Lysine-Based Small Molecule Sensitizes Rifampicin and Tetracycline against Multidrug-Resistant Acinetobacter baumannii and Pseudomonas aeruginosa

2019 ◽  
Vol 6 (1) ◽  
pp. 91-99
Author(s):  
Mohini Mohan Konai ◽  
Jayanta Haldar
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Acinetobacter Baumannii ◽  
Small Molecule ◽  
Multidrug Resistant

scholarly journals Prevalence of multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa in an Italian hospital

2013 ◽  
Vol 6 (3) ◽  
pp. 179-185 ◽  
Author(s):  
M.A. De Francesco ◽  
G. Ravizzola ◽  
L. Peroni ◽  
C. Bonfanti ◽  
N. Manca
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Acinetobacter Baumannii ◽  
Multidrug Resistant ◽  
Italian Hospital

scholarly journals A Rapid Phenotypic Whole-Cell Screening Approach for the Identification of Small-Molecule Inhibitors That Counter β-Lactamase Resistance in Pseudomonas aeruginosa

2017 ◽  
Vol 23 (1) ◽  
pp. 55-64 ◽  
Author(s):  
Deanna Collia ◽  
Thomas D. Bannister ◽  
Hao Tan ◽  
Shouguang Jin ◽  
Taimour Langaee ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Small Molecule ◽  
Small Molecule Inhibitors ◽  
Laboratory Strain ◽  
Multidrug Resistant ◽  
First Line ◽  
Strain Pao1 ◽  
Whole Cell ◽  
Bacterial Sensitivity ◽  
Opportunistic Human Pathogen

Pseudomonas aeruginosa is an opportunistic human pathogen that is prevalent in hospitals and continues to develop resistance to multiple classes of antibiotics. Historically, β-lactam antibiotics have been the first line of therapeutic defense. However, the emergence of multidrug-resistant (MDR) strains of P. aeruginosa, such as AmpC β-lactamase overproducing mutants, limits the effectiveness of current antibiotics. Among AmpC hyperproducing clinical isolates, inactivation of AmpG, which is essential for the expression of AmpC, increases bacterial sensitivity to β-lactam antibiotics. We hypothesize that inhibition of AmpG activity will enhance the efficacy of β-lactams against P. aeruginosa. Here, using a highly drug-resistant AmpC-inducible laboratory strain PAO1, we describe an ultra-high-throughput whole-cell turbidity assay designed to identify small-molecule inhibitors of the AmpG. We screened 645,000 compounds to identify compounds with the ability to inhibit bacterial growth in the presence of cefoxitin, an AmpC inducer, and identified 2663 inhibitors that were also tested in the absence of cefoxitin to determine AmpG specificity. The Z′ and signal-to-background ratio were robust at 0.87 ± 0.05 and 2.2 ± 0.2, respectively. Through a series of secondary and tertiary studies, including a novel luciferase-based counterscreen, we ultimately identified eight potential AmpG-specific inhibitors.

scholarly journals Evaluation of Moringa Peregrina (Forsk) Fiori, Leaf and Seed Extract Against Multidrug Resistant Strains of Bacteria and Fungus of Clinical Origin

2021 ◽  
Vol 3 (1) ◽  
pp. 20-26
Author(s):  
Suliman Mansour Albalawi ◽  
Abdulrahman K. Al-Asmari ◽  
Syed Rafatullah ◽  
Maysa Mahfoud
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Growth Inhibition ◽  
Acinetobacter Baumannii ◽  
Bacterial Resistance ◽  
Antimicrobial Agents ◽  
Colorimetric Assay ◽  
Multidrug Resistant ◽  
Klebsiella Pneumonia ◽  
Isolation And Purification ◽  
Moringa Peregrina

  The emergence of antibiotic resistant microorganism strains has become a critical concern in the treatment of infectious diseases and makes the search of an alternative therapy a must. The study was designed to evaluate the in vitro antimicrobial activities of the Moringa peregrina (MP) leave (MPL) and seed (MPS) extracts. Antimicrobial assays were performed using a microplate growth inhibition assay against 11 multidrug-resistant (MDR) strains. Following qualitative analysis, dose-response assays were performed using the MTT colorimetric assay. The results showed a strong correlation between the MPL and MPS extract concentration and growth inhibition (P<0.001). MP extract revealed a remarkable antimicrobial effect and inhibited the growth and survival of MDR pathogens which include Escherichia coli; Pseudomonas aeruginosa; Klebsiella pneumonia; Acinetobacter baumannii; Staphylococcus aureus between (88.6-94.7 %) and between (62.3- 88.7%) against Candida Kefyer; Candida parapsilosis; Candida albicans; Candida glabrata; Aspergillus flavus and Fusarium oxysporum. MIC50 ranging from ≤6.25 to 25 mg/mL. Acinetobacter baumannii and Pseudomonas aeruginosa were the most susceptible to MP extracts (MIC50 < 6.25 mg/mL). These results support the use of MP in Arab traditional medicine as natural antimicrobial agents. Additionally, the use of such naturally occurring adjuvant derived from medicinal plants can be used as an adjuvant with synthetic antibiotics to combat bacterial resistance and to enhance the antibacterial potential. Further studies are recommended on isolation and purification of novel antimicrobial molecules to treat the infections caused by microbes.  

scholarly journals In VitroActivity of RX-P873 against Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter baumannii

2015 ◽  
Vol 59 (4) ◽  
pp. 2280-2285 ◽  
Author(s):  
Robert K. Flamm ◽  
Paul R. Rhomberg ◽  
Ronald N. Jones ◽  
David J. Farrell
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Acinetobacter Baumannii ◽  
Active Agent ◽  
Multidrug Resistant ◽  
Surveillance Program ◽  
Gram Negative ◽  
Content Type ◽  
Highly Active ◽  
Bacterial Ribosome

ABSTRACTRX-P873 is a novel antibiotic from the pyrrolocytosine series which exhibits high binding affinity for the bacterial ribosome and broad-spectrum antibiotic properties. The pyrrolocytosines have shownin vitroactivity against multidrug-resistant Gram-negative and Gram-positive strains of bacteria known to cause complicated urinary tract, skin, and lung infections, as well as sepsis.Enterobacteriaceae(657),Pseudomonas aeruginosa(200), andAcinetobacter baumannii(202) isolates from North America and Europe collected in 2012 as part of a worldwide surveillance program were testedin vitroby broth microdilution using Clinical and Laboratory Standards Institute (CLSI) methodology. RX-P873 (MIC90, 0.5 μg/ml) was >32-fold more active than ceftazidime and inhibited 97.1% and 99.5% ofEnterobacteriaceaeisolates at MIC values of ≤1 and ≤4 μg/ml, respectively. There were only three isolates with an MIC value of >4 μg/ml (all were indole-positiveProtea). RX-P873 (MIC50/90, 2/4 μg/ml) was highly active againstPseudomonas aeruginosaisolates, including isolates which were nonsusceptible to ceftazidime or meropenem. RX-P873 was 2-fold less active againstP. aeruginosathan tobramycin (MIC90, 2 μg/ml; 91.0% susceptible) and colistin (MIC90, 2 μg/ml; 99.5% susceptible) and 2-fold more potent than amikacin (MIC90, 8 μg/ml; 93.5% susceptible) and meropenem (MIC90, 8 μg/ml; 76.0% susceptible). RX-P873, the most active agent againstAcinetobacter baumannii(MIC90, 1 μg/ml), was 2-fold more active than colistin (MIC90, 2 μg/ml; 97.0% susceptible) and 4-fold more active than tigecycline (MIC90, 4 μg/ml). This novel agent merits further exploration of its potential against multidrug-resistant Gram-negative bacteria.

scholarly journals Treatment of multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii pneumonia

2005 ◽  
Vol 4 (2) ◽  
pp. 149-150 ◽  
Author(s):  
Matthew E. Falagas ◽  
Sofia K. Kasiakou ◽  
Argyris Michalopoulos
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Acinetobacter Baumannii ◽  
Multidrug Resistant

scholarly journals Activity of cefiderocol against high-risk clones of multidrug-resistant Enterobacterales, Acinetobacter baumannii, Pseudomonas aeruginosa and Stenotrophomonas maltophilia

2020 ◽  
Vol 75 (7) ◽  
pp. 1840-1849 ◽  
Author(s):  
Mercedes Delgado-Valverde ◽  
M del Carmen Conejo ◽  
Lara Serrano ◽  
Felipe Fernández-Cuenca ◽  
Álvaro Pascual
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Acinetobacter Baumannii ◽  
Stenotrophomonas Maltophilia ◽  
Enterobacter Cloacae ◽  
Multidrug Resistant ◽  
In Vitro Activity ◽  
Carbapenem Resistant ◽  
Excellent Activity ◽  
In Vitro Antibacterial Activity

Abstract Background Cefiderocol is a novel siderophore cephalosporin, developed for activity against MDR Gram-negative bacilli (MDR-GNB). Objectives To assess the in vitro antibacterial activity of cefiderocol against a collection of MDR-GNB clinical isolates from hospitals in southern Spain. Methods Two hundred and thirty-one isolates of successful clones were tested: 125 Enterobacterales (121 ESBL- and/or carbapenemase-producing Klebsiella pneumoniae and 4 carbapenemase-producing Enterobacter cloacae), 80 Acinetobacter baumannii, 6 Pseudomonas aeruginosa and 20 Stenotrophomonas maltophilia. Ceftolozane/tazobactam, ceftazidime, ceftazidime/avibactam, cefepime, aztreonam, meropenem, amikacin, ciprofloxacin, colistin and tigecycline were used as comparators against Enterobacterales, P. aeruginosa and A. baumannii. Minocycline, levofloxacin and trimethoprim/sulfamethoxazole were studied against S. maltophilia instead of aztreonam, ciprofloxacin and cefepime. MICs were determined by broth microdilution according to CLSI guidelines. MIC determination was performed in CAMHB for all antimicrobials except cefiderocol, where iron-depleted CAMHB was used. Results Cefiderocol showed potent in vitro activity against the isolates analysed. MIC50 and MIC90 values were in the ranges 0.125–8 mg/L and 0.5–8 mg/L, respectively, and 98% of isolates were inhibited at ≤4 mg/L. Only five isolates showed cefiderocol MICs of &gt;4 mg/L: three ST2/OXA-24/40-producing A. baumannii, one ST114/VIM-1-producing E. cloacae and one ST114/VIM-1 + OXA-48-producing E. cloacae. All KPC-3-producing K. pneumoniae were susceptible to cefiderocol, even those resistant to ceftazidime/avibactam. P. aeruginosa isolates showed cefiderocol MICs of &lt;4 mg/L, including those resistant to ceftolozane/tazobactam. S. maltophilia isolates displayed cefiderocol MICs of &lt;4 mg/L, including those resistant to levofloxacin and/or trimethoprim/sulfamethoxazole. Conclusions Cefiderocol showed excellent activity against MDR-GNB, including carbapenem-resistant isolates, and was the most active antimicrobial tested against this collection.

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