scholarly journals O6‐2: A novel broad‐spectrum peptide therapy for acute and chronic lung infections with multidrug‐resistant gram‐negative bacteria

Respirology ◽  
2021 ◽  
Vol 26 (S3) ◽  
pp. 18-18
Antibiotics ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 718 ◽  
Author(s):  
Gervonne Barran ◽  
Jolanta Kolodziejek ◽  
Laurent Coquet ◽  
Jérôme Leprince ◽  
Thierry Jouenne ◽  
...  

Ocellatins are peptides produced in the skins of frogs belonging to the genus Leptodactylus that generally display weak antimicrobial activity against Gram-negative bacteria only. Peptidomic analysis of norepinephrine-stimulated skin secretions from Leptodactylus insularum Barbour 1906 and Leptodactylus nesiotus Heyer 1994, collected in the Icacos Peninsula, Trinidad, led to the purification and structural characterization of five ocellatin-related peptides from L. insularum (ocellatin-1I together with its (1–16) fragment, ocellatin-2I and its (1–16) fragment, and ocellatin-3I) and four ocellatins from L. nesiotus (ocellatin-1N, -2N, -3N, and -4N). While ocellatins-1I, -2I, and -1N showed a typically low antimicrobial potency against Gram-negative bacteria, ocellatin-3N (GIFDVLKNLAKGVITSLAS.NH2) was active against an antibiotic-resistant strain of Klebsiella pneumoniae and reference strains of Escherichia coli, K. pneumoniae, Pseudomonas aeruginosa, and Salmonella typhimurium (minimum inhibitory concentrations (MICs) in the range 31.25–62.5 μM), and was the only peptide active against Gram-positive Staphylococcus aureus (MIC = 31.25 μM) and Enterococcus faecium (MIC = 62.5 μM). The therapeutic potential of ocellatin-3N is limited by its moderate hemolytic activity (LC50 = 98 μM) against mouse erythrocytes. The peptide represents a template for the design of long-acting, non-toxic, and broad-spectrum antimicrobial agents for targeting multidrug-resistant pathogens.


mSphere ◽  
2017 ◽  
Vol 2 (5) ◽  
Author(s):  
Michael P. Motley ◽  
Bettina C. Fries

ABSTRACT With the problem of multidrug-resistant Gram-negative pathogens becoming increasingly dire, new strategies are needed to protect and treat infected patients. Though abandoned in the past, monoclonal antibody therapy against Gram-negative bacteria remains a potential solution and has potential advantages over the broad-spectrum antibiotics they were once replaced by. With the problem of multidrug-resistant Gram-negative pathogens becoming increasingly dire, new strategies are needed to protect and treat infected patients. Though abandoned in the past, monoclonal antibody therapy against Gram-negative bacteria remains a potential solution and has potential advantages over the broad-spectrum antibiotics they were once replaced by. This Perspective reviews the prospect of utilizing monoclonal antibody therapy against these pathogens, as well as the challenges of doing so and the current therapy targets under investigation.


Molecules ◽  
2018 ◽  
Vol 23 (5) ◽  
pp. 1212 ◽  
Author(s):  
Mirjana Skočibušić ◽  
Renata Odžak ◽  
Alma Ramić ◽  
Tomislav Smolić ◽  
Tomica Hrenar ◽  
...  

2006 ◽  
Vol 17 (5) ◽  
pp. 267-269 ◽  
Author(s):  
JM Conly ◽  
BL Johnston

The polymyxins were discovered in the 1940s and represent a group of closely related polypeptide antibiotics obtained fromBacillus polymyxa, which was originally isolated from soil (1,2). Although they have been used extensively worldwide in topical otic and ophthalmic solutions for decades, the intravenous formulations were gradually abandoned in most parts of the world in the early 1980s because of the reported high incidence of nephrotoxicity (3-5). As a result, the use of polymyxin preparations has been mainly restricted to the treatment of lung infections due to multidrug-resistant (MDR) gram-negative bacteria in patients with cystic fibrosis (6,7). The emergence of bacteria resistant to most classes of commercially available antibiotics and the shortage of novel antimicrobial agents with activity against gram-negative microorganisms have led to the reemergence of polymyxins as a valuable addition to the therapeutic armamentarium. It was thus considered timely to review colistin and its emerging role in managing infections due to MDR gram-negative bacteria.


2020 ◽  
Vol 63 (13) ◽  
pp. 6941-6958 ◽  
Author(s):  
Pietro Picconi ◽  
Charlotte K. Hind ◽  
Kazi S. Nahar ◽  
Shirin Jamshidi ◽  
Lucia Di Maggio ◽  
...  

2021 ◽  
Author(s):  
Xukai Jiang ◽  
Nitin A. Patil ◽  
Mohammad A. K. Azad ◽  
Hasini Wickremasinghe ◽  
Heidi Yu ◽  
...  

Multidrug-resistant Gram-negative bacteria have been an urgent threat to global public health. Novel antibiotics are desperately needed to combat these 'superbugs'.


Antibiotics ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 340
Author(s):  
Raquel Bandeira da Silva ◽  
Mauro José Salles

Gram-negative bacteria (GNB), including multidrug-resistant (MDR) pathogens, are gaining importance in the aetiology of prosthetic joint infection (PJI). This retrospective observational study identified independent risk factors (RFs) associated with MDR-GNB PJI and their influence on treatment outcomes. We assessed MDR bacteria causing hip and knee PJIs diagnosed at a Brazilian tertiary hospital from January 2014 to July 2018. RFs associated with MDR-GNB PJI were estimated by bivariate and multivariate analyses using prevalence ratios (PRs) with significance at p < 0.05. Kaplan–Meier analysis was performed to evaluate treatment outcomes. Overall, 98 PJI patients were analysed, including 56 with MDR-GNB and 42 with other bacteria. Independent RFs associated with MDR-GNB PJI were revision arthroplasty (p = 0.002), postoperative hematoma (p < 0.001), previous orthopaedic infection (p = 0.002) and early infection (p = 0.001). Extensively drug-resistant GNB (p = 0.044) and comorbidities (p = 0.044) were independently associated with MDR-GNB PJI treatment failure. In sum, MDR-GNB PJI was independently associated with previous orthopaedic surgery, postoperative local complications and pre-existing infections and was possibly related to selective pressure on bacterial skin colonisation by antibiotics prescribed for early PJI. Infections due to MDR-GNB and comorbidities were associated with higher treatment failure rates.


ACS Omega ◽  
2021 ◽  
Author(s):  
Faizan Abul Qais ◽  
Mohammad Shavez Khan ◽  
Iqbal Ahmad ◽  
Fohad Mabood Husain ◽  
Rais Ahmad Khan ◽  
...  

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