scholarly journals Antimicrobial Activity and Toxicity of the Major Lipopeptide Components of Polymyxin B and Colistin: Last-Line Antibiotics against Multidrug-Resistant Gram-Negative Bacteria

2015 ◽  
Vol 1 (11) ◽  
pp. 568-575 ◽  
Author(s):  
Kade D. Roberts ◽  
Mohammad A. K. Azad ◽  
Jiping Wang ◽  
Andrew S. Horne ◽  
Philip E. Thompson ◽  
...  
2019 ◽  
Vol 40 (6) ◽  
pp. 838-845 ◽  
Author(s):  
Ojas Jyoti Singh Pujji ◽  
Kiran Kishor Nakarmi ◽  
Basudha Shrestha ◽  
Shankar Man Rai ◽  
Steven Leonard Alexander Jeffery

AbstractIn Nepal, burn is the third most common injury after falls and road traffic accidents. Infection is the leading cause of mortality in burn injury. A profile exploring predominant flora and antimicrobial sensitivity is important to facilitate treatment ahead of microbiology results and to aid prevention of multidrug-resistant organisms. The aim of this study was to document epidemiological and bacteriological data of burn wound infections at a tertiary level burns center in Nepal. Samples were collected from January 2017 to May 2017, over a period of 5 months. Patient notes were referred to and information regarding baseline characteristics and burn wound infection data was collected. A total of 76 patients were included in the study during the 5-month period, which resulted in 113 samples being included for review. Females were injured most with burns 70% (n = 53) compared with males 30% (n = 23). Only 6 (8%) of 77 patients lived locally in Kathmandu. The average distance traveled by patients was 233 km (median 208, range 0–765, SD 181). Average TBSA% of burn was 22% (median 20, range 3–50, SD 12). Gram-negative organisms predominated, with Acinetobacter spp. in 42 cases (55%), Pseudomonas aeruginosa in 26 cases (34%), and Enterobacter spp. in 16 cases (21%). Colistin, polymyxin B, and tigecycline were found to be most sensitive covering 108, 98, and 94 organisms. Gram-negative bacteria colonized the majority of burn wounds. Colistin, polymyxin B, and tigecycline were the most sensitive to gram-negative bacteria. Gram-positive Staphylococcus aureus was sensitive most to vancomycin and tigecycline.


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.


PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e10176
Author(s):  
Maki K. Ohno ◽  
Teruo Kirikae ◽  
Eisaku Yoshihara ◽  
Fumiko Kirikae ◽  
Isao Ishida

Background Antimicrobial peptides have a broad spectrum of antimicrobial activities and are attracting attention as promising next-generation antibiotics against multidrug-resistant (MDR) bacteria. The all-d-enantiomer [D(KLAKLAK)2] has been reported to have antimicrobial activity against Escherichia coli and Pseudomonas aeruginosa, and to be resistant to protein degradation in bacteria because it is composed of D-enantiomer compounds. In this study, we demonstrated that modification of [D(KLAKLAK)2] by the addition of an L-cysteine residue to its N- or C- terminus markedly enhanced its antimicrobial activities against Gram-negative bacteria such as MDR Acinetobacter baumannii, E. coli, and P. aeruginosa. Methods The peptides [D(KLAKLAK)2] (DP), DP to which L-cysteine was added at the N-terminus C-DP, and DP to which L-cysteine was added at the C-terminus DP-C, were synthesized at >95% purity. The minimum inhibitory concentrations of peptides and antibiotics were determined by the broth microdilution method. The synergistic effects of the peptides and the antibiotics against MDR P. aeruginosa were evaluated using the checkerboard dilution method. In order to assess how these peptides affect the survival of human cells, cell viability was determined using a Cell Counting Kit-8. Results C-DP and DP-C enhanced the antimicrobial activities of the peptide against MDR Gram-negative bacteria, including A. baumannii, E. coli, and P. aeruginosa. The antimicrobial activity of DP-C was greater than that of C-DP, with these peptides also having antimicrobial activity against drug-susceptible P. aeruginosa and drug-resistant P. aeruginosa overexpressing the efflux pump components. C-DP and DP-C also showed antimicrobial activity against colistin-resistant E. coli harboring mcr-1, which encodes a lipid A modifying enzyme. DP-C showed synergistic antimicrobial activity against MDR P. aeruginosa when combined with colistin. The LD50 of DP-C against a human cell line HepG2 was six times higher than the MIC of DP-C against MDR P. aeruginosa. The LD50 of DP-C was not altered by incubation with low-dose colistin. Conclusion Attachment of an L-cysteine residue to the N- or C-terminus of [D(KLAKLAK)2] enhanced its antimicrobial activity against A. baumannii, E. coli, and P. aeruginosa. The combination of C-DP or DP-C and colistin had synergistic effects against MDR P. aeruginosa. In addition, DP-C and C-DP showed much stronger antimicrobial activity against MDR A. baumannii and E. coli than against P. aeruginosa.


2017 ◽  
Vol 9 (02) ◽  
pp. 081-083 ◽  
Author(s):  
Chinjal A. Panchal ◽  
Sweta Sunil Oza ◽  
Sanjay J. Mehta

Abstract CONTEXT: Metallo-β-lactamase (MBL)-producing bacteria lead to resistance to carbapenem an antibiotic that used as the last resort for treatment of multidrug-resistant bacteria, extended spectrum beta-lactamases, and AmpC β-lactamase-producing Gram-negative bacteria (GNB). The emergence of MBL-producing GNB is challenge to microbiology laboratories because there are no standardized guidelines available to detect them. The aim of this study was to compare four phenotypic methods to detect MBL production in GNB and to determine antibiotic sensitivity of MBL-producing isolates. MATERIALS AND METHODS: A total of 107 clinical isolates of GNB were tested for MBL production. Imipenem (IPM)-resistant GNB were taken as positive for MBL screening. MBL detection was done using ethylene diamine tetra acetic acid (EDTA) as MBL inhibitor. Four phenotypic methods were evaluated: (1) Combined disk synergy test (CDST) with 0.5M EDTA (CDST-0.5 M EDTA), (2) CDST with 0.1 M EDTA (CDST-0.1 M EDTA), (3) double-disk synergy test (DDST) with 0.5M EDTA (DDST-0.5 M EDTA), and (4) DDST with 0.1 M EDTA (DDST-0.1 M EDTA). RESULTS: Out of 107 GNB, 30 were resistant to IPM considered as screening positive. Out of 30, 21 (70%) isolates were MBL positive by CDST-0.1 M EDTA, 19 (63.33%) by CDST-0.5M EDTA, 17 (56.67%) by DDST-0.1 M EDTA, and 16 (53.33%) by DDST-0.5M EDTA. All MBL-producing Gram-negative Bacilli were resistant to ampicillin/sulbactam. Polymyxin B was found to be the most sensitive drug. CONCLUSION: CDST-0.1 M EDTA is the most sensitive method MBL detection. The detection of MBL-producing GNB is very important to control spread of the resistance.


1996 ◽  
Vol 40 (6) ◽  
pp. 1438-1441 ◽  
Author(s):  
A Kubo ◽  
C S Lunde ◽  
I Kubo

Combinations of polymyxins and phytochemicals were tested for antimicrobial activity against two gram-negative bacteria. Various degrees of potentiation were found against Pseudomonas aeruginosa and Escherichia coli with (E)-2-hexenal and indole. Three-compound combinations were found to further increase the activity of polymyxin B sulfate and colistin methanesulfonate against both bacteria. Combinations with colistin against P. aeruginosa resulted in the highest degree of potentiation, with a 512-fold increase in colistin antimicrobial activity. These results indicate the potential efficacy of phytochemical combinations with antibiotics to enhance total biological activity.


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