scholarly journals Stimulation of innate immunity by susceptible and multidrug-resistant Pseudomonas aeruginosa: an in vitro and in vivo study

2004 ◽  
Vol 135 (2) ◽  
pp. 240-246 ◽  
Author(s):  
E. J. GIAMARELLOS-BOURBOULIS ◽  
D. PLACHOURAS ◽  
A. TZIVRA ◽  
V. KOUSOULAS ◽  
N. BOLANOS ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Innate Immunity ◽  
Multidrug Resistant ◽  
In Vivo Study ◽  
Stimulation Of

scholarly journals In vitro and in vivo Pharmacodynamics of Colistin and Aztreonam Alone and in Combination against Multidrug-Resistant Pseudomonas aeruginosa

Chemotherapy ◽  
2016 ◽  
Vol 62 (2) ◽  
pp. 105-110 ◽  
Author(s):  
Yuka Yamagishi ◽  
Mao Hagihara ◽  
Hideo Kato ◽  
Jun Hirai ◽  
Naoya Nishiyama ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antimicrobial Activity ◽  
Antimicrobial Resistance ◽  
Multidrug Resistant ◽  
In Vivo Study ◽  
Infection Model ◽  
High Dose ◽  
Combination Therapies

Background: Reports of Pseudomonas aeruginosa with high antimicrobial resistance have steadily emerged, threatening the utility of a mainstay in antipseudomonal therapy. This study evaluated the antimicrobial activities of various combination therapies against P. aeruginosa with high antimicrobial resistance, including multidrug-resistant P. aeruginosa (MDRP) using an in vitro and in vivo study. Methods: We evaluated 24 combination therapies, including colistin, aztreonam, meropenem, ceftazidime, ciprofloxacin, amikacin, rifampicin, arbekacin and piperacillin against 15 MDRP isolates detected at Aichi Medical University Hospital with the break-point checkerboard method. Based on the results of the in vitro study, we evaluated antimicrobial activity against highly antimicrobial-resistant P. aeruginosa with an in vivo murine thigh infection model. Results: The combination regimens including colistin and aztreonam showed higher antimicrobial activity against the 15 MDRP isolates. In the in vivo study, the high-dose colistin monotherapy (16 mg/kg every 12 h) achieved greater log10 CFU changes than the normal-dose colistin regimen (8 mg/kg every 12 h) against 5 P. aeruginosa isolates, including 2 MDRP isolates (p < 0.05). Aztreonam monotherapy (400 mg every 8 h) yielded bacterial densities similar to untreated control mice for the MDRP isolate evaluated. The combination therapy with a higher dose of colistin had superior antimicrobial activity against 5 P. aeruginosa with colistin (MIC 0.5 μg/ml) and aztreonam (MIC ≥128 μg/ml) than colistin monotherapy. Conclusion: The data suggest that the combination treatment of colistin and aztreonam could be the most useful for treating highly resistant P. aeruginosa with a higher susceptibility to colistin, including MDRP infections.

scholarly journals Design of Epitope-Based Peptide Vaccine against Pseudomonas aeruginosa Fructose Bisphosphate Aldolase Protein Using Immunoinformatics

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Mustafa Elhag ◽  
Ruaa Mohamed Alaagib ◽  
Nagla Mohamed Ahmed ◽  
Mustafa Abubaker ◽  
Esraa Musa Haroun ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Peptide Vaccine ◽  
Multidrug Resistant ◽  
Fructose Bisphosphate ◽  
Mhc I ◽  
Mhc Ii ◽  
Fructose Bisphosphate Aldolase ◽  
Hospital Acquired

Pseudomonas aeruginosa is a common pathogen that is responsible for serious hospital-acquired infections, ventilator-associated pneumonia, and various sepsis syndromes. Also, it is a multidrug-resistant pathogen recognized for its ubiquity and its intrinsically advanced antibiotic-resistant mechanisms. It usually affects immunocompromised individuals but can also infect immunocompetent individuals. There is no vaccine against it available till now. This study predicts an effective epitope-based vaccine against fructose bisphosphate aldolase (FBA) of Pseudomonas aeruginosa using immunoinformatics tools. The protein sequences were obtained from NCBI, and prediction tests were undertaken to analyze possible epitopes for B and T cells. Three B cell epitopes passed the antigenicity, accessibility, and hydrophilicity tests. Six MHC I epitopes were found to be promising, while four MHC II epitopes were found promising from the result set. Nineteen epitopes were shared between MHC I and II results. For the population coverage, the epitopes covered 95.62% worldwide excluding certain MHC II alleles. We recommend in vivo and in vitro studies to prove its effectiveness.

Peptide polymer displaying potent activity against clinically isolated multidrug resistant Pseudomonas aeruginosa in vitro and in vivo

2020 ◽  
Vol 8 (2) ◽  
pp. 739-745 ◽  
Author(s):  
Weinan Jiang ◽  
Ximian Xiao ◽  
Yueming Wu ◽  
Weiwei Zhang ◽  
Zihao Cong ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antimicrobial Activity ◽  
Host Defense ◽  
Multidrug Resistant ◽  
Host Defense Peptide

Host defense peptide mimicking peptide polymer displayed potent in vitro and in vivo antimicrobial activity against clinically isolated multidrug resistant Pseudomonas aeruginosa.

scholarly journals Synergistic Efficacy of Aedes aegypti Antimicrobial Peptide Cecropin A2 and Tetracycline against Pseudomonas aeruginosa

2017 ◽  
Vol 61 (7) ◽  
Author(s):  
Zhaojun Zheng ◽  
Nagendran Tharmalingam ◽  
Qingzhong Liu ◽  
Elamparithi Jayamani ◽  
Wooseong Kim ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Aedes Aegypti ◽  
Mammalian Cells ◽  
Galleria Mellonella ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Synergistic Activity ◽  
Content Type

ABSTRACT The increasing prevalence of antibiotic resistance has created an urgent need for alternative drugs with new mechanisms of action. Antimicrobial peptides (AMPs) are promising candidates that could address the spread of multidrug-resistant bacteria, either alone or in combination with conventional antibiotics. We studied the antimicrobial efficacy and bactericidal mechanism of cecropin A2, a 36-residue α-helical cationic peptide derived from Aedes aegypti cecropin A, focusing on the common pathogen Pseudomonas aeruginosa. The peptide showed little hemolytic activity and toxicity toward mammalian cells, and the MICs against most clinical P. aeruginosa isolates were 32 to 64 μg/ml, and its MICs versus other Gram-negative bacteria were 2 to 32 μg/ml. Importantly, cecropin A2 demonstrated synergistic activity against P. aeruginosa when combined with tetracycline, reducing the MICs of both agents by 8-fold. The combination was also effective in vivo in the P. aeruginosa/Galleria mellonella model (P < 0.001). We found that cecropin A2 bound to P. aeruginosa lipopolysaccharides, permeabilized the membrane, and interacted with the bacterial genomic DNA, thus facilitating the translocation of tetracycline into the cytoplasm. In summary, the combination of cecropin A2 and tetracycline demonstrated synergistic antibacterial activity against P. aeruginosa in vitro and in vivo, offering an alternative approach for the treatment of P. aeruginosa infections.

scholarly journals A Galleria mellonella infection model reveals double and triple antibiotic combination therapies with enhanced efficacy versus a multidrug-resistant strain of Pseudomonas aeruginosa

2014 ◽  
Vol 63 (7) ◽  
pp. 945-955 ◽  
Author(s):  
Jessica Krezdorn ◽  
Sophie Adams ◽  
Peter J. Coote
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Resistant Strain ◽  
Galleria Mellonella ◽  
Multidrug Resistant ◽  
Therapeutic Benefit ◽  
Infection Model ◽  
Combination Therapies ◽  
Multidrug Resistant Strain

The aim of this study was to compare the inhibitory effect of antibiotic combinations in vitro with efficacy in Galleria mellonella larvae in vivo to identify efficacious combinations that target Pseudomonas aeruginosa. P. aeruginosa NCTC 13437, a multidrug-resistant strain resistant to β-lactams and aminoglycosides, was used. Susceptibility to cefotaxime, piperacillin, meropenem, amikacin, levofloxacin and colistin alone, or in dual or triple combinations, was measured in vitro via a 24 h time-kill assay. In vitro results were then compared with the efficacy of the same dual or triple antibiotic combinations versus G. mellonella larvae infected with P. aeruginosa. G. mellonella haemolymph burden of P. aeruginosa was determined over 96 h post-infection and treatment with the most potent combination therapies. Many dual and triple combinations of antibiotics displayed synergistic inhibition of multidrug-resistant P. aeruginosa in vitro. There was little correlation between combinations that were synergistic in vitro and those that showed enhanced efficacy in vivo versus infected G. mellonella larvae. The most potent dual and triple combinations in vivo were cefotaxime plus piperacillin, and meropenem plus piperacillin and amikacin, respectively. Fewer combinations were found to offer enhanced therapeutic benefit in vivo compared with in vitro. The therapeutic benefit arising from treatment with antibiotic combinations in vivo correlated with reduced larval burden of P. aeruginosa. This study has identified antibiotic combinations that merit further investigation for their clinical potential and has demonstrated the utility of using G. mellonella to screen for novel antibiotic treatments that demonstrate efficacy in vivo.

scholarly journals Multicenter Evaluation of Ceftazidime-Avibactam and Ceftolozane-Tazobactam Inhibitory Activity against Meropenem-Nonsusceptible Pseudomonas aeruginosa from Blood, Respiratory Tract, and Wounds

2017 ◽  
Vol 61 (10) ◽  
Author(s):  
Mordechai Grupper ◽  
Christina Sutherland ◽  
David P. Nicolau
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Inhibitory Activity ◽  
Clinical Utility ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Broth Microdilution ◽  
Content Type ◽  
Carbapenem Resistant

ABSTRACT The recent escalation of occurrences of carbapenem-resistant Pseudomonas aeruginosa has been recognized globally and threatens to erode the widespread clinical utility of the carbapenem class of compounds for this prevalent health care-associated pathogen. Here, we compared the in vitro inhibitory activity of ceftazidime-avibactam and ceftolozane-tazobactam against 290 meropenem-nonsusceptible Pseudomonas aeruginosa nonduplicate clinical isolates from 34 U.S. hospitals using reference broth microdilution methods. Ceftazidime-avibactam and ceftolozane-tazobactam were active, with ceftolozane-tazobactam having significantly higher inhibitory activity than ceftazidime-avibactam. The heightened inhibitory activity of ceftolozane-tazobactam was sustained when the site of origin (respiratory, blood, or wound) and nonsusceptibility to other β-lactam antimicrobials was considered. An extensive genotypic search for enzymatically driven β-lactam resistance mechanisms revealed the exclusive presence of the VIM metallo-β-lactamase among only 4% of the subset of isolates nonsusceptible to ceftazidime-avibactam, ceftolozane-tazobactam, or both. These findings suggest an important role for both ceftazidime-avibactam and ceftolozane-tazobactam against carbapenem-nonsusceptible Pseudomonas aeruginosa. Further in vitro and in vivo studies are needed to better define the clinical utility of these novel therapies against the increasingly prevalent threat of multidrug-resistant Pseudomonas aeruginosa.

scholarly journals A preliminary study of in vitro and in vivo synergistic effects of ciprofloxacin and D-tyrosine against Pseudomonas aeruginosa isolates

2020 ◽  
Vol 19 (8) ◽  
pp. 1731-1736
Author(s):  
Huirong Li ◽  
Wei Jiang ◽  
Xiaoshuang He ◽  
Mengting Chen
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Synergistic Effects ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Infection Model ◽  
Antimicrobial Effects ◽  
Kill Curve ◽  
Zebrafish Infection

Purpose: To investigate the synergistic antimicrobial effects of ciprofloxacin and D-tyrosine against drug-resistant bacteria.Method: The antimicrobial effects of ciprofloxacin and D-tyrosine on clinical isolates of multidrugresistant (MDR) Pseudomonas aeruginosa (P. aeruginosa) no. 3556 were determined in vitro based on time-kill curve, and in vivo in P. aeruginosa-zebrafish infection model. Furthermore, 30 clinical isolates of multidrug-resistant P. aeruginosa were used in vitro to ascertain the synergistic effect of the two agents.Results: Combined use of ciprofloxacin and D-tyrosine produced synergistic effects against the clinical isolate of P. aeruginosa no. 3556 in vitro and in vivo. Synergism occurred in 96.67 % (95 % CI, range 83.33 - 99.41 %) of the clinical isolates, and ciprofloxacin dose was reduced in 90 % (95 % CI, range 74.38 - 96.54 %) of the clinical isolates in vitro.Conclusion: These preliminary results suggest that the combination of ciprofloxacin and D-tyrosine is a promising therapeutic strategy against MDR P. aeruginosa infections. Keywords: Ciprofloxacin, D-tyrosine, Synergistic, P. aeruginosa, Zebrafish infection model, Time-killing curve

scholarly journals Host cystathionine-γ lyase derived hydrogen sulfide protects against Pseudomonas aeruginosa sepsis

2021 ◽  
Vol 17 (3) ◽  
pp. e1009473
Author(s):  
Georgios Renieris ◽  
Dionysia-Eirini Droggiti ◽  
Konstantina Katrini ◽  
Panagiotis Koufargyris ◽  
Theologia Gkavogianni ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Hydrogen Sulfide ◽  
Quorum Sensing ◽  
Sodium Thiosulfate ◽  
Multidrug Resistant ◽  
Aminooxyacetic Acid ◽  
Myeloperoxidase Activity ◽  
Synthesis Inhibitor

Hydrogen sulfide (H2S) has recently been recognized as a novel gaseous transmitter with several anti-inflammatory properties. The role of host- derived H2S in infections by Pseudomonas aeruginosa was investigated in clinical and mouse models. H2S concentrations and survival was assessed in septic patients with lung infection. Animal experiments using a model of severe systemic multidrug-resistant P. aeruginosa infection were performed using mice with a constitutive knock-out of cystathionine-γ lyase (Cse) gene (Cse-/-) and wild-type mice with a physiological expression (Cse+/+). Experiments were repeated in mice after a) treatment with cyclophosphamide; b) bone marrow transplantation (BMT) from a Cse+/+ donor; c) treatment with H2S synthesis inhibitor aminooxyacetic acid (ΑΟΑΑ) or propargylglycine (PAG) and d) H2S donor sodium thiosulfate (STS) or GYY3147. Bacterial loads and myeloperoxidase activity were measured in tissue samples. The expression of quorum sensing genes (QS) was determined in vivo and in vitro. Cytokine concentration was measured in serum and incubated splenocytes. Patients survivors at day 28 had significantly higher serum H2S compared to non-survivors. A cut- off point of 5.3 μΜ discriminated survivors with sensitivity 92.3%. Mortality after 28 days was 30.9% and 93.7% in patients with H2S higher and less than 5.3 μΜ (p = 7 x 10−6). In mice expression of Cse and application of STS afforded protection against infection with multidrug-resistant P. aeruginosa. Cyclophosphamide pretreatment eliminated the survival benefit of Cse+/+ mice, whereas BMT increased the survival of Cse-/- mice. Cse-/- mice had increased pathogen loads compared to Cse+/+ mice. Phagocytic activity of leukocytes from Cse-/- mice was reduced but was restored after H2S supplementation. An H2S dependent down- regulation of quorum sensing genes of P.aeruginosa could be demonstrated in vivo and in vitro. Endogenous H2S is a potential independent parameter correlating with the outcome of P. aeruginosa. H2S provides resistance to infection by MDR bacterial pathogens.

scholarly journals ANTIMICROBIAL ACTIVITY OF PINEAPPLE (ANANAS COMOSUS L. MERR) EXTRACT AGAINST MULTIDRUG-RESISTANT OF PSEUDOMONAS AERUGINOSA: AN IN VITRO STUDY

2017 ◽  
Vol 6 (5) ◽  
pp. 118 ◽  
Author(s):  
Rahmat Sayyid Zharfan ◽  
Priyo Budi Purwono ◽  
Arifa Mustika
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Minimum Inhibitory Concentration ◽  
Inhibitory Concentration ◽  
Minimum Bactericidal Concentration ◽  
Agar Plate ◽  
Multidrug Resistant ◽  
Ananas Comosus ◽  
Tract Infections

Pseudomonas aeruginosa is the main cause of nosocomial infection which is responsible for 10% of hospital-acquired infection. Pseudomonas aeruginosa tends to mutate and displays potential for development of antibiotic resistance. Approximately, 10% of global bacterial isolates are found as Multidrug-resistant Pseudomonas aeruginosa. Pseudomonas aeruginosa have a quite tremendous severity index, especially on pneumonia and urinary tract infections, even sepsis, which 50% mortality rate. Pineapple (Ananas comosus L. Merr) has antimicrobial properties. The active antimicrobial compounds in Ananas comosus L. Merr include saponin and bromelain. This research aims to find the potency of antimicrobial effect of pineapple (Ananas comosus L. Merr) extract towards Multidrug-resistant Pseudomonas aeruginosa. Multidrug-resistant Pseudomonas aeruginosa specimen is obtained from patient’s pus in orthopaedic department, Dr Soetomo Public Hospital, Surabaya. Multidrug-resistant Pseudomonas aeruginosa specimen is resistant to all antibiotic agents except cefoperazone-sulbactam. This research is conducted by measuring the Minimum Inhibitory Concentration (MIC) through dilution test with Mueller-Hinton broth medium. Pineapple extract (Ananas comosus L. Merr.) is dissolved in aquadest, then poured into test tube at varying concentrations (6 g/ml; 3 g/ml; 1.5 g/ml; 0.75 g/ml, 0.375 g/ml; and 0.1875 g/ml). After 24 hours’ incubation, samples are plated onto nutrient agar plate, to determine the Minimum Bactericidal Concentration (MBC). The extract of pineapple (Ananas comosus L. Merr) has antimicrobial activities against Multidrug-resistant Pseudomonas aeruginosa. Minimum Inhibitory Concentration (MIC) could not be determined, because turbidity changes were not seen. The Minimum Bactericidal Concentration (MBC) of pineapple extract (Ananas comosus L. Merr) to Multidrug-resistant Pseudomonas aeruginosa is 0.75 g/ml. Further study of in vivo is needed.

Biocontrôle de l’infection à Pseudomonas aeruginosa multi-résistant par les bactériophages en aquaculture en Côte d’Ivoire

2020 ◽  
Vol 154 ◽  
pp. 15940-15949
Author(s):  
Amian Aristide KOUDOU ◽  
Solange KAKOU-NGAZOA ◽  
Audrey ADDABLAH ◽  
Kouadio Bernard ALLALI ◽  
Serge AOUSSI ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Cote D'ivoire ◽  
Oreochromis Niloticus ◽  
Côte D’Ivoire ◽  
Bacterial Load ◽  
Multidrug Resistant ◽  
Cote D’Ivoire ◽  
Côte D'ivoire

Objectif : Cette étude a pour objectif d’évaluer la réduction de l’infection à Pseudomonas aeruginosa par les bactériophages en aquaculture Méthodologie et résultats : Le phage (PaBor1a) de la bio-collection des phages de l’Institut Pasteur de Côte d’Ivoire et la souche Pseudomonas aeruginosa (PA001-2018) multi-résistante isolée des poissons piscicoles ont été utilisés pour cette étude. D’une part dans les conditions in vitro, 100 µl d’une solution de phage (108 UFP) et de PA001-2018 ont été mis en culture dans 5 ml de bouillon Luria Bethani pendant 24 h. D’autre part dans les conditions in vivo, un aquarium de 5 L d’eau contenant 6 poissons (Oreochromis niloticus) a été inoculé avec 100 µl de PA001-2018 et du phage PaBor1a pendant 24 h. En présence du phage, la charge bactérienne a été réduite après 2-4 h dans les tests in vitro et in vivo. La décroissance de la population bactérienne et la croissance de celle du phage ont été parallèlement observée. Ce résultat démontre l’efficacité du phage PaBor1a dans le contrôle de la bactérie PA001- 2018 multi-résistante. Conclusion et applications des résultats: La réduction de la charge bactérienne montre le bio contrôle de l’infection à Pseudomonas aeruginosa par le phage PaBor1a. Ce résultat se propose comme alternative thérapeutique pour la lutte contre les infections bactérienne en aquaculture par la méthode balnéaire Mots clés : aquaculture, Oreochromis niloticus, multi-résistant, phages, Pseudomonas aeruginosa. Koudou et al., J. Appl. Biosci. 2020 Biocontrôle de l’infection à Pseudomonas aeruginosa multi-résistant par les bactériophages en aquaculture en Côte d’Ivoire 15941 Biocontrol of multidrug-resistant Pseudomonas aeruginosa infection by bacteriophages in Cote d’Ivoire aquaculture ABSTRACT Objective: To evaluate the reduction of Pseudomonas aeruginosa multi-resistant infection in aquaculture tests by phage activity. Methodology and Results: The phage (PaBor1a) from the phage bio-collection of the Pasteur Institute of Côte d'Ivoire was used against multi-resistant Pseudomonas aeruginosa (PA001-2018) isolated from aquaculture fish in this study. The test in vitro was conducted by culture of , the phage (108 PFU) and 100 µl of PA001- 2018 in 3 ml of Luria Bethani broth for 24 h. And the test in vivo occurs in aquarium tank of 5 L containing 6 fishes (Oreochromis niloticus), and inoculated with 100 µl of PA001-2018 and phage PaBor1a (108 PFU) for 24 h. The negative tests were conducted without phage PaBor1a under the same conditions. The results shows that the presence of the phage, the bacterial load was reduced after 2- 4 h in both tests. Bacterial decay and phage growth were observed in parallel. This result demonstrates the efficacy of phage PaBor1a against the multidrug resistant PA001- 2018 bacteria in aquarium tank. Conclusion and applications of results: reduction of bacterial load show the bio control of Pseudomonas aeruginosa infection by phage PaBor1a. This result is proposed as a therapeutic alternative in aquaculture against bacterial infection in aquaculture by washing method Keywords: aquaculture, Pseudomonas aeruginosa, multi-resistant, phages

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