Zhou Liu ◽  
Yuxin Zhong ◽  
...  
Keyword(s):  
Mouse Model ◽  
Acinetobacter Baumannii ◽  
Multilocus Sequence Typing ◽  
Core Genome ◽  
Medical Intervention ◽  
Genomic Region ◽  
Multi Drug Resistance ◽  
Comparative Genomic ◽  
Low Grade ◽  
Carbapenem Resistant

ABSTRACTAcinetobacter baumannii is an important human pathogen due to its multi-drug resistance, but is usually with low-grade virulence. Although a mouse model revealed different virulence grades of clinical carbapenem-resistant A. baumannii (CRAB) strains, the genetic basis remains unknown. We collected 61 CRAB isolates from intensive care unit of Shenzhen People’s Hospital (Shenzhen, China), and analyzed them used whole genome sequencing (WGS), multilocus sequence typing (MLST) and core genome MLST (cgMLST), transmission chain reconstruction and Comparative genomic tools. A mouse pneumonia model was used to confirm the hypervirulent phenotype. Eleven complex types (CT) were identified based on core genome multilocus sequence typing scheme. CT512 showed higher transmissibility and bloodstream infection rates than other CTs. A genomic region Lyb-2-4 was shared by CT512 and CT2092 but not CT2085. The mortality rates of patient infected with CRAB harboring Lyb-2-4 was significantly higher than those infected with CRAB isolates without Lyb-2-4 (77.8% vs 24.5%, p < 0.01). In the mouse model, the survival rates of strains containing the Lyb-2-4 region (LAC-4, 5122 and 2092) were significantly lower than for strains without Lyb-2-4 (7152, 71517, 20859 and ATCC17978). One open reading frame (ORF) was a marker for the presence of Lyb-2-4, and PCR of a segment of this ORF, designated as hvcT, served as a tag for hypervirulent CRAB. Our study should be very useful in advising the clinician to implement medical intervention earlier, and also making the worldwide surveillance of these hypervirulent CRAB strains easier.IMPORTANCEHypervirulent CRAB strains are expected to pose a threat to human health because infection of these strains is associated with high mortality and multidrug resistance. The rapid hypervirulent CRAB identification assay will facilitate prompt medical intervention. Our findings should provoke surveillance for hypervirulent CRAB strains harboring Lyb-2-4 in other countries. Further research should focus on the mechanism of hypervirulence, the acquisition of this genomic region and the development of control measures to prevent further dissemination.

scholarly journals In Vitro Activity of Cefepime-Zidebactam, Ceftazidime-Avibactam, and Other Comparators against Clinical Isolates of Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii: Results from China Antimicrobial Surveillance Network (CHINET) in 2018

2020 ◽  
Vol 65 (1) ◽  
pp. e01726-20
Author(s):  
Yang Yang ◽  
Yan Guo ◽  
Dandan Yin ◽  
Yonggui Zheng ◽  
Shi Wu ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Acinetobacter Baumannii ◽  
Clinical Isolates ◽  
Surveillance Network ◽  
Gram Negative ◽  
Content Type ◽  
Highly Active ◽  
Carbapenem Resistant ◽  
Almost All

ABSTRACTThis study evaluated the in vitro activity of cefepime-zidebactam in comparison with that of ceftazidime-avibactam and other comparators against clinically significant Gram-negative bacillus isolates. A total of 3,400 nonduplicate Gram-negative clinical isolates were collected from 45 medical centers across China in the CHINET Program in 2018, including Enterobacterales (n = 2,228), Pseudomonas aeruginosa (n = 657), and Acinetobacter baumannii (n = 515). The activities of cefepime-zidebactam and 20 comparators were determined by broth microdilution as recommended by the Clinical and Laboratory Standards Institute. Cefepime-zidebactam demonstrated potent activity against almost all Enterobacterales (MIC50/90, 0.125/1 mg/liter) and good activity against P. aeruginosa (MIC50/90, 2/8 mg/liter). Among the 373 carbapenem-resistant Enterobacteriaceae isolates, 57.3% (213/373) and 15.3% (57/373) were positive for blaKPC-2 and blaNDM, respectively. Cefepime-zidebactam showed a MIC of ≤2 mg/liter for 92.0% (196/213) of blaKPC-2 producers and 79.7% (47/59) of blaNDM producers. Ceftazidime-avibactam showed good in vitro activity against Enterobacterales (MIC50/90, 0.25/2 mg/liter; 94.0% susceptible) and P. aeruginosa (MIC50/90, 4/16 mg/liter; 86.9% susceptible). Ceftazidime-avibactam was active against 9.1% of carbapenem-resistant Escherichia coli isolates (63.6% were blaNDM producers) and 84.6% of Klebsiella pneumoniae isolates (74.3% were blaKPC producers). Most (90.1%) blaKPC-2 producers were susceptible to ceftazidime-avibactam. Cefepime-zidebactam demonstrated limited activity (MIC50/90, 16/32 mg/liter) against the 515 A. baumannii isolates (79.2% were carbapenem resistant), and ceftazidime-avibactam was less active (MIC50/90, 64/>64 mg/liter). Cefepime-zidebactam was highly active against clinical isolates of Enterobacterales and P. aeruginosa, including blaKPC-2-positive Enterobacterales and blaNDM-positive Enterobacterales and carbapenem-resistant P. aeruginosa. And ceftazidime-avibactam was highly active against blaKPC-2-positive Enterobacterales and carbapenem-resistant P. aeruginosa.

scholarly journals Therapeutic Efficacy of Bacteriophage Therapy to Treat Carbapenem Resistant Klebsiella Pneumoniae in Mouse Model

2021 ◽  
Vol 19 (1) ◽  
pp. 76-82
Author(s):  
Gunaraj Dhungana ◽  
Madhav Regmi ◽  
Prashant Paudel ◽  
Apsara Parajuli ◽  
Elisha Upadhyay ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Mouse Model ◽  
Therapeutic Efficacy ◽  
Phage Therapy ◽  
Bacterial Load ◽  
Health Concern ◽  
Klebsiella Pneumonia ◽  
Lytic Bacteriophage ◽  
Bacteriophage Therapy ◽  
Carbapenem Resistant

Background: Global emergence of carbapenem-resistant Klebsiella pneumoniae is a major public health concern. Phage therapy – application of lytic phage to kill pathogenic bacteria – is considered as one of the promising alternatives to tackle this antibiotic crisis in recent days. This study aimed to isolate, characterize and evaluate therapeutic efficacy of a novel K. pneumoniae phage in mouse model.Methods: A novel lytic bacteriophage (phage) Kp_Pokalde_002 was isolated against carbapenem-resistant K. pneumoniae (Kp56) and characterized. Safety parameters of the phage were evaluated by bioinformatic analysis of its genome. A lethal dose (~1×107 CFU/mouse) of Kp56 was determined and administrated in the mice. The infected mice were treated with phage Kp_Pokalde_002 at a multiplicity of infection (MOI) 1.0 (~1×107 PFU/mouse) via both oral and intraperitoneal (IP) routes.Results: Isolated phage comprised an icosahedral capsid with a short tail. Based on genome analysis, the phage was strictly lytic belonging the Podoviridae family (T7-like viruses) and free from any virulent and antibiotic-resistant genes. The phage was stable up to 60 °C for 30 minutes and effective between pH 4 to 11 (optimum pH 9). The phage exhibited a short latent period (20 minutes) with burst size of 121 phage particles per infected cell. The infected mice were rescued with the phage therapy via both oral and IP route. Significant reduction of bacterial load (3-7 log10 CFU/ml) in the blood and lung was observed in the treatment group.Conclusions: We provide an evidence of successful phage therapy against carbapenem-resistant K. pneumoniae infected mouse model using locally isolated lytic phage.Keywords: Bacteriophage; klebsiella pneumonia; phage therapy

Decreased carO gene expression and OXA-type carbapenemases among extensively drug-resistant Acinetobacter baumannii strains isolated from burn patients in Tehran, Iran

2020 ◽  
Author(s):  
Elham Abbasi ◽  
Hossein Goudarzi ◽  
Ali Hashemi ◽  
Alireza Salimi Chirani ◽  
Abdollah Ardebili ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acinetobacter Baumannii ◽  
High Rate ◽  
Burn Patients ◽  
Drug Resistant ◽  
Disc Diffusion ◽  
Carbapenem Resistant ◽  
Extensively Drug Resistant ◽  
Sds Page ◽  
Extensively Drug Resistance

AbstractA major challenge in the treatment of infections has been the rise of extensively drug resistance (XDR) and multidrug resistance (MDR) in Acinetobacter baumannii. The goals of this study were to determine the pattern of antimicrobial susceptibility, blaOXA and carO genes among burn-isolated A. baumannii strains. In this study, 100 A. baumannii strains were isolated from burn patients and their susceptibilities to different antibiotics were determined using disc diffusion testing and broth microdilution. Presence of carO gene and OXA-type carbapenemase genes was tested by PCR and sequencing. SDS-PAGE was done to survey CarO porin and the expression level of carO gene was evaluated by Real-Time PCR. A high rate of resistance to meropenem (98%), imipenem (98%) and doripenem (98%) was detected. All tested A. baumannii strains were susceptible to colistin. The results indicated that 84.9% were XDR and 97.9% of strains were MDR. In addition, all strains bore blaOXA-51 like and blaOXA-23 like and carO genes. Nonetheless, blaOXA-58 like and blaOXA-24 like genes were harbored by 0 percent and 76 percent of strains, respectively. The relative expression levels of the carO gene ranged from 0.06 to 35.01 fold lower than that of carbapenem-susceptible A. baumannii ATCC19606 and SDS – PAGE analysis of the outer membrane protein showed that all 100 isolates produced CarO. The results of current study revealed prevalence of blaOXA genes and changes in carO gene expression in carbapenem resistant A.baumannii.

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