scholarly journals Activity of isolated specific bacteriophage in treatment of chronic osteomyelitis induced by multiple drug resistance Pseudomonas aeruginosa in Rabbits

2018 ◽  
Vol 41 (2) ◽  
pp. 146-156
Author(s):  
Sarhan Rashid Sarhan
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Chronic Osteomyelitis ◽  
Multiple Drug Resistance ◽  
Inflammatory Cells ◽  
Treated Group ◽  
Sewage Water ◽  
Multiple Drug ◽  
In Vivo Evaluation ◽  
Specific Bacteriophage

     This study was conducted to find out the possibility of using the Pseudomonas aeruginosa specific-bacteriophage as an alternative to antibiotics in treatment of chronic osteomyelitis in rabbits by injection of Pseudomonas aeruginosa suspension in tibia. The current study included an isolation of bacteriophage from sewage water by using agar overlay method and also an isolation of the bacteria from patients suffering from post-traumatic bone infection. The second experiment was in-vivo evaluation of phage activity in treatment of chronic osteomyelitis in rabbits. All animals of infected groups with Pseudomonas aeruginosa before treatment exhibited histopathological changes after 35 days of infection, the infected groups showed chronic osteomyelitis represented by sever chronic inflammatory cells infiltrates mainly lymphocytes, and macrophages and hemorrhage between bone trabeculae, also some sections showed extensive fibrosis in the marrow spaces. The treated group with P. aeruginosa specific – bacteriophage (1.5 ×107) PFU/ml for 10 days showed early repair elucidated by presence whorls of chondrocytes, and also the presence of multiple osteoblasts indicated bone formations. Also the presence of extensive fibrosis in the marrow space with present of osteoblasts indicated bone formations and repair.

scholarly journals In vivo evaluation of a recombinant N-acylhomoserine lactonase formulated in a hydrogel using a murine model infected with MDR Pseudomonas aeruginosa clinical isolate, CCASUP2

AMB Express ◽  
2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Masarra M. Sakr ◽  
Walid F. Elkhatib ◽  
Khaled M. Aboshanab ◽  
Eman M. Mantawy ◽  
Mahmoud A. Yassien ◽  
...  
Keyword(s):  
Survival Rate ◽  
Murine Model ◽  
Histopathological Examination ◽  
Healing Process ◽  
Bacterial Count ◽  
Treated Group ◽  
Control Group ◽  
In Vivo Evaluation ◽  
Systemic Spread

AbstractFailure in the treatment of P. aeruginosa, due to its broad spectrum of resistance, has been associated with increased patient mortality. One alternative approach for infection control is quorum quenching which was found to decrease virulence of such pathogen. In this study, the efficiency of a recombinant Ahl-1 lactonase formulated as a hydrogel was investigated to control the infection of multidrug resistant (MDR) P. aeruginosa infected burn using a murine model. The recombinant N-acylhomoserine lactonase (Ahl-1) was formulated as a hydrogel. To test its ability to control the infection of MDR P. aeruginosa, a thermal injury model was used. Survival rate, and systemic spread of the infection were evaluated. Histopathological examination of the animal dorsal skin was also done for monitoring the healing and cellular changes at the site of infection. Survival rate in the treated group was 100% relative to 40% in the control group. A decrease of up to 3 logs of bacterial count in the blood samples of the treated animals relative to the control group and a decrease of up to 4 logs and 2.3 logs of bacteria in lung and liver samples, respectively were observed. Histopathological examination revealed more enhanced healing process in the treated group. Accordingly, by promoting healing of infected MDR P. aeruginosa burn and by reducing systemic spread of the infection as well as decreasing mortality rate, Ahl-1 hydrogel application is a promising strategy that can be used to combat and control P. aeruginosa burn infections.

Detection of Metalo-Beta-Lactamase Gene in Carbapenem Resistant Pseudomonas Aeruginosa Isolated From Lahore, Pakistan

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Humera Kausar ◽  
Shabbir Hussain ◽  
Afia Muhammad Akram
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Multiple Drug Resistance ◽  
Diffusion Method ◽  
Multiple Drug ◽  
Carbapenem Resistant ◽  
Routine Laboratory Examination ◽  
Polymerase Chain ◽  
Biochemical Testing ◽  
Resistance Rates ◽  
Lactamase Gene

Pseudomonas aeruginosa is a widespread organism, caused severe nosocomial infection in human andassociated with multiple drug resistance (MDR) Objective: The present study was carried out to observecurrent antimicrobial resistant pattern of Pseudomonas aeruginosa in Lahore and to detect the Metallobeta-lactamase (MBL) gene in carbapenem resistant Pseudomonas aeruginosa Methods: By screening360 samples total 123 Pseudomonas aeruginosa was identified by standard microbiology techniques suchas microscopy and biochemical testing. The isolated Pseudomonas aeruginosa was evaluated for drugresistance by disc diffusion method and polymerase chain reaction (PCR) was used to identify thecarbapenem resistance causing gene (bla-VIM and bla-IMP) Results: Following antibiotic resistantpattern was observed, Gentamycin (59.00%), Ceftazidime (58.7%), Ceftriaxone (58.00%), Cefotazime(57.0%) and Ciprofloxacin (55.00%). Resistance rates to carbapenem group of antibiotics is Doripenem(30.5%) Meropenem (31.0%) and Imipenem (28.0%). Out of 123 samples of Pseudomonas aeruginosa, 28isolates were found resistant to carbapenem group of antibiotic which was supposed to be highlysensitive for this bacterium. Molecular based identification of resistance genes showed that bla-IMP genewas present in 32.1% (09) and bla-VIM was found positive in 17.8% (04) samples. Metallo-beta-lactamasesproducing genes (bla-VIM and bla-IMP), among carbapenem resistant Pseudomonas aeruginosa weredetected in 28.1% of samples. If other carbapenem resistant gene were also included this number mightbe higher Conclusions: PCR based test should be included in routine laboratory examination for quickdetection of the resistance causing genes.

scholarly journals Optimized Chitosan/Anion Polyelectrolyte Complex Based Inserts for Vaginal Delivery of Fluconazole: In Vitro/In Vivo Evaluation

Pharmaceutics ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 227 ◽  
Author(s):  
Bayan Darwesh ◽  
Hibah Aldawsari ◽  
Shaimaa Badr-Eldin
Keyword(s):  
Vaginal Delivery ◽  
Polyelectrolyte Complex ◽  
Inflammatory Cells ◽  
Antifungal Drugs ◽  
Vaginal Candidiasis ◽  
Histological Evaluation ◽  
Anionic Polymer ◽  
In Vivo Evaluation

(1) Background: Fluconazole, used orally for vaginal candidiasis, has reported gastrointestinal side effects. Therefore, researchers directed towards the drug vaginal delivery. However, vaginal delivery is limited by poor retention and leakage. Thus, this work aimed at exploring chitosan/anion polyelectrolyte complex (PEC) for the formulation of fluconazole vaginal inserts with controlled release and appreciable mucoadhesion. (2) Methods: PECs were prepared and assessed for interactions. Fluconazole PEC based vaginal inserts were prepared by lyophilization using mannitol. 3151 factorial design was applied to investigate the effect of the anion type and Chitosan/anion ratio on the inserts mucoadhesion and release properties. The optimized insert [based on 5:5 chitosan: anionic polymer (sodium alginate)] release was modulated by the release retardant; Compritol® 888. The selected formulation was subjected to microbiological and histological evaluation. (3) Results: Fluconazole inserts showed satisfactory drug content, acceptable friability percentages and highest swelling indices at six hours. Statistical analysis showed significant effect of the studied factors on detachment force and release properties. Microbiological assays revealed significantly higher antifungal activity of inserts compared to fluconazole solution. Reduced inflammatory cells were confirmed by histological evaluation. (4) Conclusion: CH/Alg based vaginal insert could be a promising platform for vaginal delivery of antifungal drugs used for vaginal candidiasis treatment.

scholarly journals Detection of VIM and NDM-1 metallo-beta-lactamase genes in carbapenem-resistant Pseudomonas aeruginosa clinical strains in Bahrain

2019 ◽  
Vol 11 (02) ◽  
pp. 138-143 ◽  
Author(s):  
Ronni Mol Joji ◽  
Nouf Al-Rashed ◽  
Nermin Kamal Saeed ◽  
Khalid Mubarak Bindayna
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Multiple Drug Resistance ◽  
Infectious Agent ◽  
Carbapenem Resistance ◽  
Conventional Polymerase Chain Reaction ◽  
Control Measures ◽  
Multiple Drug ◽  
Beta Lactamase ◽  
Infection Control Measures ◽  
Carbapenem Resistant

Abstract INTRODUCTION: Carbapenem-resistant Pseudomonas aeruginosa has emerged as a life-threatening infectious agent worldwide. Carbapenemase genes are reported to be some of the most common mechanisms for carbapenem resistance in P. aeruginosa. No reports are available from the Kingdom of Bahrain about carbapenem resistance and the underlying cause. In this study, we determined to study the presence of the metallo-beta-lactamase (M β L) genes of VIM family and NDM-1 in carbapenem-resistant P. aeruginosa strains. METHODOLOGY: Fifty carbapenem-resistant P. aeruginosa isolates were obtained from three main hospitals of Bahrain. They were subjected to antimicrobial susceptibility testing by disc diffusion test. Subsequently, MβL was detected by imipenem-ethylene diamine tetraacetic acid (EDTA) combined disc test and conventional polymerase chain reaction. RESULTS: Among 50 P. aeruginosa strains, 40 (80%) were imipenem resistant. Among the 40 imipenem-resistant strains, 35 (87.5%) strains were positive for the imipenem-EDTA combined disc test, and 21 (52%) were carrying MβL genes. Nineteen (47.5%) strains were positive for the VIM gene; one (2.5%) strain was carrying the NDM-1 gene, while one strain was carrying both the VIM and NDM-1 genes. None of the imipenem sensitive strains carried the VIM or NDM-1 gene. CONCLUSION: This is the first study to report the presence of the VIM family gene and NDM-1 genes in imipenem-resistant P. aeruginosa isolates in the Kingdom of Bahrain. The study also confirms the multiple drug resistance by the MβL strains, attention should therefore from now on, be focused on prevention of further spread of such isolates by firm infection control measures, and to reduce its threat to public health.

scholarly journals Promising Recent Strategies with Potential Clinical Translational Value to Combat Antibacterial Resistant Surge

Medicines ◽  
2019 ◽  
Vol 6 (1) ◽  
pp. 21 ◽  
Author(s):  
Partha Karmakar ◽  
Vishwanath Gaitonde
Keyword(s):  
Small Molecule ◽  
Multiple Drug Resistance ◽  
Resistance Mechanism ◽  
Multiple Drug ◽  
Antibacterial Efficacy ◽  
Small Particles ◽  
Near Future ◽  
Metal Polymer

Multiple drug resistance (MDR) for the treatment of bacterial infection has been a significant challenge since the beginning of the 21st century. Many of the small molecule-based antibiotic treatments have failed on numerous occasions due to a surge in MDR, which has claimed millions of lives worldwide. Small particles (SPs) consisting of metal, polymer or carbon nanoparticles (NPs) of different sizes, shapes and forms have shown considerable antibacterial effect over the past two decades. Unlike the classical small-molecule antibiotics, the small particles are less exposed so far to the bacteria to trigger a resistance mechanism, and hence have higher chances of fighting the challenge of the MDR process. Until recently, there has been limited progress of clinical treatments using NPs, despite ample reports of in vitro antibacterial efficacy. In this review, we discuss some recent and unconventional strategies that have explored the antibacterial efficacy of these small particles, alone and in combination with classical small molecules in vivo, and demonstrate possibilities that are favorable for clinical translations in near future.

scholarly journals Upregulation of activin signaling in experimental colitis

2009 ◽  
Vol 297 (4) ◽  
pp. G768-G780 ◽  
Author(s):  
You-Qing Zhang ◽  
Silvia Resta ◽  
Barbara Jung ◽  
Kim E. Barrett ◽  
Nora Sarvetnick
Keyword(s):  
Epithelial Cells ◽  
Growth Inhibition ◽  
Experimental Colitis ◽  
Inflammatory Cells ◽  
Treated Group ◽  
Activin Signaling ◽  
Mediators Of Inflammation ◽  
Induced Apoptosis

Several lines of studies have suggested that activins are critical mediators of inflammation and tissue repair. As activins and their receptors are expressed in the gastrointestinal tract, we tested the hypothesis that activin signaling is involved in the development of colitis by using two murine models of colitis induced by dextran sodium sulfate (DSS) or in mdr1a−/− mice. By immunohistochemistry, expression of activins was found increased in both models and correlated with the severity of inflammation. Activin expression was observed in macrophages as well as in some nonmacrophage cells. Furthermore, while activin receptors are normally expressed in colonic epithelial cells, their expression was further increased in both epithelial cells and inflammatory cells in inflamed colonic mucosa. Moreover, in vitro studies showed that activin A inhibited proliferation and induced apoptosis of intestinal epithelial cells, and this growth inhibition was largely reversed by administration of the activin inhibitor, follistatin. Because we also observed an increased number of apoptotic epithelial cells in both colitis models, the upregulation of activins occurring in colitis could be involved both in the inflammatory process and in growth inhibition of the intestinal epithelium. Importantly, in vivo administration of follistatin attenuated inflammatory cell infiltration during colitis. Rectal bleeding was reduced, and the integrity of epithelium was preserved in the DSS/follistatin-treated group compared with the group treated with DSS alone. Bromodeoxyuridine incorporation studies showed an increase in proliferative epithelial cells in the DSS/follistatin-treated group, suggesting that follistatin accelerates epithelial cell proliferation/repair during colitis. Overall, our results reveal that activin signaling may play an important role in the pathogenesis and resolution of colitis. These findings suggest new therapeutic options in inflammatory bowel diseases.

Mechanism Research of Reversal of Multidrug Resistance by the Application of 5-Bromotetrandrine and Magnetic Nanoparticle of Fe3O4 Combined with Daunorubicin in a Human-Nude Mice Xenograft Model

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5058-5058
Author(s):  
Bao-An Chen ◽  
Ya-nan Wu ◽  
Jian Cheng ◽  
Feng Gao ◽  
Wen-lin Xu ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Nude Mice ◽  
Magnetic Nanoparticle ◽  
Multiple Drug Resistance ◽  
Xenograft Model ◽  
Tumor Formation ◽  
Multiple Drug ◽  
Inhibition Rate ◽  
Group 5

Abstract Objective: To establish the xenograft leukemia model with stable multiple drug resistance in nude mice; to investigate the reversal effect of 5-Bromotetrandrine and Magnetic nanoparticle of Fe3O4 combined with DNR in vivo and to search for the possible reversal mechanisms. Methods: K562 and K562/A02 cells were respectively inoculated subcutaneously into back of athymic nude mice (1×107 cells/each) to establish the xenograft models. The tumor formation was evaluated by animal ultrasonic inspection. Tumors-bearing nude mice were assigned randomly to five groups which were treated with NS (A group); DNR 1mg/kg (B group); nanoparticle of Fe3O4 combined with DNR 0.63mg/kg(C group): 5-BrTet 2.5mg/kg combined with DNR(D group); 5-Bromotetrandrine 2.5mg/kg and Magnetic nanoparticle of Fe3O4 combined with DNR 0.63mg/kg(E group) respectively. The incidence of tumor formation, growth characteristics, weight and volume of tumor were observed. The histopathologic examination of tumors and organs were detected. For resistant tumors, the protein levels of P-glycoprotein (P-gp) were detected by Western blot. Results: The tumor incidence was 100% in the nude mice inoculated with either K562 or K562/A02 cells. In 6 to 9 days,the tumors reached a volume of more than 1 00 mm3. In vivo, MTT assay showed K562/A02 tumor maintained the drug resistance. For K562 cells xenograft tumors, there were no apparent differences in tumor suppression effect between the B AC AD AE group. For K562/A02 cells xenograft tumors, 5-BrTet and Magnetic nanoparticle of Fe3O4 combined with DNR significantly suppressed growth of tumor: the inhibition rate was 62.76% while DNR alone be used, the inhibition rate was 3.68%. Pathologic examination of resistant tumors showed the tumors necrosis obviously in E group. Application of 5-BrTet and Magnetic nanoparticle of Fe3O4 inhibited the overexpression of P-gp. Conclusion: The xenograft leukemia nude mice model was maintain the multiple drug resistance. 5-Bromotetrandrine and Magnetic nanoparticle of Fe3O4 combined with DNR had a significant tumor-suppressing effect on MDR leukemia cells xenograft model.

scholarly journals In Vitro and In Vivo Evaluation of BO-2727 against Imipenem- and/or Meropenem-resistant Pseudomonas aeruginosa.

1997 ◽  
Vol 50 (2) ◽  
pp. 135-138 ◽  
Author(s):  
KANEYOSHI SHIBATA ◽  
YUKA ADACHI ◽  
EIICHIRO KATO ◽  
RIE NAGANO ◽  
AISAKU FUSE ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
In Vivo Evaluation

scholarly journals Role of NADPH Phagocyte Oxidase in Host Defense against Acute Respiratory Acinetobacter baumannii Infection in Mice

2008 ◽  
Vol 77 (3) ◽  
pp. 1015-1021 ◽  
Author(s):  
Hongyu Qiu ◽  
Rhonda KuoLee ◽  
Greg Harris ◽  
Wangxue Chen
Keyword(s):  
Acinetobacter Baumannii ◽  
Host Defense ◽  
Multiple Drug Resistance ◽  
Bacterial Pathogen ◽  
Inflammatory Cells ◽  
Multiple Drug ◽  
Moderate Increase ◽  
Phagocyte Oxidase ◽  
Bacterial Replication

ABSTRACT Acinetobacter baumannii is an emerging bacterial pathogen that rapidly develops multiple-drug resistance and is responsible for many nosocomial pulmonary infections. This study investigated the role of the NADPH phagocyte oxidase (phox) and inducible nitric oxide synthase (NOS2) in the host defense against respiratory infection with A. baumannii in mouse models of intranasal A. baumannii infection. gp91phox−/− mice showed higher susceptibility to A. baumannii infection than wild-type (WT) C57BL/6 mice, with significantly greater bacterial counts in their lungs (1,000-fold) (P < 0.005) and spleens (10-fold) (P < 0.05). Moreover, all of the gp91phox−/− mice succumbed to infection within 48 h. In contrast, only a moderate increase in bacterial burdens was detected in the lungs of NOS2−/− mice, and all NOS2−/− mice survived infection. Compared to WT mice, the pulmonary influx of inflammatory cells and serum and local inflammatory cytokine/chemokine responses were not obviously impaired at 4 h and were significantly higher at 24 h (P < 0.05) in gp91phox−/− mice, but NADPH-deficient neutrophils were unable to control bacterial replication and extrapulmonary dissemination. Thus, NADPH phagocyte oxidase appears to play a crucial role in the neutrophil-mediated host defense against A. baumannii.

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